Biogeographic patterns of meio- and micro-eukaryotic communities in dam-induced river-reservoir systems.

Although the Three Gorges Dam (TGD) is the world's largest hydroelectric dam, little is known about the spatial-temporal patterns and community assembly mechanisms of meio- and micro-eukaryotes and its two subtaxa (zooplankton and zoobenthos). This knowledge gap is particularly evident across various habitats and during different water-level periods, primarily arising from the annual regular dam regulation. To address this inquiry, we employed mitochondrial cytochrome c oxidase I (COI) gene-based environmental DNA (eDNA) metabarcoding technology to systematically analyze the biogeographic pattern of the three communities within the Three Gorges Reservoir (TGR). Our findings reveal distinct spatiotemporal characteristics and complementary patterns in the distribution of meio- and micro-eukaryotes. The three communities showed similar biogeographic patterns and assembly processes. Notably, the diversity of these three taxa gradually decreased along the river. Their communities were less shaped by stochastic processes, which gradually decreased along the longitudinal riverine-transition-lacustrine gradient. Hence, deterministic factors, such as seasonality, environmental, and spatial variables, along with species interactions, likely play a pivotal role in shaping these communities. Environmental factors primarily drive seasonal variations in these communities, while hydrological conditions, represented as spatial distance, predominantly influence spatial variations. These three communities followed the distance-decay pattern. In winter, compared to summer, both the decay and species interrelationships are more pronounced. Taken together, this study offers fresh insights into the composition and diversity patterns of meio- and micro-eukaryotes at the spatial-temporal level. It also uncovers the mechanisms behind community assembly in various environmental niches within the dam-induced river-reservoir systems. KEY POINTS: • Distribution and diversity of meio- and micro-eukaryotes exhibit distinct spatiotemporal patterns in the TGR. • Contribution of stochastic processes in community assembly gradually decreases along the river. • Deterministic factors and species interactions shape meio- and micro-eukaryotic community.

Supervised machine learning improves general applicability of eDNA metabarcoding for reservoir health monitoring.

Effective and standardized monitoring methodologies are vital for successful reservoir restoration and management. Environmental DNA (eDNA) metabarcoding sequencing offers a promising alternative for biomonitoring and can overcome many limitations of traditional morphological bioassessment. Recent attempts have even shown that supervised machine learning (SML) can directly infer biotic indices (BI) from eDNA metabarcoding data, bypassing the cumbersome calculation process of BI regardless of the taxonomic assignment of eDNA sequences. However, questions surrounding the general applicability of this taxonomy-free approach to monitoring reservoir health remain unclear, including model stability, feature selection, algorithm choice, and multi-season biomonitoring. Here, we firstly developed a novel biological integrity index (Me-IBI) that integrates multitrophic interactions and environmental information, based on taxonomy-assigned eDNA metabarcoding data. The Me-IBI can better distinguish the actual health status of the Three Gorges Reservoir (TGR) than physicochemical assessments and have a clear response to human activity. Then, taking this reliable Me-IBI as a supervised label, we compared the impact of selecting different numbers of features and SML algorithms on the stability and predictive performance of the model for predicting ecological conditions in multiple seasons using taxonomy-free eDNA metabarcoding data. We discovered that even with a small number of features, different SML algorithms can establish a stable model and obtain excellent predictive performance. Finally, we proposed a four-step strategy for standardized routine biomonitoring using SML tools. Our study firstly explores the general applicability problem of the taxonomy-free eDNA-SML approach and establishes a solid foundation for the large-scale and standardized biomonitoring application.

[Mechanism of Kaixin Powder prescriptions Buxin Decoction regulating PI3K/AKT signaling pathway to protect cardiovascular system: based on network pharmacology and experimental verification].

This study established the EA.hy926 cell myocardial ischemia model to compare the effects of two Kaixin Powder prescriptions, Buxin Decoction(BXD) and Dingzhi Pills(DZP), at three dosages(500, 200, and 100 µg·mL~(-1)) on the cell viability. Further, the public databases(TCMSP, TCMID, SYMMAP, and STRING) and the network pharmacology methods such as KEGG pathway enrichment were employed to decipher the possible molecular mechanism of BXD in exerting the cardioprotective effect. The pharmacological effect of BXD was evaluated with the rat model of isoprenaline(ISO)-induced myocardial ischemia. The expression levels of proteins involved in the phosphatidylinositol-3-kinase/protein kinase B(PI3 K/AKT) signaling pathway were measured by Western blot. BXD significantly increased the viability of EA.hy926 cells, showing the performance superior to DZP. The network pharmacology analysis predicted that BXD might exert cardiac protection through the PI3 K/AKT signaling pathway. The in vivo experiment on rats showed that BXD treatment significantly increased the cardiac ejection fraction(EF), fractional shortening(FS), diastolic left ventricular anterior wall(LVAWd), systolic left ventricular anterior wall(LVAWs), and diastolic left ventricular posterior wall(LVPWd), significantly decreased the beat per minute(BPM) and diastolic left ventricular internal diameter(LVIDd), and significantly improved the ST segment in the electrocardiogram. The pathological results(Masson staining) showed that BXD restored the myocardial thickness, decreased the collagen fiber, increased the muscle fiber, and reduced the infarct area to alleviate myocardial ischemia. Furthermore, BXD lowered the serum levels of inflammatory cytokines [tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6)] and myocardial enzymes [creatine kinase(CK) and lactate dehydrogenase(LDH)], increased the p-AKT/AKT ratio, up-regulated the protein levels of PI3 K, NF-κB, IKK-α, and Bcl-xl, and down-regulated that of the apoptotic protein Bax. In conclusion, BXD may exert cardiac protection effect by regulating the PI3 K/AKT signaling pathway.

Antidepressant Mechanism of Kaixinsan and Its Active Compounds Based on Upregulation of Antioxidant Thioredoxin.

Objectives: Kaixinsan (KXS), a traditional Chinese medicine formula, has been demonstrated to be effective in the treatment of depression. The present study applied a network pharmacology approach to dig out the new targets and mechanism of action of KXS and the active compounds in the treatment of depression. Methods: A network pharmacology approach based on public databases including ADME (absorption, distribution, metabolism, and excretion) evaluation, targets prediction, construction of networks, and molecule docking was used and validated the predicted new antioxidant targets and mechanisms in vitro. Based on an in vitro experiment, we verified the AKT1/Nrf2 pathway related to the thioredoxin (Trx) antioxidant mechanism. Results: The present study sorted 31 pharmacologically active components (kaempferol, ginsenoside rh2, ginsenoside rh4, stigmasterol, etc.) through the ADME algorithm from KXS. 136 potential molecular targets (AKT1, TNF, IL-1b, JUN, ESR1, NOS3, etc.) were predicted, of which there were 69 targets clearly related to depression. By compound-depression targets (C-DTs) network constructed, and protein-protein interaction networks (PPI) and KEGG pathway enrichment analyzed, we identified active compounds mediating depression-related targets to exert synergism on the predictive AKT1/Nrf2 pathway related to thioredoxin (Trx) antioxidant mechanism and other inflammation-related signaling pathways as well as neurotransmitter related signaling pathways. In the H2O2 induced SH-SY5Y cell damage model, this showed kaempferol and ginsenoside rh2 could enhance the activity of the Trx system by upregulation of AKT1 to activate Nrf2 in vitro. Conclusions: Taken together, by comprehensive systems pharmacology approach analysis, we found that KXS and its active compounds might exhibit antioxidant effects by stimulating the AKT1/Nrf2 pathway in the treatment of depression, which might shed new light on innovative therapeutic tactics for the new aspects for depression in traditional Chinese medicine in future studies.

Generation and application of a novel high-throughput detection based on RPA-CRISPR technique to sensitively monitor pathogenic microorganisms in the environment.

Staphylococcus aureus (S. aureus) is an important opportunistic human and animal pathogen that can cause a wide diversity of infections. Due to its environmental health risks, it is crucial to establish a time-saving, high-throughput, and highly sensitive technique for water quality surveillance. In this study, we developed a novel method to detect S. aureus in the water environment based on recombinase polymerase amplification (RPA) and CRISPR/Cas12a. This method utilizes isothermal amplification of nucleic acids and the trans-cleavage activity of the CRISPR/Cas12a system to generate fluorescence signals with a single-stranded DNA-fluorophore-quencher (ssDNA-FQ) reporter and a naked-eye detected lateral flow assay (LFA). Our RPA-CRISPR/Cas12a detection system can reduce the detection time to 35 min and enhance the high-throughput detection threshold to ≥5 copies of pathogen DNA, which is more sensitive than that of reported. Moreover, in the lower reaches of the Jialing River in Chongqing, China, 10 water samples from the mainstream and 7 ones from tributaries were successfully monitored S. aureus for less than 35 min using RPA-CRISPR/Cas12a detection system. Taken together, a novel high-throughput RPA-CRISPR detection was established and firstly applied for sensitively monitoring S. aureus in the natural water environment.

A novel WH-flags method based on reducing the acidity of molybdenum blue (MB) reaction and stabilization by EDTA for quickly detecting phosphorus in water.

There are two popular methods to measure reactive phosphorus (P) and total P: the GB11893-89 method in China and the 4500-P E method of the APHA in the US. However, their drawbacks, including long reaction time and narrow linear range, cannot satisfy the demand for modern analytic techniques. Here, based on reducing the acidity of the molybdenum blue (MB) reaction, and then stabilizing with EDTA, we have developed a novel method (WH-flags) to quickly measure both reactive P and total P. In the WH-flags method, "W" stands for Wide linear ranges (0-1.4 mg L-1 for reactive P & 0-1.8 mg L-1 for total P), "H" stands for High tolerance of different matrices (it can be adapted to a wide spectrum of samples), "f" is fast reaction time (2 min), "l" is long stabilization (40 min), "a" stands for appropriate recovery rates (89.1-103.2%), "g" is good precision and accuracy (CVs < 5% & Res < 5%) and "s" is small volume of samples (5-10 mL). The WH-flags method showed good linearity (R2 > 0.999). The WH-flags method should have broad application in monitoring P from different aqueous samples in the future.

Design, synthesis, and cytotoxic activity of novel 2H-imidazo[1,2-c]pyrazolo[3,4-e]pyrimidine derivatives.

In this study, a series of novel 2H-imidazo [1, 2-c] pyrazolo [3, 4-e] pyrimidine derivatives were designed, synthesized, and evaluated for their cytotoxic activities. The in vitro cell growth inhibition assay of the target compounds indicated their selectivity in inhibiting the proliferation of blood tumor cells (K562, U937) and solid tumor cells (HCT116, HT-29). Compound 9b exhibited the highest antiproliferative activities against K562 (IC50 = 5.597 µM) and U937 (IC50 = 3.512 µM). Based on the flow cytometry assays, compound 9b caused obvious induction of cell apoptosis and cell arrest at the S phase. Furthermore, western blot analysis revealed that compound 9b upregulated the expression of Bax, downregulated the levels of Bcl-2, and further activated caspase-3 in K562 cells. Therefore, compound 9b may be a potential anticancer agent that deserves further investigation.

Improved two-step optimization procedure used for designing an apodizer and Lyot stop in the Lyot coronagraph.

The Lyot coronagraph is a widely known astronomical instrument used to realize direct imaging of exoplanets, and designing transmittance of an apodizer and Lyot stop is the key to obtaining high-contrast imaging. In this paper a new (to the best of our knowledge) optimization procedure used to design the apodizer and Lyot stop in the Lyot coronagraph is proposed. A two-step optimization program is established to obtain the optimum transmittance of an apodizer and Lyot stop in a sequential way. By using the optimized apodizer and Lyot stop obtained through the proposed optimization procedure, both the stellar light and its diffraction light could be strongly suppressed. Numerical results indicate that such an optimized Lyot coronagraph can produce a 1e-10 extinction of the stellar light near the diffraction limit (1.59λ/D), and a high contrast imaging of 1e-07 could still be obtained even with the influence of light intensity of planets themselves. In addition, the two-step optimization procedure brings in two benefits. First, the two-step optimization is approximately 1000 times faster than the joint optimization method [J. Astron. Telesc. Instrum. Syst.2, 011012 (2016)2329-412410.1117/1.JATIS.2.1.011012]. Second, the optimum transmittance of the Lyot stop is binary, and therefore, the requirements of the production process are reduced, resulting in a greatly reduced cost. At the same time, the performance of the optimized Lyot coronagraph is also analyzed in the case of a monochromatic light incident and bandwidth light incident, and the effect of the diameter of the Lyot stop on the results is also discussed in this paper, which makes sense when designing a coronagraph.

Clinical Value of 99mTc-3PRGD2 SPECT/CT in Differentiated Thyroid Carcinoma with Negative 131I Whole-Body Scan and Elevated Thyroglobulin Level.

The aim of this study was to assess the usefulness of integrin imaging with 99mTc-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2) single photon emission computed tomography (SPECT)/computed tomography (CT) in detecting recurrent disease in patients with differentiated thyroid cancer (DTC), negative radioiodine whole-body scan (WBS) and high serum thyroglobulin (Tg). Thirty-seven patients who underwent total thyroidectomy followed by radioactive iodine ablation and had negative radioiodine WBS but elevated Tg levels were included. 99mTc-3PRGD2 SPECT/CT was performed 1 week after the negative diagnostic 131I WBS. Diagnostic performance indicators, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), for 99mTc-3PRGD2 SPECT/CT was calculated. The correlations between SPECT/CT results and clinic-pathological characteristics were examined. In 30 (81.1%) of the 37 patients, 99mTc-3PRGD2 SPECT/CT showed positive uptake. The sensitivity, specificity, PPV, and NPV of SPECT/CT to detect recurrent disease at follow-up were 96.6%, 75%, 93.3% and 85.7%, respectively. The sensitivity and PPV of SPECT/CT increased with increasing serum Tg levels. 99mTc-3PRGD2 SPECT/CT showed high sensitivity and PPV in the detection of recurrence among DTC patients with higher Tg levels and negative WBS, and the probability of obtaining a positive SPECT/CT result was related with the level of Tg.