Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

The PA-PB1 interface of the influenza polymerase is an attractive site for antiviral drug design. In this study, we designed and synthesized a mini-library of indazole-containing compounds based on rational structure-based design to target the PB1-binding interface on PA. Biological evaluation of these compounds through a viral yield reduction assay revealed that compounds 27 and 31 both had a low micromolar range of the half maximal effective concentration (EC₅₀) values against A/WSN/33 (H1N1) (8.03 μmol/L for 27; 14.6 μmol/L for 31), while the most potent candidate 24 had an EC₅₀ value of 690 nM. Compound 24 was effective against different influenza strains including a pandemic H1N1 strain and an influenza B strain. Mechanistic studies confirmed that compound 24 bound PA with a K _d which equals to 1.88 μmol/L and disrupted the binding of PB1 to PA. The compound also decreased the lung viral titre in mice. In summary, we have identified a potent anti-influenza candidate with potency comparable to existing drugs and is effective against different viral strains. The therapeutic options for influenza infection have been limited by the occurrence of antiviral resistance, owing to the high mutation rate of viral proteins targeted by available drugs. To alleviate the public health burden of this issue, novel anti-influenza drugs are desired. In this study, we present our discovery of a novel class of indazole-containing compounds which exhibited favourable potency against both influenza A and B viruses. The EC₅₀ of the most potent compounds were within low micromolar to nanomolar concentrations. Furthermore, we show that the mouse lung viral titre decreased due to treatment with compound 24. Thus our findings identify promising candidates for further development of anti-influenza drugs suitable for clinical use.

Targeted protein degradation via nanoparticle-based universal strategy modifies nanoparticles with antibodies and ingeniously utilizes its cellular transport characteristics. This strategy achieved targeted degradation of extracellular proteins without complex design.Image 1.

Objective To analyze the hotspots and frontiers of traditional Chinese medicine treatment for allergic rhinitis(AR)in China,aiming to provide reference for the treatment of AR patients in China.Methods Literatures related to traditional Chinese medicine treatment of AR published by CNKI,Wanfang Data and VIP database from January 2004 to December 2023 were searched,and CiteSpace software was used for visual analysis of the number of literatures,key words,research institutions and authors.Results A total of 1604 literatures were included,and the annual number of literatures generally showed an upward trend.The research frontiers in the last 5 years include medication patterns,immune function,quality of life,data mining,and thumbtack needle.The top five institutions in terms of publications were Beijing University of Traditional Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Nanjing University of Traditional Chinese Medicine,the First Affiliated Hospital of Beijing University of Traditional Chinese Medicine,and Chengdu University of Traditional Chinese Medicine.The core authors were Yuan Weiling,Yan Daonan,Zhao Jiping,Zhang Qinxiu,and Feng Weiyun.Conclusion The application of traditional Chinese medicine in treatment of AR has always been in a high research heat,and giving full play to the characteristics of traditional Chinese medicine can be the development direction of AR research in the future.

Objective:By analyzing the genetic risk of triglyceride-glucose index(Tyg)and insulin resistance(IR)for cardiovascular disease(CVD), to elucidate the extent to which the contribution of Tyg to the risk of CVD development is influenced by IR genetic risk.Methods:In this study, we selected data from a cohort of elderly people in the Kunshan community, screened 7, 385 individuals with both clinical and genomic data, and calculated the polygenic risk score of insulin resistance(IRPRS)for each participant based on publicly available IR genome-wide association data, and assessed the effect of genetic risk and Tyg level on the risk of developing CVD using a multivariate Cox proportional risk model.Calculating interactions to assess the effects of genetic risk and Tyg levels on the risk of developing CVD, the effects of Tyg tertile grouping and IRPRS on the risk of developing CVD were assessed using a multivariate Cox proportional risk model, and subgroup analyses were performed for gender to assess the effects of Tyg tertile grouping and IRPRS on the risk of developing CVD by gender.Results:In the univariate Cox model, Q3 and IRPRS with the highest TYG levels were significantly associated with the risk of CVD, respectively( HR=1.59, 95% CI: 1.33-1.89; P<0.001; HR=1.61, 95% CI: 1.18-2.20; P=0.003).After adjusting for multiple confounders, the Q3 Group with the highest TYG level was still significantly associated with the risk of CVD( HR=1.28, 95% CI: 1.05-1.57; P=0.014), the Association of TYG with the risk of CVD did not change significantly( HR=1.29, 95% CI: 1.05-1.57; P=0.014).We conducted a subgroup analysis by sex and found that among older men, 13, the highest levels of TYG and IRPRS were significantly associated with CVD risk, respectively( HR=1.70, 95% CI: 1.31.2.20; P<0.001; HR=1.98, 95% CI: 1.24-3.15; P=0.004).After adding IRPRS to the model, the Association of TYG with the risk of CVD remained unchanged( HR=1.69, 95% CI: 1.31-2.19; P<0.001).After adjusting for various confounders, Tyg remained significantly associated with the risk of CVD( HR=1.39, 95% CI: 1.04-1.88; P=0.028), the results showed that TYG remained significantly associated with the risk of CVD( HR=1.41, 95% CI: 1.05-1.90; P=0.023), and the association did not decrease.No Association of IRPRS with CVD risk was found in older women. Conclusions:IRPRS and TYG are the risk factors of CVD, and diet, exercise, drugs and other external factors on TYG are the main risk factors of CVD.For individuals with high genetic factors, the risk of CVD can still be reduced by lifestyle adjustments such as diet, exercise and drug intervention.

ObjectiveTo explore the mechanism of modified Xiehuangsan in treating tic disorders （TD） based on microglial polarization and the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor （NF）-κB pathway. MethodsSeventy-two Sprague-Dawley （SD） rats were randomly assigned into six groups： control， model， tiapride （0.025 g·kg^-1）， and low-， medium-， and high-dose （12， 24， 48 g·kg^-1， respectively） modified Xiehuangsan， with 12 rats in each group. Except the control group， the other groups received intraperitoneal injection of 3，3'-iminodipropionitrile （IDPN） for 7 consecutive days for the modeling of TD. After successful modeling， the control and model groups were given normal saline via gavage， and the other groups were administrated with corresponding drugs by gavage. After 28 days of continuous intervention， rat behaviors were observed， and the modified Xiehuangsan group showing the best anti-TD effect was selected for deciphering the treatment mechanism. Hematoxylin and eosin staining was conducted to observe morphological changes in the rat striatum. Immunohistochemistry was employed to detect the expression of CD16 and CD206 in the striatum. Real-time PCR was employed to measure the mRNA levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， IL-4， TLR4， MyD88， and NF-κB p65 in the striatum. Western blot was employed to determine the protein levels of ionized calcium-binding adapter molecule 1 （Iba1）， Fc receptor family for immunoglobulin （Ig）G type Ⅲ （CD16）， mannose receptor （CD206）， TLR4， MyD88， and NF-κB p65 in the striatum. ResultsCompared with the control group， the model group showed increased stereotyped behaviors， locomotor activity， total movement distance， and movement speed， shortened resting time （P<0.01）， and noticeable pathological changes in the striatum. Compared with the model group， the tiapride group and modified Xiehuangsan groups exhibited reduced stereotyped behavior， locomotor activity， total movement distance， and movement speed， prolonged resting time （P<0.05， P<0.01）， and alleviated pathological changes in the striatum. Among the modified Xiehuangsan groups， the high-dose group had the best intervention effect and the mildest pathological changes. Therefore， the high-dose group was selected for further research. Compared with the control group， the modeling of TD increased Iba1 and CD16 expression （P<0.05， P<0.01）， up-regulated the mRNA levels of IL-1β and TNF-α （P<0.05， P<0.01）， down-regulated the mRNA level of IL-4 （P<0.05）， up-regulated the mRNA and protein levels of TLR4 and MyD88 （P<0.05， P<0.01）， and up-regulated the protein level of NF-κB p65 （P<0.01）. Compared with the model group， modified Xiehuangsan reduced Iba1 and CD16 expression （P<0.05， P<0.01）， up-regulated the protein level of CD206 （P<0.05， P<0.01）， down-regulated the mRNA levels of IL-1β and TNF-α （P<0.05）， up-regulated the mRNA level of IL-4 （P<0.01）， and down-regulated the mRNA and protein levels of TLR4， MyD88， and NF-κB p65 （P<0.05， P<0.01）. ConclusionModified Xiehuangsan demonstrated a definite therapeutic effect on TD in rats. It may reduce neuroinflammation in TD rats by regulating the polarization of microglia in the striatum via the TLR4/MyD88/NF-κB signaling pathway.

Objective: To investigate the association between plant-based diet and different types of obesity, so as to provide references for obesity prevention. Methods: Residents aged 35-75 years from 33 counties (cities, districts) in Zhejiang Province were selected as study subjects using a multistage stratified random sampling method between April and December 2024. Demographic information and living behaviors were collected using questionnaire surveys. Height, weight and waist circumference were measured, and body mass index (BMI) was calculated. BMI ≥28.0 kg/m2 was defined as obesity, waist circumference ≥90 cm in males or ≥85 cm in females was defined as central obesity, and individual with obesity who also had central obesity was defined as having compound obesity. Food intake over a 3-day period was collected using the consecutive 3-day 24-hour dietary recall method. The plant diet index (PDI), healthful plant diet index (HPDI), and unhealthful plant diet index (UPDI) were calculated, and categorized into quintiles (Q1-Q5) based on their distribution. Association between the PDI, PDI, UPDI and different types of obesity were analyzed using multivariable logistic regression models. Results: A total of 4 882 individuals were surveyed, including 2 233 males (45.74%) and 2 649 females (54.26%). The average age was (55.42±12.14) years. There were 537 individuals of obesity, 1 718 individuals of central obesity, and 500 individuals of compound obesity, with detection rates of 11.00%, 35.19%, and 10.24%, respectively. Multivariable logistic regression analysis showed that, after adjusting for demographic information and living behaviors, compared with Q1 group, HPDI Q5 group showed a 29.6% lower risk of obesity (OR=0.704, 95%CI: 0.525-0.943) and a 32.1% lower risk of compound obesity (OR=0.679, 95%CI: 0.502-0.918). Conversely, the UPDI Q5 group exhibited a 39.5% higher risk of obesity (OR=1.395, 95%CI: 1.032-1.886) and a 39.8% higher risk of compound obesity (OR=1.398, 95%CI: 1.025-1.907). No statistically significant association was found between PDI and obesity, central obesity, and compound obesity (all P>0.05). As HPDI increased, the risks of obesity and compound obesity showed decreasing trends; as UPDI increased, the risks of obesity and compound obesity showed increasing trends (all Ptrend<0.05). Conclusion A healthful plant-based diet is associated with reduced risks of obesity and compound obesity, while an unhealthful plant-based diet is associated with increased risks of obesity and compound obesity.

Nuclear medicine plays a pivotal role in diagnosis and treatment of tumors.The development of radionuclide probes with high affinity and specificity is an effective approach to achieve precise diagnosis and treatment of tumors.With high binding affinity,rapid tissue penetration and excellent pharmacokinetic properties,bicyclic peptide-based radionuclide probes demonstrate remarkable advantages in diagnosis and targeted therapy of tumors.The structural characteristics and design strategies of bicyclic peptide-based radionuclide probes were reviewed in this article,mainly focused on research progresses in targeting tumor-associated receptors.

OBJECTIVE To explore the epidemiological characteristics of human immunodeficiency virus(HIV)/ac-quired immune deficiency syndrome(AIDS)complicated with anorectal diseases and analyze the clinical character-istics of the HIV-positive patients with perianal abscess.METHODS Totally 152 HIV/AIDS patients who were complicated with anorectal diseases and were treated in The Eighth Hospital of Wuhan from Jan.2020 to Dec.2023 were recruited as the research subjects,36 of whom had perianal abscess.The manifestations of anorec-tal diseases,treatment status and incidence rates of the diseases among the patients with different clinical charac-teristics in the different years were statistically analyzed.The clinical characteristics of the HIV-positive patients with perianal abscess were observed.RESULTS Of the 152 HIV/AIDS patients complicated with anorectal disea-ses,51.97％had mixed hemorrhoid,and 23.68％had perianal abscess.The number of patients with HIV/AIDS complicated with anorectal diseases gradually increased from 2020 to 2023;while the incidence rate of male,aged between 30 and 40 years old,married individuals,those with primary school education or below and famers were relatively high.Among the HIV/AIDS patients complicated with anorectal diseases,139 underwent surgical pro-cedures,and 23 did not.Among the 36 HIV-positive patients with perianal abscess,97.22％were male,50.00％were aged between 20 and 30 years old,and 44.44％were married.CONCLUSIONS The number of HIV/AIDS patients complicated with anorectal diseases is gradually increased from 2020 to 2023;the incidence rates are rela-tively high among the patients who are male,aged between 30 and 40 years old,married,with primary school edu-cation or below and famers.Perianal abscess and mixed hemorrhoid are the major types of anorectal diseases.Sur-gical procedures are recommended for HIV/AIDS patients complicated with anorectal diseases,while the HIV-positive patients with perianal abscess are dominated by the population of male,aged between 20 and 30 years old and married.It is necessary to attach great importance to the detection of pathological characteristics of the HIV-positive patients with perianal abscess so as to take appropriate treatment measures to improve the therapeutic effect.

OBJECTIVE To explore the epidemiological characteristics of human immunodeficiency virus(HIV)/ac-quired immune deficiency syndrome(AIDS)complicated with anorectal diseases and analyze the clinical character-istics of the HIV-positive patients with perianal abscess.METHODS Totally 152 HIV/AIDS patients who were complicated with anorectal diseases and were treated in The Eighth Hospital of Wuhan from Jan.2020 to Dec.2023 were recruited as the research subjects,36 of whom had perianal abscess.The manifestations of anorec-tal diseases,treatment status and incidence rates of the diseases among the patients with different clinical charac-teristics in the different years were statistically analyzed.The clinical characteristics of the HIV-positive patients with perianal abscess were observed.RESULTS Of the 152 HIV/AIDS patients complicated with anorectal disea-ses,51.97％had mixed hemorrhoid,and 23.68％had perianal abscess.The number of patients with HIV/AIDS complicated with anorectal diseases gradually increased from 2020 to 2023;while the incidence rate of male,aged between 30 and 40 years old,married individuals,those with primary school education or below and famers were relatively high.Among the HIV/AIDS patients complicated with anorectal diseases,139 underwent surgical pro-cedures,and 23 did not.Among the 36 HIV-positive patients with perianal abscess,97.22％were male,50.00％were aged between 20 and 30 years old,and 44.44％were married.CONCLUSIONS The number of HIV/AIDS patients complicated with anorectal diseases is gradually increased from 2020 to 2023;the incidence rates are rela-tively high among the patients who are male,aged between 30 and 40 years old,married,with primary school edu-cation or below and famers.Perianal abscess and mixed hemorrhoid are the major types of anorectal diseases.Sur-gical procedures are recommended for HIV/AIDS patients complicated with anorectal diseases,while the HIV-positive patients with perianal abscess are dominated by the population of male,aged between 20 and 30 years old and married.It is necessary to attach great importance to the detection of pathological characteristics of the HIV-positive patients with perianal abscess so as to take appropriate treatment measures to improve the therapeutic effect.