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Ting-Ting Chen,* Feng Xiao,* Nan Li, Shan Shan, Meng Qi, Zi-Ying Wang, Sheng-Nan Zhang, Wei Wei, Wu-Yi Sun Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei, Anhui Province, 230032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wu-Yi Sun; Wei WeiInstitute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, 81 Meishan Road, Hefei, Anhui Province, 230032, People’s Republic of ChinaTel/Fax +86 551 65161209Email sunwuyi51@aliyun.com; wwei@ahmu.edu.cnAbstract: Fibrosis is the final stage of the development of chronic inflammation. It is characterized by excessive deposition of the extracellular matrix, leading to tissue structure damage and organ dysfunction, which is a serious threat to human health and life. However, the molecular mechanism of fibrosis is still unclear. Inflammasome is a molecular complex of proteins that has been becoming a key innate sensor for host immunity and is involved in pyroptosis, pathogen infection, metabolic syndrome, cellular stress, and tumor metastasis. Inflammasome signaling and downstream cytokine responses mediated by the inflammasome have been found to play an important role in fibrosis. The inflammasome regulates the secretion of IL-1β and IL-18, which are both critical for the process of fibrosis. Recently, researches on the function of inflammasome have attracted extensive attention, and data derived from these researches have increased our understanding of the effects and regulation of inflammasome during fibrosis. In this review, we emphasize the growing evidence for both indirect and direct effects of inflammasomes in triggering fibrosis as well as potential novel targets for antifibrotic therapies.Keywords: inflammasome, fibrosis, NLRP3, AIM2, caspase-1

Shan-Shan Su,1,* Sheng-Nan Zhang,1,* Jun-Ru Ye,1 Ling-Na Xu,1 Peng-Cheng Lin,1 Han-Yan Xu,1 Qing Wu,2 Yu-Ping Li1 1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325015, People’s Republic of China; 2The Center of Laboratory and Diagnosis, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325015, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yu-Ping LiDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, South Baixiang, Ouhai District, Wenzhou, Zhejiang Province 325015, People’s Republic of ChinaTel/fax +86 577 5557 9273Email wzliyp@163.comBackground: Patients with high-titer anti-IFN-γ autoantibodies present disseminated non-tuberculous mycobacterial (NTM) and other opportunistic infections. Due to its rare occurrence and non-specific symptoms, this syndrome is difficult to diagnose during early disease stages. Here, we report a case with high-concentrations of serum anti-IFN-γ autoantibodies who presented with disseminated Talaromyces marneffei and NTM disease accompanied Sweet’s syndrome.Case presentation: A 62-year-old Chinese woman with no previous history was admitted to our hospital in August 2016 due to intermittent fever for 2 years, left chest wall redness, and swelling for 3 months. During hospitalization, the patient was confirmed with disseminated T. marneffei and successfully treated with antifungal therapy. In July 2017, upon second admission, Mycobacterium avium intracellular (MAC) pulmonary infection was established after positive cultures from the right lung tissue. The patient failed treatment after 1 month of anti-NTM therapy due to side effects. In May 2018, she was confirmed as having disseminated MAC disease accompanied by hand rashes, which was considered as Sweet’s syndrome. High-level anti-IFN-γ antibodies in the patient serum were detected upon comparison with normal controls (2.85-fold increase). Following anti-NTM therapy, both symptoms and pulmonary infiltration gradually improved, and joint destruction and lymphadenitis remained.Conclusions: Patients with anti-interferon-γ autoantibodies should be considered for severe, recurrent infections in adults in the absence of other known risk factors. Sweet’s syndrome is a common skin manifestation of the syndrome.Keywords: Talaromyces marneffei, Mycobacterium avium, Sweet’s syndrome, autoantibodies, interferon-gamma

We present extensive photometry at ultraviolet (UV), optical, and near-infrared (NIR) wavelengths, as well as dense sampling of optical spectra, for the normal Type Ia supernova (SN Ia) 2005cf. The optical photometry, performed at eight different telescopes, shows a 1σ scatter of ≲0.03 mag after proper corrections for the instrument responses. From the well-sampled light curves, we find that SN 2005cf reached a B-band maximum at 13.63 0.02 mag, with an observed luminosity decline rate Δm 15(B) = 1.05 0.03 mag. The correlations between the decline rate and various color indexes, recalibrated on the basis of an expanded SN Ia sample, yield a consistent estimate for the host-galaxy reddening of SN 2005cf, E(B - V)host = 0.10 0.03 mag. The UV photometry was obtained with the Hubble Space Telescope and the Swift Ultraviolet/Optical Telescope, and the results match each other to within 0.1-0.2 mag. The UV light curves show similar evolution to the broadband U, with an exception in the 2000-2500 spectral range (corresponding to the F220W/uvm2 filters), where the light curve appears broader and much fainter than that on either side (likely owing to the intrinsic spectral evolution). Combining the UV data with the ground-based optical and NIR data, we establish the generic UV-optical-NIR bolometric light curve for SN 2005cf and derive the bolometric corrections in the absence of UV and/or NIR data. The overall spectral evolution of SN 2005cf is similar to that of a normal SN Ia, but with variety in the strength and profile of the main feature lines. The spectra at early times displayed strong, high-velocity (HV) features in the CaII H&K doublet and NIR triplet, which were distinctly detached from the photosphere (v 10,000 km s-1) at a velocity ranging from 20,000 to 25,000 km s -1. One interesting feature is the flat-bottomed absorption observed near 6000 in the earliest spectrum, which rapidly evolved into a triangular shape and then became a normal SiII λ6355 absorption profile at about one week before maximum brightness. This premaximum spectral evolution is perhaps due to the blending of the SiIIλ6355 at photospheric velocity and another HV absorption component (e.g., an SiII shell at a velocity 18,000 km s -1) in the outer ejecta, and may be common in other normal SNe Ia. The possible origin of the HV absorption features is briefly discussed. © 2009. The American Astronomical Society.

Lin Wu, Wei Yang, Su-ning Zhang, Ji-bin Lu Department of Thoracic Surgery, Sheng Jing Hospital of China Medical University, Shenyang, People’s Republic of China Objective: Alpinetin is a novel flavonoid that has demonstrated potent antitumor activity in previous studies. However, the efficacy and mechanism of alpinetin in treating lung cancer have not been determined. Methods: We evaluated the impact of different doses and durations of alpinetin treatment on the cell proliferation, the apoptosis of lung cancer cells, as well as the drug-resistant lung cancer cells. Results: This study showed that the alpinetin inhibited the cell proliferation, enhanced the apoptosis, and inhibited the PI3K/Akt signaling in lung cancer cells. Moreover, alpinetin significantly increased the sensitivity of drug-resistant lung cancer cells to the chemotherapeutic effect of cis-diammined dichloridoplatium. Taken together, this study demonstrated that alpinetin significantly suppressed the development of human lung cancer possibly by influencing mitochondria and the PI3K/Akt signaling pathway and sensitized drug-resistant lung cancer cells. Conclusion: Alpinetin may be used as a potential compound for combinatorial therapy or as a complement to other chemotherapeutic agents when multiple lines of treatments have failed to reduce lung cancer. Keywords: alpinetin, cell proliferation and apoptosis, drug resistance reversal, PI3K/Akt, lung cancer

Crystal TY Lee, Shinan Zhang, Yiu Yan Leung, Samantha KY Li, Cissy C Tsang, Chun-Hung Chu Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, People’s Republic of China Objectives: To study patients’ satisfaction and prevalence of complications in surgical extraction of impacted third molar by senior dentists and recently graduated dentists in a university dental clinic. Method: Patients who had impacted third molar extraction in a university dental clinic by two associate dentists who had 15 years of experience were evaluated in this study. Patients’ age, sex, history of pericoronitis, tooth extracted, and radiographic assessment of the impacted tooth were recorded. Immediately after suture removal, the patients were invited to indicate their satisfaction on a Likert scale of 1–5. Results: A total of 546 patients received extraction, and 251 patients were operated by associate dentists. Patient satisfaction was higher among those who had noncomplicated surgery (P=0.007), short treatment time (P

Based on the suspension of a missile using folding rotary wings and airbags, in order to improve the basic parameters and motion characteristics of the rotor during the unfolding process and analyze the aerodynamic characteristics of the entire device in the suspension state, after proposing a scheme of double-spin mechanism, the main folding and unfolding mechanism, initial driving device, rotating driving device, and locking mechanism were designed, and the simulation research is studied by the Automatic Dynamic Analysis of Mechanical System and Ansys Fluent Fluid Simulation software, respectively. The results show that the rotation rate was controlled at 41.8 mm/s, the various motion parameters are reasonable, and the operation process is relatively smooth, with high reliability. The speed and pressure value at the tip of the rotor are higher and the aerodynamic disturbance is obvious, which has a great influence on the aerodynamic performance. The speed and pressure distribution of the surrounding flow field is stable, the lift provided is 46 N, and the lift coefficient is 0.55, which can ensure the long-time suspension state of the missile. This paper puts forward a valuable design idea and has practical reference value for the research of the suspended missile. [ABSTRACT FROM AUTHOR]

AIM: To evaluate the added value of diffusion-weighted imaging (DWI) combined with conventional magnetic resonance imaging (MRI) in the detection of new, very small hepatocellular carcinoma lesions (<=1 cm) in patients with hepatocellular carcinoma following interventional therapy compared to conventional MRI alone. MATERIALS AND METHODS: After interventional therapy, 45 patients with hepatocellular carcinoma underwent conventional MRI and DWI with a b-value of 0 and 700 s/mm(2). Twenty-one new, small hepatocellular carcinoma lesions were confirmed in 16 patients at follow-up MRI. Two observers independently retrospectively analysed the two imaging sets in random order. The diagnostic performance using each imaging set was evaluated by received operating characteristic curve analysis. RESULTS: Twenty-one new, very small hepatocellular carcinoma lesions found in 16 patients was confirmed as the final result. The area under the receiver operating characteristic curve of the DWI/conventional MRI combination (observer 1, 0.952; observer 2, 0.976) and conventional MRI images alone (observer 1, 0.905; observer 2, 0.905) were statistically significant. The kappa value of the DWI/conventional MRI combination was 0.884, and that of conventional MRI was 0.722. Among the 21 lesions, 100% (21/21) of the lesions were both recognized by two independent reviewers on DWI, while only 76% (16/21) and 71% (15/21) of the lesions were regarded as very small hepatocellular carcinomas on conventional MRI. CONCLUSION: Due to the higher detection rate of new subcentimetre lesions in hepatocellular carcinoma patients following interventional therapy, DWI could be considered complementary to conventional MRI in the diagnosis of hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Palm fungi are a diverse and unique group mostly found on Arecaceae hosts. They have been studied for approximately 200 years resulting in a large number of known fungal species representing over 700 genera. The timeline of palm fungal studies could be roughly divided into three phases, based on the methods and frequency of reports. They are the "Historical palm fungi era", "Classical palm fungi era" and "Molecular palm fungi era". In the first two periods, the identification of palm fungi was based on morphology, which resulted in a considerable number of morphological species scattered across the data in books, monographs and papers. With the advancement of molecular techniques, studies on palm fungi accelerated. A large number of new species were introduced in the molecular era, especially from Asia, including China and Thailand. However, there is a necessity to link these three generations of studies into a single platform combining data related to host factors, geography and utilisation. Herein, we introduce the palm fungi website: https://palmfungi.org, an integrated data platform for interactive retrieval, based on palm and fungal species. This website is not only a portal for the latest, comprehensive species information on palm fungi, but also provides a new platform for fungal researchers to explore the host-specificity of palm fungi. Additionally, this study uses palmfungi.org and related data to briefly discuss the current status of research on the distribution of palm fungi populations, showing how palmfungi.org links fungi with their palm hosts. Furthermore, the website will act as a platform for collaboration amongst taxonomists, plant pathologists, botanists, ecologists and those who are interested in palms and their relationship with ecological sustainability., Competing Interests: No conflict of interest to declare Disclaimer: This article is (co-)authored by any of the Editors-in-Chief, Managing Editors or their deputies in this journal., (Yinru Xiong, Manawasinghe S. Ishara, Kevin D. Hyde, Joanne E. Taylor, Alan Phillips, Diana Santos Pereira, Li Lu, Sheng-Nan Zhang, Ausana Mapook, Biao Xu.)

Selective electrocatalytic transformation of alcohols to aldehydes offers an efficient and environmentally friendly platform for the simultaneous production of fine chemicals and pure hydrogen gas. However, traditional alcohol oxidation reactions (AORs) in aqueous electrolyte unavoidably face competitive reactions (e.g., water oxidation and overoxidations reactions) for the presence of active oxygen species from water oxidation, causing an unwanted decrease in final efficiency and selectivity. Here, we developed an integrated all-solid proton generator-transfer electrolyzer to trigger the pure alcohol splitting reaction (ASR). In this splitting process, only O-H and C-H bonds can be cleaved at the proton generator (Pt nanoparticles), thereby completely avoiding all competitive reactions involving oxygen active species to give a > 99% selectivity to aldehydes. The as-generated protons are transported to the cathode by a three-dimensional (3D) conducting network (assemblies of ionomers and carbon spheres) for efficient hydrogen production. Unlike the poor selectivity (<22%) and durability (<3 h) of a conventional AOR electrolyzer, this ASR electrolyzer could be continuously operated at a low cell voltage of 1.2 V for at least 10 days to give a high Faradaic efficiency of 80-93% for aldehyde production.

Objective: To investigate long-term health-related quality of life (HRQoL) and related factors in children with severe hemophilia A (HA) who received regular low-dose prophylaxis. Methods: Clinical data of severe HA children who began to receive regular low-dose coagulation factor Ⅷ (FⅧ) prophylaxis in Peking Union Medical College Hospital from January 1, 2008 to December 31, 2011 were retrospectively enrolled. The longest last follow-up period was May 31, 2023. The attendance of school or work and daily physical activity during the last follow-up were investigated. The patients were divided into full attendance group and incomplete attendence group according to attendance. The patients were divided into into exercise attainment group (reached Chinese sports recommendation) and exercise nonattainment group according to the exercise status. Barthel score was used to assess activities of daily living and Haemo-QoL was used to assess quality of life. Long-term HRQoL for children aged 8-16 years and patients aged 17 years and above were assessed using Haemo-QoL SF and Haem-A-QoL versions, respectively. Spearman correlation analysis was used to examine the correlation between treatment conditions and Haemo-QoL scores. Results: A total of 22 cases were enrolled, the prophylaxis initiation age ranged from 1.8-17.9 (10.4±3.8) years old. The average prophylactic FⅧ dose during low-dose prophylaxis was 24.2 U/kg per week and the follow-up time was 6.3-15.1 (9.6±2.8) years. At the last follow-up, the age of the patients was (20.2±5.4) years, of which 14 (63.6%) were adults over 18 years old. There were 15 patients in the full attendance group and 7 patients in the incomplete attendence group. Compared with the full attendance group, the incomplete attendence group had a smaller preventive treatment dose [ M ( Q 1, Q 3 ), (28.4±11.1) vs (15.3±3.7) U/kg, P =0.012], shorter preventive treatment time [148. 1 (18.6, 346.5) vs 48.0 (32.0, 156.9) weeks, P =0.017], and higher annual joint bleeding rate (AJBR) [12.5 (6.0, 22.3) vs 14.2 (13.2, 17.8) times, P =0.017]. There were 7 cases in the exercise attainment group and 15 cases in the exercise nonattainment group. Compared to the exercise attainment group, the exercise nonattainment group had shorter preventive treatment time[313. 7 (156.9, 366.0) vs 48.0 (16.5, 108.9) weeks, P =0.006], a higher AJBR [7.0 (5.1, 10.0) vs 23.3 (12.5, 29.8), P =0.003] and a higher hemophilia joint health score (HJHS) [9.0 (2.0, 15.5) vs 23.0 (12.0, 27.8), P =0.014]. Barthel score showed 81.8% (18 cases) of the patients' living ability was not influenced by the illness. In Haemo-QoL score, the total score of Haemo-QoL SF in 7 cases was (47.6±17.0) scores, the total score of Haem-A-QoL in 15 cases was (45.2±22.6) scores. The daily activity dimension of the Haem-A-QoL score was the lowest [38.2 (10.9, 45.5) scores], which was positively correlated with the starting age of prophylactic initiation ( r =0.501, P =0.057), and negatively correlated with the duration of prophylaxis ( r =-0.545, P =0.036). Conclusions: Regular low-dose prophylaxis could improve the long-term HRQoL of some children with severe HA, and children with higher prophylactic doses and longer prophylactic treatment time have higher quality of life.

Background: Erythrocyte dysfunction is a characteristic of diabetes mellitus (DM). However, erythrocyte-associated biomarkers do not adequately explain the high prevalence of DM. Here, we describe red blood cell distribution width to albumin ratio (RAR) as a novel inflammatory biomarker for evaluating an association with DM prevalence and prognosis of all-cause mortality., Methods: Data analyzed in this study were extracted from the National Health and Nutrition Examination Survey (NHANES) 1999-2020. A total of 40,558 participants (non-DM and DM) were enrolled in the study; RAR quartiles were calibrated at Q1 [2.02,2.82] mL/g, Q2 (2.82,3.05] mL/g, Q3 (3.05,3.38] mL/g, and Q4 (3.38,12.08] mL/g. A total of 8,482 DM patients were followed (for a median of 84 months), of whom 2,411 died and 6,071 survived. The prevalence and prognosis associated with RAR and DM were analyzed; age and sex were stratified to analyze the prevalence of RAR in DM and the sensitivity of long-term prognosis., Results: Among non-DM ( n =30,404) and DM ( n =10,154) volunteers, DM prevalence in RAR quartiles was 8.23%, 15.20%, 23.92%, and 36.39%. The multivariable odds ratio (OR) was significant for RAR regarding DM, at 1.68 (95% CI 1.42, 1.98). Considering Q1 as a foundation, the Q4 OR was 2.57 (95% CI 2.11, 3.13). The percentages of DM morbidity varied across RAR quartiles for dead ( n =2,411) and surviving ( n =6,071) DM patients. Specifically, RAR quartile mortality ratios were 20.31%, 24.24%, 22.65%, and 29.99% (P<0.0001). The multivariable hazard ratio (HR) for RAR was 1.80 (95% CI 1.57, 2.05). Considering Q1 as a foundation, the Q4 HR was 2.59 (95% CI 2.18, 3.09) after adjusting for confounding factors. Sensitivity analysis revealed the HR of male DM patients to be 2.27 (95% CI 1.95, 2.64), higher than females 1.56 (95% CI 1.31, 1.85). DM patients who were 60 years of age or younger had a higher HR of 2.08 (95% CI1.61, 2.70) as compared to those older than 60 years, who had an HR of 1.69 (95% CI 1.47, 1.94). The HR of RAR in DM patients was optimized by a restricted cubic spline (RCS) model; 3.22 was determined to be the inflection point of an inverse L-curve. DM patients with a RAR >3.22 mL/g suffered shorter survival and higher mortality as compared to those with RAR ≤3.22 mL/g. OR and HR RAR values were much higher than those of regular red blood cell distribution width., Conclusions: The predictive value of RAR is more accurate than that of RDW for projecting DM prevalence, while RAR, a DM risk factor, has long-term prognostic power for the condition. Survival time was found to be reduced as RAR increased for those aged ≤60 years among female DM patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Wang, Gao, Zhang, Zhang, Xu, Yao, Yang and Yan.)

Cadmium (Cd) and sulfamethoxazole (SMX) frequently coexist in farmlands, yet their synergistic toxicological impacts on terrestrial invertebrates remain unexplored. In this study, earthworms were exposed to artificial soils percolated with Cd (5 mg/kg), SMX (5 mg/kg) or combination of them for 7 days, followed by a 12-day elimination phase in uncontaminated soil. The uptake of Cd and SMX by the earthworms, along with their subcellular distribution, was meticulously analyzed. Additionally, a suite of biomarkers-including superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and weight loss-were evaluated to assess the health status of the earthworms and the toxicological effects of the Cd and SMX mixture. Notably, the cotreatment with Cd and SMX resulted in a significantly higher weight loss in Eisenia fetida (41.25 %) compared to exposure to Cd alone (26.84 %). Moreover, the cotreatment group exhibited substantially higher concentrations of Cd in the total internal body, fraction C (cytosol), and fraction E (tissue fragments and cell membranes) in Eisenia fetida compared to Cd alone counterparts. The combined exposure also significantly elevated the SMX levels in the total body and fraction C compared with the SMX-only treated earthworms. Additionally, Eisenia fetida subjected to the combined treatment showed markedly increased activities of SOD, CAT, and MDA compared to those treated with Cd alone. The effect addition indices (EAIs), ranging from 1.00 to 2.23, unequivocally demonstrated a synergistic effect of the combined treatments. Interestingly, relocating the earthworms to clean soil did not mitigate the observed adverse effects. These findings underscore the increased risk posed by the Cd-SMX complex to terrestrial invertebrates in agricultural areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Polycystic ovary syndrome (PCOS) infertility has attracted great attention from researchers due to its high incidence. Numerous studies have shown that Chinese medicine is effective in treating this disease, but there is a wide variety of Chinese medicine therapies available, and there is a lack of comparative evaluation of the efficacy of various Chinese medicine combination therapies in the clinic, which requires further in-depth exploration. This study aims to evaluate the efficacy of a combined traditional Chinese medicine (TCM) therapy for the treatment of infertility with PCOS using network meta-analysis (NMA)., Methods: In PubMed, web of Science, Cochrane Library, Embase, China Knowledge Network, Wanfang Data, VIP Database, China Biomedical Literature Database (SinoMed) databases, searchs were conducted for information about the randomized controlled trials (RCTs) of combined TCM therapy for the treatment of infertility with PCOS. Quality evaluation was performed using the Cochrane 5.3 risk of bias assessment tool, and NMA using Stata 16.0., Results: This study comprised 28 RCTs using 8 combined TCM therapies in total. The results of the NMA showed that moxibustion + herbal, fire acupuncture + herbal, acupuncture + herbal, electroacupuncture + herbal, and acupoint application + herbal improved the clinical pregnancy rate better than acupuncture, herbal, and western medicines monotherapy (P < .05). Additionally, ear point pressure + herbal enema + herbal, acupuncture and moxibustion + herbal, fire acupuncture + herbal, and acupuncture + herbal improved the ovulation rate better than acupuncture, herbal, and western medicines monotherapy (P < .05). Moxibustion + herbal, fire acupuncture + herbal, and acupuncture + herbal are the 3 most effective therapies for improving the clinical pregnancy rate. Fire acupuncture + herbal, acupuncture + herbal, and ear point pressure + herbal enema + herbal are the 3 most effective therapies for improving the ovulation rate., Conclusion: The combined TCM therapy demonstrated better efficacy for the treatment of infertility with PCOS compared to acupuncture, herbal, and western medicines monotherapy. However, the optimal treatment therapy varied depending on the outcome indicators. Further large sample, high-quality, and standardized RCTs are needed to verify these findings., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Intelligent manufacturing technologies, including databases, mathematical modeling, and information systems have played a significant role in process control, production management, and supply chain management in traditional Chinese medicine(TCM) industry. However, their ability to process and utilize unstructured data, such as research and development reports, batch production records, quality inspection records, and supplier documents, is relatively weak. For text, images, language, and other unstructured data, generative artificial intelligence(AI) technology has shown strong potential for development in extracting information, extracting knowledge, semantic retrieval, and content generation. Generative AI is expected to provide a feasible set of tools for the utilization of unstructured data resources in the TCM industry. Based on years of research and industrial application experience in TCM intelligent manufacturing technology, this study reviewed the current situation of intelligent manufacturing in TCM and the utilization of unstructured data, analyzed the application value of generative AI in the TCM manufacturing process and supply chain, summarized four typical application scenarios, including intelligent pharmaceutical knowledge base/knowledge graph, intelligent on-the-job trai-ning, intelligent production quality control, and intelligent supply chain. Furthermore, this study also explained the data collection and processing, business process design, application potential, and value of each scenario based on industry demands. Finally, based on the integration of generative AI and TCM industrial models, the study proposed a preliminary concept of a smart industrial brain for TCM, aiming to provide a reference for the application of AI technology in the field of TCM manufacturing.

The excitation-dependent emission properties of carbon dots (Cdots) are extensively reported, but their red emission is often weak, limiting their wider application. Here we introduce ethidium bromide, as a functional precursor with red emission, to enhance the red emission for Cdots, with comparable intensity at a broad wavelength range to multi-emission Cdots (M-Cdots). We found that Cdots prepared with ethidium bromide/ethylenediamine exhibited strong blue and red emission at 440 and 615 nm, with optimal excitation at 360 and 470 nm as M-Cdots, respectively, but the Cdots from single ethidium bromide (EB-Cdots) possessed weak red emission. M-Cdots exhibited a broad absorption band at 478 nm, but a band blue-shifted to 425 nm was observed for EB-Cdots, while no absorption was observed at 478-425 nm for the Cdots prepared with citric acid and ethylenediamine. Thus, we proposed that C=O and C=N formed a π-conjugation structure as the absorption band at 478 nm for the red emission of M-Cdots, as also confirmed with the excitation at 470 nm. Moreover, the π-conjugation structure is fragile and sensitive to harsh conditions, so red emission was difficult to observe for the Cdots prepared with citric acid/ethylenediamine or single ethidium bromide. M-Cdots possess two centers for blue and red emission with different structures. The dual emission was therefore used for ratiometric sensing with dichromate (Cr 2 O 7 2- ) and formaldehyde (HCHO) as the targets using the intensity ratio of the emissions at 615 and 440 nm. Due to the comparable intensity at a broad wavelength range, we designed encryption codes with five excitations at 360, 400, 420, 450, and 470 nm as the inputs, and the emission colors were used for information decoding. Thus, we determined why red emission was difficult to realize for Cdots, and our results could motivate the design of red-emission Cdots for extensive applications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Omics, bioinformatics, molecular docking, and experimental validation were used to elucidate the hepatoprotective effects, mechanisms, and active compounds of Shandougen (SDG) based on the biolabel-led research pattern. Integrated omics were used to explore the biolabels of SDG intervention in liver tissue. Subsequently, bioinformatics and molecular docking were applied to topologically analyze its therapeutic effects, mechanisms, and active compounds based on biolabels. Finally, an animal model was used to verify the biolabel analysis results. Omics, bioinformatics, and molecular docking revealed that SDG may exert therapeutic effects on liver diseases in the multicompound and multitarget synergistic modes, especially liver cirrhosis. In the validation experiment, SDG and its active compounds (betulinic acid and gallic acid) significantly improved the liver histopathological damage in the CCl 4 -induced liver cirrhosis model. Meanwhile, they also produced significant inhibitory effects on the focal adhesion pathway (integrin alpha-1, myosin regulatory light chain 2, laminin subunit gamma-1, etc.) and alleviated the associated pathological processes: focal adhesion (focal adhesion kinase 1)-extracellular matrix (collagen alpha-1(IV) chain, collagen alpha-1(VI) chain, and collagen alpha-2(VI) chain) dysfunction, carcinogenesis (alpha-fetoprotein, NH 3 , and acetylcholinesterase), inflammation (tumor necrosis factor alpha, interleukin-1 [IL-1], IL-6, and IL-10), and oxidative stress (reactive oxygen species, malonaldehyde, and superoxide dismutase). This study provides new evidence and insights for the hepatoprotective effects, mechanisms, and active compounds of SDG., (© 2024 John Wiley & Sons, Ltd.)

Objective: To investigate the effect of TLK2 expression regulated by miR-21 on proliferation and apoptosis of acute myeloid leukemia cells., Methods: Seventy patients with AML admitted to our hospital from January 2019 to July 2022 were selected, while 30 patients with iron deficiency anemia were selected as the control group. Bone marrow mononuclear cells (BMMNCs) of the patients were obtained using Ficoll density gradient centrifugation. RT-qPCR was used to determine the expression levels of miR-21 and TLK2 mRNA in BMMNCs. Mimics-miR-21, mimics-NC, inhibitor-miR-21, inhibitor-NC and NC were transfected into HL-60 cells using liposome-mediated transfection technology. CCK-8 method was used to determine the activity of transfected HL-60 cells after treatment with cytarabine. The apoptosis rate of HL-60 transfected cells was determined by TUNEL method. The expression of TLK2 mRNA in HL-60 cells transfected with inhibitor-miR-21 was determined by RT-qPCR., Results: The relative expression levels of miR-21 and TLK2 mRNA in BMMNCs of AML patients were significantly higher than those of controls (both P < 0.05). After HL-60 cells were treated with cytarabine, both the cell activity of inhibitor-miR-21 group and mimics-miR-21 group decreased significantly with the increase of cytarabine concentration (both P < 0.05). However, at each concentration point of cytarabine, the cell activity of inhibitor-miR-21 group was lower than that of control group ( P < 0.05), while mimics-miR-21 group was higher than control group ( P < 0.05). After HL-60 cells were treated with cytarabine, the apoptosis rate of inhibitor-miR-21 group was significantly increased ( P < 0.05), while that of mimics-miR-21 group was significantly decreased ( P < 0.05). After HL-60 cells were treated with inhibitor-miR-21, the relative expression of TLK2 mRNA decreased significantly ( P < 0.05)., Conclusion: miR-21 is highly expressed in AML patients, which may promote the apoptosis of AML cells by inhibiting the expression of TLK2 .

Background: The role of exosomes derived from HepG2.2.15 cells, which express hepatitis B virus (HBV)-related proteins, in triggering the activation of LX2 liver stellate cells and promoting liver fibrosis and cell proliferation remains elusive. The focus was on comprehending the relationship and influence of differentially expressed microRNAs (DE-miRNAs) within these exosomes., Aim: To elucidate the effect of exosomes derived from HepG2.2.15 cells on the activation of hepatic stellate cell (HSC) LX2 and the progression of liver fibrosis., Methods: Exosomes from HepG2.2.15 cells, which express HBV-related proteins, were isolated from parental HepG2 and WRL68 cells. Western blotting was used to confirm the presence of the exosomal marker protein CD9. The activation of HSCs was assessed using oil red staining, whereas DiI staining facilitated the observation of exosomal uptake by LX2 cells. Additionally, we evaluated LX2 cell proliferation and fibrosis marker expression using 5-ethynyl-2'-deoxyuracil staining and western blotting, respectively. DE-miRNAs were analyzed using DESeq2. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were used to annotate the target genes of DE-miRNAs., Results: Exosomes from HepG2.2.15 cells were found to induced activation and enhanced proliferation and fibrosis in LX2 cells. A total of 27 miRNAs were differentially expressed in exosomes from HepG2.2.15 cells. GO analysis indicated that these DE-miRNA target genes were associated with cell differentiation, intracellular signal transduction, negative regulation of apoptosis, extracellular exosomes, and RNA binding. KEGG pathway analysis highlighted ubiquitin-mediated proteolysis, the MAPK signaling pathway, viral carcinogenesis, and the toll-like receptor signaling pathway, among others, as enriched in these targets., Conclusion: These findings suggest that exosomes from HepG2.2.15 cells play a substantial role in the activation, proliferation, and fibrosis of LX2 cells and that DE-miRNAs within these exosomes contribute to the underlying mechanisms., Competing Interests: Conflict-of-interest statement: All authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Patients with triple-negative breast cancer (TNBC) have a poor prognosis due to the lack of effective molecular targets for therapeutic intervention. Here we found that the long noncoding RNA (lncRNA) MILIP supports TNBC cell survival, proliferation, and tumorigenicity by complexing with transfer RNAs (tRNA) to promote protein production, thus representing a potential therapeutic target in TNBC. MILIP was expressed at high levels in TNBC cells that commonly harbor loss-of-function mutations of the tumor suppressor p53, and MILIP silencing suppressed TNBC cell viability and xenograft growth, indicating that MILIP functions distinctively in TNBC beyond its established role in repressing p53 in other types of cancers. Mechanistic investigations revealed that MILIP interacted with eukaryotic translation elongation factor 1 alpha 1 (eEF1α1) and formed an RNA-RNA duplex with the type II tRNAs tRNALeu and tRNASer through their variable loops, which facilitated the binding of eEF1α1 to these tRNAs. Disrupting the interaction between MILIP and eEF1α1 or tRNAs diminished protein synthesis and cell viability. Targeting MILIP inhibited TNBC growth and cooperated with the clinically available protein synthesis inhibitor omacetaxine mepesuccinate in vivo. Collectively, these results identify MILIP as an RNA translation elongation factor that promotes protein production in TNBC cells and reveal the therapeutic potential of targeting MILIP, alone and in combination with other types of protein synthesis inhibitors, for TNBC treatment., Significance: LncRNA MILIP plays a key role in supporting protein production in TNBC by forming complexes with tRNAs and eEF1α1, which confers sensitivity to combined MILIP targeting and protein synthesis inhibitors., (©2024 The Authors; Published by the American Association for Cancer Research.)

Papillary thyroid carcinoma (PTC) is generally recognized as a slow-growing tumor. However, a small subset of patients may still experience relapse or metastasis shortly after therapy, leading to a poor prognosis and raising concerns about excessive medical treatment. One major challenge lies in the inadequacy of effective biomarkers for accurate risk stratification. Long non-coding RNAs (lncRNAs), which are closely related to malignant characteristics and poor prognosis, play a significant role in the genesis and development of PTC through various pathways. The objective of this review is to provide a comprehensive summary of the biological functions of lncRNAs in PTC, identify prognosis-relevant lncRNAs, and explore their potential mechanisms in drug resistance to BRAF kinase inhibitors, tumor dedifferentiation, and lymph node metastasis. By doing so, this review aims to offer valuable references for both basic research and the prediction of PTC prognosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Hydrogen production from photocatalysis via the usage of multicomponent photocatalysts represents a promising pathway for carbon peaking and carbon neutrality, owing to their structural advantages in dealing with the three crucial processes in photocatalysis, namely, light harvesting, charge transfer, and surface redox reactions. We demonstrate the fabrication of a MOF-based multicomponent photocatalyst, denoted as semiconductor/MOF/cocatalyst, by a one-pot electrochemical synthetic route. The as-fabricated multicomponent photocatalyst has a clean interface among the components, leading to close connections that contribute to high-quality heterojunction and facilitate photogenerated charge transfer and separation, thereby the efficient hydrogen evolution. The hydrogen production rate of the resultant ZrO 2 /Zr-MOF/Pt is 1327 μmol ⋅ g -1  ⋅ h -1 , which is much higher than that of ZrO 2 /Zr-MOF (15 μmol ⋅ g -1  ⋅ h -1 ) and pure Zr-MOF (10.1 μmol ⋅ g -1  ⋅ h -1 ), as well as the photodeposited-Pt products ZrO 2 /Zr-MOF/Pt PD (287 μmol ⋅ g -1  ⋅ h -1 ) and Zr-MOF/Pt PD (192 μmol ⋅ g -1  ⋅ h -1 ) obtained by the step-wise synthetic approach. The work gives a good inspiration for the rational design and construction of MOF-based multicomponent photocatalysts through the one-pot electrosynthesis., (© 2024 Wiley-VCH GmbH.)

Microcystins (MCs) are the most widespread, frequently found, and seriously toxic cyanobacterial toxins in aquatic environments. Microcystin-leucine-arginine (MCLR) and microcystin-arginine-arginine (MCRR) are the most studied MCs. Normally, their levels are low and they coexist in the environment; however, they may also interact with each other. The developmental toxicity of MCLR in the presence of MCRR in the early life stage of zebrafish (from 2 to 120 h post fertilization) was investigated for the first time in this study. Our findings revealed that MCRR treatment marginally elevated thyroxine (T4) and 3,5,3'-triiodothyronine (T3) levels, whereas MCLR treatment alone resulted in a significant increase in T3 and T4 levels, indicating a cooperative effect. Furthermore, clear changes in the expression levels of genes involved in growth and development, accompanied by growth inhibition, were observed after co-treatment with MCRR and MCLR. In addition, zebrafish larvae subjected to MCRR and/or MCLR treatment showed increased levels of superoxide dismutase, glutathione, and malondialdehyde, and decreased levels of catalase in the MCRR + MCLR group, indicating oxidative stress and lipid peroxidation. Thus, we investigated the synergistic developmental toxicity of MCRR and MCLR during the early life stages of zebrafish development., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest in the present experiment., (Copyright © 2023. Published by Elsevier Inc.)

A biolabel-led research based on multi-omics and bioinformatics was applied to analyze the application value of Eucommiae folium (EF) in liver cirrhosis, as well as the mechanism of action and material basis. Multi-omics were used to analyze the biolabels and key pathways of EF intervention in liver tissue. Subsequently, based on the information, bioinformatics was used to analyze the application value of EF in liver disease, as well the mechanism of action and material basis. Finally, histopathological and target expression analyses in an animal model were used to verify biolabels analysis results. Multi-omics showed that 18 proteins and 10 metabolites involved in five key pathways were screened as biolabels. Bioinformatics suggested that the application value of EF for liver cirrhosis may be the highest among the liver diseases that it may treat. Additionally, EF and five active compounds (curcumol, eucalyptol, (+)-catechin, naringenin, and quercetin) may protect the cirrhotic liver against the excessive energy expenditure and hepatic stellate cells activation through suppressing the oxidative phosphorylation pathway in a CCl 4 -induced mouse model. This study provides reference and evidence for the application value of EF in liver diseases, especially liver cirrhosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The conventional Walsh function just takes values of +1 and -1 and can only track limited signal states. However, based on the characteristics of Walsh functions that can capture the frequency of square wave signals, this article proposes a generalized Walsh transform algorithm to process multi-valued rectangular wave signals. As an extension of the traditional Walsh functions, generalized Walsh functions have advantages in signal frequency matching and sequency spectrum amplitude extraction, which makes them well suited to express the valuable signal. First, we infer the invariance displacement theory in the time and sequency domains, limiting the value of a circular time shift to ensure the concentrated distribution of the signal sequency energy. This limitation lays a good foundation for constructing generalized Walsh functions. Then, two types of generalized Walsh functions are built by combining the characteristics of different periodic rectangular waves. We deduce two properties of orthogonality and completeness to prove the ability of the constructed functions to match the frequency and the extracted energy. Finally, we compare multiple filtering methods to verify the reliability of the proposed method., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background/purpose: Excessive host immune response is thought to be an important cause of periodontal tissue damage during periodontitis. The potent chemotaxis produced by locally released chemokines is the key signal to trigger this response. Here, we aimed to investigate the expression of CXC chemokine receptor 1 (CXCR1), and chemokines interleukin-8 (IL-8) and pro-platelet basic protein (PPBP) in human inflammatory gingival tissues compared with healthy tissues., Materials and Methods: A total of 54 human gingival tissues, 27 healthy and 27 inflammatory samples, were collected. Fifteen specimens of each group were employed for quantitative reverse transcription polymerase chain reaction to determine the mRNA levels of CXCR1, IL-8, and PPBP. Six samples of each group were used for Western blotting to investigate the protein expression of CXCR1 and for enzyme-linked immunosorbent assay to evaluate the protein levels of IL-8 and PPBP, respectively., Results: The mRNA levels of chemokine receptor CXCR1, chemokine IL-8, and PPBP in inflammatory gingival tissues were significantly higher than those in healthy controls ( P  < 0.05). The protein levels of CXCR1, IL-8, and PPBP in inflammatory gingival tissues were also significantly higher than those in healthy gingival tissues ( P  < 0.05)., Conclusion: When compared to healthy gingival tissues, the expression of CXCR1, IL-8, and PPBP in inflammatory gingival tissues is higher., Competing Interests: The authors have no conflicts of interest in this study., (© 2023 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Ancient Chinese medicine literature and modern pharmacological studies show that Sophora tonkinensis Gagnep. (ST) has a protective effect on the heart. A biolabel research based on omics and bioinformatics and experimental validation were used to explore the application value of ST in the treatment of heart diseases. Therapeutic potential, mechanism of action, and material basis of ST in treating heart diseases were analyzed by proteomics, metabolomics, bioinformatics, and molecular docking. Cardioprotective effects and mechanisms of ST and active compounds were verified by echocardiography, HE and Masson staining, biochemical analysis, and ELISA in the isoproterenol hydrochloride-induced myocardial ischemia (MI) mice model. The biolabel research suggested that the therapeutic potential of ST for MI may be particularly significant among the heart diseases it may treat. In the isoprenaline hydrochloride-induced MI mice model, ST and its five active compounds (caffeic acid, gallic acid, betulinic acid, esculetin, and cinnamic acid) showed significant protective effects against echocardiographic changes and histopathological damages of the ischemic myocardial tissue. Meanwhile, they showed a tendency to correct mitochondrial structure and function damage and the abnormal expression of 12 biolables (DCTN1, DCTN3, and SCARB2, etc.) in the vesicle-mediated transport pathway, inflammatory cytokines (IL-1β, IL-6, and IL-10, etc.), and low density lipoprotein receptor (LDLR). The biolabel research identifies a new application value of ST in the treatment of heart diseases. ST and its active compounds inhibit mitochondrial impairments, inflammation, and LDLR deficiency through regulating the vesicle-mediated transport pathway, thus achieving the purpose of treating MI., Competing Interests: Declaration of Competing Interest All authors declare no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: A biolabel research based on multi-omics, informatics, molecular docking, and experimental verification was used to investigate the cardioprotective effect and pharmaceutically active compounds of Eucommiae Folium (EF)., Key Findings: Based on the biolabel research pattern, metabonomics, proteomics, and bioinformatics indicated that EF has a therapeutic potential for a variety of heart diseases, especially cardiomyopathy, and the most critical mechanism involved is the diabetic cardiomyopathy pathway. Bioinformatics, cheminformatics, and molecular docking showed that 24 EF compounds may play a therapeutic role in diabetic cardiomyopathy via this pathway. Among which, four compounds (kaempferol, esculetin, (+)-catechin, and astragalin) showed appropriate pharmacokinetic parameters and formed stable binding with biolabels in the pathway. In diabetic cardiomyopathy db/db mice, histopathological analysis, mitochondrial swelling and membrane potential assay, ELISA, and biochemical analysis demonstrated that EF and four active compounds had obvious hypoglycemic effects and attenuated myocardial damage and related pathological processes, such as mitochondrial dysfunction, calcium dyshomeostasis, insulin resistance, and oxidative stress., Conclusions: This study provides new evidence and insights into the effect, mechanism, and material basis of EF in treating diabetic cardiomyopathy., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The application of new-generation information technologies such as big data, the internet of things(IoT), and cloud computing in the traditional Chinese medicine(TCM)manufacturing industry is gradually deepening, driving the intelligent transformation and upgrading of the TCM industry. At the current stage, there are challenges in understanding the extraction process and its mechanisms in TCM. Online detection technology faces difficulties in making breakthroughs, and data throughout the entire production process is scattered, lacking valuable mining and utilization, which significantly hinders the intelligent upgrading of the TCM industry. Applying data-driven technologies in the process of TCM extraction can enhance the understanding of the extraction process, achieve precise control, and effectively improve the quality of TCM products. This article analyzed the technological bottlenecks in the production process of TCM extraction, summarized commonly used data-driven algorithms in the research and production control of extraction processes, and reviewed the progress in the application of data-driven technologies in the following five aspects: mechanism analysis of the extraction process, process development and optimization, online detection, process control, and production management. This article is expected to provide references for optimizing the extraction process and intelligent production of TCM.

Recently, the incidence of autoimmune hepatitis (AIH) has gradually increased, and the disease can eventually develop into cirrhosis or even hepatoma if left untreated. AIH patients are often characterized by gut microbiota dysbiosis, but whether gut microbiota dysbiosis contributes to the progression of AIH remains unclear. In this study, we investigate the role of gut microbiota dysbiosis in the occurrence and development of AIH in mice with dextran sulfate sodium salt (DSS) induced colitis. C57BL/6J mice were randomly divided into normal group, S100-induced AIH group, and DSS+S100 group (1 % DSS in the drinking water), and the experimental cycle lasted for four weeks. We demonstrate that DSS administration aggravates hepatic inflammation and disruption of the intestinal barrier, and significantly changes the composition of gut microbiota in S100-induced AIH mice, which are mainly characterized by increased abundance of pathogenic bacteria and decreased abundance of beneficial bacteria. These results suggest that DSS administration aggravates liver injury of S100-induced AIH, which may be due to DSS induced gut microbiota dysbiosis, leading to disruption of the intestinal barrier, and then, the microbiota translocate to the liver, aggravating hepatic inflammation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Objective: To investigate and analyze the allocation status of oral health resources in Yunnan Province at the end of the 13th Five-Year Plan, providing a scientific basis for the rational resource allocation and formulation regional oral health plan for government health administrative departments. Methods: With the method of general survey, a cross-sectional study was conducted to investigate the allocation of material and human resources of all kinds of stomatological medical institutions registered in the health administrative departments in Yunnan before January 1, 2020. The general situation of oral health resources was analyzed by descriptive statistical analysis. Results: There were 2 712 stomatological medical institutions in Yunnan, 634 public and 2 078 non-public included. The largest number was in Kunming (1 167) and the least in Diqing (19). There were 9 018 dental chairs in total, among which 2 584 in public and 6 434 in non-public. Kunming had the largest number of chairs (3 612) and Nujiang had the least (57). There were 702 oral and maxillofacial surgical beds, all of which were distributed in public. There were 15 148 stomatological personnel, including 3 667 in public and 11 481 in non-public. The average ratio of stomatologist to population was 1∶6 615. Dehong (1∶6 620) was close to this average level, while Kunming (1∶2 283) and Yuxi (1∶4 936) were lower than the average and the other 13 states (cities) were higher. The population ratio of licensed stomatologist was only 1∶9 110. The average ratio of stomatologist to nurses was 1∶0.94. Honghe (1∶1.05), Kunming (1∶1.00), Yuxi (1∶1.18) and Qujing (1∶0.94) was better than or reached the average level, while the other 13 states (cities) were lower than this average. And this ratio in public comprehensive medical institutions was only 1∶0.38. Conclusions: The distribution of oral health resources in Yunnan was unbalanced between public and non-public institutions and among states (cities), mainly distributed in economically developed states (cities) and non-public institutions. For the oral health in Yunnan Province, the workforce was insufficient and the structure was unreasonable, and the proportion of nurses was seriously insufficient in public comprehensive medical institutions.

The interleukin-1 receptor associated kinase 4 (IRAK-4) is a member of serine-threonine kinase family, which plays an important role in the regulation of interleukin-1 receptors (IL-1R) and Toll-like receptors (TLRs) related signaling pathways. At present, the IRAK-4 mediated inflammation and related signaling pathways contribute to inflammation, which are also responsible for other autoimmune diseases and drug resistance in cancers. Therefore, targeting IRAK-4 to develop single-target, multi-target inhibitors and proteolysis-targeting chimera (PROTAC) degraders is an important direction for the treatment of inflammation and related diseases. Moreover, insight into the mechanism of action and structural optimization of the reported IRAK-4 inhibitors will provide the new direction to enrich the clinical therapies for inflammation and related diseases. In this comprehensive review, we introduced the recent advance of IRAK-4 inhibitors and degraders with regards to structural optimization, mechanism of action and clinical application that would be helpful for the development of more potent chemical entities against IRAK-4., Competing Interests: Declaration of competing interest All authors have approved the final submission to the journal. The authors declare no conflict of interest., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Autoimmune hepatitis (AIH) is a progressive hepatitis syndrome characterized by high transaminase levels, interface hepatitis, hypergammaglobulinemia, and the presence of autoantibodies. Misdiagnosis or delayed treatment of AIH can lead to cirrhosis or liver failure, which poses a major risk to human health. β-Arrestin2, a key scaffold protein for intracellular signaling pathways, has been found to be involved in many autoimmune diseases such as Sjogren's syndrome and rheumatoid arthritis. However, whether β-arrestin2 plays a role in AIH remains unknown. In the present study, S-100-induced AIH was established in both wild-type mice and β-arrestin2 knockout (Arrb2 KO) mice, and the experiments identified that liver β-arrestin2 expression was gradually increased, and positively correlated to serum ANA, ALT and AST levels during AIH progression. Furthermore, β-arrestin2 deficiency ameliorated hepatic pathological damage, decreased serum autoantibody and inflammatory cytokine levels. β-arrestin2 deficiency also inhibited hepatocyte apoptosis and prevented the infiltration of monocyte-derived macrophages into the damaged liver. In vitro experiments revealed that β-arrestin2 knockdown suppressed the migration and differentiation of THP-1 cells, whereas β-arrestin2 overexpression promoted the migration of THP-1 cells, which was regulated by the activation of the ERK and p38 MAPK pathways. In addition, β-arrestin2 deficiency attenuated TNF-α-induced primary hepatocyte apoptosis by activating the Akt/GSK-3β pathway. These results suggest that β-arrestin2 deficiency ameliorates AIH by inhibiting the migration and differentiation of monocytes, decreasing the infiltration of monocyte-derived macrophages into the liver, thereby reducing inflammatory cytokines-induced hepatocytes apoptosis. Therefore, β-arrestin2 may act as an effective therapeutic target for AIH., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Accretion of material onto a black hole drags any magnetic fields present inwards, increasing their strength. Theory predicts that sufficiently strong magnetic fields can halt the accretion flow, producing a magnetically arrested disk (MAD). We analyzed archival multiwavelength observations of an outburst from the black hole x-ray binary MAXI J1820+070 in 2018. The radio and optical fluxes were delayed compared with the x-ray flux by about 8 and 17 days, respectively. We interpret this as evidence for the formation of a MAD. In this scenario, the magnetic field is amplified by an expanding corona, forming a MAD around the time of the radio peak. We propose that the optical delay is due to thermal viscous instability in the outer disk.

Epilepsy is a chronic brain disease and often occurs suddenly for no reason. Eucommiae folium (EF), an edible herb, can be used in the treatment of various kinds of brain diseases in clinic. From the perspective of safety and efficacy, EF is especially suitable for the treatment of chronic brain diseases. With the help of biolabels, this study was aimed to explore the value and feasibility of EF in the treatment of epilepsy. Proteomics and metabolomics were used to explore the biolabels of EF intervention in brain tissues. Bioinformatics was then applied to topologically analyze its neuroprotective effects and mechanisms and material basis based on biolabels, which were validated in an animal model. The biolabel-led research revealed that EF may exert the therapeutic potential to treat brain diseases through the interaction between multiple compounds and multiple targets, among which its therapeutic potential for epilepsy is particularly prominent. In the pentylenetetrazole-induction model, EF and four active compounds (oleamide, catechol, chlorogenic acid, and kaempferol) protected epileptic hippocampal neurons (Nissl and FJB staining) against mitochondrial dysfunction (MYH6, MYL3, and MYBPC3, etc.) and calcium overload (TNNI3, TNNC1, and TNNT2, etc.) through the hypertrophic cardiomyopathy pathway. This study provides new evidence and insights for the neuroprotective effects of EF, in which four active compounds may be potential drug candidates for the treatment of epilepsy., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Normal levels of reactive oxygen species (ROS) play an important role in regulating follicular growth, angiogenesis and sex hormone synthesis in ovarian tissue. When the balance between ROS and antioxidants is disrupted, however, it can cause serious consequences of oxidative stress (OS), and the quantity and quality of oocytes will decline. Therefore, this review discusses the interrelationship between OS and premature ovarian insufficiency (POI), the potential mechanisms and the methods by which antioxidants can improve POI through controlling the level of OS. We found that OS can mediate changes in genetic materials, signal pathways, transcription factors and ovarian microenvironment, resulting in abnormal apoptosis of ovarian granulosa cells (GCs) and abnormal meiosis as well as decreased mitochondrial Deoxyribonucleic Acid(mtDNA) and other changes, thus accelerating the process of ovarian aging. However, antioxidants, mesenchymal stem cells (MSCs), biological enzymes and other antioxidants can delay the disease process of POI by reducing the ROS level in vivo ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shi, Zhu, Zhang, Ma, Han, Jiang and Zhang.)

Copper (Cu) and iron (Fe) share similar characteristics and participate as coenzymes in several physiological processes. Both Cu excess and Fe deficiency result in chlorosis, however, the crosstalk between the two is not clear in rice. In this study, we performed transcriptome analysis for Cu excess and Fe deficiency in rice. Some WRKY family members (such as WRKY26) and some bHLH family members (such as late flowering) were selected as novel potential transcription factors involved in the regulation of Cu detoxification and Fe utilization, respectively. These genes were induced under corresponding stress conditions. Many Fe uptake-related genes were induced by Cu excess, while Cu detoxification-related genes were not induced by Fe deficiency. Meanwhile, some genes, such as metallothionein 3a, gibberellin 3beta-dioxygenase 2 and WRKY11, were induced by Cu excess but repressed by Fe deficiency. Concisely, our results highlight the crosstalk between Cu excess and Fe deficiency in rice. Cu excess caused Fe deficiency response, while Fe deficiency did not lead to Cu toxicity response. Metallothionein 3a might be responsible for Cu toxicity-induced chlorosis in rice. The crosstalk between Cu excess and Fe deficiency might be regulated by gibberellic acid., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Cadmium (Cd) contamination in food has raised broad concerns in food safety and human health. The toxicity of Cd to animals/humans have been widely reported, yet little is known about the health risk of dietary Cd intake at the epigenetic level. Here, we investigated the effect of a household Cd-contaminated rice (Cd-rice) on genome-wide DNA methylation (DNAm) changes in the model mouse. Feeding Cd-rice increased kidney Cd and urinary Cd concentrations compared with the Control rice (low-Cd rice), whereas supplementation of ethylenediamine tetraacetic acid iron sodium salt (NaFeEDTA) in the diet significantly increased urinary Cd and consequently decreased kidney Cd concentrations. Genome-wide DNAm sequencing revealed that dietary Cd-rice exposure caused the differentially methylated sites (DMSs), which were mainly located in the promoter (32.5%), downstream (32.5%), and intron (26.1%) regions of genes. Notably, Cd-rice exposure induced hypermethylation at the promoter sites of genes Caspase-8 and interleukin-1β (Il-1β), and consequently, their expressions were down-regulated. The two genes are critical in apoptosis and inflammation, respectively. In contrast, Cd-rice induced hypomethylation of the gene midline 1 (Mid1), which is vital to neurodevelopment. Furthermore, 'pathways in cancer' was significantly enriched as the leading canonical pathway. Supplementation of NaFeEDTA partly alleviated the toxic symptoms and DNAm alternations induced by Cd-rice exposure. These results highlight the broad effects of elevated dietary Cd intake on the level of DNAm, providing epigenetic evidence on the specific endpoints of health risks induced by Cd-rice exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In Alzheimer's disease, the transporter P-glycoprotein is responsible for the clearance of amyloid-β in the brain. Amyloid-β correlates with the sphingomyelin metabolism, and sphingomyelin participates in the regulation of P-glycoprotein. The amyloid cascade hypothesis describes amyloid-β as the central cause of Alzheimer's disease neuropathology. Better understanding of the change of P-glycoprotein and sphingomyelin along with amyloid-β and their potential association in the pathological process of Alzheimer's disease is critical. Herein, we found that the expression of P-glycoprotein in APP/PS1 mice tended to increase with age and was significantly higher at 9 and 12 months of age than that in wild-type mice at comparable age. The functionality of P-glycoprotein of APP/PS1 mice did not change with age but was significantly lower than that of wild-type mice at 12 months of age. Decreased sphingomyelin levels, increased ceramide levels, and the increased expression and activity of neutral sphingomyelinase 1 were observed in APP/PS1 mice at 9 and 12 months of age compared with the levels in wild-type mice. Similar results were observed in the Alzheimer's disease mouse model induced by intracerebroventricular injection of amyloid-β1-42 and human cerebral microvascular endothelial cells treated with amyloid-β1-42. In human cerebral microvascular endothelial cells, neutral sphingomyelinase 1 inhibitor interfered with the changes of sphingomyelin metabolism and P-glycoprotein expression and functionality caused by amyloid-β1-42 treatment. Neutral sphingomyelinase 1 regulated the expression and functionality of P-glycoprotein and the levels of sphingomyelin and ceramide. Together, these findings indicate that neutral sphingomyelinase 1 regulates the expression and function of P-glycoprotein via the sphingomyelin/ceramide pathway. These studies may serve as new pursuits for the development of anti-Alzheimer's disease drugs., Competing Interests: None

Asexual and sexual morphs of saprobic bambusicolous fungi were collected from freshwater and terrestrial habitats in Sichuan Province, China. Taxonomic identification of these fungi was carried out on the basis of morphological comparison, culture characteristics, and molecular phylogeny. Multi-gene phylogeny based on combined SSU, ITS, LSU, rpb2, and tef1α sequence data was performed to determine their phylogenetic placement, and the result showed that these fungi belong to Savoryellaceae. Morphologically, four asexual morphs are similar to Canalisporium and Dematiosporium , while a sexual morph well-fits to Savoryella . Three new species, Canalisporium sichuanense , Dematiosporium bambusicola , and Savoryella bambusicola are identified and described. Two new records, C. dehongense and D. aquaticum, were recovered from the bamboo hosts in terrestrial and freshwater habitats, respectively. In addition, the nomenclatural confusion of C. dehongense and C. thailandense is discussed.

Micro-pore optics (MPO) has been employed in space x-ray telescopes for large field-of-view observations. For x-ray focal plane detectors with visible photon sensing capability, the optical blocking filter (OBF) on MPO devices is critical for preventing signal contamination by those photons. In this work, we designed a piece of equipment to measure the light transmission with high accuracy. The transmittance test results of the MPO plates meet the design requirements of less than 5×10 -4 . Based on the multilayer homogeneous film matrix method, we estimated possible combinations of film thicknesses (with alumina) that show a good agreement with the OBF design.