[Severity Differences and Mechanisms of Algal Blooms Among Sections in Pengxi River of the Three Gorges Reservoir].

Since the impoundment of the Three Gorges Dam, 50% of the first-order tributaries in the reservoir area have had frequent algal blooms but with variations regarding the geographical locations of the seriously bloomed sections and the scope of the latter being influenced by the mainstream. This study took the Pengxi River, a first-order tributary of the reservoir area, as an example in order to explore the difference in eutrophication among the river sections and the influence of the Yangtze River on its tributaries. During the spring bloom season of 2019, sampling was carried out in one-week intervals for a total duration of one month. Seven sampling sections (PX1-PX7) were set up from the confluence to upstream. According to the profiles of vertical water temperature and conductivity of each section, the influence scope and form of the backwater of the Yangtze River were inferred; in addition, severity differences and mechanisms of algal blooms among sections were explored through the comparison of the hydrology, water quality, and sediment nutrients among Gaoyang Lake (PX5), which has had serious algal blooms, and the upstream (PX6) and downstream (PX4) sections of PX5, which are both 4 km away from PX5. The results showed that during the sampling month, the average ρ(Chl-a) in the confluence area of the Pengxi River (PX1-PX4) and in the upstream (PX5-PX7) were in the range of 14.55-44.00 µg·L-1 and 42.66-175.40 µg·L-1, respectively. The ρ(Chl-a) of PX5 was up to 413.00 µg·L-1, which was significantly higher than that of other sections (P<0.05). Temperature and conductivity results showed that the backwater from Yangtze River flowed into the Pengxi River from the middle and bottom layers during the period from April to May. The confluence (PX1-PX4) sections were in the intersection area of the backwater from Yangtze River and the upstream of the Pengxi River; thus, the waterbody was unstable, which was not conducive to the formation of algal blooms. However, the upstream (PX5-PX7) sections were not directly affected by the backwater from Yangtze River, leading the nutrient exchange mainly vertically. Most averages of n(TN)/n(TP) and n(DTN)/n(DTP) of PX4-PX6 were all greater than 16, indicating a phosphorus-limited state. During sampling, the average sediment total phosphorus of PX5 was 91% of that in upstream PX6, which was only 4 km away, whereas the surface water total phosphorus of PX5 was 180% of that in PX6. The important reason for this phenomenon is that the water surface width of PX5 was 3.6-4.7 times that of PX6, indicating longer wind fetch in the former section. Owing to the mountainous landscape in the Three Gorges Reservoir (TGR) region where windy weather is rare, the disturbance effect of wind and waves on PX5 was stronger than that of PX6, and the nutrients released from the sediment at the PX5 section caused by wind and waves resupplied the surface water more easily, causing more serious algal blooms at PX5 than those at the remaining sections in the Pengxi River. The main causes of the algal blooms in the tributaries of the TGR area lied in the stability of water stratification and the supply of internal phosphorus. The stability of water stratification was mainly affected by the backwater from Yangtze River, and the supply of internal phosphorus in the algal bloom season was affected by the special water stratification phenomenon of the tributaries of TGR-the "surface density layers." The duration and degree of weather disturbance to the surface density layers can be used to predict the time and scale of algal blooms.

Promoted Spore Formation of Bacillus amyloliquefaciens fmbJ by its Secondary Metabolite Bacillomycin D Coordinated with Mn2.

In Bacillus, the spore formation process is associated with the synthesis and release of secondary metabolites. A large number of studies have been conducted to systematically elucidate the pathways and mechanisms of spore formation. However, there are no studies have explored the relationship between secondary metabolites and spores. In this study, we investigated the relationship between its secondary metabolite bacillomycin D (BD) and spores using the simpler dipicolonic acid fluorimetry assay for spore counting in Bacillus amyloliquefaciens fmbJ. Our results showed that BD could promote the spore formation of B. amyloliquefaciens fmbJ and had a synergistic effect with certain concentrations of Mn2+. When 15.6 mg/L of BD and 1 mM of Mn2+ were added, the number of fmbJ spores increased from 1.42 × 108 CFU/mL to 2.02 × 108 CFU/mL after 36 h of incubation. The expressions of spore formation (kinA, kinB, kinC, kinD, kinE and spo0A) and Mn-related genes (mntA, mntH, mneS, mneP) were studied by RT-PCR. The results indicated that BD and Mn2+ promoted the spore formation of fmbJ by stimulating the transcription of kinB, kinD and increasing the influence of spo0F-spo0A phosphorylation transmission. This study provided a new idea to improve the spore production of B. amyloliquefaciens and laid the foundation for its industrial production. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-022-01026-9.

Application of Scanning Magnetic Resonance Imaging in the Diagnosis of Prenatal Placental Implantation and Related Care.

In order to solve the problem of scanning magnetic resonance imaging in prenatal diagnosis, the application and research of placental implantation have been proposed. Placental implantation is a serious obstetric emergency, which refers to the abnormal attachment of placental villi caused by the dysplasia of decidual basal layer. A study from the United States showed that the incidence of placental implantation in pregnant women during delivery increased from 9.9/30000 to 11.6/20000 from 2006 to 2019, which increased the risk of prenatal or postpartum hemorrhage, hysterectomy, stillbirth, abdominal organ injury, and so on. Clinically, patients can show severe prenatal or postpartum hemorrhage, postpartum placental retention, uterine perforation, and secondary infection, which may seriously endanger the lives of pregnant mothers and fetuses. Placental implantation can also have no obvious symptoms before delivery, which leads to insufficient prenatal diagnosis. Gielchinsky retrospectively studied 410 patients with placental implantation and found that only 9 patients were detected by prenatal ultrasound or magnetic resonance imaging (MRI), and the detection rate was only 6.6%. It can be seen that if the accurate diagnosis of placental implantation can be made before prenatal or symptoms appear, clinical intervention treatment can be carried out in time to reduce the probability of hysterectomy and improve the examination means of patients' prerecovery. At present, studies at home and abroad suggest that it has good clinical application value and research prospect in the clinical diagnosis of placental implantation.

[River-Lake States in the Tributary of the Three Gorges Reservoir Area and Their Effects on the Phosphorus Content of Different Forms in the Sediment].

The unique operation mode of the Three Gorges Dam has determined that the tributaries of the Three Gorges Reservoir (TGR) are significantly different from natural rivers in terms of hydrodynamics. The aim of this study was to explore the dynamic changes of internal phosphorus in tributary sediments under special water transfer mechanisms in the reservoir area. In 2016, we conducted samplings eight times (January, March-August, and October, once a month) in the Gaoyang Lake, which is located in the middle section of the Pengxi River, the largest tributary in the northern bank of the TGR. Samples of the adjacent overlying (AOL) water and sediment were collected, and a series of analyses were carried out on the flow velocity, water depth, and alkaline phosphatase activity (APA) of sediments. The results indicated that the waterbody types of the Gaoyang Lake can be divided into two hydrological states:deep lakes before May and June and typical rivers from May and June until the Three Gorges Dam re-flooding in autumn. The concentration of dissolved phosphorus in the AOL water during the lake state was 42.48% higher than that in the river state, which was beneficial for the weakly bounded phosphorus (NH4Cl-P) in the sediment surface to be in an adsorption-releasing equilibrium state. At the beginning of the spring algal bloom, with the increase in water temperature and APA in the sediments, the content of potential mobile phosphorus (PMP) in the sediments increased; however, the stable-form phosphorus content decreased, showing a tendency of transformation between these two forms of phosphorus, which may be one of the available phosphorus sources for algal blooms. The stable-form phosphorus content in the sediments of the Gaoyang Lake accounted for approximately 81.79% of the total phosphorus content, its coefficient of variation was relatively small (2.90%-4.21%), and there was a significant trend of accumulation over time (P<0.05). The study revealed the transformation of different phosphorus forms in sediments and their relationship with the state shift of the waterbodies, and provided a reference to understand the internal phosphorus cycle in other tributaries of the TGR area or other reservoir tributaries under similar situations.

Discovery of new small-molecule cyclin-dependent kinase 6 inhibitors through computational approaches.

Excessive cell proliferation due to cell cycle disorders is one of the hallmarks of breast cancer. Cyclin-dependent kinases (CDKs), which are involved in the transition of the cell cycle from G1 phase to S phase by combining CDKs with cyclin, are considered promising targets with broad therapeutic potential based on their critical role in cell cycle regulation. Pharmacological evidence has shown that abnormal cell cycle due to the overexpression of CDK6 is responsible for the hyperproliferation of cancer cells. Blocking CDK6 expression inhibits tumour survival and growth. Therefore, CDK6 can be regarded as a potential target for anticancer therapeutics. Thus, small molecules that can be considered CDK inhibitors have been developed into promising anticancer drugs. In this study, combined structure-based and ligand-based in silicon models were created to identify new chemical entities against CDK6 with the appropriate pharmacokinetic properties. The database used to screen drug-like compounds in this thesis was based on the best E-pharmacophore hypothesis and the best ligand-based drug hypothesis. As a result, 147 common compounds were identified by further molecular docking. Surprisingly, the in vitro evaluation results of 20 of those compounds showed that the two had good CDK6 inhibitory effects. The best compound was subjected to kinase panel screening, followed by molecular dynamic simulations. The 50-ns MD studies revealed the pivotal role of VAL101 in the binding of inhibitors to CDK6. Overall, the identification of two new chemical entities with CDK6 inhibitory activity demonstrated the feasibility and potential of the new method.

Structure-activity relationships of Wee1 inhibitors: A review.

Wee1 kinase plays an important role in regulating G2/M checkpoint and S phase, and the inhibition of it will lead to mitotic catastrophe in cancer cells with p53 mutation or deletion. Therefore, the mechanism of Wee1 kinase in cancer treatment and the development of its inhibitors have become a research hotspot. However, although a variety of Wee1 inhibitors with different scaffolds and considerable activity have been successfully identified, so far no one has systematically summarized the structure-activity relationships (SARs) of Wee1 inhibitors. Previous reviews mainly focused on its mechanism and clinical application. To facilitate the rational design and development of Wee1 inhibitors in the future, this paper systematically summarizes its structural types, SARs and binding modes according to the Wee1 inhibitors reported in scientific journals, and also summarizes the regulatory effect of Wee1 kinase on cell cycle and the progress of its inhibitors in clinical application.

Development of selective mono or dual PROTAC degrader probe of CDK isoforms.

Cyclin-dependent kinase (CDK) family members are promising molecular targets in discovering potent inhibitors in disease settings, they function differentially. CDK2, CDK4 and CDK6, directly regulate the cell cycle, while CDK9 primarily modulates the transcription regulation. In discovering inhibitors of these CDKs, toxicity associated with off-target effect on other CDK homologs often posts as a clinical issue and hinders their further therapeutic development. To improve efficacy and reduce toxicity, here, using the Proteolysis Targeted Chimeras (PROTACs) approach, we design and further optimize small molecule degraders targeting multiple CDKs. We showed that heterobifunctional compound A9 selectively degraded CDK2. We also identified a dual-degrader, compound F3, which potently induced degradation of both CDK2 (DC50: 62 nM) and CDK9 (DC50: 33 nM). In human prostate cancer PC-3 cells, compound F3 potently inhibits cell proliferation by effectively blocking the cell cycle in S and G2/M phases. Our preliminary data suggests that PROTAC-oriented CDK2/9 degradation is potentially an effective therapeutic approach.