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Epimedium is widely used in traditional Chinese medicine and contains rich bioactive compounds. These compounds often have a methyl group at their 4'-OH position catalyzed by methyltransferases. Therefore, studying methyltransferases in Epimedium plants is of great significance. In this study, a flavonol methyltransferase, EpOMT4, was isolated from Epimedium pseudowushanense B.L. Guo. The recombinant enzyme regiospecifically transferred a methyl group to the 4'-OH position of 8-prenylkaempferol forming icaritin. The study demonstrates that enzymatic methylation of flavonoids in Epimedium plants holds significant potential and could provide a promising alternative method for the biosynthetic production of bioactive methylated prenylflavonoids.

Background: The ectopic superior parathyroid in the tracheoesophageal groove and paraesophageal region is rare. Hyperparathyroidism results when these glands become hyperfunctioning. That may necessitate surgical intervention in the form of parathyroidectomy, which requires a transsternal or transthoracic approach due to a deeply seated mediastinal parathyroid gland. Minimally invasive strategies have emerged recently as an alternative approach with less morbidity., Case Presentation: We present a case of the paraesophageal ectopic parathyroid gland in the superior posterior mediastinum, which was successfully treated with thoracoscopic resection., Conclusion: The current imaging tools improve the thoracoscopic management of mediastinal parathyroid glands. Video-assisted thoracoscopic surgery (VATS) can provide access and exposure to ectopic parathyroid adenoma with low morbidity and financial burden., (© 2024. The Author(s).)

Sesquiterpene synthases (STPSs) catalyze carbocation-driven cyclization reactions that can generate structurally diverse hydrocarbons. The deprotonation-reprotonation process is widely used in STPSs to promote structural diversity, largely attributable to the distinct regio/stereoselective reprotonations. However, the molecular basis for reprotonation regioselectivity remains largely understudied. Herein, we analyzed two highly paralogous STPSs, Artabotrys hexapetalus (-)-cyperene synthase (AhCS) and ishwarane synthase (AhIS), which catalyze reactions that are distinct from the regioselective protonation of germacrene A (GA), resulting in distinct skeletons of 5/5/6 tricyclic (-)-cyperene and 6/6/5/3 tetracyclic ishwarane, respectively. Isotopic labeling experiments demonstrated that these protonations occur at C3 and C6 of GA in AhCS and AhIS, respectively. The cryo-electron microscopy-derived AhCS complex structure provided the structural basis for identifying different key active site residues that may govern their functional disparity. The structure-guided mutagenesis of these residues resulted in successful functional interconversion between AhCS and AhIS, thus targeting the three active site residues [L311-S419-C458]/[M311-V419-A458] that may act as a C3/C6 reprotonation switch for GA. These findings facilitate the rational design or directed evolution of STPSs with structurally diverse skeletons., (© 2024 Wiley-VCH GmbH.)

Background: The use of adjuvant chemotherapy (ACT) in completely resected stage IB NSCLC is still controversial. This study aims to investigate the efficacy of ACT in pathological stage IB non-small cell lung cancer (NSCLC) with high risk factors., Methods: Patients with pT2aN0M0 stage IB NSCLC who underwent complete resection from 2013 to 2017 were retrospectively analyzed. Univariate and multivariable logistic regression analysis was used to assess potential independent risk factors associated with poor prognosis. To compare survival between patients who received ACT and those who did not., Results: In univariate and multivariate analyses, adenocarcinomas with predominantly micropapillary (MIP) and solid patterns (SOL), poorly differentiated squamous cell carcinoma (SCC), number of lymph nodes dissected less than 16 and tumor size larger than 36 mm were identified as high-risk factors for recurrence. In patients with high risk factors for recurrence, ACT resulted in significantly longer DFS (HR, 0.4689, 95%CI, 1.193-3.818; p = 0.0108) and OS (HR, 0.4696, 95%CI, 0.6578-6.895; p = 0.2073), although OS failed to reach statistically significance. After propensity score matching (PSM), 67 pairs of patients were 1:1 matched in the two groups and all baseline characteristics were well balanced. The results also demonstrated that ACT was associated with improved DFS (HR, 0.4776, 95%CI, 0.9779-4.484; p = 0.0440) while OS was not significantly different (92.5% vs. 91.0%; HR, 0.6167, 95%CI, 0.1688-2.038; p = 0.7458). In patients with low-risk factors for recurrence, DFS (HR, 0.4831, 95%CI, 0.03025-7.715; p = 0.6068) and OS (HR, 0.969, 95%CI, 0.08364-11.21; p = 0.9794) was not significantly different between those who received ACT and those who did not., Conclusion: In patients with completely resected stage IB NSCLC, ACT can improve survival in patients with high risk for recurrence. Further large multicenter studies are needed to confirm these findings., (© 2023. The Author(s).)

Background: There is consensus that postoperative adjuvant therapy is not recommended in patients with stage 1a non-small cell lung cancer (NSCLC). Meanwhile, it is still controversial whether postoperative adjuvant chemotherapy is recommended for NSCLC patients with T2aN0M0 (stage 1b). In some patients with stage 1b NSCLC without pleural invasion, tumor diameter was measured between 3 and 4 cm by preoperative imaging and less than 3 cm by postoperative pathology specimens. TNM staging in such patients is both radiologic stage 1b and pathologic stage 1a. Thoracic surgeons are often confused about whether such patients with NSCLC will require subsequent treatment and how the survival prognosis for this group of patients will be., Methods: All data of radiographic TNM stage 1b patients who underwent radical R0 resection at the department of thoracic surgery, the First Affiliated Hospital of Soochow University between January 2013 and July 2017 were retrieved, and 208 patients were finally included in the study. Clinical data, including imaging data, pathology data, were obtained by reviewing the patients' electronic medical records. Disease-free survival (DFS) and overall survival (OS) were obtained by telephone interview. Statistical analysis was performed using SPSS (SPSS 26.0 for windows, SPSS)., Results: A total of 208 patients were included in this study, 61 patients with T-stage migration (observation group) and 147 patients without T-stage migration (control group). There were significant statistical differences between the two groups in terms of preoperative FEV 1 /FVC and tumor diameter (specimens, CT and 3-dimensional measurements). Logistic regression results showed that lower FEV 1 /FVC and smaller CT measurements would make the patient's T stage more likely to migrate. Bland-Altman plots showed that tumor length measured by imaging was significantly higher than that measured by pathological specimens. Taking DFS as the outcome, the survival curve of the observation group was significantly better than that of the control group. Similarly, there was a significant difference in OS between the two groups., Conclusions: For NSCLC patients whose preoperative imaging evaluation was stage 1b (tumor diameter more than 3 cm, no main bronchus, pleura, no atelectasis), the presence of lung tissue with smaller tumor diameter and/or higher air content may indicate that the postoperative pathological staging may be changed to stage 1a (tumor diameter less than 3 cm). These patients had better survival prognosis than those who did not undergo TNM stage change and were diagnosed with stage 1b non-small cell lung cancer before and after surgery., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Postoperative patients with lung cancer mostly experience different degrees of dyspnea and decreased activity tolerance, and these symptoms all significantly affect postoperative quality of life. The concept of pulmonary rehabilitation applicable to patients with chronic respiratory diseases is also applicable to patients with postoperative lung cancer. The current application of postoperative pulmonary rehabilitation for lung cancer is inconsistent, and reliable guidelines are lacking. The purpose of this study was to further verify the efficacy and feasibility of postoperative pulmonary rehabilitation for lung cancer patients, and to find a suitable local pulmonary rehabilitation program for postoperative patients with lung cancer that is clinically promoted in our department through this study., Methods: We collected the clinical data of patients undergoing video-assisted thoracoscopic surgery (VATS) wedge resection or lobectomy. The patients were divided into rehabilitation group (using three-ball breathing apparatus after discharge) and control group (routine follow-up after discharge) according to whether the patients were trained with three-ball breathing apparatus after operation. The detailed method using three-ball apparatus is as follows. To begin with, patients are required to put themselves in a comfortable position. Then, after the three-ball breathing apparatus put on the same plane of their eyes, patients hold the tube in their mouth closely and control their breath slowly. When patients inhale to their largest extent, the balls will rise up accordingly. Then they exhale. The evaluation results of pulmonary function, activity tolerance, anxiety scores and others were collected. All data was gathered at the First Affiliated Hospital of Soochow University. The effects of pulmonary rehabilitation training on wedge resection and lobectomy were compared., Results: A total of 210 patients were included in this study, including 126 patients with VATS wedge resection and 84 patients with VATS lobectomies. No discrepancy was noticed when FEV 1 loss between two groups were compared in the wedge resection patients, and the same results were also shown in patients undergoing lobectomy (12.8% ± 2.0% vs. 12.7% ± 1.9%, P = 0.84, wedge resection; 12.6% ± 2.9% vs. 12.1% ± 1.8%, P = 0.37, lobectomy). The loss of FVC in the control group was greater than that in the rehabilitation group for patients undergoing lobectomy (11.7% ± 5.2%, vs. 17.1% ± 5.6%, P < 0.001, lobectomy). No difference was found in the wedge resection patients between the control and rehabilitation groups (6.6% ± 2.8%, vs. 6.4% ± 3.2%, P = 0.76, lobectomy). Moreover, all patients showed no significant difference in 6MWD regardless of surgical procedure and with or without breathing exercises at T3 (392.6 ± 50.6 m, rehabilitation group vs. 394.0 ± 46.6 m, control group. P = 0.87, wedge resection; 381.3 ± 38.9 m, rehabilitation group vs. 369.1 ± 49.3 m, control group. P = 0.21, lobectomy)., Conclusions: For patients after thoracoscopic pulmonary wedge resection, the use of three-ball apparatus did not significantly improve postoperative pulmonary function and activity tolerance, dyspnea, and anxiety symptoms. In patients after thoracoscopic lobectomy, respiratory trainers were able to improve postoperative lung function but were unable to significantly improve dyspnea and anxiety symptoms. There was a significant benefit for the use of three-ball apparatus in patients after thoracoscopic lobectomy, whereas there was no significant benefit for the use of respiratory trainers after wedge resection. Registry: Medical Ethics Committee of the First Affiliated Hospital of Soochow University., Registration Number: no. 2022455., (© 2023. The Author(s).)

Anhydroicaritin ( 1a ), baohuoside ( 1b ) and icariin ( 1c ) were recognized as major pharmacologically active ingredients of Epimedium plants. Their primary means of acquisition were chemical isolation from plants. However, it suffers from low yield, environmental pollution and shortage of plants. Herein, to remedy these problems, biosynthesis was explored to obtain the three active ingredients. Fortunately, with SfFPT as 8-prenyltransferase, EpPF3RT and Ep7GT as glycosyltransferases, kaempferide ( 1 ) was transferred to 1a , 1b and 1c enzymatically. Thus, we report the details of this method. This approach represents a promising environmental friendly alternative for the production of these compounds from an abundant analogue.

Background: In the treatment of peripheral early-staged lung cancer and benign lesions, segmentectomy and wedge resection are both reliable treatment methods. It is debatable that how much pulmonary function will be lost after different sublobar resection in the treatment of early-staged deep-located peripheral NSCLC (non-small cell lung cancer). The purpose of this study was to explore postoperative pulmonary function changes of sublobar resection in enrolled patients with non-subpleural peripheral nodules., Methods: We collected clinical data of patients undergoing VATS (video-assisted thoracoscopic surgery) segmentectomy or wedge resection for single nodule. These nodules were confirmed as peripheral non-subpleural nodules by preoperative 3D imaging. Patients were divided into two groups according to the operation procedure. Demographic characteristics, pulmonary function, postoperative outcomes, and others were collected. All data was gathered at the First Affiliated Hospital of Soochow University. Outcomes after wedge resection were compared with those after segmentectomy resection., Results: A total of 88 patients were included in this study, including 46 patients with VATS wedge resection and 42 patients with VATS segmentectomy. No difference was detected when comparing FEV 1 (forced expiratory volume in 1 s) loss between these two groups (17.6 ± 2.1%, wedge resection vs. 19.4 ± 5.4%, segmentectomy, P = 0.176). FVC (forced vital capacity) loss (8.7 ± 2.3%, wedge resection vs. 17.1 ± 2.2%, segmentectomy, P < 0.001) and MVV (maximum ventilatory volume) loss (11.5 ± 3.1%, wedge resection vs. 20.6 ± 7.8%, segmentectomy, P < 0.001) in segmentectomy group was significantly higher than those in wedge resection group. Discrepancies were investigated when comparing duration of surgery (70 ± 22 min, wedge resection vs. 111 ± 52 min, segmentectomy, P = 0.0002), postoperative drainage (85 ± 45 mL, wedge resection vs. 287 ± 672 mL, segmentectomy, P = 0.0123), and treatment hospitalization expenses [35148 ± 889CNY, wedge resection vs. 52,502 (38,276-57,772) CNY, segmentectomy, P < 0.0002]. No significant difference was found between air leak time (1.7 ± 0.7 days, wedge resection vs. 2.5 ± 1.7 days, segmentectomy, P = 0.062) and hospitalization time (2.7 ± 0.7 days, wedge resection vs. 3.5 ± 1.7 days, segmentectomy, P = 0.051)., Conclusions: For patients with peripheral non-subpleural nodules, we observed that patients who underwent wedge resection had less lung function loss than those who underwent segmentectomy when their lung function was reviewed at the 6th month after surgery. Patients undergoing wedge resection had partial advantages over patients with segmental resection in terms of hospitalization cost, operation time and postoperative drainage, etc. Wedge resection, as a treatment for peripheral non-subpleural pulmonary nodules, seemed to have more advantages in preserving patients' pulmonary function., (© 2022. The Author(s).)

Three new sesquiterpenoids trichoacorenols B-C and cyclonerodiol B (1-3), along with three known ones (4-6), were isolated from the mangrove plant endophytic fungus Trichoderma sp. Xy24 using various column chromatography techniques. The structures of these compounds were determined on the basis of extensive spectroscopic data analyses. Compounds 1, 2, 4, and 5 were four acorane sesquiterpenes, 3 and 6 were two monocyclic sesquiterpenediols. Compounds 3 and 5 exhibited significant neural anti-inflammatory activity by inhibiting LPS-induced NO production in BV2 cells with the inhibitory rates of 75.0% and 39.2% at 0.1 μM, respectively, which are more potent than curcumin, a positive control with the inhibitory rate of 21.1% at 0.1 μM.

Two new flavonoids (1 and 2), along with 14 known ones (3-16), were isolated from the cultured cells of Glycyrrhiza uralensis. Most of them were prenylated flavonoids. Their structures were elucidated on the basis of spectroscopic data analysis. All compounds showed non-cytotoxicity against five human tumor cell lines. The results suggest that plant cultured cells can yield the secondary metabolites that have not been found in parent plant.