Assessment of in-situ monitoring and tracking the vertical migration of cyanobacterial blooms using LISST-HAB.

Cyanobacterial harmful algal blooms (cyanoHABs) are becoming increasingly common in aquatic ecosystems worldwide. However, their heterogeneous distributions make it difficult to accurately estimate the total algae biomass and forecast the occurrence of surface cyanoHABs by using traditional monitoring methods. Although various optical instruments and remote sensing methods have been employed to monitor the dynamics of cyanoHABs at the water surface (i.e., bloom area, chlorophyll a), there is no effective in-situ methodology to monitor the dynamic change of cell density and integrated biovolume of algae throughout the water column. In this study, we propose a quantitative protocol for simultaneously measurements of multiple indicators (i.e., biovolume concentration, size distribution, cell density, and column-integrated biovolume) of cyanoHABs in water bodies by using the laser in-situ scattering and transmissometry (LISST) instrument. The accuracy of measurements of the biovolume and colony size of algae was evaluated and exceeded 95% when the water bloom was dominated by cyanobacteria. Furthermore, the cell density of cyanobacteria was well estimated based on total biovolume and mean cell volume measured by the instrument. Therefore, this methodology has the potential to be used for broader applications, not only to monitor the spatial and temporal distribution of algal biovolume concentration but also monitor the vertical distribution of cell density, biomass and their relationship with size distribution patterns. This provides new technical means for the monitoring and analysis of algae migration and early warning of the formation of cyanoHABs in lakes and reservoirs.

Chlorinated Oligomers with Regulate Planarity Achieving Superior Photovoltaic Performance.

Chlorine substitution, as an effective and low-cost modification strategy, has been applied in the design of donor and acceptor structures in organic solar cells. We synthesized a series of chlorinated dimerized acceptors to investigate the effect of chlorine numbers and locations on the photovoltaic properties. The results show that the planarity and morphology of DYV-γ-2Cl are greatly improved due to the appropriate numbers and positions of the substituted chlorine atoms. Therefore, the device based on PM6:DYV-γ-2Cl achieves a superior power conversion efficiency (PCE) of 15.54% among the three oligomeric acceptors with optimized molecular planarity and film morphology. This work demonstrated the positive effect of suitable numbers and the substitution positions of chlorines on the molecular arrangement and photovoltaic properties of the corresponding dimerized acceptors.

[Comparative study on excretion of Shuganning Injection and Scutellariae Radix extract in bile, urine, and feces of rats].

Scutellariae Radix extract is one of the important components in Shuganning Injection. In this study, an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method was established for simultaneously determining five components in Shuganning Injection and Scutellariae Radix extract in bile, urine, and feces of rats, so as to reveal the difference in the excretion process of Shuganning Injection and Scutellariae Radix extract in rats and explore the law of the excretion process of the five components in vivo before and after the compatibility of Scutellariae Radix. Rats were injected with Shuganning Injection and Scutellariae Radix extract(4.2 mL·kg~(-1)), respectively, and the excretion of baicalin, baicalein, oroxylin A, oroxylin A-7-O-ß-D-glucuronide, and scutellarin in bile, urine, and feces of rats in 24 h was observed. The results showed that except for baicalin, the other four index components were excreted as prototype components in a high proportion after intravenous injection of Shuganning Injection and Scutellariae Radix extract in rats, respectively. The excretion of each component was relatively high in urine and less in feces and bile. After the compatibility of Scutellariae Radix extract, the accumulative excretion of five index components in rats all decreased. Among them, the cumulative excretion of baicalein in bile, urine, and feces significantly decreased by 26.67%, 48.11%, and 31.01%. The cumulative excretion of baicalin in bile, urine, and feces decreased significantly by 70.69%, 19.43%, and 31.22%. The result showed that the five index components in Scutellariae Radix extract were mainly excreted by the kidneys, and other components in Shuganning Injection delayed the excretion process and prolonged the residence time. This study is of great significance for elucidating the compatibility rationality of Shuganning Injection.

Toxoplasma gondii suppresses proliferation and migration of breast cancer cells by regulating their transcriptome.

BACKGROUND: Breast cancer is the most common cancer in women worldwide. Toxoplasma gondii (T. gondii) has shown anticancer activity in breast cancer mouse models, and exerted beneficial effect on the survival of breast cancer patients, but the mechanism was unclear. METHODS: The effect of tachyzoites of T. gondii (RH and ME49 strains) on human breast cancer cells (MCF-7 and MDA-MB-231 cells) proliferation and migration was assessed using cell growth curve and wound healing assays. Dual RNA-seq was performed for T. gondii-infected and non-infected cells to determine the differentially expressed genes (DEGs). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction Networks analysis (PPI) were performed to explore the related signaling pathway and hub genes. Hub genes were validated using the Kaplan-Meier plotter database, and Pathogen Host Interaction (PHI-base) database. The results were verified by qRT-PCR. RESULTS: The tachyzoites of T. gondii decreased the expression of Ki67 and increased the expression of E-cadherin, resulting in suppressing the proliferation and migration of infected human breast cancer cells. The inhibitory effect of T. gondii on breast cancer cells showed a significant dose-response relationship. Compared with the control group, 2321 genes were transcriptionally regulated in MCF-7 cells infected with T. gondii, while 169 genes were transcriptionally regulated in infected MDA-MB-231 cells. Among these genes, 698 genes in infected MCF-7 cells and 67 genes in infected MDA-MB-231 cells were validated by the publicly available database. GO and KEGG analyses suggested that several pathways were involved in anticancer function of T. gondii, such as ribosome, interleukin-17 signaling, coronavirus disease pathway, and breast cancer pathway. BRCA1, MYC and IL-6 were identified as the top three hub genes in infected-breast cancer cells based on the connectivity of PPI analysis. In addition, after interacting with breast cancer cells, the expression of ROP16 and ROP18 in T. gondii increased, while the expression of crt, TgIST, GRA15, GRA24 and MIC13 decreased. CONCLUSIONS: T. gondii transcriptionally regulates several signaling pathways by altering the hub genes such as BRCA1, MYC and IL-6, which can inhibit the breast tumor growth and migration, hinting at a potential therapeutic strategy.

Salt reduction policy for out of home sectors: a supplementary document for the salt reduction strategy to prevent and control non-communicable diseases (NCDS) in Malaysia 2021-2025.

Cardiovascular diseases (CVDs) are the major cause of death among Malaysians. Reduction of salt intake in populations is one of the most cost-effective strategies in the prevention of CVDs. It is very feasible as it requires low cost for implementation and yet could produce a positive impact on health. Thus, salt reduction initiatives have been initiated since 2010, and two series of strategies have been launched. However, there are issues on its delivery and outreach to the target audience. Further, strategies targeting out of home sectors are yet to be emphasized. Our recent findings on the perceptions, barriers and enablers towards salt reduction among various stakeholders including policy-makers, food industries, food operators, consumers and schools showed that eating outside of the home contributed to high salt intake. Foods sold outside the home generally contain a high amount of salt. Thus, this supplementary document is being proposed to strengthen the Salt Reduction Strategy to Prevent and Control Non-communicable Diseases (NCDs) for Malaysia 2021-2025 by focussing on the strategy for the out-of-home sectors. In this supplementary document, the Monitoring, Awareness and Product (M-A-P) strategies being used by the Ministry of Health (MOH) are adopted with a defined outline of the plan of action and indicators to ensure that targets could be achieved. The strategies will involve inter-sectoral and multi-disciplinary approaches, including monitoring of salt intake and educating consumers, strengthening the current enforcement of legislation on salt/sodium labelling and promoting research on reformulation. Other strategies included in this supplementary document included reformulation through proposing maximum salt targets for 14 food categories. It is hoped that this supplementary document could strengthen the current the Salt Reduction Strategy to Prevent and Control NCDs for Malaysia 2021-2025 particularly, for the out-of-home sector, to achieve a reduction in mean salt intake of the population to 6.0 g per day by 2025.

The complex transcriptional regulation of heat stress response in maize.

As one of the most important food and feed crops worldwide, maize suffers much more tremendous damages under heat stress compared to other plants, which seriously inhibits plant growth and reduces productivity. To mitigate the heat-induced damages and adapt to high temperature environment, plants have evolved a series of molecular mechanisms to sense, respond and adapt high temperatures and heat stress. In this review, we summarized recent advances in molecular regulations underlying high temperature sensing, heat stress response and memory in maize, especially focusing on several important pathways and signals in high temperature sensing, and the complex transcriptional regulation of ZmHSFs (Heat Shock Factors) in heat stress response. In addition, we highlighted interactions between ZmHSFs and several epigenetic regulation factors in coordinately regulating heat stress response and memory. Finally, we laid out strategies to systematically elucidate the regulatory network of maize heat stress response, and discussed approaches for breeding future heat-tolerance maize.

Key role of hydrogen atoms in the preparation of sulfidated zero valent iron.

Sulfidated zero valent iron (ZVI) is a popular material for the reductive degradation of halogenated organic pollutants. Simple and economic synthesis of this material is highly demanded. In this study, sulfidated micro/nanostructured ZVI (MNZVI) particles were prepared by simply heating MNZVI particles and sulfur elements (S0) in pure water (50℃). The iron oxides on the surface of MNZVI particles were conducive to sulfidation reaction, indicating the formation of iron-sulphide minerals (FeSx) on the surface of MNZVI particles might not be from the direct reaction of Fe0 with S0 (Fe0 and S0 acted as reductant and oxidant, respectively). As an important reductant, hydrogen atom (H•) can be generated from the reduction of H+ by MNZVI particles and participate in the formation of FeSx. Quenching experiment and cyclic voltammetry analysis proved the existence of H• on the surface of MNZVI particles. DFT calculation found that the potential barrier of H•/S0 and Fe0/S0 were 1.91 and 7.24 eV, respectively, indicating that S0 would preferentially react with H• instead of Fe0. The formed H• can quickly react with S0 to generate hydrogen sulfide (H2S), which can further react with iron oxides such as α-Fe2O3 on the surface of MNZVI particles to form FeSx. In addition, the H2 partial pressure in water significantly affected the amount of H• generated, thereby affecting the sulfidation efficiency. For TCE degradation, as the sulfur loading of sulfidated MNZVI particles increased, the contribution of H• significantly decreased while the contribution of direct electron transfer increased. This study provided new insights into the synthesis mechanism of sulfidated ZVI in water.

Trivalent Phosphine-Catalyzed [4+1] Spiro-annulation Reaction Using Allenyl Imide and Methylene Cyclocompounds.

The trivalent phosphine-catalyzed [4+1] spiro-annulation reaction of allenyl imide and activated methylene cyclocompounds has been developed for the construction of various spiro-2-cyclopenten-1-ones. Oxindoles, 3-isochromanones, and 2-indanones are selected as 1C synthons to capture the in situ-generated bis-electrophilic α,ß-unsaturated ketenyl phosphonium intermediate, affording the corresponding monospiro- and bispiro-cyclopentenones in good to excellent yields (≤91%) under mild conditions. The primary attempt at asymmetric catalysis using monophosphine (R)-SITCP provides promising enantioselectivity (45% ee). A plausible reaction mechanism is also proposed.

Identification and functional analysis of circpdlim5a generated from pdlim5a gene splicing in the skeletal muscle of Japanese flounder (Paralichthys olivaceus).

Circular RNAs (circRNAs) are non-coding RNAs with endogenous regulatory functions, including regulating skeletal muscle development. However, its role in the development of skeletal muscle in Japanese flounder (Paralichthys olivaceus) is not clear. Therefore we screened a candidate circpdlim5a, which is derived from the gene pdlim5a, from the skeletal muscle transcriptome of Japanese flounder. We characterized circpdlim5a, which was more stable compared to the linear RNA pdlim5a. Distributional characterization of circpdlim5a showed that circpdlim5a was predominantly distributed in the nucleus and was highly expressed in the skeletal muscle of adult Japanese flounder (24 months). When we further studied the circpdlim5a function, we found that it inhibited the expression of proliferation and differentiation genes according to the over-expression experiment of circpdlim5a in myoblasts. We concluded that circpdlim5a may inhibit the proliferation and differentiation of myoblasts and thereby inhibit skeletal muscle development in Japanese flounder. This experiment provides information for the study of circRNAs by identifying circpdlim5a and exploring its function, and offers clues for molecular breeding from an epigenetic perspective.

GRK2 mediated degradation of SAV1 initiates hyperplasia of fibroblast-like synoviocytes in rheumatoid arthritis.

Hyperplasia and migration of fibroblast-like synoviocytes (FLSs) are the key drivers in the pathogenesis of rheumatoid arthritis (RA) and joint destruction. Abundant Yes-associated protein (YAP), which is a powerful transcription co-activator for proliferative genes, was observed in the nucleus of inflammatory FLSs with unknown upstream mechanisms. Using Gene Expression Omnibus database analysis, it was found that Salvador homolog-1 (SAV1), the pivotal negative regulator of the Hippo-YAP pathway, was slightly downregulated in RA synovium. However, SAV1 protein expression is extremely reduced. Subsequently, it was revealed that SAV1 is phosphorylated, ubiquitinated, and degraded by interacting with an important serine-threonine kinase, G protein-coupled receptor (GPCR) kinase 2 (GRK2), which was predominately upregulated by GPCR activation induced by ligands such as prostaglandin E2 (PGE2) in RA. This process further contributes to the decreased phosphorylation, nuclear translocation, and transcriptional potency of YAP, and leads to aberrant FLSs proliferation. Genetic depletion of GRK2 or inhibition of GRK2 by paroxetine rescued SAV1 expression and restored YAP phosphorylation and finally inhibited RA FLSs proliferation and migration. Similarly, paroxetine treatment effectively reduced the abnormal proliferation of FLSs in a rat model of collagen-induced arthritis which was accompanied by a significant improvement in clinical manifestations. Collectively, these results elucidate the significance of GRK2 regulation of Hippo-YAP signaling in FLSs proliferation and migration and the potential application of GRK2 inhibition in the treatment of FLSs-driven joint destruction in RA.

Seed and Soil: Consensus Molecular Subgroups (CMS) and Tumor Microenvironment Features Between Primary Lesions and Metastases of Different Organ Sites in Colorectal Cancer.

Purpose: Consensus molecular subtypes (CMS) are mainly used for biological interpretability and clinical stratification of colorectal cancer (CRC) in primary tumors (PT) but few in metastases. The heterogeneity of CMS distribution in metastases and the concordance of CMS between PT and metastases still lack sufficient study. We used CMS to classify CRC metastases and combine it with histopathological analysis to explore differences between PT and distant metastases. Patients and Methods: We obtained gene expression profiles for 942 PT samples from TCGA database (n=376) and GEO database (n=566), as well as 442 metastasis samples from GEO database. Among these, 765 PT samples and 442 metastasis samples were confidently identified with CMS using the "CMS classifier" and enrolled for analysis. Clinicopathological manifestation and CMS classification of CRC metastases were assessed with data from GEO, TCGA, and cBioPortal. Overall, 105 PT-metastasis pairs were extracted from 10 GEO datasets to assess CMS concordance. Tumor microenvironment (TME) features between PT and metastases were analyzed by immune-stromal infiltration with ESTIMATE and xCell algorithms. Finally, TME features were validated with multiplex immunohistochemistry in 27 PT-metastasis pairs we retrospectively collected. Results: Up to 64% of CRC metastases exhibited concordant CMS groups with matched PT, and the TME of metastases was similar to that of PT. For most common distant metastases, liver metastases were predominantly CMS2 and lung and peritoneal metastases were mainly CMS4, highlighting "seed" of tumor cells of different CMS groups had a preference for metastasis to "soil" of specific organs. Compared with PT, cancer-associated fibroblasts (CAF) reduced in liver metastases, CD4+T cells and M2-like macrophages increased in lung metastases, and M2-like macrophages and CAF increased in peritoneal metastases. Conclusion: Our findings underscore the importance of CMS-guided specific organ monitoring and treatment post-primary tumor surgery for patients. Differences in immune-stromal infiltration among different metastases provide targeted therapeutic opportunities for metastatic CRC.

Novel PET Imaging Probe for Quantitative Detection of Senescence In Vivo.

Real-time detection of cellular senescence remains a clinical challenge. Here, we aimed to develop a positron emission tomography (PET) imaging probe targeting senescence-associated ß-galactosidase (SA-ß-Gal), the most widely used biomarker of cellular senescence, and investigate its performance for real-time in vivo quantitative detection of cellular senescence. A stable PET imaging agent [68Ga]Ga-BGal was obtained with a high labeling yield (90.0 ± 4.3%) and a radiochemical purity (>95%). [68Ga]Ga-BGal displayed high sensitivity and specificity for ß-Gal both in vitro and in vivo. The reaction and uptake of the probe correlated with the ß-Gal concentration and reaction time. In PET imaging, high ß-Gal-expressing CT26.CL25 tumors and doxorubicin-treated HeLa tumors showed high signals from [68Ga]Ga-BGal, while a low signal was observed in CT26.WT and untreated HeLa tumors. In summary, we showcased successful PET imaging of senescence in preclinical models using probe [68Ga]Ga-BGal. This finding holds the potential for translating senescence imaging into clinical applications.

Development and External Validation of Machine Learning Models for Diabetic Microvascular Complications: Cross-Sectional Study With Metabolites.

BACKGROUND: Diabetic kidney disease (DKD) and diabetic retinopathy (DR) are major diabetic microvascular complications, contributing significantly to morbidity, disability, and mortality worldwide. The kidney and the eye, having similar microvascular structures and physiological and pathogenic features, may experience similar metabolic changes in diabetes. OBJECTIVE: This study aimed to use machine learning (ML) methods integrated with metabolic data to identify biomarkers associated with DKD and DR in a multiethnic Asian population with diabetes, as well as to improve the performance of DKD and DR detection models beyond traditional risk factors. METHODS: We used ML algorithms (logistic regression [LR] with Least Absolute Shrinkage and Selection Operator and gradient-boosting decision tree) to analyze 2772 adults with diabetes from the Singapore Epidemiology of Eye Diseases study, a population-based cross-sectional study conducted in Singapore (2004-2011). From 220 circulating metabolites and 19 risk factors, we selected the most important variables associated with DKD (defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2) and DR (defined as an Early Treatment Diabetic Retinopathy Study severity level ≥20). DKD and DR detection models were developed based on the variable selection results and externally validated on a sample of 5843 participants with diabetes from the UK biobank (2007-2010). Machine-learned model performance (area under the receiver operating characteristic curve [AUC] with 95% CI, sensitivity, and specificity) was compared to that of traditional LR adjusted for age, sex, diabetes duration, hemoglobin A1c, systolic blood pressure, and BMI. RESULTS: Singapore Epidemiology of Eye Diseases participants had a median age of 61.7 (IQR 53.5-69.4) years, with 49.1% (1361/2772) being women, 20.2% (555/2753) having DKD, and 25.4% (685/2693) having DR. UK biobank participants had a median age of 61.0 (IQR 55.0-65.0) years, with 35.8% (2090/5843) being women, 6.7% (374/5570) having DKD, and 6.1% (355/5843) having DR. The ML algorithms identified diabetes duration, insulin usage, age, and tyrosine as the most important factors of both DKD and DR. DKD was additionally associated with cardiovascular disease history, antihypertensive medication use, and 3 metabolites (lactate, citrate, and cholesterol esters to total lipids ratio in intermediate-density lipoprotein), while DR was additionally associated with hemoglobin A1c, blood glucose, pulse pressure, and alanine. Machine-learned models for DKD and DR detection outperformed traditional LR models in both internal (AUC 0.838 vs 0.743 for DKD and 0.790 vs 0.764 for DR) and external validation (AUC 0.791 vs 0.691 for DKD and 0.778 vs 0.760 for DR). CONCLUSIONS: This study highlighted diabetes duration, insulin usage, age, and circulating tyrosine as important factors in detecting DKD and DR. The integration of ML with biomedical big data enables biomarker discovery and improves disease detection beyond traditional risk factors.

A new method for deep learning detection of defects in X-ray images of pressure vessel welds.

Given that defect detection in weld X-ray images is a critical aspect of pressure vessel manufacturing and inspection, accurate differentiation of the type, distribution, number, and area of defects in the images serves as the foundation for judging weld quality, and the segmentation method of defects in digital X-ray images is the core technology for differentiating defects. Based on the publicly available weld seam dataset GDX-ray, this paper proposes a complete technique for fault segmentation in X-ray pictures of pressure vessel welds. The key works are as follows: (1) To address the problem of a lack of defect samples and imbalanced distribution inside GDX-ray, a DA-DCGAN based on a two-channel attention mechanism is devised to increase sample data. (2) A convolutional block attention mechanism is incorporated into the coding layer to boost the accuracy of small-scale defect identification. The proposed MAU-Net defect semantic segmentation network uses multi-scale even convolution to enhance large-scale features. The proposed method can mask electrostatic interference and non-defect-class parts in the actual weld X-ray images, achieve an average segmentation accuracy of 84.75% for the GDX-ray dataset, segment and accurately rate the valid defects with a correct rating rate of 95%, and thus realize practical value in engineering.

Carboxymethyl cellulose stabilization induced changes in particle characteristics and dechlorination efficiency of sulfidated nanoscale zero-valent iron.

Polymer stabilization, exemplified by carboxymethyl cellulose (CMC), has demonstrated effectiveness in enhancing the transport of nanoscale zero-valent iron (nZVI). And, sulfidation is recognized for enhancing the reactivity and selectivity of nZVI in dechlorination processes. The influence of polymer stabilization on sulfidated nZVI (S-nZVI) with various sulfur precursors remains unclear. In this study, CMC-stabilized S-nZVI (CMC-S-nZVI) was synthesized using three distinct sulfur precursors (S2-, S2O42-, and S2O32-) through one-step approach. The antioxidant properties of CMC significantly elevated the concentration of reduced sulfur species (S2-) on CMC-S-nZVIs, marking a 3.1-7.0-fold increase compared to S-nZVIs. The rate of trichloroethylene degradation (km) by CMC-S-nZVIs was observed to be 2.2-9.0 times higher than that achieved by their non-stabilized counterparts. Among the three CMC-S-nZVIs, CMC-S-nZVINa2S exhibited the highest km. Interesting, while the electron efficiency of CMC-S-nZVIs surged by 7.9-12 times relative to nZVI, it experienced a reduction of 7.0-34% when compared with S-nZVIs. This phenomenon is attributed to the increased hydrophilicity of S-nZVI particles due to CMC stabilization, which inadvertently promotes the hydrogen evolution reaction (HER). In conclusion, the findings of this study underscores the impact of CMC stabilization on the properties and dechlorination performance of S-nZVI sulfidated using different sulfur precursors, offering guidance for engineering CMC-S-nZVIs with desirable properties for contaminated groundwater remediation.

Dimerized Acceptors with Conjugate-Break Linker Enable Highly Efficient and Mechanically Robust Organic Solar Cells.

Designing new acceptors is critical for intrinsically stretchable organic solar cells (IS-OSCs) with high efficiency and mechanical robustness. However, nearly all stretchable polymer acceptors exhibit limited efficiency and high-performance small molecular acceptors are very brittle. In this regard, we select thienylene-alkane-thienylene (TAT) as the conjugate-break linker and synthesize four dimerized acceptors by the regulation of connecting sites and halogen substitutions. It is found that the connecting sites and halogen substitutions considerably impact the overall electronic structures, aggregation behaviors, and charge transport properties. Benefiting from the optimization of the molecular structure, the dimerized acceptor exhibits rational phase separation within the blend films, which significantly facilitates exciton dissociation while effectively suppressing charge recombination processes. Consequently, FDY-m-TAT-based rigid OSCs render the highest power conversion efficiency (PCE) of 18.07 % among reported acceptors containing conjugate-break linker. Most importantly, FDY-m-TAT-based IS-OSCs achieve high PCE (14.29 %) and remarkable stretchability (crack-onset strain [COS]=18.23 %), significantly surpassing Y6-based counterpart (PCE=12.80 % and COS=8.50 %). To sum up, these findings demonstrate that dimerized acceptors containing conjugate-break linkers have immense potential in developing highly efficient and mechanically robust OSCs.

Integrated evaluation of the impact of water diversion on water quality index and phytoplankton assemblages of eutrophic lake: A case study of Yilong Lake.

Water diversion has been widely utilized to enhance lake water quality and mitigate cyanobacterial blooms. However, previous studies have mainly focused on investigating the effects of water diversion on water quality or aquatic ecological health. Consequently, there is limited research investigating the combined impact of water diversion on the water quality and the ecological health of eutrophic lakes, and whether the WQI and phytoplankton assemblages demonstrate similar patterns following water diversion. In this study, the effects of water diversion on the ecosystem health of eutrophic lakes were comprehensively evaluated based on the WQI indices and phytoplankton assemblages during the NWDP-21 and WDP-22. The results showed that the annual mean of WQI increased from 52.02 to 54.36 after water diversion, which improved the water quality of the lake, especially NH3-N and TN decreased by 58.6% and 15.2%, respectively. The phytoplankton assemblages changed significantly before and after water diversion, and we observed that the total biomass of phytoplankton decreased by 12.3% and phytoplankton diversity indices (Shannon-Wiener diversity, Pielou evenness, and Simpson index) increased by 8.6%-8.9% after water diversion, with an improvement in the connectivity and stability of the phytoplankton. Notably, enhanced adaptations of rare sub-communities for resource use in water diversion environments, and water diversion inhibited the dispersal ability of dominant functional groups, and the effects of hydrological disturbances on the structure of phytoplankton assemblage favored the ecological health of eutrophic lakes. VPA analysis further reveals that water diversion alters the drivers of phytoplankton functional group biomass and phytoplankton diversity. The results of the PLS-PM analysis clarify that water diversion indirectly impacts the total phytoplankton biomass and phytoplankton diversity primarily by modifying light availability. Significant correlations are observed between the dominant functional groups biomass and diversity indices of WQI. The trends in changes observed in water quality indices and phytoplankton following water diversion align with the evaluation of water ecological health. This study provides valuable guidance for the ecological management of the diversion project in Yilong Lake and serves as a reference for similar projects in other lakes.

On-Chip Fabrication-Tolerant Exceptional Points Based on Dual-Scatterer Engineering.

The intriguing and anomalous optical characteristics of exceptional points (EPs) in optical resonators have attracted significant attention. While EP-related phenomena have been observed by perturbing resonators with off-chip components, implementing EPs fully on-chip remains challenging due to their extreme susceptibility to fabrication errors. In this Letter, we propose a succinct and compact approach to reach EP in an on-chip integrated silicon microring resonator by manipulating the evolution of backscatterings with two nanocylinders of disparate diameters. The theoretical analysis unveils that the fabrication constraints could be significantly relieved by increasing the difference in diameters of the nanocylinders. The evolution from non-EP to EP is traced experimentally through the step-by-step tuning of the angular and radial positions of nanocylinders. The proposed method opens a pathway toward the on-chip high-density integration of non-Hermitian devices.

Time-resolved cryo-EM of G-protein activation by a GPCR.

G-protein-coupled receptors (GPCRs) activate heterotrimeric G proteins by stimulating guanine nucleotide exchange in the Gα subunit1. To visualize this mechanism, we developed a time-resolved cryo-EM approach that examines the progression of ensembles of pre-steady-state intermediates of a GPCR-G-protein complex. By monitoring the transitions of the stimulatory Gs protein in complex with the ß2-adrenergic receptor at short sequential time points after GTP addition, we identified the conformational trajectory underlying G-protein activation and functional dissociation from the receptor. Twenty structures generated from sequential overlapping particle subsets along this trajectory, compared to control structures, provide a high-resolution description of the order of main events driving G-protein activation in response to GTP binding. Structural changes propagate from the nucleotide-binding pocket and extend through the GTPase domain, enacting alterations to Gα switch regions and the α5 helix that weaken the G-protein-receptor interface. Molecular dynamics simulations with late structures in the cryo-EM trajectory support that enhanced ordering of GTP on closure of the α-helical domain against the nucleotide-bound Ras-homology domain correlates with α5 helix destabilization and eventual dissociation of the G protein from the GPCR. These findings also highlight the potential of time-resolved cryo-EM as a tool for mechanistic dissection of GPCR signalling events.