The association between serum copper concentration and prevalence of diabetes among US adults with hypertension (NHANES 2011-2016).

The objective of this study was to examine the association between the serum copper concentration and the prevalence of diabetes among US adults with hypertension using the data from the National Health and Nutrition Examination Survey (NHANES). The study population was selected from adults aged over 20 years old in the three survey cycles of NHANES from 2011 to 2016. Logistic regression model analyses were applied to determine the independent risky effect of copper to the prevalence of diabetes. Also, a restricted cubic spline (RCS) model was performed to explore the potential nonlinear association between serum copper concentration and the prevalence of diabetes. A total of 1786 subjects (742 cases and 1044 controls) were included, and 924 were men (51.7%), and 742 (41.5%) were diabetic. Compared with non-diabetic individuals, the concentration of serum copper in diabetic patients with hypertension was higher. After adjusting for age, sex, race, education, marital status, body mass index (BMI), family poverty income ratio (PIR), smoking, alcohol drinking, physical activity, systolic blood pressure (SBP), diastolic blood pressure (DBP), and hyperlipidemia, the highest quartile of serum copper concentration significantly increased the risk of diabetes as compared with the lowest quartile (OR: 1.38, 95% CI: 1.01-1.92, ptrend = 0.036). The results of RCS analysis showed significant non-linear relationship between serum copper concentration and prevalence of diabetes (p-non-linear = 0.010). This study finds that serum copper concentration are significantly associated with risk of diabetes in hypertensive patients, which suggests copper as an important risk factor of diabetes development.

Transplantation of miR-193b-3p-Transfected BMSCs Improves Neurological Impairment after Traumatic Brain Injury through S1PR3-Mediated Regulation of the PI3K/AKT/mTOR Signaling Pathway.

The aim of the present study was to explore the molecular mechanisms by which miR-193b-3p-trans-fected bone marrow mesenchymal stem cells (BMSCs) transplantation improves neurological impairment after traumatic brain injury (TBI) through sphingosine-1-phosphate receptor 3 (S1PR3)-mediated regulation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway at the cellular and animal levels. BMSCs were transfected with miR-193b-3p. A TBI cell model was established by oxygen-glucose deprivation (OGD)-induced HT22 cells, and a TBI animal model was established by controlled cortical impact (CCI). Cell apoptosis was detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL), and cell activity was detected by a cell counting kit 8 (CCK-8) assay. Western blot analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of related proteins and genes. In this study, transfection of miR-193b-3p into BMSCs significantly enhanced BMSCs proliferation and differentiation. Transfection of miR-193b-3p reduced the levels of the interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-alpha (TNF-α) inflammatory factors in cells and mouse models, and it inhibited neuronal apoptosis, which alleviated OGD-induced HT22 cell damage and neural function damage in TBI mice. Downstream experiments showed that miR-193b-3p targeting negatively regulated the expression of S1PR3, promoted the activation of the PI3K/AKT/mTOR signaling pathway, and inhibited the levels of apoptosis and inflammatory factors, which subsequently improved OGD-induced neuronal cell damage and nerve function damage in TBI mice. However, S1PR3 overexpression or inhibition of the PI3K/AKT/mTOR signaling pathway using the IN-2 inhibitor weakened the protective effect of miR-193b-3p-transfected BMSCs on HT22 cells. Transplantation of miR-193b-3p-transfected BMSCs inhibits neurological injury and improves the progression of TBI in mice through S1PR3-mediated regulation of the PI3K/AKT/mTOR pathway.

Nipped-A regulates the Drosophila circadian clock via histone deubiquitination.

Psychiatric diseases are often accompanied by circadian disruptions, but the molecular underpinnings remain largely unclear. To address this, we screened genes that have been previously reported to be associated with psychiatric diseases and found that TRRAP, a gene associated with schizophrenia, is involved in circadian rhythm regulation. Knocking down Nipped-A, the Drosophila homolog of human TRRAP, leads to lengthened period of locomotor rhythms in flies. Molecular analysis demonstrates that NIPPED-A sets the pace of the clock by increasing the mRNA and protein levels of core clock genes timeless (tim) and Par domain protein 1ε (Pdp1ε). Furthermore, we found that NIPPED-A promotes the transcription of tim and Pdp1ε possibly by facilitating deubiquitination of histone H2B via the deubiquitination module of the transcription co-activator Spt-Ada-Gcn5 acetyltransferase complex. Taken together, these findings reveal a novel role for NIPPED-A in epigenetic regulation of the clock.

Gene therapy in Aß-induced cell and mouse models of Alzheimer's disease through compensating defective mitochondrial complex I function.

BACKGROUND: Alzheimer's disease (AD) is the most common neurogenerative disorder without effective treatments. Defects in mitochondrial complex I are thought to contribute to AD pathogenesis. The aim of this study is to explore whether a novel gene therapy transducing yeast complex I gene NDI1 can be used to treat AD with severely reduced complex I function in cell and animal models. METHODS: The differentiated human neural cells were induced by Aß1-42 to establish the AD cell model, and adeno-associated virus serotype 9 (AAV9) was used to transduce yeast NDI1 into the cell model. Aß1-42 was injected into the hippocampus area of the brain to establish the AD mouse model. AAV9-NDI1 was injected stereotaxically into the hippocampus area to test the therapeutic effect. RESULTS: The expressed yeast complex I had an ameliorating effect on the defective function of human complex I and cellular pathological characteristics in the AD cell model. Furthermore, AAV9-NDI1 gene therapy in the hippocampus had a therapeutic effect on various aspects of mitochondrial function, histopathological characteristics and neurological defects in the AD mouse model. In addition, AAV9-NDI1 injection into the hippocampus of normal mice did not cause any adverse effect. CONCLUSIONS: Compensating mitochondrial complex I function with yeast NDI1 is effective for gene therapy in Aß-induced AD cell and mouse models. The results of this study offer a novel strategy and approach for treating AD types characterized by complex I abnormalities.

Progress in Identification of UDP-Glycosyltransferases for Ginsenoside Biosynthesis.

Ginsenosides, the primary pharmacologically active constituents of the Panax genus, have demonstrated a variety of medicinal properties, including anticardiovascular disease, cytotoxic, antiaging, and antidiabetes effects. However, the low concentration of ginsenosides in plants and the challenges associated with their extraction impede the advancement and application of ginsenosides. Heterologous biosynthesis represents a promising strategy for the targeted production of these natural active compounds. As representative triterpenoids, the biosynthetic pathway of the aglycone skeletons of ginsenosides has been successfully decoded. While the sugar moiety is vital for the structural diversity and pharmacological activity of ginsenosides, the mining of uridine diphosphate-dependent glycosyltransferases (UGTs) involved in ginsenoside biosynthesis has attracted a lot of attention and made great progress in recent years. In this paper, we summarize the identification and functional study of UGTs responsible for ginsenoside synthesis in both plants, such as Panax ginseng and Gynostemma pentaphyllum, and microorganisms including Bacillus subtilis and Saccharomyces cerevisiae. The UGT-related microbial cell factories for large-scale ginsenoside production are also mentioned. Additionally, we delve into strategies for UGT mining, particularly potential rapid screening or identification methods, providing insights and prospects. This review provides insights into the study of other unknown glycosyltransferases as candidate genetic elements for the heterologous biosynthesis of rare ginsenosides.

Antioxidant aromatic compounds from Amomum villosum and target prediction of active ingredients.

The dried fruit of Amomum villosum is an important spice and medicinal plant that has received great attention in recent years due to its high content of bioactive components and its potential for food additives and drug development. However, the stems and leaves of A. villosum are usually disposed of as waste. Based on the study of the fruits of A. villosum, we also systematically studied its stems and leaves. Fourteen aromatic compounds (1-14) were isolated and identified from A. villosum, including five new compounds (1-5) and nine known compounds (6-14). Among them, compounds 2-5, 8-10, 12-13 were obtained from the fruits of A. villosum, and compounds 1, 6-7,11, 14 were isolated from the stems and leaves of A. villosum. Based on chemical evidence and spectral data analysis (UV, ECD, Optical rotation data, 1D and 2D-NMR, and HR-ESI-MS), the structures of new compounds were elucidated. Furthermore, all compounds were tested for their effects on the survival rate of BV-2 cells in the presence of hydrogen peroxide. Among them, compound 5 showed antioxidant effects. Through network pharmacology screening and the cell thermal shift assay (CETSA), the Phosphoglycerate Mutase 5 (PGAM5) protein was identified as the antioxidant target of compound 5. Molecular docking results showed that compound 5 maintains binding to PGAM5 by forming hydrogen bond interactions with Lys93 and Agr214. In summary, A. villosum had potential medicinal and food values due to the diverse bioactive components.

Phenolics and terpenoids with good anti-inflammatory activity from the fruits of Amomum villosum and the anti-inflammatory mechanism of active diterpene.

The fruits of Amomum villosum are often considered a medicinal and food homologous material and have been found to have therapeutic effects in chronic enteritis, gastroenteritis, and duodenal ulcer. The aim of this study is to discover the anti-inflammatory active ingredients from dried ripe fruits of A. villosum and to elucidate the molecular mechanisms. We verified that the inhibitory activity of the ethyl acetate extract was superior to Dexamethasone (Dex), so we ultimately chose to study the ethyl acetate extract from the fruits of A. villosum. A total of 33 compounds were isolated from its ethyl acetate extract, including nine known diterpenoids (compounds 1-9), twelve known sesquiterpenoids (compounds 10-21), ten known phenolics (compounds 22, 23, 25-29, 31-33) and two new phenolics (24 and 30). On the basis of chemical evidences and spectral data analysis (UV, ECD, Optical rotation data, 1D and 2D-NMR, HR-ESI-MS, NMR chemical shift calculations), the structures of new compounds were elucidated. Among these compounds, isocoronarin D (5) was found to have good anti-inflammatory activity. Further research has found that isocoronarin D can down-regulate the protein levels of COX2 and NOS2, activate Nrf2/Keap1 and suppress NF-κB signaling pathway in LPS-induced RAW264.7 cells. In addition, isocoronarin D inhibited inflammasome assembly during inflammasome activation by hampering the binding of NLRP3 and ASC. Further evidence revealed that isocoronarin D suppressed the assembly of the NLRP3 inflammasome via blocking the formation of ASC specks. From these results, isocoronarin D may be the important bioactive compound of A. villosum and exhibits anti-inflammatory effects by regulating the NF-κB/Nrf2/NLRP3 axis in macrophages.

Recent advances in the natural product analogues for the treatment of neurodegenerative diseases.

Neurodegenerative diseases (NDs) represent a hallmark of numerous incapacitating and untreatable conditions, the incidence of which is escalating swiftly, exemplified by Alzheimer's disease and Parkinson's disease. There is an urgent necessity to create pharmaceuticals that exhibit high efficacy and minimal toxicity in order to address these debilitating diseases. The structural complexity and diversity of natural products confer upon them a broad spectrum of biological activities, thereby significantly contributing to the history of drug discovery. Nevertheless, natural products present challenges in drug discovery, including time-consuming separation processes, low content, low bioavailability, and other related issues. To address these challenges, numerous analogs of natural products have been synthesized. This methodology enables the rapid synthesis of analogs of natural products with the potential to serve as lead compounds for drug development, thereby paving the way for the discovery of novel pharmaceuticals. This paper provides a summary of 127 synthetic analogues featuring various natural product structures, including flavonoids, alkaloids, coumarins, phenylpropanoids, terpenoids, polyphenols, and amides. The compounds are categorized based on their efficacy in treating various diseases. Furthermore, this article delves into the structure-activity relationship (SAR) of certain analogues, offering a thorough point of reference for the systematic development of pharmaceuticals aimed at addressing neurodegenerative conditions.

Simultaneous identification and enantioseparation of ofloxacin and duloxetine without the single standard and computational calculation of their inclusion complexes.

Given the markedly different pharmacological activities between enantiomeric isomers, it is crucial to encourage the stereoselective determination of chiral drugs in the biological and pharmaceutical fields, and the combination of drugs makes this analysis more complicated and challenging. Herein, a capillary electrophoresis (CE) method for the enantioseparation of ofloxacin and duloxetine was established, enabling the simultaneous identification of four isomers in nonracemic mixtures with enantiomeric excess (ee%) values exceeding 5%. This was achieved through the integration of theoretical simulation and electron circular dichroism (ECD), all without reliance on individual standards. Molecular modeling explained and verified the migration time differences of these isomers in electrophoretic separation. Moreover, the correlation coefficients (R2 ) between the enantiomeric peak area differentials and ee% were both above 0.99. Recovery rates were quantified using bovine serum as the matrix, with results ranging from 93.32% to 101.03% (RSD = 0.030) and 92.69% to 100.52% (RSD = 0.028) for these two chiral drugs at an ee value of 23.1%, respectively.

Enhancement of Frozen-Thawed Human Sperm Quality with Zinc as a Cryoprotective Additive.

BACKGROUND Cryopreservation preserves male fertility, crucial in oncology, advanced age, and infertility. However, it damages sperm motility, membrane, and DNA. Zinc (Zn), an antioxidant, shows promise in improving sperm quality after thawing, highlighting its potential as a cryoprotectant in reproductive medicine. MATERIAL AND METHODS Gradient concentration of ZnSO4 (0, 12.5, 25, 50, and 100 µM) was added in the Glycerol-egg yolk-citrate (GEYC) cryopreservative medium as an extender. Alterations in sperm viability and motility parameters after cryopreservation were detected in each group. Sperm plasma membrane integrity (PMI), acrosome integrity (ACR), DNA fragment index (DFI), and changes in sperm mitochondrial function were examined, including: mitochondrial potential (MMP), sperm reactive oxygen species (ROS), and sperm ATP. RESULTS We found that 50 µM ZnSO4 was the most effective for the curvilinear velocity (VCL) and the average path velocity (VAP) of sperm after cryo-resuscitation. Compared to the Zn-free group, sperm plasma membrane integrity (PMI) was increased, DNA fragmentation index (DFI) was decreased, reactive oxygen species (ROS) was reduced, and mitochondrial membrane potential (MMP) was increased after cryorevival in the presence of 50 µM ZnSO4. CONCLUSIONS Zn ion is one of the antioxidants in the cell. The results of our current clinical study are sufficient to demonstrate that Zn can improve preserves sperm quality during cryopreservation when added to GEYC. The addition of 50 µM ZnSO4 increased curve velocity, mean path velocity, sperm survival (or plasma membrane integrity), and mitochondrial membrane potential while reducing ROS production and DNA breaks compared to GEYC thawed without ZnSO4.

Responses of Vallisneria natans and Pistia stratiotes to Cu2+ and Mn2+ stress: Occurrence of caffeic acid and its degradation kinetics during chlorination.

Macrophytes are crucial in maintaining the equilibrium of aquatic ecosystems. However, the pattern of macrophyte-derived caffeic acid (CA) release under heavy metal stress is yet to be fully understood. More importantly, due to its functional groups, CA may be a precursor to the formation of disinfection by-products, posing threats to water ecology and even safety of human drinking water. This study analyzed the responses of CA released by Vallisneria natans (V. natans) and Pistia stratiotes (P. Stratiotes) when exposed to Cu2+ and Mn2+ stress. Additionally, the CA levels in two constructed wetland ponds were detected and the degradation kinetics of CA during chlorination were investigated. Results indicated that CA occurred in two constructed wetland ponds with the concentrations of 44.727 µg/L (planted with V. natans) and 61.607 µg/L (planted with P. Stratiotes). Notably, heavy metal stress could significantly affect CA release from V. natans and P. Stratiotes. In general, under Cu2+ stress, V. natans secreted far more CA than under Mn2+ stress, the level could reach up to 435.303 µg/L. However, compared to V. natans, P. Stratiotes was less affected by Cu2+ and Mn2+ stress, releasing a maximum CA content of 55.582 µg/L under 5 mg/L Mn2+ stress. Aquatic macrophytes secreted more CA in response to heavy metal stresses and protected macrophytes from harmful heavy metals. CA degradation followed the pseudo first-order kinetics model, and the chlorination of CA conformed to a second-order reaction. The reaction rate significantly accelerated as NaClO, pH, temperature and Br- concentration increased. A new pathway for CA degradation and a new DBP 2, 2, 3, 3-tetrachloropropanal were observed. These findings pointed at a new direction into the adverse effect of CA, potentially paving the way for new strategies to solve drinking water safety problems.

The Validity of a Dual-Force Plate for Assessing Counter-Movement Jump Performance.

The objective of this study was to assess the concurrent validity of the Kunwei force plate system in relation to variables during a counter-movement jump (CMJ) task, in comparison to the Kistler in-ground force plate system, which is considered the "gold standard". METHODS: In a single testing session, the Kunwei force plates were placed directly on top of the in-ground Kistler force plate. This allowed for the simultaneous collection of vertical ground reaction forces from 30 participants (male, age = 22.8 ± 2.8 years, body mass = 74.3 ± 12.3 kg, height 178.2 ± 4.6 cm) during CMJ tests. The consistency between force plate systems was assessed using ordinary least products regression (OLPR) with bootstrapped 95% confidence intervals and the Interclass Correlation Coefficient (ICC). RESULTS: There was no fixed or proportional bias in the CMJ variables measured between the force plate systems. The variables exhibited a strong correlation across the force plates during the CMJ task (ICC > 0.950, p < 0.01). CONCLUSION: The findings of this study indicate that there was no statistical difference between the Kunwei and Kistler force plate systems when evaluating common CMJ strategy and outcome variables, which are considered the gold standard. Hence, the Kunwei force plate can be regarded as a reliable substitute for the established industry benchmark in evaluating the force-time characteristics of the CMJ. Researchers, athletes, and coaches have the option to utilize this affordable and portable choice as a substitute for the more expensive laboratory-based force plate system. This alternative allows for the precise measurement of CMJ performance and force-time variables.

Coumarins and flavones with anti-inflammatory activity isolated from the branches and leaves of Daphne retusa.

In this study, two new (1, 13) and fourteen known (2-12, 14-16) compounds were isolated from the branches and leaves of Daphne retusa. On the basis of chemical evidence and spectral data analysis (UV, ECD NMR, and HR-ESI-MS), the structures of new compounds were elucidated. Furthermore, all compounds have been tested for their inhibitory effects on NO production in LPS-induced RAW 264.7 cells, and compound 3 showed obvious inhibitory effect. Through target screening and molecular docking technology, potential binding targets for compound 3 to exert anti-inflammatory effects have been predicted.

Potential diagnostic biomarkers: 6 cuproptosis- and ferroptosis-related genes linking immune infiltration in acute myocardial infarction.

The current diagnostic biomarkers of acute myocardial infarction (AMI), troponins, lack specificity and exist as false positives in other non-cardiac diseases. Previous studies revealed that cuproptosis, ferroptosis, and immune infiltration are all involved in the development of AMI. We hypothesize that combining the analysis of cuproptosis, ferroptosis, and immune infiltration in AMI will help identify more precise diagnostic biomarkers. The results showed that a total of 19 cuproptosis- and ferroptosis-related genes (CFRGs) were differentially expressed between the healthy and AMI groups. Functional enrichment analysis showed that the differential CFRGs were mostly enriched in biological processes related to oxidative stress and the inflammatory response. The immune infiltration status analyzed by ssGSEA found elevated levels of macrophages, neutrophils, and CCR in AMI. Then, we screened 6 immune-related CFRGs (CXCL2, DDIT3, DUSP1, CDKN1A, TLR4, STAT3) to construct a nomogram for predicting AMI and validated it in the GSE109048 dataset. Moreover, we also identified 5 pivotal miRNAs and 10 candidate drugs that target the 6 feature genes. Finally, RT-qPCR analysis verified that all 6 feature genes were upregulated in both animals and patients. In conclusion, our study reveals the significance of immune-related CFRGs in AMI and provides new insights for AMI diagnosis and treatment.

Mechanisms regulating wound healing: Functional changes in biology mediated by lactate and histone lactylation.

The high incidence, low healing rate and huge economic burden of wounds (especially chronic wounds) worldwide remain a great challenge for clinical staff and patients. The various stages of wound healing are regulated by paracrine or autocrine cytokines and growth factors, and the study of their intrinsic mechanisms is a prerequisite for better wound treatment. Lactate, the end product of glycolysis, plays a role in all stages of wound healing, and recent studies have identified lactate as an epigenetic regulator that regulates gene expression through histone lysine lactylation and stimulates posttranslational modifications to regulate related gene expression, thereby causing a series of biological functional changes. This article reviews the progress of research on lactate and lactylation during wound healing or in related diseases, including its involvement in immune regulation, inflammation control, and proliferative remodeling, and finally describes the prospects for lactate therapy regarding wound healing.

The committed oligodendrocyte precursor cell, a newly-defined intermediate progenitor cell type in oligodendroglial lineage.

In the central nervous system, oligodendrocytes (OLs) produce myelin sheaths that provide trophic support to neuronal axons and increase the propagation speed of action potential. OLs are constantly generated from OL precursor cells (OPCs) throughout life span. The production of myelinating OLs consists of three canonical stages: OPCs, newly-formed OLs (NFOs), and mature myelinating OLs. Recently, single-cell RNA transcriptomic analyses identified a new population of oligodendroglial cells, namely differentiation committed OPCs (COPs). COPs represent a critical intermediate population between OPCs and NFOs, as revealed by specific expression of G-protein coupled receptor 17 (GPR17). The dysregulation of COPs leads to the remyelination failure in demyelinating diseases and impairs the replacement of lost myelin sheaths due to aging. Hence, understanding the development of COPs and their underlying regulatory network will be helpful in establishing new strategies for promoting myelin repair in demyelinating diseases. This review summarizes the current knowledge on the development and functions of COPs under both physiological and pathological conditions. Overall, COPs function as "checkpoints" to prevent inappropriate precocious OL differentiation and myelination through expressing distinct regulatory factors. Deepening our understanding of COPs may not only advance our knowledge of how OL lineage progresses during development, but also open the door to new treatments for demyelinating diseases.

Metal Cation-Doped ns-Cucurbit[10]uril: Adsorption of Para-Phenylenediamine.

The separation of phenylenediamine (PDA) isomers is crucial in the field of chemical manufacturing. Herein, we presented a strategy for the separation of PDA isomers (para-phenylenediamine, p-PDA; meta-phenylenediamine, m-PDA; ortho-phenylenediamine, o-PDA) using four supramolecular framework materials of ns-cucurbit[10]uril (ns-Q[10]), (1) ns-Q[10](Cd), (2) ns-Q[10](Mn), (3) ns-Q[10](Cu), (4) ns-Q[10](Pb). Our findings indicated that these supramolecular framework materials of ns-Q[10] showed remarkable selectivity for para-phenylenediamine (p-PDA) in p-PDA, m-PDA, and o-PDA mixtures, respectively. The variations in selectivity observed in these four single-crystal structures arose from variations in the thermodynamic stabilities and binding modes of the host-guest complexes. Importantly, the supramolecular framework based on ns-Q[10] exhibited selective accommodation of p-PDA over its isomers. This study highlighted the practical application of ns-Q[10] in effectively separating PDA isomers and demonstrated the potential utility of ns-Q[10] in isolating other organic molecules.

Red Room-Temperature Phosphorescence Supramolecular Assemblies Based on Cucurbit[7]uril: Reversible Temperature Stimulation Response and Cell-Specific Silver Ion Imaging.

Solid-state materials with efficient room-temperature phosphorescence (RTP) emission have been widely used in materials science, and organic RTP-emitting systems with heavy-metal doping in aqueous solutions have attracted much attention in recent years. A novel supramolecular interaction was induced by host-guest assembly using cucurbit[7]uril (Q[7]) as the host and brominated naphthalimide phosphor as the guest. This interaction was further enhanced through synergistic chelation stimulated by analytical silver ion complexation. This approach facilitated the system's structural rigidity, intersystem crossing, and oxygen shielding. We achieved deep red phosphorescence emission in aqueous solution and ambient conditions along with quantitative determination of silver ions. The new complex exhibited good reversible thermoresponsive behavior and was successfully applied for the first time to target phosphorescence imaging of silver ions in the mitochondria of A549 cancer cells. These results are beneficial for constructing novel RTP systems with stimulus-responsive luminescence in aqueous solution, contributing to future research in bioimaging, detection, optical sensors, and thermometry materials.

Structure-Based Drug Design and Synthesis of Pyrrolidine-2,5-diones as Novel TNF-α Inhibitors.

Tumor necrosis factor α (TNF-α) inhibitors are the treatment of choice for autoimmune diseases including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and Crohn's disease. Herein, some Benpyrine derivatives with stronger binding affinity, better activity, better solubility, and higher synthetic efficiency were identified using structure-based drug design and optimization strategies. Among the synthesized series of compounds, 10 directly binds to TNF-α and blocks the activation of TNF-α-trigged caspase and NF-κB signaling pathway. Compound 10 represents a promising scaffold for the further development of TNF-α inhibitors. Drug development based on compound 10 may provide a new strategy for the treatment of TNF-α-mediated autoimmune diseases.

Patients' perspectives on, experience with and concerns about crohn's disease: insights from Chinese social media.

AIM: The aim of this study was to explore the experience and perceptions of patients with Crohn's disease in China. METHODS: Data mining was used to investigate posts in Crohn's disease online medical communities. The data were collected through the crawler code, and latent Dirichlet allocation (LDA) and grounded theory were used to mine the theme features after data cleaning. RESULTS: In analyzing the topic characteristics of online posts, LDA divided 6757 posts into 15 topics on four aspects: seeking disease information, making decisions on medication use, psychological burden, and communicating about diet and nutrition. CONCLUSION: Overall, social media is patient-centric and helps us better understand the experiences and perceptions of patients. This study can help medical staff predict the thoughts and concerns of Crohn's disease patients during the treatment process, facilitate doctor-patient communication, and assist in the formulation of medical policies.