Degradation Behavior of Medical MgZZC-1 in Various Simulated Body Fluids.

Magnesium-based biodegradable metal bone implants exhibit superior mechanical properties compared to biodegradable polymers for orthopedic and cardiovascular stents. In this study, MgZZC-x (x = 1, 1.2) alloys were screened by in vitro biocompatibility tests in three simulated body fluids under nontoxic conditions. The MgZZC-1 alloys with better biocompatibility were selected to predict the days required for complete degradation. The evolution of degradation products was analyzed, and the mechanism of formation of the product film was inferred. A degradation kinetic model was established to investigate the effect of MEM components on the degradation of the alloys. The results demonstrate that the proteins in MEM can greatly retard the degradation progress by attaching to the surface of MgZZC-1 alloys, which are predicted to degrade completely within 341 days. The carbonate and phosphate buffers were adjusted to pH in MEM solution, delaying the degradation of magnesium alloys. This process in MEM more accurately reflects the actual degradation in the body and is superior to that in Hanks and SBF solutions. This study will promote the application of biodegradable materials in clinical medicine.

ACE2 mediates tryptophan alleviation on diarrhea by repairing intestine barrier involved mTOR pathway.

The membrane-delimited receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), angiotensin-converting enzyme 2 (ACE2), which is expressed in the intestine, collaborates with broad neutral amino acid transporter 1 (B0AT1). Tryptophan (Trp) is transported into intestinal epithelial cells by ACE2 and B0AT1. However, whether ACE2 and its binding protein B0AT1 are involved in Trp-mediated alleviation of intestinal injury is largely unknown. Here, we used weaned piglets and IPEC-J2 cells as models and found that ACE2/B0AT1 alleviated lipopolysaccharide (LPS)-induced diarrhea and promoted intestinal barrier recovery via transport of Trp. The levels of the aryl hydrocarbon receptor (AhR) and mechanistic target of rapamycin (mTOR) pathways were altered by ACE2. Dietary Trp supplementation in LPS-treated weaned piglets revealed that Trp alleviated diarrhea by promoting ACE2/B0AT1 expression, and examination of intestinal morphology revealed that the damage to the intestinal barrier was repaired. Our study demonstrated that ACE2 accompanied by B0AT1 mediated the alleviation of diarrhea by Trp through intestinal barrier repair via the mTOR pathway.

Study on the effects of rapamycin and the mTORC1/2 dual inhibitor OSI-027 on the metabolism of colon cancer cells based on UPLC-MS/MS metabolomics.

mTORC1/2 dual inhibitors may be more effective than mTORC1 inhibitor rapamycin. However, their metabolic impacts on colon cancer cells remain unexplored. We conducted a comparative analysis of the anti-proliferative effects of rapamycin and the novel OSI-027 in colon cancer cells HCT-116, evaluating their metabolic influences through ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Our results demonstrate that OSI-027 more effectively inhibits colon cancer cell proliferation than rapamycin. Additionally, we identified nearly 600 metabolites from the spectra, revealing significant differences in metabolic patterns between cells treated with OSI-027 and rapamycin. Through VIP value screening, we pinpointed crucial metabolites contributing to these distinctions. For inhibiting glycolysis and reducing glucose consumption, OSI-027 was likely to be more potent than rapamycin. For amino acids metabolism, although OSI-027 has a broad effect as rapamycin, their effects in degrees were not exactly the same. These findings address the knowledge gap regarding mTORC1/2 dual inhibitors and lay a foundation for their further development and research.

A theory based study on diabetes self-management in older Chinese adults.

Approximately 1 in 3 (or 80 million) Chinese age 60 years or older are living with type 2 diabetes in China. New perspectives are needed to understand the intricate phenomenon of diabetes self-management (DSM) in older Chinese adults. Guided by the expanded Tripartite Model of Self-Management, this study aimed to identify the inter-relationships between the tripartite components simultaneously and their influencing factors. This cross-sectional study included a stratified random sample of 98 community-dwelling adults age 60 or older with type 2 diabetes. Findings revealed distinct predictors for knowledge about DSM, DSM behaviors and coping. There were significant inter-relationships among the tripartite components. The theoretical model was a good fit for the data. This study provides valuable insights into the complex relationships between knowledge about DSM, DSM behaviors, and coping strategies, offering direct implications for improving the health outcomes of older adults with diabetes.

Molecular, biological characterization and drug sensitivity of chidamide-resistant MCF7 cells.

Background: Chidamide (CHI) is a subtype-selective histone deacetylase inhibitor (HDACI) developed in China and approved as a second-line treatment combined with the aromatase inhibitor for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. However, drug resistance is commonly occurred after a long period of medication. This study aimed to investigate the characterization of induced resistance to CHI and explore the potential cross-resistance to chemotherapeutic agents. Methods: CHI with gradually increasing concentrations was added to breast cancer MCF7 cells to establish a CHI-resistant MCF7 (MCF7-CHI-R) cell line. Cell counting kit-8 (CCK-8) assays were performed to detect half-maximal inhibitory concentration (IC50) of CHI. Colony formation was used to determine the proliferation inhibition rate. Western blot analysis was conducted to detect expressions of protein related with cell cycle, apoptosis, ferroptosis, and histone deacetylase (HDAC). Flow cytometry was used to analyze apoptosis and cell cycle. Results: The IC50 value of CHI of MCF7-CHI-R cells was increased in comparison with MCF7 cells. And CHI led to cell cycle arrest and ferroptosis, which were not exhibited in MCF7-CHI-R cells. Moreover, HDAC activity decreased in MCF7-CHI-R cells in comparison with MCF7 cells, and HDAC1 and HDAC10 might be involved in the resistance to CHI. In addition, MCF7-CHI-R cells were resistant to gemcitabine (GEM), doxorubicin (ADM), docetaxel (DXT), albumin-bound paclitaxel (nab-PTX) and paclitaxel (PTX). Conclusions: The MCF7-CHI-R was established and the anti-ferroptosis pathway activation was involved in the resistance of MCF-CHI-R cells. Also, MCF7-CHI-R cells were resistant to GEM, ADM, DXT, nab-PTX and PTX.

First report of Corynespora cassiicola causing leaf spot on Nanhaia speciosa in China.

Nanhaia speciosa, commonly known as Niudali, is a medicinal woody vine belonging to the Leguminosae family. Valued for its culinary and medicinal properties, it is extensively cultivated, covering approximately 5,973 hm2 in the Guangxi Zhuang Autonomous Region of China. The edible tubers of this plant are reported to possess antibacterial and antioxidant effects (Luo et al., 2023; Shu et al., 2020). In July 2021, a Niudali plantation in Yulin, Guangxi, China (22°64'N; 110°29'E) exhibited leaf spot symptoms, with an incidence rate exceeding 40% across a 46,690 m2 area. Initially, small circular, pale yellow spots appeared on the leaves, which subsequently evolved into dark brown lesions surrounded by yellow halos, ultimately leading to foliage wilting. Leaves exhibiting typical symptoms were collected for pathogen investigation. The leaves were thoroughly washed with sterile water and small tissue fragments (5×5 mm) were excised from the lesion periphery. These fragments were surface-sterilized with 75% ethanol and 1% NaClO, rinsed three times with sterile water, and subsequently cultured on potato dextrose agar (PDA) at 28 °C in darkness for 7 days. Through single-spore isolation, seven isolates with similar morphological traits were obtained. After 7 days of incubation on PDA at 28 °C in dark, the colonies exhibited a white to grey coloration on the upper surface with abundant aerial hyphae, while the underside appeared dark black. The conidia, cylindrical or obclavate in shape, were straight, pale brown, and measured 30.1-128.9 µm × 4.8-15.0 µm (n=50). The morphological characteristics matched those of Corynespora sp.(Wang et al. 2021). For molecular identification, the isolate N5-2 underwent DNA sequence analysis using genomic DNA and primers ITS1/ITS4 and EF1-688F/EF1-1251R. The sequences (ITS: OP550425; TEF1-α: OQ117118) were deposited in GenBank, exhibiting 98% identity to C. cassiicola (OP981637) for TEF1-α and 99% homology to C. cassiicola (OP957070) for ITS. Based on the concatenated ITS and TEF1-α, a maximum likelihood phylogenetic analyses using MEGA7.0 clustered the isolate with C. cassiicola. Consequently, the fungus was identified as C. cassiicola based on its morphological and molecular features. In the pathogenicity test on 1-year-old Nanhaia speciosa seedlings, leaves were gently scratched and inoculated with mycelial plugs (5 mm). Control seedlings received PDA plugs. Five leaves per plant and five plants per treatment were selected for assessment. All seedling were maintained in a greenhouse (12/12h light/dark cycle, 25 ± 2°C, 90% humidity). After a 7-day incubation period, all leaves subjected to fungal inoculation exhibited symptoms consistent with those observed in the field, while control plants remained symptom-free. The fungus was successfully reisolated from the infected leaves in three successive trials, fulfilling Koch's postulates. While C. cassiicola is well-documented for inducing leaf spots on various plant species, including Jasminum nudiflorum, Strobilanthes cusia, Acanthus ilicifolius, Syringa species (Hu et al., 2023; Liu et al., 2023; Xie et al., 2021; Wang et al., 2021), this study represents the first report of C. cassiicola causing leaf spots on Nanhaia speciosa in China. The identification of this pathogen in Nanhaia speciosa has significant implications for future epidemiological investigations and serves as a valuable reference for controlling leaf spot disease in Nanhaia speciosa.

A fully digital workflow for the design and manufacture of a class of metal orthodontic appliances.

Background: Traditional working procedures requires a lot of clinical processes and processing time. Methods: The orthodontic metal appliances were made by applying oral scanners, digital images, computer-aided design and computer-aided manufacturing (CAD-CAM) printers. Results: The computer digital technology simplified the manufacturing process for dental appliances and shorten the duration for clinical operation and technical processing. Conclusions: The technique described in this paper can guarantee the accuracy of orthodontic appliances and bring revolution the field. Clinical significance: The CAD-CAM technology provides a fully digital workflow for manufacturing metal orthodontic appliances, which saves a considerable amount of labor and material costs, and significantly reduces heavy metal pollution in the working environment of dental technicians.

Occurrence and recovery of vocal cord paralysis after minimally invasive McKeown esophagectomy, risk factors, and clinical outcome.

BACKGROUND: This study aimed to observe the occurrence of recurrent laryngeal nerve injury after McKeown esophagectomy for esophageal squamous cell carcinoma, as well as its recovery and influencing factors within 7 months after surgery. METHODS: From July 2020 to July 2021, among all patients who underwent minimally invasive McKeown esophagectomy, 90 patients who developed vocal cord paralysis after surgery were included in the study. These patients underwent endoscopic vocal cord function assessment every 1 to 2 months and continued until 7 months postoperatively. RESULTS: Among all 388 patients undergoing esophagectomy, 23.2% (90/388) of patients suffered postoperative vocal cord paralysis. Left, right, and bilateral injuries were confirmed in 73 (81.1%), 12 (13.3%), and 5 patients (5.6%), respectively. With a median recovery time being 183 days, the cumulative overall recovery rate was 65.4% at 7 months, 68.6% for the left side, 55.6% for the right, and 20.0% for bilateral injuries. In multivariable analysis, cervical paraoesophageal lymph node dissection and conventional thoracoscopic-assisted esophagectomy were demonstrated to be independent risk factors associated with non-recovery of vocal cord paralysis. CONCLUSIONS: After intensive endoscopic follow-up, a cumulative vocal cord paralysis recovery rate of 65.4% within 7 months was observed in patients after minimally invasive McKeown esophagectomy. Cervical paraoesophageal lymph node dissection and conventional thoracoscopic-assisted esophagectomy were demonstrated to be risk factors hindering vocal cord paralysis recovery.

[Research Progress on Pollution Characteristics, Degradation, and Transformation of Typical PPCPs in the Process of Wastewater Treatment].

Pharmaceuticals and personal care products (PPCPs) have received extensive attention as a new type of pollutant inin the 21st century, and the ecological and health risks caused by PPCPs have gradually been recognized by government regulatory agencies. Daily use of PPCPs has led to their frequent detection and high concentrations in the influent, effluent, and sludge of wastewater treatment plants, but traditional wastewater treatment processes can't remove them effectively. Most research about enhancing the removal of PPCPs through microbial degradation, photodegradation, and ozonation is still in the laboratory research stage, and the removal effects are not satisfactory when applied to actual sewage treatment. Therefore, the effective removal of PPCPs from domestic wastewater is a critical technical problem that urgently needs to be studied and solved in the coming years. At present, many scholars do not have a comprehensive understanding about the degradation and transformation behaviors of microbes, ultraviolet, and ozone for typical PPCPs in the wastewater treatment process, so it is necessary to conduct a systematic analysis and discussion. In this study, 16 typical PPCPs frequently detected in sewage treatment plants were selected as research objects through a literature review. The occurrence, removal characteristics, and sludge adsorption properties of typical PPCPs in wastewater treatment plants were analyzed and summarized. The degradation and transformation behavior of typical PPCPs under microbial, ultraviolet, and ozone treatments in the wastewater treatment process were also discussed. Finally, based on current research gaps, some research directions for the removal and transformation of PPCPs in wastewater were proposed:① investigation into the removal characteristics of PPCPs by actual biochemical treatment; ② study on the mechanism of microbial degradation and transformation of typical PPCPs during biochemical treatment; ③ study on the degradation and transformation mechanism of typical PPCPs by UV/ozone in an actual sewage system; and ④ research on the application technology of removing PPCPs from sewage via microbial degradation, photodegradation, ozone oxidation, etc. The relevant results of this study can provide a reference for the pollution control of typical PPCPs in the sewage treatment process.

Experimental Validation of Two Types of Force Actuators: A Performance Comparison.

This paper experimentally investigates the performance of piezoelectric force actuators. Using the same encapsulated piezoelectric stack, an inertial-type actuator and a frame-type actuator are constructed for performance comparison. The experimental results are also used to validate the recently established actuator models, whilst the mechanical and piezoelectrical parameters of the models are experimentally identified. The performance of the actuators is described by the transmitted force(s) and input power flow from the actuators to the base structure with reference to the same electrical input voltage to the stack. The validation is deemed successful due to the strong agreement observed between the measured and predicted actuator performances. Additionally, it is discovered that the frame-type actuator has the capacity to produce significantly higher transmitted forces and input power flow to the base structure compared to the inertial-type actuator. The mechanism underlying the performance disparity between these two types of actuators is also examined. This paper clarifies the mechanism, shedding light on the design and optimization of piezoelectric actuators.

Advances in 2,3-Dimethylmaleic Anhydride (DMMA)-Modified Nanocarriers in Drug Delivery Systems.

Cancer represents a significant threat to human health. The cells and tissues within the microenvironment of solid tumors exhibit complex and abnormal properties in comparison to healthy tissues. The efficacy of nanomedicines is inhibited by the presence of substantial and complex physical barriers in the tumor tissue. The latest generation of intelligent drug delivery systems, particularly nanomedicines capable of charge reversal, have shown promise in addressing this issue. These systems can transform their charge from negative to positive upon reaching the tumor site, thereby enhancing tumor penetration via transcytosis and promoting cell internalization by interacting with the negatively charged cell membranes. The modification of nanocarriers with 2,3-dimethylmaleic anhydride (DMMA) and its derivatives, which are responsive to weak acid stimulation, represents a significant advance in the field of charge-reversal nanomedicines. This review provides a comprehensive examination of the recent insights into DMMA-modified nanocarriers in drug delivery systems, with a particular focus on their potential in targeted therapeutics. It also discusses the synthesis of DMMA derivatives and their role in charge reversal, shell detachment, size shift, and ligand reactivation mechanisms, offering the prospect of a tailored, next-generation therapeutic approach to overcome the diverse challenges associated with cancer therapy.

Orally administered yeast-derived ß-glucan alleviates mast cell-dependent airway hyperresponsiveness and inflammation in a murine model of asthma.

BACKGROUND: Particulate ß-glucans (WGP) are natural compounds with regulatory roles in various biological processes, including tumorigenesis and inflammatory diseases such as allergic asthma. However, their impact on mast cells (MCs), contributors to airway hyperresponsiveness (AHR) and inflammation in asthma mice, remains unknown. METHODS: C57BL/6 mice underwent repeated OVA sensitization without alum, followed by Ovalbumin (OVA) challenge. Mice received daily oral administration of WGP (OAW) at doses of 50 or 150 mg/kg before sensitization and challenge. We assessed airway function, lung histopathology, and pulmonary inflammatory cell composition in the airways, as well as proinflammatory cytokines and chemokines in the bronchoalveolar lavage fluid (BALF). RESULTS: The 150 mg/kg OAW treatment mitigated OVA-induced AHR and airway inflammation, evidenced by reduced airway reactivity to aerosolized methacholine (Mch), diminished inflammatory cell infiltration, and goblet cell hyperplasia in lung tissues. Additionally, OAW hindered the recruitment of inflammatory cells, including MCs and eosinophils, in lung tissues and BALF. OAW treatment attenuated proinflammatory tumor necrosis factor (TNF)-α and IL-6 levels in BALF. Notably, OAW significantly downregulated the expression of chemokines CCL3, CCL5, CCL20, CCL22, CXCL9, and CXCL10 in BALF. CONCLUSION: These results highlight OAW's robust anti-inflammatory properties, suggesting potential benefits in treating MC-dependent AHR and allergic inflammation by influencing inflammatory cell infiltration and regulating proinflammatory cytokines and chemokines in the airways.

[Discrimination of anti-tumor and cardioprotective effect quality markers from Aidi Injection based on "spider web" mode].

Chinese medicinal preparations play an equally important role in reducing toxicity and treating tumors. Few studies discriminate the quality markers(Q-markers) conferring different therapeutic effects of traditional Chinese medicine preparations. Therefore, we take Aidi Injection(AD) as an example to comprehensively identify the Q-markers of anti-tumor and cardioprotective effects based on the "spider web" mode. Firstly, based on the principle of measurability, the chemical components in the prescription were qualitatively analyzed, and then the components with high content and capable to be measured were quantitatively analyzed as measurable evaluation indexes. Based on the principle of stability, the effects of light and temperature on the content of each component of AD were investigated as indicators of stability. Based on the principle of compatibility, the compounds were classified according to the law of compatibility of sovereign, minister, assistant, and guide medicinal materials in the prescription. Based on the principle of efficacy, the anti-tumor and antiangiogenic activities of the Q-markers were evaluated, and their synergistic effects with doxorubicin(DOX) in inhibiting tumorigenesis and angiogenesis and lowering cardiotoxicity were evaluated as the evaluation indexes of effectiveness. The seven-dimensional spider web of "compatibility-content-stability-antitumor activity-synergistic anti-tumor activity with DOX-antiangiogenic activity-synergistic anti-angiogenic activity with DOX" and the four-dimensional spider web of "compatibility-content-stability-protective effects against DOX-induced myocardial toxicity" were established, on the basis of which the Q-markers of anti-tumor and cardioprotective effects of AD were comprehensively analyzed. The results showed that 12 components were selected as the Q-markers of AD, among which cantharidin, ginsenoside Re, ginsenoside Rb_1, astragaloside Ⅱ, cryptochlorogenic acid, and ginsenoside Rg_2 were the anti-tumor Q-markers of AD. Ginsenoside Rd, isofraxidin, syringin, eleutheroside E, calycosin-7-O-ß-D-glucoside, and azelaic acid were the cardioprotective Q-markers of AD. Taking into account both the anti-tumor and cardioprotective effects, these Q-markers could cover the four herbs constituting the prescription. The findings provides a scientific basis for the quality control of AD and an effective method for identifying comprehensive and reasonable Q-markers for the two effects of Chinese medicinal preparations.

Novel BODIPY-based nano-biomaterials with enhanced D-A-D structure for NIR-triggered photodynamic and photothermal therapy.

Near-infrared (NIR) responsive nanoparticles are an important platform for multimodal phototherapy. Importantly, the simultaneous NIR-triggered photodynamic (PDT) and photothermal (PTT) therapy is a powerful approach to increase the antitumor efficiency of phototherapic nanoparticles due to the synergistic effect. Herein, a boron dipyrromethene (BODIPY)-based amphiphilic dye with enhanced electron donor-acceptor-donor (D-A-D) structure (BDP-AP) was designed and synthesized, which could self-assemble into stable nanoparticles (BDP-AP NPs) for the synergistic NIR-triggered PDT/PTT therapy. BDP-AP NPs synchronously generated singlet oxygen (1O2) and achieved preeminent photothermal conversion efficiency (61.42%). The in vitro and in vivo experiments showed that BDP-AP NPs possessed negligible dark cytotoxicity and infusive anticancer performance. BDP-AP NPs provide valuable guidance for the construction of PDT/PTT-synergistic NIR nanoagents to improve the efficiency of photoinduced cancer therapy in the future.

Construction of atom co-sharing Bi/Bi4O5Br2 nanosheet heterojunction for plasmonic-enhanced visible-light-driven photocatalytic antibacterial activity.

The rapid advancement of photodynamic therapy (PDT) antibacterial materials has led to promising alternatives to antibiotics for treating bacterial infections. However, antibacterial drugs have poor light absorption and utilization rates, which limits their practical application. Constructing two-dimensional (2D) heterojunctions from materials with matching photophysical properties has emerged as a highly effective strategy for achieving high-efficiency photo-antibacterial performance. Here, we designed and prepared an atom co-sharing Bi/Bi4O5Br2 nanosheet heterojunction by a simple in situ reduction. This heterojunction material combines outstanding biocompatibility with excellent bactericidal efficiency, which exceeded 90 % against Escherichia coli (a Gram-negative bacterium) and Staphylococcus aureus (a Gram-positive bacterium) under visible light irradiation, around nine-fold higher than that with pure Bi4O5Br2 nanosheets. The results suggest that localized surface plasmon resonance (LSPR) of shared Bi atoms on the Bi4O5Br2 nanosheets promotes light utilization and the separation and transfer of photo-generated charges, thus producing more abundant reactive oxygen species (ROS), which can partake in the PDT antibacterial effect. Our study underscores the potential utility of LSPR-enhanced Bi-based nanosheet heterojunctions for safe and efficient PDT to combat bacterial infections.

Neuroinflammation in dementia: A meta-analysis of PET imaging studies.

BACKGROUND: Dementia is a major public health challenge for aging societies worldwide. Neuroinflammation is thought to be a key factor in dementia development. The aim of this study was to comprehensively assess translocator protein (TSPO) expression by positron emission tomography (PET) imaging to reveal the characteristics of neuroinflammation in dementia. METHODS: We used a meta-analysis to retrieve literature on TSPO expression in dementia using PET imaging technology, including but not limited to the quality of the study design, sample size, and the type of TSPO ligand used in the study. For the included studies, we extracted key data, including TSPO expression levels, clinical characteristics of the study participants, and specific information on brain regions. Meta-analysis was performed using R software to assess the relationship between TSPO expression and dementia. RESULTS: After screening, 12 studies that met the criteria were included. The results of the meta-analysis showed that the expression level of TSPO was significantly elevated in patients with dementia, especially in the hippocampal region. The OR in the hippocampus was 1.50 with a 95% CI of 1.09 to 1.25, indicating a significant increase in the expression of TSPO in this region compared to controls. Elevated levels of inflammation in the prefrontal lobe and cingulate gyrus are associated with cognitive impairment in patients. This was despite an OR of 1.00 in the anterior cingulate gyrus, indicating that TSPO expression in this region did not correlate significantly with the findings. The overall heterogeneity test showed I² = 51%, indicating moderate heterogeneity. CONCLUSION: This study summarizes the existing literature on TSPO expression in specific regions of the brain in patients with dementia, and also provides some preliminary evidence on the possible association between neuroinflammation and dementia. However, the heterogeneity of results and limitations of the study suggest that we need to interpret these findings with caution. Future studies need to adopt a more rigorous and consistent methodological design to more accurately assess the role of neuroinflammation in dementia, thereby providing a more reliable evidence base for understanding pathological mechanisms and developing potential therapeutic strategies.

LC-MS-based rheumatoid arthritis serum metabolomics reveals the role of deoxyinosine in attenuating collagen-induced arthritis in mice.

Rheumatoid arthritis (RA) is a persistent autoimmune condition with no identified cure currently. Recently, scientists have applied metabolomics to investigate altered metabolic profiles and unique diseases-associated metabolic signatures. Herein, we applied metabolomics approach to analyze serum samples of 41 RA patients and 42 healthy controls (HC) with the aim to characterize RA patients' metabolic profile, investigate related underlying pathological processes, and identify target metabolites. By utilizing ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry, we found 168 proposed metabolites and 45 vital metabolic pathways. Our analysis revealed that deoxyinosine (DI), a metabolite of the purine metabolic pathway, was the most significant reduced metabolite in RA patients. Furthermore, through targeted detection, we confirmed lower concentration of DI in RA patients' peripheral blood. Moreover, DI inhibited lipopolysaccharide-induced inflammation both in vitro and in vivo. We further assessed DI's therapeutic potential in a collagen-induced arthritis (CIA) murine model. The results revealed that DI attenuated CIA, as evidenced by significantly lowered clinical scores of arthritis, alleviated joint swelling, and mitigated bone destruction. Moreover, we elucidated the underlying mechanism by which DI increased the population of myeloid-derived suppressor cells (MDSCs) and suppressed the proliferation of induced T cells. Collectively, these findings suggested that DI potentially ameliorated RA by inducing immunosuppressive MDSCs. The study provides key observations on RA pathogenesis and may contribute to developing novel therapeutic strategies for this debilitating condition.

Exploring the Dynamic Invasion Pattern of the Black-Headed Fall Webworm in China: Susceptibility to Topography, Vegetation, and Human Activities.

The fall webworm (FWW), H. cunea (Drury) (Lepidoptera: Erebidae: Arctiidae), is an extremely high-risk globally invasive pest. Understanding the invasion dynamics of invasive pests and identifying the critical factors that promote their spread is essential for devising practical and efficient strategies for their control and management. The invasion dynamics of the FWW and its influencing factors were analyzed using standard deviation ellipse and spatial autocorrelation methods. The analysis was based on statistical data on the occurrence of the FWW in China. The dissemination pattern of the FWW between 1979 and 2022 followed a sequence of "invasion-occurrence-transmission-outbreak", spreading progressively from coastal to inland regions. Furthermore, areas with high nighttime light values, abundant ports, and non-forested areas with low vegetation cover at altitudes below 500 m were more likely to be inhabited by the black-headed FWW. The dynamic invasion pattern and the driving factors associated with the fall webworm (FWW) provide critical insights for future FWW management strategies. These strategies serve not only to regulate the dissemination of insects and diminish migratory tendencies but also to guarantee the implementation of efficient early detection systems and prompt response measures.

Timosaponin Aâ ¢ induces drug-metabolizing enzymes by activating constitutive androstane receptor (CAR) via dephosphorylation of EGFR signaling pathway.

This study aims to assess the impact of Timosaponin AⅢ (T-AⅢ) on drug-metabolizing enzymes in anticancer treatment. In vivo experiments were conducted in nude mice and ICR mice. Following 24 days of T-AⅢ administration, nude mice exhibited induction of CYP2B10, MDR1, and CYP3A11 in the liver. In the liver of ICR mice, CYP2B10 and MDR1 were up-regulated after 3 days of T-AⅢ administration. In vitro assessments were conducted using HepG2 cells to ascertain the effects and underlying mechanisms. In HepG2 cells, T-AⅢ induced the expression of CYP2B6, MDR1, and CYP3A4, along with CAR activation. CAR siRNA reversed the T-AⅢ-induced increases in CYP2B6 and CYP3A4. Furthermore, other CAR target genes displayed significant up-regulation. Up-regulation of mCAR was observed in the livers of nude mice and ICR mice. Subsequent findings demonstrated that T-AⅢ activated CAR by inhibiting ERK1/2 phosphorylation, partially reversed by the MAPK/MEK activator t-BHQ. Inhibition of the ERK1/2 signaling pathway was also observed in vivo. Lastly, T-AⅢ inhibited the phosphorylation of EGFR at Tyr1173 and Tyr845, and it suppressed EGF-induced phosphorylation of EGFR, ERK, and CAR. Additionally, T-AⅢ inhibited EGFR phosphorylation in nude mice. Our results demonstrated that T-AⅢ is a novel CAR activator through inhibition of the EGFR pathway.