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Antisense oligonucleotides (ASOs) were the first modality to pioneer targeted gene knockdown in the treatment of amyotrophic lateral sclerosis (ALS) caused by mutant superoxide dismutase 1 (SOD1). RNA interference (RNAi) is another mechanism of gene silencing in which short interfering RNAs (siRNAs) effectively degrade complementary transcripts. However, delivery to extrahepatic tissues like the CNS has been a bottleneck in the clinical development of RNAi. Herein, we identify potent siRNA duplexes for the knockdown of human SOD1 in which medicinal chemistry and conjugation to an accessory oligonucleotide (ACO) enable activity in CNS tissues. Local delivery via intracerebroventricular or intrathecal injection into SOD1G93A mice delayed disease progression and extended animal survival with superior efficacy compared with an ASO resembling tofersen in sequence and chemistry. Treatment also prevented disease-related declines in motor function, including improvements in animal mobility, muscle strength, and coordination. The ACO itself does not target any specific complementary nucleic acid sequence; rather, it imparts benefits conducive to bioavailability and delivery through its chemistry. The complete conjugate (i.e., siRNA-ACO) represents a novel modality for delivery of duplex RNA (e.g., siRNA) to the CNS that is currently being tested in the clinic for treatment of ALS.

Anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) have demonstrated substantial effectiveness in individuals with advanced ALK-positive non-small cell lung cancer (NSCLC). However, the controversy over using ALK-TKIs for neoadjuvant therapy in ALK-positive NSCLC has not been fully explored. This case study describes the clinical progression of a patient initially diagnosed with unresectable stage III (cT1bN2M0) lung adenocarcinoma, who was later discovered to harbor an ALK mutation through next-generation sequencing. The patient underwent surgery to achieve a radical resection of the right upper lung lesion after neoadjuvant therapy with lorlatinib and a pathological complete response (pCR) was confirmed by pathological analysis. To our knowledge, it has never been reported that neoadjuvant therapy with lorlatinib resulted in pCR for an ALK-positive patient with stage III NSCLC who was initially unresectable. Therefore, our findings indicate that utilizing ALK-TKIs as neoadjuvant therapy could be considered a viable choice for ALK-positive NSCLC patients.

Farnesoid X receptor (FXR) is widely accepted as a promising target for various liver diseases; however, panels of ligands in drug development show limited clinical benefits, without a clear mechanism. Here, we reveal that acetylation initiates and orchestrates FXR nucleocytoplasmic shuttling and then enhances degradation by the cytosolic E3 ligase CHIP under conditions of liver injury, which represents the major culprit that limits the clinical benefits of FXR agonists against liver diseases. Upon inflammatory and apoptotic stimulation, enhanced FXR acetylation at K217, closed to the nuclear location signal, blocks its recognition by importin KPNA3, thereby preventing its nuclear import. Concomitantly, reduced phosphorylation at T442 within the nuclear export signals promotes its recognition by exportin CRM1, and thereby facilitating FXR export to the cytosol. Acetylation governs nucleocytoplasmic shuttling of FXR, resulting in enhanced cytosolic retention of FXR that is amenable to degradation by CHIP. SIRT1 activators reduce FXR acetylation and prevent its cytosolic degradation. More importantly, SIRT1 activators synergize with FXR agonists in combating acute and chronic liver injuries. In conclusion, these findings innovate a promising strategy to develop therapeutics against liver diseases by combining SIRT1 activators and FXR agonists.

Background: Non–small cell lung cancer (NSCLC) with TP53 mutations has a worse prognosis. It was generally more resistant to chemotherapy and radiation. Our aim was to investigate the correlation between the TP53 co-mutated gene and clinical features, and prognostic value in patients with NSCLC. Methods: Seventy-three patients with a diagnosis of NSCLC at our hospital were recruited. They were divided into the TP53 mutation status (minor) ( TP53 MU) and TP53 wild-type (major) ( TP53 WT) groups according to their clinical characteristics after their mutation data and clinical information were collected. Serum markers were compared between groups using Mann-Whitney U test. Other clinical factors were compared between groups using χ2 test and Fisher exact test. The log-rank test was used to compare survival curves. Results: Of the 73 patients with NSCLC, 37 (50.68%) were found to carry TP53 mutation. TP53 MU and TP53 WT groups (n = 36) showed a significant difference in the number of smokers, incidence of squamous cell carcinoma, EGFR mutation, and number of advanced patients (P

Ectopic adrenocorticotropic hormone syndrome (EAS) is a condition of hypercortisolism caused by non-pituitary tumors that secrete adrenocorticotropic hormone (ACTH). A rare occurrence of this syndrome is due to an ACTH-producing neuroendocrine tumor that originates from the gallbladder. One patient with severe hypokalemia and alkalosis was admitted to our hospital. Clinical presentations and radiographic findings confirmed the diagnosis of an aggressive ACTH-producing gallbladder malignancy with multiple liver metastases. The diagnosis was verified by pathological and immunohistochemical measurements from a biopsy of the hepatic metastasis. A literature review identified only four similar cases had been reported. Despite being rare and having a poor prognosis, hormone-producing neuroendocrine tumors that derive from the gallbladder should be considered in the differential diagnosis of ectopic ACTH syndrome.

Abstract Objective Diabetes is a major cause of the progression of acute kidney injury (AKI). Few prediction models have been developed to predict the renal prognosis in diabetic patients with AKI so far. The aim of this study was to develop and validate a predictive model to identify high-risk individuals with non-recovery of renal function at 90 days in diabetic patients with AKI. Methods Demographic data and related laboratory indicators of diabetic patients with AKI in the First Affiliated Hospital of Guangxi Medical University from January 31, 2012 to January 31, 2022 were retrospectively analysed, and patients were followed up to 90 days after AKI diagnosis. Based on the results of Logistic regression, a model predicting the risk of non-recovery of renal function at 90 days in diabetic patients with AKI was developed and internal validated. Consistency index (C-index), calibration curve, and decision curve analysis were used to evaluate the differentiation, accuracy, and clinical utility of the prediction model, respectively. Results A total of 916 diabetic patients with AKI were enrolled, with a male to female ratio of 2.14:1. The rate of non-recovery of renal function at 90 days was 66.8% (612/916). There were 641 in development cohort and 275 in validation cohort (ration of 7:3). In the development cohort, a prediction model was developed based on the results of Logistic regression analysis. The variables included in the model were: diabetes duration (OR = 1.022, 95% CI 1.012–1.032), hypertension (OR = 1.574, 95% CI 1.043–2.377), chronic kidney disease (OR = 2.241, 95% CI 1.399–3.591), platelet (OR = 0.997, 95% CI 0.995–1.000), 25-hydroxyvitamin D3 (OR = 0.966, 95% CI 0.956–0.976), postprandial blood glucose (OR = 1.104, 95% CI 1.032–1.181), discharged serum creatinine (OR = 1.003, 95% CI 1.001–1.005). The C-indices of the prediction model were 0.807 (95% CI 0.738–0.875) and 0.803 (95% CI 0.713–0.893) in the development and validation cohorts, respectively. The calibration curves were all close to the straight line with slope 1. The decision curve analysis showed that in a wide range of threshold probabilities. Conclusion A prediction model was developed to help predict short-term renal prognosis of diabetic patients with AKI, which has been verified to have good differentiation, calibration degree and clinical practicability.

When a short-circuit fault occurs in the power grid, induction motors in the distribution network will contribute to the short-circuit current. Accurate short-circuit current calculation of the motors requires detailed modeling of distribution network. This method is not suitable for large-scale power grid. In this paper, an equivalent modeling method of induction motor contribution to short-circuit current is proposed, which is suitable for large-scale grid calculation and without changing the basic algorithm of short-circuit current or the basic data structure of electromechanical transient. An example of Central China Power Grid is shown, and the accuracy of the proposed method is verified by actual fault inversion.

Summary: Background: Intratumor heterogeneity (ITH) has been associated with poor prognosis in advanced non-small cell cancer (NSCLC) patients receiving immune checkpoint blockade (ICB) therapies. However, there is currently no evidence supporting an ITH metric as a predictor of clinical benefit from ICB. The unique advantages of blood make it a promising material for ITH estimation and relevant applications. This study aims to develop and validate a blood-based ITH index for predicting ICB response. Methods: NSCLC patients from the OAK and POPLAR clinical trials were used as the training cohorts for algorithm development. Survival analyses with overall survival (OS) and progression-free survival (PFS) as endpoints were performed to assess clinical response. The predictive value of bITH was subsequently validated with an independent cohort of 42 NSCLC patients treated with PD-1 blockade. Findings: bITH was significantly associated with the differential OS and PFS elicited by atezolizumab vs. docetaxel in both univariable and multivariable analyses in the OAK patients, suggesting bITH as an independent predictor for response to ICB. Moreover, compared with blood tumor mutation burden (bTMB), bITH enabled greater OS segregation and comparable PFS segregation, and obtained a predictive role regardless of bTMB status. Moreover, the association between bITH and PFS was validated with an independent cohort. Interpretation: Patients with low blood-based ITH metric manifest significant OS and PFS benefit from immunotherapy versus chemotherapy. Future research is awaited to corroborate our findings and to enrich the clinical utility of ITH. Funding: This study was supported by the National Natural Science Foundation of China (Nos. 81972718 and 81572321), the Natural Scientific Foundation of Zhejiang Province, China (No. LY19H160007), the Science and Technology Program for Health and Medicine in Zhejiang Province, China (No. 2021KY541), the Scientific Research Project, Science and Technology Department of Sichuan Province (No. 21YYJC1616), the Scientific Research Project, Sichuan Medical Association (No. S20002), Wu Jieping Medical Foundation (No. 320.6750), and 2018 Entrepreneurial Leading Talent of Guangzhou Huangpu District and Guangzhou Development District (No. 2022-L023).

Abstract Background Cough is a common complication after pulmonary surgery. Previous studies lacked a standard measure to assess postoperative cough-related quality of life and recovery. The purpose of this study is to compare postoperative cough regarding changes in health-related quality of life (HRQOL) and recovery trajectory between video-assisted thoracic surgery (VATS) lobectomy and sublobectomy (segmentectomy or wedge resection) for early-stage non-small cell lung cancer (NSCLC) patients via the Leicester Cough Questionnaire in Mandarin Chinese (LCQ-MC). Methods Overall, 156 patients with NSCLC underwent either VATS lobectomy or VATS sublobectomy; LCQ-MC was used to report the impact of postoperative cough on HRQOL for 6 months after surgery. The total scores of LCQ-MC range from 3 to 21, with a higher score indicating better health. Recovery from postoperative cough was defined as LCQ-MC scores returning to preoperative levels. The sensitivity of LCQ-MC to changes in postoperative cough recovery over time was evaluated via its ability to distinguish between surgery types. Results The VATS sublobectomy group reported significantly higher mean LCQ-MC scores at 1 month after surgery, but no significant difference postoperatively at 3 and 6 months after surgery, and returned to preoperative physical (69 vs. 99 days), psychological (67 vs. 99 days), social (50 vs. 98 days) and total (69 vs. 99 days) scores faster than the VATS lobectomy group (all p

The existing national standard requires that the contribution of induction motor load to short circuit current be considered, but the lack of induction motor modeling method suitable for power grid simulation calculation in China affects the popularization and application of national standard algorithm. Based on the simulation and calculation of Central China Power Grid, considering the distribution characteristics of medium and low voltage motors on the short-circuit current of high voltage bus, the equivalent method of 110 kV/220 kV bus conversion coefficient of motor contribution short-circuit current in distribution network is put forward.

IntroductionCysteine Protease Inhibitor 1 (CST1), a cystatin superfamily protein with the effect on the inhibition of cysteine protease activity, is reported to be involved in the development of many malignancies. MiR-942-5p has been demonstrated its regulatory effects on some malignancies. However, the roles of CST1 and miR-942-5p on esophageal squamous cell carcinoma (ESCC) are still unknown up to now.MethodsThe expression of CST1 in ESCC tissues was analyzed by TCGA database, immunohistochemistry, and RT-qPCR, respectively. Matrigel-uncoated or-coated transwell assay was used to determine the effect of CST1 on migration and invasion of ESCC cells. Regulatory effect of miR-942-5p on CST1 was detected by dual luciferase assay.ResultsCST1 was ectopically highly expressed in ESCC tissues, and had the effect on promoting the migration and invasion of ESCC cells by upregulating phosphorylated levels of key effectors including MEK1/2, ERK1/2, and CREB in MEK/ERK/CREB pathway. Dual-luciferase assay results showed that miR-942-5p had a regulatory effect on targeting CST1.ConclusionsCST1 plays a carcinogenic role on ESCC, and miR-942-5p can regulate the migration and invasion of ESCC cells by targeting CST1 to downregulate MEK/ERK/CREB signaling pathway, suggesting that miR-942-5p/CST1 axis might be a promising target for diagnosis and treatment of ESCC.

IntroductionThe impact of rib invasion on the non-small cell lung cancer (NSCLC) T classifications remains unclear. Our study aims to verify the impact of rib invasion on survival in patients with NSCLC through multicenter data from the Surveillance, Epidemiology, and End Results (SEER) database, and proposed a more appropriate pT for the forthcoming 9th tumor-node-metastasis (TNM) classifications.MethodThe SEER database was used to collect T2b-4N0-2M0 NSCLC cases from the period of 2010-2015 according to the 7th TNM classification system. Subsequently, the T classification was restaged according to the 8th TNM classification system based on the following codes: tumor size and tumor extension. Cases with T1-2 disease and incomplete clinicopathological information were excluded. Finally, 6479 T3 and T4 NSCLC patients were included in the present study and divided into a rib invasion group (n = 131), other pT3 group (n = 3835), and pT4 group (n = 2513). Propensity-score matching (PSM) balanced the known confounders of the prognosis, resulting in two sets (rib invasion group vs. other pT3 and pT4 group). Overall survival (OS) and cancer-specific survival (CSS) were investigated using Kaplan-Meier survival curves, and predictive factors of OS and CSS were assessed by Cox regression.ResultSurvival outcomes of the rib invasion group were worse than the other pT3 group (OS: 40.5% vs. 46.5%, p = 0.035; CSS: 49.2% vs. 55.5%, p = 0.047), but comparable to the pT4 group (OS: 40.5% vs. 39.9%, p = 0.876; CSS: 49.2% vs. 46.3%, p = 0.659). Similar results were obtained after PSM. Multivariate analyses for all patients revealed that age at diagnosis, gender, N stage, T stage, surgical modalities, and adjuvant therapy had a predictive value for the prognosis.ConclusionThe rib invasion group had a worse prognosis than the other pT3 groups, but was similar to the pT4 group. Our recommendation is to change the classification of rib invasion to pT4 disease and further validate this in the forthcoming 9th TNM classification.

Abstract Background Cytochrome P450 epoxygenase 2J2 (CYP2J2) metabolizes arachidonic acid to epoxyeicosatrienoic acids (EETs), which exert anti-inflammatory, anti-apoptotic, pro-proliferative, and antioxidant effects on the cardiovascular system. However, the role of CYP2J2 and EETs in pulmonary arterial hypertension (PAH) with lung ischemia–reperfusion injury (LIRI) remains unclear. In the present study, we investigated the effects of CYP2J2 overexpression and exogenous EETs on PAH with LIRI in vitro and in vivo. Methods CYP2J2 gene was transfected into rat lung tissue by recombinant adeno-associated virus (rAAV) to increase the levels of EETs in serum and lung tissue. A rat model of PAH with LIRI was constructed by intraperitoneal injection of monocrotaline (50 mg/kg) for 4 weeks, followed by clamping of the left pulmonary hilum for 1 h and reperfusion for 2 h. In addition, we established a cellular model of human pulmonary artery endothelial cells (HPAECs) with TNF-α combined with anoxia/reoxygenation (anoxia for 8 h and reoxygenation for 16 h) to determine the effect and mechanism of exogenous EETs. Results CYP2J2 overexpression significantly reduced the inflammatory response, oxidative stress and apoptosis associated with lung injury in PAH with LIRI. In addition, exogenous EETs suppressed inflammatory response and reduced intracellular reactive oxygen species (ROS) production and inhibited apoptosis in a tumor necrosis factor alpha (TNF-α) combined hypoxia-reoxygenation model of HPAECs. Our further studies revealed that the anti-inflammatory effects of CYP2J2 overexpression and EETs might be mediated by the activation of PPARγ; the anti-apoptotic effects might be mediated by the PI3K/AKT pathway. Conclusions CYP2J2 overexpression and EETs protect against PAH with LIRI via anti-inflammation, anti-oxidative stress and anti-apoptosis, suggesting that increased levels of EETs may be a promising strategy for the prevention and treatment of PAH with LIRI. Graphical Abstract

BackgroundConsidering the absence of apparent symptoms at the early stage, most patients with lung adenocarcinoma (LUAD) present at an advanced stage, leading to a dismal 5-year survival rate of

Background Programmed cell death protein 1 (PD-1) inhibitors are the first-line treatment for advanced non-small-cell lung cancer (NSCLC) patients. However, their efficacy in metastatic NSCLC patients remains controversial. Aim of the study The aim of our study was to evaluate the prognosis of advanced metastatic NSCLC patients treated with PD-1 inhibitors, and discuss the predictive effect of metastatic site on the long-term outcome. Methods The Embase, Ovid Medline, Cochrane Central Register of Controlled Trials, and PubMed databases were systematically screened up to February 10, 2020. Twenty-five eligible studies, involving 8,067 patients that assessed the impact of metastatic sites on survival outcome were incorporated in our study. Overall survival (OS) and progression-free survival (PFS) were described as hazard ratio (HR) with 95% confidence interval (CI). Results Among the advanced NSCLC patients, the median proportion of brain, liver, bone, and adrenal gland metastases were 21%, 17%, 35%, and 21%, respectively. Patients with metastases to the brain, liver, and bone had worse OS compared to patients without these metastases when treated with PD-1 inhibitors. Similarly, patients with metastasis to the brain and liver were more likely to progress when treated with PD-1 inhibitors. Besides, patients with multiple metastatic sites had worse PFS compared to patients with one metastatic site, while no significant difference was found in terms of OS. Conclusions Based on the findings of our systematic review and meta-analysis, metastatic sites were independent predictors of the survival outcome for advanced NSCLC patients treated with PD-1 inhibitors.

Abstract Background Metastasis and disease refractoriness remain as major challenges for non-small cell lung cancer (NSCLC) treatment and understanding the underlying molecular mechanisms is of scientific and clinical value. Therefore, in this study, we aimed to explore the effects of circMED13L_012 on the proliferation, migration, invasion and drug-resistance of NSCLC tumor cells. Methods In this study, we utilized clinical samples and NSCLC cell lines to explore the association between circMED13L_012 expressions and tumor cell metastasis and chemo resistance. CCK8 and transwell assay were conducted to explore the impact of circMED13_012 on NSCLC tumor proliferation and migrative capabilities. Dual-luciferase reporter gene assay was conducted to validate the circMED13L_012 interaction network. Results Our results demonstrated that circMED13L_012 exhibited significantly elevated average level in our clinical samples of NSCLC, compared with normal tissues. circMED13L_012 level was positively correlated with disease stage and metastatic status. Increased circMED13L_012 expression was associated with the enhanced migration, proliferation and chemo resistance of NSCLC cell lines. Further experiments indicated that circMED13L_012 promoted malignant behavior of NSCLC tumor cells by targeting MAPK8 through modulation miR-433-3p expression. Conclusions Our study for the first time demonstrated that circMED13L_012–miR-433-3p–MAPK8 axis played important role for NSCLC pathogenesis, which could be potential therapeutic target for the development of future NSCLC treatment.

FXR agonists have been investigated for the treatment of non-alcoholic steatohepatitis and liver fibrosis but the clinical efficacy is not optimal. Here the authors show that enhanced FXR SUMOylation in activated hepatic stellate cells reduces FXR signaling and that this can be rescued by SUMOylation inhibitors.

Objective. The study aimed to evaluate the value of bedside echocardiography (TTE) and lower extremity blood vessels in diagnosis and prognosis of acute pulmonary embolism (APE). Methods. A retrospective study was performed on 53 patients with APE diagnosed by CT pulmonary angiography (CTPA) (systemic systolic blood pressure was >90 mmHg at time of consultation, and systemic systolic blood pressure decreased by

Obeticholic acid (OCA), the first FXR-targeting drug, has been claimed effective in the therapy of liver fibrosis. However, recent clinical trials indicated that OCA might not be effective against liver fibrosis, possibly due to the lower dosage to reduce the incidence of the side-effect of pruritus. Here we propose a combinatory therapeutic strategy of OCA and apoptosis inhibitor for combating against liver fibrosis. CCl4-injured mice, d-galactosamine/LPS (GalN/LPS)-treated mice and cycloheximide/TNFα (CHX/TNFα)-treated HepG2 cells were employed to assess the effects of OCA, or together with IDN-6556, an apoptosis inhibitor. OCA treatment significantly inhibited hepatic stellate cell (HSC) activation/proliferation and prevented fibrosis. Elevated bile acid (BA) levels and hepatocyte apoptosis triggered the activation and proliferation of HSCs. OCA treatment reduced BA levels but could not inhibit hepatocellular apoptosis. An enhanced anti-fibrotic effect was observed when OCA was co-administrated with IDN-6556. Our study demonstrated that OCA inhibits HSCs activation/proliferation partially by regulating BA homeostasis and thereby inhibiting activation of HSCs. The findings in this study suggest that combined use of apoptosis inhibitor and OCA at lower dosage represents a novel therapeutic strategy for liver fibrosis. KEY WORDS: Obeticholic acid, Liver fibrosis, Bile acid, Hepatocellular apoptosis, IDN-6556, Farnesoid X receptor, Hepatic stellate cell

The deficit in speech sound production in some children with autism spectrum disorder (ASD) adds to their communication barriers. The 3-D virtual environments have been implemented to improve their communication abilities. However, there were no previous studies on the use of a 3-D virtual pronunciation tutor designed specifically to train pronunciation for children with ASD. To fill this research gap, the current study developed and evaluated a 3-D virtual tutor which served as a multimodal and real-data-driven speech production tutor to present both places and manners of Mandarin articulation. Using an eye-tracking technique (RED 5 Eye Tracker), Experiment 1 objectively investigated children's gauged attention distribution online while learning with our computer-assisted 3-D virtual tutor in comparison to a real human face (HF) tutor. Eye-tracking results indicated most participants showed more interests in the visual speech cues of the 3-D tutor, and paid some degree of absolute attention to the additional visual speech information of both articulatory movements and airflow changes. To further compare treatment outcomes, training performance was evaluated in Experiment 2 with the ASD learners divided into two groups, with one group learning from the HF tutor and the other from the 3-D tutor (HF group vs. 3-D group). Both groups showed improvement with the help of computer-based training in the post-intervention test based on the calculation of a 5-point Likert scale. However, the 3-D group showed much higher gains in producing Mandarin stop and affricate consonants, and apical vowels. We conclude that our 3-D virtual imitation intervention system provides an effective approach of audiovisual pronunciation training for children with ASD.

In order to understand the spatial distribution and ecological risk of heavy metal pollution in the sediments of the Three Gorges Reservoir, surface sediment samples in six typical tributaries and estuaries were analyzed. The heavy metal content in sediment was detected by ICP-MS (PE Elan DRC Ⅱ, PerkinElmer, Waltham, MA, USA) after digestion by mixed acid. The data were evaluated and analyzed using multiple methods, including the potential ecological risk index, the geoaccumulation index (Igeo), and cluster analysis. The results show that the tributary surface sediments were polluted by heavy metals to a certain extent. Cu, Zn, Pb, and Cr have been enriched in sediments in recent years. The results of Igeo show that the pollution degree is as follows: Pb > Cu > Zn > Cr > Cd > Ni > As > Hg. According to the potential ecological risk index, the grades of Yunyang, Xiaojiang, and Xinjin are all medium risk, and Cd has the highest contribution rate. Combined with field investigation data, cluster analysis, and correlation analysis, we conclude that Cu, Zn, and Cr are likely to come from agricultural chemical fertilizers and industrial sewage, while Pb mainly comes from the discharge of ship fuel.

The effects of stocking both filter-feeding fish and piscivorous fish were compared to the effects of stocking only filter-feeding fish for suppressing algal blooms and improving water quality in the impoundment area of Xiaojiang River where catfish were dominant. Using only filter-feeding fish for algal suppression and water quality control was more effective in the short-term, but use of both filter-feeding fish and piscivorous fish was better in the long-term. Obvious suppression of phytoplankton biomass (PB) only occurred during the first 14 days regardless of the fish stocked. Adding fish to the enclosure clearly alters phytoplankton community structure and introducing piscivorous fish to an enclosure stocked with filter-feeding fish changed the relative densities of dominant algae species. While stocking filter-feeding fish decreased total nitrogen concentration by removing phytoplankton, it did not effectively decrease total phosphorus and Chlorophyll a concentrations. Introducing piscivorous fish to the enclosure weakened the relationship between nutrients and phytoplankton. Results indicate that stocking only filter-feeding fish to improve water quality and suppress phytoplankton in an impoundment area is insufficient and other technologies and means should be applied simultaneously.

Reproductive allocation is a key process in the plant life cycle and aquatic plants exhibit great diversity in their reproductive systems. In the present study, we conduct a field investigation of three aquatic macrophytes: Stuckenia pectinata, Myriophyllum spicatum, and Potamogeton perfoliatus. Our results showed that widespread species, including S. pectinata and M. spicatum had greater plasticity in their allocation patterns in the form of increased sexual and asexual reproduction, and greater potential to set seeds and increase fitness in more eutrophic environments. P. perfoliatus also exhibited a capacity to adopt varied sexual reproductive strategies such as setting more offspring for the future, although only in clear conditions with low nutrient levels. Our results establish strategies and mechanisms of some species for tolerating and surviving in varied eutrophic lake conditions.

Abstract Photosystem II (PSII) catalyzes water oxidation and plastoquinone reduction by utilizing light energy. It is highly susceptible to photodamage under high-light conditions and the damaged PSII needs to be restored through a process known as the PSII repair cycle. The detailed molecular mechanism underlying the PSII repair process remains mostly elusive. Here, we report biochemical and structural features of a PSII-repair intermediate complex, likely arrested at an early stage of the PSII repair process in the green alga Chlamydomonas reinhardtii. The complex contains three protein factors associated with a damaged PSII core, namely Thylakoid Enriched Factor 14 (TEF14), Photosystem II Repair Factor 1 (PRF1), and Photosystem II Repair Factor 2 (PRF2). TEF14, PRF1 and PRF2 may facilitate the release of the manganese-stabilizing protein PsbO, disassembly of peripheral light-harvesting complexes from PSII and blockage of the QB site, respectively. Moreover, an α-tocopherol quinone molecule is located adjacent to the heme group of cytochrome b 559, potentially fulfilling a photoprotective role by preventing the generation of reactive oxygen species.

Abstract Photosynthetic organisms have evolved an essential energy-dependent quenching (qE) mechanism to avoid any lethal damages caused by high light. While the triggering mechanism of qE has been well addressed, candidates for quenchers are often debated. This lack of understanding is because of the tremendous difficulty in measuring intact cells using transient absorption techniques. Here, we have conducted femtosecond pump-probe measurements to characterize this photophysical reaction using micro-sized cell fractions of the green alga Chlamydomonas reinhardtii that retain physiological qE function. Combined with kinetic modeling, we have demonstrated the presence of an ultrafast excitation energy transfer (EET) pathway from Chlorophyll a (Chl a) Qy to a carotenoid (car) S1 state, therefore proposing that this carotenoid, likely lutein1, is the quencher. This work has provided an easy-to-prepare qE active thylakoid membrane system for advanced spectroscopic studies and demonstrated that the energy dissipation pathway of qE is evolutionarily conserved from green algae to land plants.