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Electromagnetic fields (EMFs) have emerged as an effective treatment for osteoporosis. However, the specific mechanism underlying their therapeutic efficacy remains controversial. Herein, we confirm the pro-osteogenic effects of 15 Hz and 0.4-1 mT low-frequency sinusoidal EMFs (SEMFs) on rat bone marrow mesenchymal stem cells (BMSCs). Subsequent miRNA sequencing reveal that miR-34b-5p is downregulated in both the 0.4 mT and 1 mT SEMFs-stimulated groups. To clarify the role of miR-34b-5p in osteogenesis, BMSCs are transfected separately with miR-34b-5p mimic and inhibitor. The results indicate that miR-34b-5p mimic transfection suppress osteogenic differentiation, whereas inhibition of miR-34b-5p promote osteogenic differentiation of BMSCs. In vivo assessments using microcomputed tomography, H&E staining, and Masson staining show that miR-34b-5p inhibitor injections alleviate bone mass loss and trabecular microstructure deterioration in ovariectomy (OVX) rats. Further validation demonstrates that miR-34b-5p exerts its effects by regulating STAC2 expression. Modulating the miR-34b-5p/STAC2 axis attenuate the pro-osteogenic effects of low-frequency SEMFs on BMSCs. These studies indicate that the pro-osteogenic effect of SEMFs is partly due to the regulation of the miR-34b-5p/STAC2 pathway, which provides a potential therapeutic candidate for osteoporosis.

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Objective: To achieve an accurate assessment of orthodontic and restorative treatments, tooth segmentation of dental panoramic X-ray images is a critical preliminary step, however, dental panoramic X-ray images suffer from poorly defined interdental boundaries and low root-to-alveolar bone contrast, which pose significant challenges to tooth segmentation. In this article, we propose a multi-feature coordinate position learning-based tooth image segmentation method for tooth segmentation. Methods: For better analysis, the input image is randomly flipped horizontally and vertically to enhance the data. Our method extracts multi-scale tooth features from the designed residual omni-dimensional dynamic convolution and the designed two-stream coordinate attention module can further complement the tooth boundary features, and finally the two features are fused to enhance the local details of the features and global contextual information, which achieves the enrichment and optimization of the feature information. Results: The publicly available adult dental datasets Archive and Dataset and Code were used in the study. The experimental results were 87.96% and 92.04% for IoU, 97.79% and 97.32% for ACC, and 86.42% and 95.64% for Dice. Conclusion: The experimental results show that the proposed network can be used to assist doctors in quickly viewing tooth positions, and we also validate the effectiveness of the proposed two modules in fusing features.

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Overuse of antibiotics leads to the proliferation of drug-resistant bacterial strains, worsening global morbidity, and mortality rates. Bioinspired nanomaterials present a promising avenue for developing nonantibiotic strategies against drug-resistant bacteria. Here, we engineer a bacteriophage-inspired artificial nanobiocatalyst via nonstoichiometric W18O49 that features a spiky topography and synergistic dual-atom sites for combating drug-resistant bacterial infection. Benefiting from the strong interaction within the synergistic Fe-O-Mo sites, the synthesized spiky artificial nanobiocatalyst exhibits superior reactive oxygen species (ROS)-catalytic activity, attributed to the regulated adsorption affinity between the reaction intermediates and catalytic sites. The experimental and theoretical investigations demonstrate that the bioinspired biocatalyst can effectively capture and kill bacteria through its spiky morphology and potent ROS-catalytic activity, which can enable a significant reduction in bacterial viability through downregulating genes associated with biosynthesis, cellular maintenance, and respiration. In vivo experiments demonstrate that the spiky artificial biocatalyst accelerates the reconstruction of drug-resistant bacteria-infected skin wounds in rabbits, exhibiting efficacy comparable to that of vancomycin. It is expected that this bioinspired study on spiky artificial nanobiocatalysts offers a straightforward path to facilitate the development of both bionic and nonantibiotic disinfection strategies.

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BACKGROUND: Wernicke encephalopathy is a neurological disorder caused by thiamine deficiency, commonly seen in alcoholic populations but also involving other circumstances that may lead to thiamine deficiency. The recognition of Wernicke encephalopathy often depends on clinicians' keen ability to detect its typical triad of features; however, most cases do not present with the full constellation of signs, which complicates the timely identification of Wernicke encephalopathy. CASE SUMMARY: This case report describes a patient with nasopharyngeal carcinoma who developed abnormal ocular function and ataxia following concurrent chemoradiotherapy, without a history of alcohol abuse. With the aid of radiological examinations, he received a timely diagnosis and treatment; however, his symptoms did not fully resolve during follow-up. CONCLUSION: For patients with malignant tumors exhibiting neurological symptoms, clinicians should consider the possibility of Wernicke encephalopathy and provide prophylactic thiamine therapy.

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The improvement of hydrogen evolution reaction kinetics can be largely accelerated by introducing a well-designed hydrogen spillover pathway into the catalysts. However, the driving force and mechanism of hydrogen migration on the surface of catalysts are poorly understood and are rarely explored in depth. Here, inspired by the specific ferroelectric property of HfO2, Mn-O-Ca sites in Mn4CaO5, and Fe-Fe sites in hydrogenases, we constructed a bioinspired HfO2 coupled with Ir catalysts (Ir/HfO2@C) with an alkaline hydrogen reverse spillover effect from HfO2 to interface and acid hydrogen spillover effect from Ir to interface. Benefiting from the bidirectional hydrogen spillover pathways controlled by pH, Ir/HfO2@C displays a narrow overpotential difference between acidic and alkaline electrolytes. Remarkably, Ir/HfO2@C shows a remarkable mass current density and turnover frequency value, far exceeding the benchmark Ir/C by 20.6 times. More importantly, this Ir/HfO2@C achieves extraordinarily low overpotentials of 146 and 39 mV at 10 mV cm-2 in seawater and alkaline seawater, respectively. The anion-exchange membrane water electrolyzer equipped with Ir/HfO2@C as a cathode exhibits excellent and stable H2-evolution performance on 2.22 V at 1.0 A cm-2. We expect that the bioinspired strategy will provide a new concept for designing catalytic materials for efficient and pH-universal electrochemical hydrogen production.

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The integration of pyroptosis and ferroptosis hybrid cell death induction to augment immune activation represents a promising avenue for anti-tumor treatment, but there is a lack of research. Herein, we developed two iridium(III)-triphenylamine photosensitizers, IrC and IrF, with the capacity to disrupt redox balance and induce photo-driven cascade damage to DNA and Kelch-like ECH-associated protein 1 (KEAP1). The activation of the absent in melanoma 2 (AIM2)-related cytoplasmic nucleic acid-sensing pathway, triggered by damaged DNA, leads to the induction of gasdermin D (GSDMD)-mediated pyroptosis. Simultaneously, iron homeostasis, regulated by the KEAP1/nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase 1 (HO-1) pathway, serves as a pivotal bridge, facilitating not only the induction of gasdermin E (GSDME)-mediated non-canonical pyroptosis, but also ferroptosis in synergy with glutathione peroxidase 4 (GPX4) depletion. The collaborative action of pyroptosis and ferroptosis generates a synergistic effect that elicits immunogenic cell death, stimulates a robust immune response and effectively inhibits tumor growth in vivo. Our work introduces the first metal-based small molecule dual-inducers of pyroptosis and ferroptosis for potent cancer immunotherapy, and highlights the significance of iron homeostasis as a vital hub connecting synergistic effects of pyroptosis and ferroptosis.

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BACKGROUND: In clinical practice guidelines, there is no consensus about the medications that should be initially offered to patients with brucellosis. To provide informative evidence, we compared and ranked brucellosis medications based on their efficacy and safety. METHODS: For this systematic review and network meta-analysis, we searched 4 English databases and 3 Chinese databases, from the date of database inception to December 13, 2023. We included randomized controlled trials (RCTs) involving children and adolescents with brucellosis, comparing different antibiotic regimens. We excluded studies explicitly targeting patients with spondylitis brucellosis, endocarditis brucellosis, and neuro-brucellosis. The primary outcomes were overall failure (efficacy) and side effects (safety). Secondary outcomes were relapse and therapeutic failure. Pairwise meta-analysis was first examined. Data were analyzed using random effects network meta-analysis, with subgroup and sensitivity analyses performed. The Confidence in Network Meta-Analysis (CINeMA) framework was used to assess the certainty of evidence. The protocol was preregistered in PROSPERO (CRD42023491331). RESULTS: Of the 11,747 records identified through the database search, 43 RCTs were included in the network meta-analysis. Compared with standard therapy (Doxycycline + Rifampicin), Rifampicin + Tetracyclines (RR 4.96; 95% CI 1.47 to 16.70; very low certainty of evidence), Doxycycline + TMP/SMX (RR 0.18; 95% CI 0.06 to 0.52; low certainty of evidence), Doxycycline + Quinolones (RR 0.27; 95% CI 0.11 to 0.71; low certainty of evidence), Streptomycin + Tetracyclines (RR 0.04; 95% CI 0.01 to 0.16; low certainty of evidence), and Single (RR 0.05; 95% CI 0.02 to 0.16; moderate certainty of evidence) were less efficacious. Doxycycline + Gentamicin ranked the best in efficacy (SUCRA values: 0.94), the second is Triple (SUCRA values: 0.87), and the third is Doxycycline + Streptomycin (SUCRA values: 0.78). CONCLUSIONS: Brucellosis medications differ in efficacy and safety. Doxycycline + Gentamicin, Triple, and Doxycycline + Streptomycin have superior efficacy and safety. Treatment of brucellosis should strike a balance between efficacy, safety, and cost.

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BACKGROUND: Patient education contributes to improve public awareness of Helicobacter pylori. Large language models (LLMs) offer opportunities to revolutionize patient education transformatively. This study aimed to assess the quality of patient educational materials (PEMs) generated by LLMs and compared with physician sourced. MATERIALS AND METHODS: Unified instruction about composing a PEM about H. pylori at a sixth-grade reading level in both English and Chinese were given to physician and five LLMs (Bing Copilot, Claude 3 Opus, Gemini Pro, ChatGPT-4, and ERNIE Bot 4.0). The assessments of the completeness and comprehensibility of the Chinese PEMs were conducted by five gastroenterologists and 50 patients according to three-point Likert scale. Gastroenterologists were asked to evaluate both English and Chinese PEMs and determine the accuracy and safety. The accuracy was assessed by six-point Likert scale. The minimum acceptable scores were 4, 2, and 2 for accuracy, completeness, and comprehensibility, respectively. The Flesch-Kincaid and Simple Measure of Gobbledygook scoring systems were employed as readability assessment tools. RESULTS: Accuracy and comprehensibility were acceptable for English PEMs of all sources, while completence was not satisfactory. Physician-sourced PEM had the highest accuracy mean score of 5.60 and LLM-generated English PEMs ranged from 4.00 to 5.40. The completeness score was comparable between physician-sourced PEM and LLM-generated PEMs in English. Chinese PEMs from LLMs proned to have lower score in accuracy and completeness assessment than English PEMs. The mean score for completeness of five LLM-generated Chinese PEMs was 1.82-2.70 in patients' perspective, which was higher than gastroenterologists' assessment. Comprehensibility was satisfactory for all PEMs. No PEM met the recommended sixth-grade reading level. CONCLUSION: LLMs have potential in assisting patient education. The accuracy and comprehensibility of LLM-generated PEMs were acceptable, but further optimization on improving completeness and accounting for a variety of linguistic contexts are essential for enhancing the feasibility.

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Maize is an important crop used for food, feed, and fuel. Abiotic stress is an important factor affecting maize yield. The EPF/EPFL gene family encodes class-specific secretory proteins that play an important role in the response to abiotic stress in plants. In order to explore and utilize the EPF/EPFL family in maize, the family members were systematically identified, and their chromosomal localization, physicochemical properties, cis-acting element prediction in promoters, phylogenetic tree construction, and expression pattern analysis were carried out using bioinformatics techniques. A total of 18 ZmEPF/EPFL proteins were identified in maize, which are mostly alkaline and a small portion acidic. Subcellular localization results showed that ZmEPF6, ZmEPF12, and ZmEPFL2 are localized in the nucleus and cytoplasm. Analysis of cis-acting elements revealed that members of the ZmEPF/EPFL family contain regulatory elements such as light response, anoxic, low temperature, and hormone response regulatory elements. RT-qPCR results showed that these family members are indeed responding to cold stress and hormone treatments. These results of this study provide a theoretical basis for improving the abiotic stress resistance of maize in future research.

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Backyard chickens usually have open housing and scavenge for food, facilitating contact with infective forms of parasites present in the environment and increasing the risk of parasitic infections. Coccidiosis and ascaridiosis are two internal parasites in scavenging chickens that cause production losses to farmers. Prevalence data of these two diseases are scarce in low-income and middle-income countries (LMICs) but necessary to assess the burden of disease in backyard chickens. This study estimates the clinical prevalence of coccidiosis and ascaridiosis at the country and regional levels in all LMICs using regression imputation methods. Regression models were developed with data of known prevalence of these parasites and using primarily climatic factors as predictors. A binomial random effects model was developed for each disease to impute prevalence. The overall estimated prevalence of coccidiosis was 0.39 (95 % CI: 0.37-0.42), with a higher mean prevalence in tropical countries. The overall estimated prevalence of ascaridiosis was 0.23 (95 % CI: 0.22-0.25) with a higher mean prevalence in countries with tropical, temperate and continental climates. The findings of this study can aid to identify the burdens of coccidiosis and ascaridiosis infections across countries and regions, which can inform disease control plans and, and encourage international alliances to facilitate access to preventive measures, improving animal health and reducing production losses.

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OBJECTIVES: Scrub typhus is underdiagnosed and underreported but emerging as a global public health problem. We aimed to provide the first comprehensive review on the seroprevalence, incidence, mortality of and risk factors for scrub typhus. METHODS: We searched PubMed, Scopus, Web of Science, China National Knowledge Infrastructure and other databases. Trended incidence and median mortality were calculated and pooled seroprevalence and risk factors for scrub typhus were evaluated using the random-effects meta-analysis. RESULTS: We included 663 articles from 29 countries/regions. The pooled seroprevalence was 10.73% (95%CI 9.47-12.13%) among healthy individuals and 22.58% (95%CI: 20.55%-24.76%) among febrile patients. Mainland China reported the highest number of cases and South Korea and Thailand had the highest incidence rates. Median mortalities were 5.00% (range: 0.00-56.00%) among hospital inpatients, 6.70% (range: 0.00-33.33%) among patients without specified admission status and 2.17% (range: 0.00-22.22%) among outpatients. The significant risk factors included agricultural work, specific vegetation exposure, other outdoor activities, risky personal health habits, and proximity to rodents, livestock, or poultry. CONCLUSIONS: Our comprehensive review elucidates the significant yet variable burden of scrub typhus across different regions, underscoring its emergence as a critical public health concern globally.

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OBJECTIVES: To observe the efficacy and safety of ginger-partitioned moxibustion combined with ringheaded thumb-tack needle stimulation in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) in patients with malignant tumors. METHODS: Patients with malignant tumors and suffering from chemotherapy were randomly divided into control group (35 cases, 4 cases dropped off) and observation group (35 cases, 2 cases dropped off). The patients of the control group were treated by orally taking ondansetron hydrochloride tablets 8 mg/time, 3 times a day for 3 d, and those of the observation group treated by ginger-partitioned moxibustion combined with ringheaded thumb-tack needle stimulation of Zusanli(ST36), Neiguan(PC6), Tianshu(ST25), Zhongwan(CV12) and Guanyuan(CV4) once a day for a total of 3 d, based on the treatment of the control group. The patients' gastrointestinal reaction degree after the 1st , 2nd and the 3rd day of treatment were recorded. The Karnofsky performance status (KPS) score (0-100 points) was used for assessing the patients' quality of life. The TCM syndrome score (4 grades：no, mild, medium and severe, i.e. 0, 2, 4 and 6 points) was given according to the patients' severity of symptoms of spleen (stomach) qi deficiency (nausea and vomiting, abdominal distension after eating, belching, loss of appetite, weakness and laziness to speak, fatigue, and loose stool). The safety of the treatment was assessed by examining the patients' blood routine, liver function and kidney function, and the adverse reactions including blisters, allergies, burns and fainting during acupuncture treatment. RESULTS: After the 2nd and 3rd day of treatment, the patients conditions of vomiting and nausea in the observation group were significantly better than those of the control group (P<0.05). The TCM syndrome score and KPS score were significantly decreased in comparison with those of pre-treatment in both groups (P<0.05), and the TCM syndrome score was obviously lower in the observation group than in the control group (P<0.05). No significant differences were found between the two groups in the KPS score after the treatment , and in the levels of white blood cells (WBC), hemoglobin (HGB), platelets (PLT), absolute neutrophil count (ANC), alanine transaminase (ALT), aspartate aminotransferase (AST), creatinine(Cr), and blood urea nitrogen (BUN). CONCLUSIONS: The use of ginger-partitioned moxibustion combined with ringheaded thumb-tack needle stimulation is safe for CINV patients, and can effectively relieve nausea and vomiting and alleviate digestive symptoms.

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Rapid urbanization will cause various land use changes and the vast occupation of green spaces, a critical factor in the deterioration of biodiversity in urbanized areas. Some species of wildlife are endangered due to habitat shrunk and fragmentation. However, Malaysia's current biodiversity protection range is still limited. The Ecological Network (EN) refers to a framework of ecological components, which can be obtained by geographical and technical approaches to support more ecological diversity ranges. Furthermore, little research has been found on EN in Malaysia and the impact of land use change on EN. Therefore, the Selangor region is selected as the study area. This paper quantifies land use change and measures the extent of land use change to obtain the EN's change. The result has shown that forestland has decreased, explored by people for housing and agriculture from 2000 to 2020. The EN has a trend of fragmentation. Overall, this study's results imply that the land use change led to EN's worsened performance from 2000 to 2020 in the study area. This paper hopes that this research could help supply information on conserving biodiversity in future development and urban sustainable planning in Malaysia.

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AIM: To explore the effect of silent information regulator factor 2-related enzyme 1 (SIRT1) on modulating apoptosis of human lens epithelial cells (HLECs) and alleviating lens opacification of rats through suppressing endoplasmic reticulum (ER) stress. METHODS: HLECs (SRA01/04) were treated with varying concentrations of tunicamycin (TM) for 24h, and the expression of SIRT1 and C/EBP homologous protein (CHOP) was assessed using real-time quantitative polymerase chain reaction (RT-PCR), Western blotting, and immunofluorescence. Cell morphology and proliferation was evaluated using an inverted microscope and cell counting kit-8 (CCK-8) assay, respectively. In the SRA01/04 cell apoptosis model, which underwent siRNA transfection for SIRT1 knockdown and SRT1720 treatment for its activation, the expression levels of SIRT1, CHOP, glucose regulated protein 78 (GRP78), and activating transcription factor 4 (ATF4) were examined. The potential reversal of SIRT1 knockdown effects by 4-phenyl butyric acid (4-PBA; an ER stress inhibitor) was investigated. In vivo, age-related cataract (ARC) rat models were induced by sodium selenite injection, and the protective role of SIRT1, activated by SRT1720 intraperitoneal injections, was evaluated through morphology observation, hematoxylin and eosin (H&E) staining, Western blotting, and RT-PCR. RESULTS: SIRT1 expression was downregulated in TM-induced SRA01/04 cells. Besides, in SRA01/04 cells, both cell apoptosis and CHOP expression increased with the rising doses of TM. ER stress was stimulated by TM, as evidenced by the increased GRP78 and ATF4 in the SRA01/04 cell apoptosis model. Inhibition of SIRT1 by siRNA knockdown increased ER stress activation, whereas SRT1720 treatment had opposite results. 4-PBA partly reverse the adverse effect of SIRT1 knockdown on apoptosis. In vivo, SRT1720 attenuated the lens opacification and weakened the ER stress activation in ARC rat models. CONCLUSION: SIRT1 plays a protective role against TM-induced apoptosis in HLECs and slows the progression of cataract in rats by inhibiting ER stress. These findings suggest a novel strategy for cataract treatment focused on targeting ER stress, highlighting the therapeutic potential of SIRT1 modulation in ARC development.

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Triclocarban (TCC) and its metabolite, 3,4-dichloroaniline (DCA), are classified as emerging organic contaminants (EOCs). Significant concerns arise from water and soil contamination with TCC and its metabolites. These concerns are especially pronounced at high concentrations of up to approximately 20 mg/kg dry weight, as observed in wastewater treatment plants (WWTPs). Here, a TCC-degrading co-culture system comprising Rhodococcus rhodochrous BX2 and Pseudomonas sp. LY-1 was utilized to degrade TCC (14.5 mg/L) by 85.9% in 7 days, showing improved degradation efficiency compared with monocultures. A combination of high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), genome sequencing, transcriptomic analysis, and quantitative reverse transcription-PCR (qRT-PCR) was performed. Meanwhile, through the combination of further experiments involving heterologous expression and gene knockout, we proposed three TCC metabolic pathways and identified four key genes (tccG, tccS, phB, phL) involved in the TCC degradation process. Moreover, we revealed the internal labor division patterns and connections in the co-culture system, indicating that TCC hydrolysis products were exchanged between co-cultured strains. Additionally, mutualistic cooperation between BX2 and LY-1 enhances TCC degradation efficiency. Finally, phytotoxicity assays confirmed a significant reduction in the plant toxicity of TCC following synergistic degradation by two strains. The in-depth understanding of the TCC biotransformation mechanisms and microbial interactions provides useful information for elucidating the mechanism of the collaborative biodegradation of various contaminants.

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Objective: To explore factors influencing the acceptance of allergen immunotherapy (AIT) for the treatment of allergic respiratory diseases by pediatric patients and their families. Methods: A total of 406 children (210 males and 196 females) attending the pediatric outpatient clinics and wards of the Renji Hospital, Shanghai Jiao Tong University School of Medicine from June 2020 to April 2022. Those who met the criteria for the AIT treatment, were included in the survey. An online 20-item questionnaire was developed. Data on patient's general characteristics, allergic disease status, family history of allergies, general family information, parental knowledge of allergic diseases, and whether the AIT treatment was recommended by a physician, were collected. The patients were divided into two groups according to their willingness to receive AIT: a reluctant or neutral group (n = 182), and a willing group (n = 224). A univariate analysis of the willingness to undergo AIT was done to detect parameters that significantly differed between the groups, and the identified factors were used as independent variables in the multifactorial logistic regression analysis. Results: The severity of allergic disease, presence of drug allergy, occurrence of severe allergic reactions, mother's education, distance from home to the hospital, parental knowledge of allergic diseases, and whether the doctor recommended AIT were all statistically different between the groups (p < 0.05). Multifactorial logistic regression analysis showed that the degree of allergic rhinitis (AR), or asthma (AS), parental knowledge of allergic diseases, and doctor's recommendation of AIT were the factors that influenced the willingness of pediatric patients to receive AIT. Conclusions: The severity of AR and AS, parental knowledge of allergic diseases, and doctor's recommendation influenced the willingness of pediatric patients to receive AIT.

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Covalent-organic frameworks (COFs) with photoinduced donor-acceptor (D-A) radical pairs show enhanced photocatalytic activity in principle. However, achieving long-lived charge separation in COFs proves challenging due to the rapid charge recombination. Here, we develop a novel strategy by combining [6 + 4] nodes to construct zyg-type 3D COFs, first reported in COF chemistry. This structure type exhibits a fused Olympic-rings-like shape, which provides a platform for stabilizing the photoinduced D-A radical pairs. The zyg-type COFs containing catalytically active moieties such as triphenylamine and phenothiazine (PTZ) show superior photocatalytic production rates of hydrogen peroxide (H2O2). Significantly, the photochromic radical states of these COFs show up to 400% enhancement in photocatalytic activity compared to the parent states, achieving a remarkable H2O2 synthesis rate of 3324 µmol g-1 h-1, which makes the PTZ-COF one of the best crystalline porous photocatalysts in H2O2 production. This work will shed light on the synthesis of efficient 3D COF photocatalysts built on topologies that can facilitate photogenerating D-A radical pairs for enhanced photocatalysis.

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G-quadruplexes (G4s) are atypical nucleic acid structures involved in basic human biological processes and are regulated by small molecules. To date, pyridostatin and its derivatives [e.g., PyPDS (4-(2-aminoethoxy)-N 2,N 6-bis(4-(2-(pyrrolidin-1-yl) ethoxy) quinolin-2-yl) pyridine-2,6-dicarboxamide)] are the most widely used G4-binding small molecules and considered to have the best G4 specificity, which provides a new option for the development of cisplatin-binding DNA. By combining PyPDS with cisplatin and its analogs, we synthesize three platinum complexes, named PyPDSplatins. We found that cisplatin with PyPDS (CP) exhibits stronger specificity for covalent binding to G4 domains even in the presence of large amounts of dsDNA compared with PyPDS either extracellularly or intracellularly. Multiomics analysis reveals that CP can effectively regulate G4 functions, directly damage G4 structures, activate multiple antitumor signaling pathways, including the typical cGAS-STING pathway and AIM2-ASC pathway, trigger a strong immune response and lead to potent antitumor effects. These findings reflect that cisplatin-conjugated specific G4 targeting groups have antitumor mechanisms different from those of classic cisplatin and provide new strategies for the antitumor immunity of metals.

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In chronic kidney disease (CKD), renal fibrosis is an unavoidable result of various manifestations. However, its pathogenesis is not yet fully understood. Here, we revealed the novel role of Homeobox D10 (HOXD10) in CKD-related fibrosis. HOXD10 expression was downregulated in CKD-related in vitro and in vivo fibrosis models. UUO model mice were administered adeno-associated virus (AAV) containing HOXD10, and HOXD10 overexpression plasmids were introduced into human proximal tubular epithelial cells induced by TGF-ß1. The levels of iron, reactive oxygen species (ROS), lipid ROS, the oxidized glutathione/total glutathione (GSSG/GSH) ratio, malonaldehyde (MDA), and superoxide dismutase (SOD) were determined using respective assay kits. Treatment with AAV-HOXD10 significantly attenuated fibrosis and renal dysfunction in UUO model mice by inhibiting NOX4 transcription, ferroptosis pathway activation, and oxidative stress. High levels of NOX4 transcription, ferroptosis pathway activation and profibrotic gene expression induced by TGF-ß1/erastin (a ferroptosis agonist) were abrogated by HOXD10 overexpression in HK-2 cells. Moreover, bisulfite sequencing PCR result determined that HOXD10 showed a hypermethylated level in TGF-ß1-treated HK-2 cells. The binding of HOXD10 to the NOX4 promoter was confirmed by chromatin immunoprecipitation (ChIP) analysis and dual-luciferase reporter assays. Targeting HOXD10 may represent an innovative therapeutic strategy for fibrosis treatment in CKD.

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Appropriate soluble carbohydrate (SCHO)-to-NDF ratios in the diet are essential for rumen health. The effects of different SCHO-to-NDF ratios (1.0, 1.5, and 2.0) on rumen barrier function and inflammation in Dumont lambs (n = 18, 6 replicates per treatment) was investigated. The SCHO:NDF ratio was altered by replacing the forage (Leynus chinensis) with corn grain. With an increase in the proportion of SCHO, the final body weight (FBW), average daily gain (ADG), soluble carbohydrate intake (SCHOI), and LPS level increased; and the neutral detergent fiber intake (NDFI), ruminal papillae height, papillae area, and pH decreased (p < 0.05, plin < 0.05). The medium CHO:NDF group had increased claudin-1 mRNA (p < 0.05, plin = 0.005, pquad = 0.003) and protein (p < 0.05, pquad < 0.001) levels; the high CHO:NDF group had increased occludin mRNA and protein (p < 0.05, plin = 0.001) levels. The level of the anti-inflammatory cytokine IL-10 was significantly greater in the medium CHO:NDF group than in the high CHO:NDF group (p < 0.05, pquad < 0.001). With an increase in the ratio of SCHO, the mRNA level and concentration of the proinflammatory cytokines IL-1ß, IL-6, and TNF-α linearly increased (p < 0.05, plin < 0.05), and those in the high CHO:NDF group were significantly greater than those in the low CHO:NDF group. The levels of phosphorylated p65 (plin = 0.003), IκB-α (plin < 0.001), and JNK (plin = 0.001) increased linearly, and those in the high CHO:NDF group were significantly greater than those in the other two groups (p < 0.05). Therefore, when the SCHO-to-NDF ratio was increased to 1.5, the rumen epithelium was not affected, but when the ratio was increased to 2.0, NF-κB and MAPK were activated in the rumen epithelium, leading to impaired barrier function and inflammation. The suitable NFC:NDF ratio for the short-term fattening of Dumont lambs was found to be 1.50.