N⁶-methyladenosine (m⁶A) modification plays a critical role in cell cycle regulation, while the mechanism of m⁶A in regulating mitosis remains underexplored. Here, we found that the total m⁶A modification level in cells increased during mitosis by the liquid chromatography-mass spectrometry/mass spectrometry and m⁶A dot blot assays. Silencing methyltransferase-like 3 (METTL3) or METTL14 results in delayed mitosis, abnormal spindle assembly, and chromosome segregation defects by the immunofluorescence. By analyzing transcriptome-wide m⁶A targets in HeLa cells, we identified polo-like kinase 1 (PLK1) as a key gene modified by m⁶A in regulating mitosis. Specifically, through immunoblotting and RNA pulldown, m⁶A modification inhibits PLK1 translation via YTH N⁶-methyladenosine RNA binding protein 1, thus mediating cell cycle homeostasis. Demethylation of PLK1 mRNA leads to significant mitotic abnormalities. These findings highlight the critical role of m⁶A in regulating mitosis and the potential of m⁶A as a therapeutic target in proliferative diseases such as cancer.
Humans ; Polo-Like Kinase 1 ; Cell Cycle Proteins/metabolism* ; Proto-Oncogene Proteins/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Mitosis/physiology* ; HeLa Cells ; Adenosine/genetics* ; Methyltransferases/metabolism* ; RNA, Messenger/metabolism* ; RNA-Binding Proteins/metabolism*

Objective To evaluate the potential risk of transmission of angiostrongyliasis by common freshwater snails in Dali Bai Autonomous Prefecture, Yunnan Province, so as to provide insights into local surveillance of angiostrongyliasis. Methods Common freshwater snails were collected from Dali Bai Autonomous Prefecture, Yunnan Province from March to April, 2020, and identified and bred in laboratory. SD rats were infected with third-stage larvae of Angiostrongylus cantonensis that were isolated from commercially available Pomacea canaliculata snails in Dali Bai Autonomous Prefecture, and freshwater snails were infected with the first-stage larvae of A. cantonensis that were isolated from the feces of SD rats 39 days post-infection at room temperature. The developmental process and morphological characteristics of worms in hosts were observed, and the percentages of A. cantonensis infections in different species of freshwater snails were calculated. Then, SD rats were infected with the third-stage larvae of A. cantonensis that were isolated from A. cantonensis-infected freshwater snails, and the larval development and reproduction was observed. Results More than 3 000 freshwater snail samples were collected from farmlands, ditches and wetlands around Erhai Lake in Dali Bai Autonomous Prefecture, and Cipangopaludina chinensis, P. canaliculata, Parafossarulus striatulus, Oncomelania hupensis robertsoni, Galba pervia, Physa acuta, Radix swinhoei, Assiminea spp., Tricula spp. and Bellamya spp. were morphologically identified. A total of 105 commercially available P. canaliculata snails were tested for A. cantonensis infections, and 2 P. canaliculata snails were found to be infected with A. cantonensis, in which the third-stage larvae of A. cantonensis were isolated. Ten species of freshwater snails were artificially infected with the third-stage larvae of A. cantonensis, and all 10 species of freshwater snails were found to be infected with A. cantonensis, with the highest positive rate of A. cantonensis infections in Bellamya spp. (62.3%, 137/204), and the lowest in C. chinensis (35.5%, 11/31). After SD rats were infected with the third-stage larvae of A. cantonensis isolated from different species of freshwater snails, mature adult worms of A. cantonensis were yielded. Conclusions Multiple species of freshwater snails may serve as intermediate hosts of A. cantonensis under laboratory conditions in Dali Bai Autonomous Prefecture of Yunnan Province. Further investigations on natural infection of A. cantonensis in wild snails in Dali Bai Autonomous Prefecture seem justified.

Extremity vascular firearm injury (EVFI) which occurs in large quantities during wartime and is dispersed in peacetime, can result in acute hemorrhagic shock and compartment syndrome, thus seriously endangering the patients′ life. Compared with vascular trauma, vascular firearm injury not only damages the arteries easily, but also has a more severe damage and a poor prognosis. At present, most of relevant reports on the clinical diagnosis and treatment of EVFI in China are based on the treatment experience in Vietnam′s self-defense counterattack and lack subsequent technology, data and wartime echelon treatment. To this end, the authors discussed the epidemiological characteristics, diagnosis and treatment of EVFI by integrating the literature published since the Afghanistan and Iraq War, aiming to provide reference for the diagnosis and treatment of EVFI in China.

Objective To investigate the effects of 6-pyruvoyl-tetrahydropterin synthase(PTS)on gastric cancer cells.Methods The expression of PTS protein and mRNA in gastric mucosal epithelial cells GES-1 and gastric cancer cell lines HGC-27 cells,MGC-803 cells,AGS cells and MKN-45 cells were determined by Western blot(WB)and reverse transcription quantitative polymerase chain reaction(RT-qPCR).AGS cells were selected for follow-up experiments.AGS cells were divided into control(NC)group,sh-PTS group,and sh-PTS+BML-284 group.Cell proliferation was measured by CCK-8.Cell migration ability was measured by scratch healing.Cell invasion and migration were measured by Transwell assay.Apoptosis was measured by flow cytometry.The protein and mRNA levels of β-catenin,c-myc,GSK-3β and Wnt5a were detected by WB and RT-qPCR.Results The expression of PTS in gastric mucosal epithelial cells GES-1 was lower than that in gastric cancer cells,and the expression of PTS was the highest in AGS cells.Knocking down PTS could inhibit proliferation,migration and invasion of gastric cancer cells,promote cell apoptosis,decreased β-catenin,c-myc,Wnt5a protein levels,and increased GSK-3β protein levels(P＜0.05).Compared with sh-PTS group,cell proliferation,migration and invasion ability of sh-PTS+BML-284 group were enhanced,apoptosis level was decreased,protein expression of β-catenin,c-myc and Wnt5a was increased,and protein expression of GSK-3β was decreased(P＜0.05).Conclusion PTS can affect proliferation,migration,invasion and apoptosis of gastric cancer cells by mediating Wnt/β-catenin pathway.

Objective To analyze the curative effect of acupuncture at Gongsun, Sifeng combined with visceral acupoint tapping in children with mesenteric lymphadenitis (type of gastrointestinal heat accumulation), and its influence on serum intestinal fatty acid-binding protein (I-FABP) and vasoactive intestinal peptide (VIP). Methods A total of 60 children with mesenteric lymphadenitis (type of gastrointestinal heat accumulation) were selected, and were divided into control group (n=30, conventional treatment combined with acupuncture at Gongsun and Sifeng acupoints) and study group (n=30, visceral acupoint tapping on the basis of the control group) according to the random number table method. The clinical efficacy, changes of main symptoms and signs were compared, and the expression levels of serum I-FABP and VIP were detected. Results The total effective rate of the study group was higher than that of the control group(P < 0.05). After 2 weeks of treatment, the serum I-FABP levels of the two groups were lower than that before treatment, and the serum I-FABP level of the study group was lower than that of the control group (P < 0.05). After 2 weeks of treatment, the serum VIP levels of the two groups were higher than that before treatment, and the serum VIP level of the study group was higher than that of the control group (P < 0.05). After 2 weeks of treatment, the improvement of main symptoms and signs in the study group was better than that in the control group (P < 0.05). Conclusion Acupuncture at Gongsun and Sifeng combined with visceral acupoint tapping can be used to treat children with mesenteric lymphadytis (gastrointestinal heat accumulation type), regulate and improve gastrointestinal function, adjust the level of serum I-FABP and VI, and relieve the main symptoms and signs of children, and can be used as an effective therapeutic method.

ObjectiveTo identify the functions of the AP2/ERF family members in Pinellia ternata and promote the genetic improvement of P. ternata varieties. MethodWe identified and conducted a systematic bioinformatics analysis of the AP2/ERF family member genes in P. ternata based on the three generations of transcriptome data. Real-time polymerase Chain reaction　（Real-time） PCR was employed to determine the expression pattern of AP2/ERF genes in different tissues and under different stress conditions. ResultA total of eight full-length AP2/ERF family members were identified from the transcriptome data， which were classified into three sub-gene families： AP2， ERF， and DREB. The deduced AP2/ERF proteins in P. ternata had the length of 251-512 aa， the theoretical pI of 5.29-11.72， the instability index of 45.90-82.41， subcellular localization in the nucleus， and conserved domains and motifs. AP2/ERF genes were expressed in different tissues of P. ternata， with high expression levels in the leaf. The stress response experiments showed that PtERF1 mainly responded to NaCl stress. The expression of PtERF2 and PtERF4 was significantly up-regulated under low temperature and polyethylene glycol （PEG）-simulated stress. PtERF3 responded to both low temperature and NaCl stress. The expression of PtERF5 was induced by high temperature， low temperature， NaCl and PEG stress. The expression of PtERF7 was up-regulated under high temperature， while that of PtERF8 under low temperature. ConclusionThe AP2/ERF genes in P. ternata can respond to stress and have the potential functions of regulating photosynthesis and improving root stress resistance.

The cell cycle is a complex process that involves DNA replication, protein expression, and cell division. Dysregulation of the cell cycle is associated with various diseases. Cyclin-dependent kinases (CDKs) and their corresponding cyclins are major proteins that regulate the cell cycle. In contrast to inhibition, a new approach called proteolysis-targeting chimeras (PROTACs) and molecular glues can eliminate both enzymatic and scaffold functions of CDKs and cyclins, achieving targeted degradation. The field of PROTACs and molecular glues has developed rapidly in recent years. In this article, we aim to summarize the latest developments of CDKs and cyclin protein degraders. The selectivity, application, validation and the current state of each CDK degrader will be overviewed. Additionally, possible methods are discussed for the development of degraders for CDK members that still lack them. Overall, this article provides a comprehensive summary of the latest advancements in CDK and cyclin protein degraders, which will be helpful for researchers working on this topic.
Humans ; Cell Cycle/physiology* ; Cell Division ; Cyclin-Dependent Kinases/metabolism* ; Cyclins/metabolism*

Craniocerebral war injury, mainly caused by weaponry equipment and wartime conditions during warfare, are characterized by high difficulty in treatment and evacuation as well as high mortality rate. The field surgical treatment of craniocerebral war injury is not only related to injury characteristics, but also to factors such as war scale, combat style, combat area and weapon power. In recent years, there have been few comprehensive reports on the characteristics and field surgical treatment of craniocerebral war injury in China. Therefore, the authors reviewed the research progress in the characteristics and field surgical treatment of craniocerebral war injuries in foreign armies since 2001, with the aim to provide a reference for relevant basic researches and war injury treatment in China.

OBJECTIVE To investigate the effects of andrographolide （Andro） on angiogenesis in rats with diabetic foot and to explore its mechanism of action based on the Hippo-Yes-associated protein （YAP） signaling pathway. METHODS The rat model of type 2 diabetes was established by using low-dose streptozotocin combined with high-fat and high-glucose diet. On the basis of successful modeling， the rat model of diabetes foot was established by scalding. Model rats were randomly divided into 5 groups with 12 rats in each group： model group， Andro low-dose， medium-dose， and high-dose groups （1， 10， and 20 mg/kg）， as well as inhibitor group （20 mg/kg Andro+100 mg/kg of verteporfin， an specific inhibitor of Hippo-YAP signaling pathway）； other 12 healthy rats were included in the Control group. Rats in each group were intragastrically and intraperitoneally injected with solvents or corresponding drugs， once a day， for 2 consecutive weeks. The wound healing， fasting blood glucose （FBG） and fasting insulin （FINS） were detected in rats after medication. HE staining was performed to observe the tissue damage and capillary number of rat trauma； the number of endothelial progenitor cells （EPCs） in peripheral blood of rats was counted by using flow cytometry； the contents of serum total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C） and low-density lipoprotein cholesterol （LDL-C） in rats were determined by fully automatic biochemical analyzer； the expressions of hypoxia- inducible factor 1α （HIF-1α）， vascular endothelial growth factor （VEGF） and Hippo-YAP signaling pathway-related proteins in the traumatic tissues of rats in each group were detected by Western blot. RESULTS Compared with Control group， the wound healing rate， capillary number， the proportion of EPCs， HDL-C content， as well as the protein expression levels of HIF-1α and VEGF and the phosphorylation levels of mammalian Ste20-like kinase 1， large tumor suppressor gene 1 and YAP proteins were significantly reduced in the model group， while the FBG， FINS levels and TC， TG and LDL-C contents were significantly increased （P＜0.05）. Compared with model group， the above indexes were significantly reversed in Andro low-dose， medium-dose and high-dose group， in a dose-dependent manner （P＜ 0.05）； verteporfin attenuated the above reversal effect of Andro （P＜0.05）. CONCLUSIONS Andro has the effects of lowering blood glucose and blood lipids， promoting blood vessel formation and wound healing in rats with diabetic foot， and its mechanism of action may be related to the activation of Hippo-YAP signaling pathway.

Objective:To investigate the risk factors of acute ischemic stroke in patients with lung cancer.Methods:Patients with lung cancer admitted to Beijing Friendship Hospital, Capital Medical University from July 2019 to August 2021 were retrospectively included. The demographics and baseline clinical data of the patients were collected. According to whether acute ischemic stroke had occurred, the patients were divided into a case group and a control group.Results:According to the propensity matching score method, 26 patients with lung cancer were included in the case group and 104 in the control group. There were significant differences in age, tumor staging, metastasis and treatment of lung cancer, hypertension, diabetes, hyperlipidemia, atrial fibrillation, alcohol consumption, diastolic blood pressure, systolic blood pressure, hemoglobin, triglyceride and squamous cell carcinoma associated antigen (SCC) between the two groups (all P<0.05). Multivariate logistic regression analysis showed that older individuals (odds ratio [ OR] 1.087, 95% confidence interval [ CI] 1.063-1.211; P=0.007), lung cancer treatment ( OR 1.698, 95% CI 1.139-2.532; P=0.009), hypertension ( OR 5.647, 95% CI 1.921-16.597; P=0.002), diabetes ( OR 3.082, 95% CI 1.020-9.311; P=0.046), hyperlipidemia ( OR 5.163, 95% CI 1.020-9.311; P=0.002), atrial fibrillation ( OR 5.105, 95% CI 1.852-14.39; P=0.006), alcohol consumption ( OR 0.30, 95% CI 0.123-0.733; P=0.008), diastolic blood pressure ( OR 1.032, 95% CI 0.123-0.733; P=0.022), systolic blood pressure ( OR 1.032, 95% CI 1.003-1.061; P=0.031), hemoglobin ( OR 1.358, 95% CI 0.985-1.871; P=0.042), and SCC ( OR 1.535, 95% CI 1.069-2.204; P=0.02) were the independent risk factors for acute ischemic stroke in patients with lung cancer. Conclusions:Lung cancer related ischemic stroke is more common in elderly patients, and such patients have higher levels of hemoglobin, triglycerides, and SCC. Age, lung cancer treatment, common vascular risk factors, hemoglobin, and SCC are the potential risk factors for acute ischemic stroke in patients with lung cancer.