1.Differences in deltamethrin resistance and kdr gene mutation in Culex tritaeniorhynchus population in and outside the Yellow Sea wetland
Xiao-er ZHANG ; Zhi-ming WU ; Ye TIAN ; Qian CUI ; Yu-qian JI ; Huan WANG ; Shu-juan YANG ; Yi-chao ZHAO ; Yu WANG ; Hua-yu YIN ; Yu DING ; Guo-jin YAN ; Min-sen ZHAO ; Shou-gang ZHANG ; Bing-dong SONG ; Hong-na CHEN ; Jian GAO ; Wei-fang YANG ; Yu-fu ZHANG ; Hui LIU ; Hong-liang CHU
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):101-107
Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.
2.Expert consensus on intraoperative repositioning for patients with spine fracture and dislocation (version 2025)
Dongmei BIAN ; Ke SUN ; Ningbo CHEN ; Caixia BAI ; Miao WANG ; Yafeng QIAO ; Fei WANG ; Hong WANG ; Feng TIAN ; Mei YAN ; Meng BAI ; Linjuan ZHANG ; Liyan ZHAO ; Yaqing CUI ; Xue JIANG ; Leling FENG ; Ning NING ; Junqin DING ; Lan WEI ; Yonghua ZHAI ; Yu ZENG ; Zengmei ZHANG ; Jiqun HE ; Fenggui BIE ; Hong CHEN ; Zengyan WANG ; Li LI ; Li ZHANG ; Yaying ZHOU ; Bing SHAO ; Ying WANG ; Caixia XIE ; Yanfeng YAO ; Jingjing AN ; Wen SHI ; Xiongtao LIU ; Xiaoyan AN ; Ning NAN ; Lan LI ; Xiaohui GOU ; Qiaomei LI ; Xiuting WU ; Yuqin ZHANG ; Jing LIU ; Fusen XIANG ; Xu XU ; Na MEI ; Jiao ZHOU ; Shan FAN ; Qian WANG ; Shuixia LI
Chinese Journal of Trauma 2025;41(2):138-147
Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.
3.Analysis of factors affecting bacterial overgrowth in small intestine of different gas-producing types
Xiao-Na LIU ; Xiao-Hui WANG ; Shao-Xin WANG ; Xi LIU ; Wei WANG ; Chang-Hao DONG ; An-Ping HU ; Li-Hong CUI
Medical Journal of Chinese People's Liberation Army 2025;50(3):254-260
Objective To explore the influencing factors of different types of small intestinal bacterial overgrowth(SIBO).Methods A total of 539 patients who were hospitalized in the Department of Gastroenterology,the Sixth Medical Center of PLA General Hospital from June 2021 to December 2021 and who underwent methane-hydrogen breath test were retrospectively selected.Based on breath test results,patients were divided into SIBO-negative group(n=300)and SIBO-positive group(n=239).The clinical data were compared between two groups.According to the specific values of breath test results,SIBO-positive patients were further divided into hydrogen-producing bacterial overgrowth(hydrogen-positive,n=103),intestinal methanogen overgrowth(methanogen-positive,n=80),and simultaneous methanogen and hydrogen-producing bacterial overgrowth(double positive,n=56)groups.Multivariate logistic regression analysis was employed to identify influencing factors of different SIBO types.Additionally,SIBO-positive patients were categorized by age into<45 years(n=23),45-60 years(n=82),60-75 years(n=124),and≥75 years(n=10)to compare SIBO positivity rates across age groups.Results The patients in SIBO-positive and double positive groups were older and had a lower body mass index(BMI)than those in SIBO-negative group,with statistically significant differences(P<0.05).Compared with the patients in SIBO-negative group,those in hydrogen-positive group showed a higher proportion of history of coronary heart disease,those in methanogen-positive group were older,and higher proportion of statin use,with statistically significant differences(P<0.05).Multivariate logistic regression analysis revealed that,among different SIBO types,a history of coronary heart disease served as an independent risk factor for hydrogen-producing bacterial overgrowth(OR=2.728,95%CI 1.271-5.857,P=0.010).For methanogen overgrowth,increasing age was identified as an independent risk factor(OR=1.040,95%CI 1.009-1.063,P=0.010),while the application of statin played the role of an independent protective factor(OR=0.420,95%CI 0.236-0.754,P=0.003).As for the simultaneous overgrowth of methane-producing and hydrogen-producing bacteria,increased BMI was found to be an independent protective factor(OR=0.870,95%CI 0.786-0.964,P=0.008).In SIBO-positive group,it was found that for patients aged<45 years,both the methane-positive rate and the double-positive rate were significantly lower than the hydrogen positivity rate(P<0.05).Moreover,among patients aged 45-60 years,the double-positive rate was significantly lower than the hydrogen positivity rate(P<0.01).When it comes to the hydrogen-positive rate,it was significantly lower for patients aged 45-60 and 60-75 years compared with that of patients aged<45 years(P<0.05).In contrast,the methane-positive rate and the double-positive rate were significantly higher for patients aged 45-60 and 60-75 years than those of patients aged<45 years(P<0.01).Conclusion A history of coronary heart disease and increasing age are independent risk factors for intestinal hydrogen-producing bacterial overgrowth and methanogen overgrowth,respectively.The application of statins and increased BMI are independent protective factors for intestinal methanogen simultaneous overgrowth of methanogen and hydrogen-producing bacteria,respectively.
4.Investigation on iodine nutrition status of children and pregnant women in different water iodine areas of Shandong Province in 2023
Na LIANG ; Jing WANG ; Ying ZHANG ; Ru CUI ; Lei ZHANG ; Xiaoming WANG ; Shuhui WEI ; Yingzheng MA ; Wen JIANG ; Qinfu WANG
Chinese Journal of Endemiology 2025;44(7):550-553
Objective:To investigate the iodine nutrition status of children and pregnant women in different water iodine areas of Shandong Province.Methods:From February to September 2023, Leling City (iodine deficient), Gaotang County (moderate iodine), and Liangshan County (high iodine) in different water iodine areas of Shandong Province were selected as survey sites. One village was selected from each county (city) in five directions: east, west, south, north, and center. Forty children aged 8 to 10 years (balanced in age, half male and half female) and 20 pregnant women were selected as survey subjects in each village. Random urine samples of children and pregnant women were collected to test for urinary iodine. Meanwhile, thyroid examinations were conducted on children to calculate the goiter rate.Results:A total of 600 urine samples of children were tested, with a median urinary iodine level of 246.0 μg/L. The median urinary iodine levels of children in iodine deficient, moderate iodine and high iodine areas were 219.6, 208.0 and 446.0 μg/L, respectively ( n = 200, 200, 200). The median urinary iodine level of children in high iodine area was significantly higher than that in iodine deficient and moderate iodine areas ( P < 0.05). A total of 600 children underwent thyroid examinations, with a goiter rate of 5.8% (35/600). The goiter rate of children in iodine deficient, moderate iodine, and high iodine areas were 4.0% (8/200), 1.0% (2/200), and 12.5% (25/200), respectively. The goiter rate of children in high iodine area was significantly higher than that in iodine deficient and moderate iodine areas ( P < 0.05). A total of 247 urine samples of pregnant women were tested, with a median urinary iodine level of 158.2 μg/L. The median urinary iodine levels of pregnant women in iodine deficient, moderate iodine, and high iodine areas were 75.3, 175.2 and 321.2 μg/L, respectively ( n = 98, 84, 65). The median urinary iodine level of pregnant women in high iodine area was significantly higher than that in iodine deficient and moderate iodine areas, and the median urinary iodine level of pregnant women in moderate iodine area was significantly higher than that in iodine deficient area ( P < 0.05). Conclusion:The urinary iodine levels of children and pregnant women and the goiter rate of children in high iodine area of Shandong Province are significantly increased, and water iodine may be a key factor affecting the iodine nutrition status of the population.
5.Investigation on iodine nutrition status of children and pregnant women in different water iodine areas of Shandong Province in 2023
Na LIANG ; Jing WANG ; Ying ZHANG ; Ru CUI ; Lei ZHANG ; Xiaoming WANG ; Shuhui WEI ; Yingzheng MA ; Wen JIANG ; Qinfu WANG
Chinese Journal of Endemiology 2025;44(7):550-553
Objective:To investigate the iodine nutrition status of children and pregnant women in different water iodine areas of Shandong Province.Methods:From February to September 2023, Leling City (iodine deficient), Gaotang County (moderate iodine), and Liangshan County (high iodine) in different water iodine areas of Shandong Province were selected as survey sites. One village was selected from each county (city) in five directions: east, west, south, north, and center. Forty children aged 8 to 10 years (balanced in age, half male and half female) and 20 pregnant women were selected as survey subjects in each village. Random urine samples of children and pregnant women were collected to test for urinary iodine. Meanwhile, thyroid examinations were conducted on children to calculate the goiter rate.Results:A total of 600 urine samples of children were tested, with a median urinary iodine level of 246.0 μg/L. The median urinary iodine levels of children in iodine deficient, moderate iodine and high iodine areas were 219.6, 208.0 and 446.0 μg/L, respectively ( n = 200, 200, 200). The median urinary iodine level of children in high iodine area was significantly higher than that in iodine deficient and moderate iodine areas ( P < 0.05). A total of 600 children underwent thyroid examinations, with a goiter rate of 5.8% (35/600). The goiter rate of children in iodine deficient, moderate iodine, and high iodine areas were 4.0% (8/200), 1.0% (2/200), and 12.5% (25/200), respectively. The goiter rate of children in high iodine area was significantly higher than that in iodine deficient and moderate iodine areas ( P < 0.05). A total of 247 urine samples of pregnant women were tested, with a median urinary iodine level of 158.2 μg/L. The median urinary iodine levels of pregnant women in iodine deficient, moderate iodine, and high iodine areas were 75.3, 175.2 and 321.2 μg/L, respectively ( n = 98, 84, 65). The median urinary iodine level of pregnant women in high iodine area was significantly higher than that in iodine deficient and moderate iodine areas, and the median urinary iodine level of pregnant women in moderate iodine area was significantly higher than that in iodine deficient area ( P < 0.05). Conclusion:The urinary iodine levels of children and pregnant women and the goiter rate of children in high iodine area of Shandong Province are significantly increased, and water iodine may be a key factor affecting the iodine nutrition status of the population.
6.Expert consensus on intraoperative repositioning for patients with spine fracture and dislocation (version 2025)
Dongmei BIAN ; Ke SUN ; Ningbo CHEN ; Caixia BAI ; Miao WANG ; Yafeng QIAO ; Fei WANG ; Hong WANG ; Feng TIAN ; Mei YAN ; Meng BAI ; Linjuan ZHANG ; Liyan ZHAO ; Yaqing CUI ; Xue JIANG ; Leling FENG ; Ning NING ; Junqin DING ; Lan WEI ; Yonghua ZHAI ; Yu ZENG ; Zengmei ZHANG ; Jiqun HE ; Fenggui BIE ; Hong CHEN ; Zengyan WANG ; Li LI ; Li ZHANG ; Yaying ZHOU ; Bing SHAO ; Ying WANG ; Caixia XIE ; Yanfeng YAO ; Jingjing AN ; Wen SHI ; Xiongtao LIU ; Xiaoyan AN ; Ning NAN ; Lan LI ; Xiaohui GOU ; Qiaomei LI ; Xiuting WU ; Yuqin ZHANG ; Jing LIU ; Fusen XIANG ; Xu XU ; Na MEI ; Jiao ZHOU ; Shan FAN ; Qian WANG ; Shuixia LI
Chinese Journal of Trauma 2025;41(2):138-147
Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.
7.Baicalein:A potential GLP-1R agonist improves cognitive disorder of diabetes through mitophagy enhancement
Liu NA ; Cui XIN ; Yan WENHUI ; Guo TINGLI ; Wang ZHUANZHUAN ; Wei XIAOTONG ; Sun YUZHUO ; Liu JIEYUN ; Xian CHENG ; Ma WEINA ; Chen LINA
Journal of Pharmaceutical Analysis 2024;14(8):1189-1204
There is increasing evidence that the activation of glucagon-like peptide-1 receptor(GLP-1R)can be used as a therapeutic intervention for cognitive disorders.Here,we have screened GLP-1 R targeted com-pounds from Scutellaria baicalensis,which revealed baicalein is a potential GLP-1 R small-molecule agonist.Mitophagy,a selective autophagy pathway for mitochondrial quality control,plays a neuro-protective role in multiple cognitive impairment diseases.We noticed that Glp1r knock-out(KO)mice present cognitive impairment symptoms and appear worse in spatial learning memory and learning capacity in Morris water maze(MWM)test than their wide-type(WT)counterparts.Our mechanistic studies revealed that mitophagy is impaired in hippocampus tissue of diabetic mice and Glp1r KO mice.Finally,we verified that the cognitive improvement effects of baicalein on diabetic cognitive dysfunction occur through the enhancement of mitophagy in a GLP-1 R-dependent manner.Our findings shed light on the importance of GLP-1 R for cognitive function maintenance,and revealed the vital significance of GLP-1R for maintaining mitochondrial homeostasis.Furthermore,we identified the therapeutic potential of baicalein in the treatment of cognitive disorder associated with diabetes.
8.Correlation analysis between improvement of anxiety symptoms and thyroid hormone levels in patients with generalized anxiety disorder
Jielin ZHU ; Wanqiu NA ; Wei JIANG ; Lijun CUI
China Modern Doctor 2024;62(33):32-36
Objective To explore the correlation between the change of the serum levels of thyroid hormone and the severity of anxiety symptoms in patients with generalized anxiety disorder after treatment with paroxetine hydrochloride.Methods 76 patients with generalized anxiety disorder treated in the Third People's Hospital of Huzhou from January to August 2023 were collected as study group,and they were divided into mild group(n=23),moderate group(n=30),and severe group(n=23),according to degree of anxiety by Hamilton anxiety scale(HAMA),69 healthy examination subjects in the same period were selected as control group.Patients in study group were treated with paroxetine hydrochloride tablets for 8 weeks,patients were evaluated anxiety symptoms,the serum levels of thyroid hormone were measured at baseline and 8 weekend,including triiodothyronine(T3),thyroxine(T4),free triiodothyronine(FT3),free thyroxine(FT4),thyroid stimulating hormone(TSH),antithyroglobulin antibody(TG),anti-thyroid peroxidase antibody(TPO).Results After 8 weeks of paroxetine hydrochloride treatment,the significant efficacy rates of mild group,moderate group,and severe group were 73.9%,76.7%,and 73.9%,with no statistically significant difference in efficacy among three groups(x2=0.073,P>0.05).In the baseline period,FT4 levels of patients in moderate group and severe group were significantly higher than those in mild group and control group,and the difference was statistically significant(P<0.05).The severity of anxiety symptoms in the baseline period of patients in moderate group and severe group showed a low positive correlation and a significant positive correlation with FT4 levels(r=0.382、0.610,P<0.05).After 8 weeks treatment,the FT4 levels of patients in moderate group and severe group decreased significantly compared to the baseline period,and the difference was statistically significant(t=2.847,3.042,P<0.05).The reduction rate of HAMA score in severe group was positively correlated with the change in FT4 level during the baseline period and at the end of 8 weeks of treatment(r=0.517,P<0.05).By a binary Logistic regression analysis showed that the higher levels of FT4 in the baseline period with the worse efficacy in moderate group and severe group.Conclusion The improvement of anxiety symptoms could be affected by high baseline levels of FT4 in generalized anxiety disorder patients with moderate to severe anxiety.
9.Clinical characteristics and management status of Turner syndrome in 1 089 children
Yan LIANG ; Haiyan WEI ; Ruimin CHEN ; Zhixin ZHANG ; Xinran CHENG ; Na TAO ; Chunlin WANG ; Yu YANG ; Ying XIN ; Xin FAN ; Xingxing ZHANG ; Geli LIU ; Shengquan CHENG ; Min ZHU ; Hongwei DU ; Yan SUN ; Linqi CHEN ; Lanwei CUI ; Xiaoping LUO
Chinese Journal of Pediatrics 2024;62(10):962-968
Objective:To investigate the clinical characteristics and management status of children with Turner syndrome (TS) in China.Methods:As a cross-sectional study, 1 089 TS patients were included in the database of the National Collaborative Alliance for the Diagnosis and Treatment of Turner Syndrome from August 2019 to November 2023. Clinical characteristics (growth development, sexual development, organ anomalies, etc.), karyotypes, auxiliary examinations, and treatments were collected and analyzed.Results:Among the 1 089 TS cases, 809 were recorded karyotypes. The karyotype distribution was as follows: 45, X in 317 cases (39.2%), X chromosome structural variants (including partial deletions of p or q arm, ring chromosome, and marker chromosome) in 89 cases (11.0%), 45, X/46, XX mosaicism in 158 cases (19.5%), mosaicism with X chromosome structural variants in 209 cases (25.8%), and presence of Y chromosome material in 36 cases (4.4%). Among the 824 TS cases, the age of diagnosis was 9.7(6.4, 12.2) years, with a height standard deviation score (HtSDS) of -3.1±1.2. Five hundred and fifty three cases underwent growth hormone (GH) stimulation test, and 352 cases (63.7%) had GH peak values <10 μg/L and 75.9% (577/760) had low IGF1 levels, with IGF1 SDS ≤-2 accounting for 38.2% (290 cases). Among 471 cases aged ≥8 years, 132 cases (28.0%) showed spontaneous sexual development (mean bone age (11.0±1.7) years), 10 cases had spontaneous menarche (mean bone age (12.0±2.2) years), and 2 cases had regular menstrual cycles. Common physical features included cubitus valgus (311 cases (28.5%)), neck webbing (188 cases (17.2%)), low posterior hairline (185 cases (17.0%)), shield chest (153 cases (14.0%)), high arched palate (127 cases (11.6%)), short fourth metacarpal (43 cases (3.9%)), and spinal abnormalities (38 cases (3.5%)). Congenital cardiovascular and urogenital anomalies occurred in 91 cases (19.4%) and 66 cases (12.0%)respectively. Abdominal ultrasound in 33 cases (7.2%) indicated fatty liver, hepatomegaly, intrahepatic bile duct stones, and splenomegaly. Among 23 cases undergoing oral glucose tolerance test (OGTT) test, 2 were diagnosed with diabetes mellitus and 4 with impaired glucose tolerance. Following diagnosis, 669 cases (80.7%) received rhGH treatment at a chronological age of (9±4) years and bone age of (8.3±3.2) years. Additionally, 112 cases (19.4%) received sex hormone replacement therapy starting at the age of (14±4) years and bone age of (12.6±1.2) years.Conclusions:The karyotypes of 45, X and mosaicism were most common in Chinese children with TS. The clinical manifestations were mainly short stature and gonadal dysplasia. However, a few TS children could be in the normal range of height, and some cases among those aged of ≥8 years old had spontaneous sexual development. Some exhibited physical features, congenital cardiovascular and urogenital anomalies, and dysfunction of the hypothalamic-pituitary-IGF1 axis. Moreover, a few of them developed impaired glucose tolerance and diabetes mellitus. Following diagnosis, most of the patients received rhGH treatment, and a few of them received sex hormone replacement therapy.
10.Development and Synthesis of Activity-based and Affinity-based Ubiquitin Probes
Ling XU ; Cui-Na WEI ; Xian-Fu LU ; Yi-Ming LI
Progress in Biochemistry and Biophysics 2024;51(3):598-623
Ubiquitination, a diverse post-translational modification, is carried out by enzymes including E1-activating enzymes, E2-conjugating enzymes, E3 ligases, and deubiquitinating enzymes (DUBs). Ubiquitin itself possesses 7 lysine residues and N-terminal methionine, allowing for the formation of polyubiquitin chains with different lengths and linkages. These chains exhibit various topologies that can be recognized by proteins containing ubiquitin-binding domain, thereby transmitting distinct cellular signals. To unravel the physiological mechanisms associated with ubiquitin, numerous ubiquitin probes have been developed. This review provides an overview of recent advancements in the field of ubiquitin probes, focusing on activity-based and affinity-based probes. Activity-based probes are designed to covalently bind to DUBs, E1s, or E3s, enabling the identification and characterization of these enzymes. Affinity-based probes, on the other hand, selectively bind to ubiquitin-binding domains, facilitating the identification of proteins that interact with ubiquitin. Moreover, this review comprehensively discusses the synthetic methodologies employed for the acquisition of ubiquitin probes. These includes meticulous discussions on the synthesis of individual monomeric modules, the establishment of isopeptide linkages, as well as the incorporation of reactive functional groups. Additionally, the review explores the emerging area of cell-penetrating ubiquitin probes and highlights their latest applications in living cells. These probes incorporate cell-penetrating peptides to enable their internalization into cells, allowing for direct visualization and manipulation of ubiquitin-modified proteins within their native environment. Overall, this review offers insights into the design, synthesis, and applications of ubiquitin probes, highlighting their significance in elucidating ubiquitin-mediated cellular processes.


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