Lignans are a powerful weapon for plants to resist stresses and have diverse bioactive functions to protect human health. Elucidating the mechanisms of stereoselective biosynthesis and response to stresses of lignans is important for the guidance of plant improvement. Here, we identified the complete pathway to stereoselectively synthesize antiviral (-)-lariciresinol glucosides in Isatis indigotica roots, which consists of three-step sequential stereoselective enzymes DIR1/2, PLR, and UGT71B2. DIR1 was further identified as the key gene in respoJanuary 2024nse to stresses and was able to trigger stress defenses by mediating the elevation in lignan content. Mechanistically, the phytohormone-responsive ERF transcription factor LTF1 colocalized with DIR1 in the cell periphery of the vascular regions in mature roots and helped resist biotic and abiotic stresses by directly regulating the expression of DIR1. These systematic results suggest that DIR1 as the first common step of the lignan pathway cooperates with PLR and UGT71B2 to stereoselectively synthesize (-)-lariciresinol derived antiviral lignans in I. indigotica roots and is also a part of the LTF1-mediated regulatory network to resist stresses. In conclusion, the LTF1-DIR1 module is an ideal engineering target to improve plant Defenses while increasing the content of valuable lignans in plants.

BACKGROUND:The type of graft selected during anterior cruciate ligament revision is considered one of the main factors affecting the postoperative outcome,but there are few reports on the comparison between different graft materials. OBJECTIVE:To explore the medium-to-long-term clinical efficacy after anterior cruciate ligament revision with autologous ligament,allogeneic ligament,and LARS artificial ligament. METHODS:A total of 67 patients with the first anterior cruciate ligament revision admitted to the Department of Joint and Sports Medicine,The Second Hospital of Tangshan from May 2011 to May 2020 were selected,including 41 males and 26 females,with a mean age of(45.83±7.39)years.They were divided into three groups according to different grafts used:autologous ligament group(n=24),allogeneic ligament group(n=22),and LARS artificial ligament group(n=21).Follow-up for more than 36 months after revision was performed to evaluate the effect of revision. RESULTS AND CONCLUSION:(1)International Knee Documentation Committee(IKDC)score,Lysholm knee score,and Tegner motor score 1 year after surgery and at the last follow-up in the three groups were higher than those before surgery(P<0.05).There were no significant differences in IKDC score,Lysholm knee score,and Tegner motor score among the three groups 1 year after surgery and the last follow-up(P>0.05).(2)The lateral differences of KT-1000 at 1 year after surgery and the last follow-up among the three groups were lower than those before surgery(P<0.05).The lateral difference of KT-1000 and the positive rate of the axial shift test in the last follow-up of the LARS artificial ligament group were higher than those in the autologous ligament group and allogeneic ligament group(P<0.05).(3)At the last follow-up,X-ray films showed no obvious enlargement of the reconstructed bone tunnel and no obvious failure of the graft fixation device.There was no obvious aggravation of osteoarthritis,but bone density decreased significantly in some elderly patients.(4)These findings suggest that anterior cruciate ligament revision with LARS artificial ligaments can obtain good initial stability,but with the extension of time,the stability of partial cases tends to decrease,even with reconstructed ligament failure.Both allogeneic and autogenous ligaments can obtain good clinical efficacy in anterior cruciate ligament revision.

Chronic intermittent hypoxia (CIH) can lead to vascular dysfunction and increase the risk of cardiovascular diseases, cerebrovascular diseases, and arterial diseases. Nevertheless, mechanisms underlying CIH-induced vascular dysfunction remain unclear. Herein, this study analyzed the role of aortic smooth muscle calciumactivated potassium (BK) channels in CIH-induced vascular dysfunction. CIH models were established in rats and rat aortic smooth muscle cells (RASMCs). Hemodynamic parameters such as mean blood pressure (MBP), diastolic blood pressure (DBP), and systolic blood pressure (SBP) were measured in rats, along with an assessment of vascular tone. NO and ET-1 levels were detected in rat serum, and the levels of ET-1, NO, eNOS, p-eNOS, oxidative stress markers (ROS and MDA), and inflammatory factors (IL-6 and TNF-α) were tested in aortic tissues. The Ca2+ concentration in RASMCs was investigated. The activity of BK channels (BKα and BKβ) was evaluated in aortic tissues and RASMCs. SBP, DBP, and MBP were elevated in CIH-treated rats, along with endothelial dysfunction, cellular edema and partial detachment of endothelial cells. BK channel activity was decreased in CIH-treated rats and RASMCs. BK channel activation increased eNOS, p-eNOS, and NO levels while lowering ET-1, ROS, MDA, IL-6, and TNF-α levels in CIH-treated rats. Ca2+ concentration increased in RASMCs following CIH modeling, which was reversed by BK channel activation. BK channel inhibitor (Iberiotoxin) exacerbated CIH-induced vascular disorders and endothelial dysfunction. BK channel activation promoted vasorelaxation while suppressing vascular endothelial dysfunction, inflammation, and oxidative stress, thereby indirectly improving CIH-induced vascular dysfunction.

Chronic intermittent hypoxia (CIH) can lead to vascular dysfunction and increase the risk of cardiovascular diseases, cerebrovascular diseases, and arterial diseases. Nevertheless, mechanisms underlying CIH-induced vascular dysfunction remain unclear. Herein, this study analyzed the role of aortic smooth muscle calciumactivated potassium (BK) channels in CIH-induced vascular dysfunction. CIH models were established in rats and rat aortic smooth muscle cells (RASMCs). Hemodynamic parameters such as mean blood pressure (MBP), diastolic blood pressure (DBP), and systolic blood pressure (SBP) were measured in rats, along with an assessment of vascular tone. NO and ET-1 levels were detected in rat serum, and the levels of ET-1, NO, eNOS, p-eNOS, oxidative stress markers (ROS and MDA), and inflammatory factors (IL-6 and TNF-α) were tested in aortic tissues. The Ca2+ concentration in RASMCs was investigated. The activity of BK channels (BKα and BKβ) was evaluated in aortic tissues and RASMCs. SBP, DBP, and MBP were elevated in CIH-treated rats, along with endothelial dysfunction, cellular edema and partial detachment of endothelial cells. BK channel activity was decreased in CIH-treated rats and RASMCs. BK channel activation increased eNOS, p-eNOS, and NO levels while lowering ET-1, ROS, MDA, IL-6, and TNF-α levels in CIH-treated rats. Ca2+ concentration increased in RASMCs following CIH modeling, which was reversed by BK channel activation. BK channel inhibitor (Iberiotoxin) exacerbated CIH-induced vascular disorders and endothelial dysfunction. BK channel activation promoted vasorelaxation while suppressing vascular endothelial dysfunction, inflammation, and oxidative stress, thereby indirectly improving CIH-induced vascular dysfunction.

Chronic intermittent hypoxia (CIH) can lead to vascular dysfunction and increase the risk of cardiovascular diseases, cerebrovascular diseases, and arterial diseases. Nevertheless, mechanisms underlying CIH-induced vascular dysfunction remain unclear. Herein, this study analyzed the role of aortic smooth muscle calciumactivated potassium (BK) channels in CIH-induced vascular dysfunction. CIH models were established in rats and rat aortic smooth muscle cells (RASMCs). Hemodynamic parameters such as mean blood pressure (MBP), diastolic blood pressure (DBP), and systolic blood pressure (SBP) were measured in rats, along with an assessment of vascular tone. NO and ET-1 levels were detected in rat serum, and the levels of ET-1, NO, eNOS, p-eNOS, oxidative stress markers (ROS and MDA), and inflammatory factors (IL-6 and TNF-α) were tested in aortic tissues. The Ca2+ concentration in RASMCs was investigated. The activity of BK channels (BKα and BKβ) was evaluated in aortic tissues and RASMCs. SBP, DBP, and MBP were elevated in CIH-treated rats, along with endothelial dysfunction, cellular edema and partial detachment of endothelial cells. BK channel activity was decreased in CIH-treated rats and RASMCs. BK channel activation increased eNOS, p-eNOS, and NO levels while lowering ET-1, ROS, MDA, IL-6, and TNF-α levels in CIH-treated rats. Ca2+ concentration increased in RASMCs following CIH modeling, which was reversed by BK channel activation. BK channel inhibitor (Iberiotoxin) exacerbated CIH-induced vascular disorders and endothelial dysfunction. BK channel activation promoted vasorelaxation while suppressing vascular endothelial dysfunction, inflammation, and oxidative stress, thereby indirectly improving CIH-induced vascular dysfunction.

Chronic intermittent hypoxia (CIH) can lead to vascular dysfunction and increase the risk of cardiovascular diseases, cerebrovascular diseases, and arterial diseases. Nevertheless, mechanisms underlying CIH-induced vascular dysfunction remain unclear. Herein, this study analyzed the role of aortic smooth muscle calciumactivated potassium (BK) channels in CIH-induced vascular dysfunction. CIH models were established in rats and rat aortic smooth muscle cells (RASMCs). Hemodynamic parameters such as mean blood pressure (MBP), diastolic blood pressure (DBP), and systolic blood pressure (SBP) were measured in rats, along with an assessment of vascular tone. NO and ET-1 levels were detected in rat serum, and the levels of ET-1, NO, eNOS, p-eNOS, oxidative stress markers (ROS and MDA), and inflammatory factors (IL-6 and TNF-α) were tested in aortic tissues. The Ca2+ concentration in RASMCs was investigated. The activity of BK channels (BKα and BKβ) was evaluated in aortic tissues and RASMCs. SBP, DBP, and MBP were elevated in CIH-treated rats, along with endothelial dysfunction, cellular edema and partial detachment of endothelial cells. BK channel activity was decreased in CIH-treated rats and RASMCs. BK channel activation increased eNOS, p-eNOS, and NO levels while lowering ET-1, ROS, MDA, IL-6, and TNF-α levels in CIH-treated rats. Ca2+ concentration increased in RASMCs following CIH modeling, which was reversed by BK channel activation. BK channel inhibitor (Iberiotoxin) exacerbated CIH-induced vascular disorders and endothelial dysfunction. BK channel activation promoted vasorelaxation while suppressing vascular endothelial dysfunction, inflammation, and oxidative stress, thereby indirectly improving CIH-induced vascular dysfunction.

Chronic intermittent hypoxia (CIH) can lead to vascular dysfunction and increase the risk of cardiovascular diseases, cerebrovascular diseases, and arterial diseases. Nevertheless, mechanisms underlying CIH-induced vascular dysfunction remain unclear. Herein, this study analyzed the role of aortic smooth muscle calciumactivated potassium (BK) channels in CIH-induced vascular dysfunction. CIH models were established in rats and rat aortic smooth muscle cells (RASMCs). Hemodynamic parameters such as mean blood pressure (MBP), diastolic blood pressure (DBP), and systolic blood pressure (SBP) were measured in rats, along with an assessment of vascular tone. NO and ET-1 levels were detected in rat serum, and the levels of ET-1, NO, eNOS, p-eNOS, oxidative stress markers (ROS and MDA), and inflammatory factors (IL-6 and TNF-α) were tested in aortic tissues. The Ca2+ concentration in RASMCs was investigated. The activity of BK channels (BKα and BKβ) was evaluated in aortic tissues and RASMCs. SBP, DBP, and MBP were elevated in CIH-treated rats, along with endothelial dysfunction, cellular edema and partial detachment of endothelial cells. BK channel activity was decreased in CIH-treated rats and RASMCs. BK channel activation increased eNOS, p-eNOS, and NO levels while lowering ET-1, ROS, MDA, IL-6, and TNF-α levels in CIH-treated rats. Ca2+ concentration increased in RASMCs following CIH modeling, which was reversed by BK channel activation. BK channel inhibitor (Iberiotoxin) exacerbated CIH-induced vascular disorders and endothelial dysfunction. BK channel activation promoted vasorelaxation while suppressing vascular endothelial dysfunction, inflammation, and oxidative stress, thereby indirectly improving CIH-induced vascular dysfunction.

OBJECTIVES: The prevalence of carbapenem-resistant Enterobacterales (CRE) presents a significant challenge in clinical anti-infective treatment. This study aims to investigate drug resistance and the molecular epidemiological characteristics of CRE in our area. Additionally, we seek to evaluate practicality of utilizing carbapenemase inhibitor enhancement test in clinical laboratory. METHODS: Non-repeated CREs isolated from clinical specimens at Xiangya Hospital, Central South University, were collected. Minimum inhibitory concentration (MIC) combined with Kirby-Bauer (KB) assay was used to detect the drug susceptibility of the strains, and 13 carbapenemase-producing genes were detected by PCR. The phenotype of 126 strains of carbapenemase-producing Enterobacterales identified by PCR was detected by the carbapenemase inhibitor enhancement test to understand the agreement between the method and the gold standard PCR results. RESULTS: Among 704 CRE strains examined, we observed significant drug resistance in 501 strains dentified as carbapenemase-producing Enterobacterales (CPE). Klebsiella pneumoniae was the predominant CPE strain, followed by Enterobacter cloacae and Escherichia coli. A total of 9 carbapenemase types were detected, including Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), Verona integron- encoded metallo-β-lactamases (VIM), imipenemase (IMP), oxacillinase-48 (OXA-48), and rare imipenem-hydrolyzing β-lactamase (IMI), adelaide imipenemase (AIM), Bicêtre carbapenemase (BIC), and guiana extended-spectrum β-lactamase (GES). The detection rate of KPC serine carbapenemase was 61.7% (309/501). The carbapenemase inhibitor enhancement test exhibited a 100% consistency rate for the strains producing Class A serine carbapenemase and/or Class B metallo-β-lactamases. CONCLUSIONS CRE strains in Changsha, Hunan, China, are wide distribution and exhibit carbapenemase production. The main mechanism of carbapenem resistance in these bacterias is predominatly attributed to the production of KPC serine carbapenemase. The presence of GES and IMI genes carried by Enterobacterales has been detected for the first time in this region. The carbapenemase inhibitor enhancement test has been proven to be an accurate method for detecting CRE producing Class A serine carbapenemase and/or Class B metallo-β-lactamases. This method offers simpicity of operation and ease of results interpretation, making it weel-suited meeting the clinical microbiology laboratory's reguirements for the detection of serine carbapenemase and metallo-β-lactamases.
Humans ; Carbapenems/pharmacology* ; Molecular Epidemiology ; Bacterial Proteins/analysis* ; beta-Lactamases/analysis* ; Klebsiella pneumoniae/genetics* ; Escherichia coli ; Microbial Sensitivity Tests ; Serine ; Anti-Bacterial Agents/pharmacology*

Population aging increases the demand for human aging research and its clinical applications.Traditionally, the chronological age(CA), that is, the age based on the calendar, is used to describe the state of aging.However, the aging process and speed among individuals are not consistent and often show clear individual differences in biological aging.Therefore, CA cannot truly reflect people's conditions of body structure and function, has drawbacks leading to unreliable and wrong assessment, and is unable to accurately describe the human body's state of aging.In recent years, it has been proposed that the biological age(BA)should be used to more comprehensively and accurately describe the stage of human aging.Combining mathematical algorithms with a variety of biomarkers, predictive models can be constructed to quantify BA.These approaches have been increasingly appreciated for their improved accuracy and received further investigation.This article reviews the value of BA, currently commonly used calculation methods and their progress and prospects in healthy aging.

Objective:To study and explore the prevalence, characteristics, preliminary risk factors, as well as their relationship with nutritional scores in liver cirrhotic patient with chronic periodontitis.Methods:163 patients with liver cirrhosis who were hospitalized in the Hepatology Division, Department of Internal Medicine at Tianjin Third Central Hospital from June to September 2018 were enrolled as the case group, while the control group consisted 140 healthy individuals enrolled during the same period. Periodontal examination, biochemical examination and oral hygiene habits were investigated. The prevalence of periodontitis in the two groups was compared, and the risk factors of severe periodontitis were conducted by multivariate regression analysis.Results:The prevalence of chronic periodontitis was significantly higher in patients with liver cirrhosis than healthy control population, and the differences were statistically significant ( P < 0.05). The prevalence of severe periodontitis and full edentulous jaws was significantly higher in patients with liver cirrhosis than healthy control group, and the differences were statistically significant ( P < 0.05 and P < 0.001). Compared with the healthy control group, the depth of periodontal pocket and the degree of attachment loss were significantly increased in the liver cirrhosis group ( P < 0.001). Multivariate regression analysis showed that liver cirrhosis was the independent risk factors for both groups of patients with severe periodontitis (χ 2 = 11.046, P < 0.001). Univariate and multivariate regression analysis showed that toothbrushing frequency, nutritional risk score, prealbumin level and Child-Pugh grade were independent risk factors for occurrence of severe periodontitis in liver cirrhotic patient (χ 2 = 5.252, P = 0.022; χ 2 = 24.162, P < 0.001; χ 2 = 4.159, P = 0.041; χ 2 = 9.249, P = 0.002). Conclusion:The prevalence of periodontitis is significantly higher in patients with liver cirrhosis than healthy individuals, and liver cirrhosis is an independent risk factor for the occurrence of severe periodontitis. Toothbrushing frequency, nutritional risk score, prealbumin level and Child-Pugh grade are risk factors for severe periodontitis in patients with liver cirrhosis.