Gene replacement therapy in Bietti crystalline corneoretinal dystrophy: an open-label, single-arm, exploratory trial.

Bietti crystalline corneoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2, which results in blindness in the working-age population, and there is currently no available treatment. Here, we report the results of the first-in-human clinical trial (NCT04722107) of gene therapy for Bietti crystalline corneoretinal dystrophy, including 12 participants who were followed up for 180-365 days. This open-label, single-arm exploratory trial aimed to assess the safety and efficacy of a recombinant adeno-associated-virus-serotype-2/8 vector encoding the human CYP4V2 protein (rAAV2/8-hCYP4V2). Participants received a single unilateral subretinal injection of 7.5 × 1010 vector genomes of rAAV2/8-hCYP4V2. Overall, 73 treatment-emergent adverse events were reported, with the majority (98.6%) being of mild or moderate intensity and considered to be procedure- or corticosteroid-related; no treatment-related serious adverse events or local/systemic immune toxicities were observed. Compared with that measured at baseline, 77.8% of the treated eyes showed improvement in best-corrected visual acuity (BCVA) on day 180, with a mean ± standard deviation increase of 9.0 ± 10.8 letters in the 9 eyes analyzed (p = 0.021). By day 365, 80% of the treated eyes showed an increase in BCVA, with a mean increase of 11.0 ± 10.6 letters in the 5 eyes assessed (p = 0.125). Importantly, the patients' improvement observed using multifocal electroretinogram, microperimetry, and Visual Function Questionnaire-25 further supported the beneficial effects of the treatment. We conclude that the favorable safety profile and visual improvements identified in this trial encourage the continued development of rAAV2/8-hCYP4V2 (named ZVS101e).

Algicidal activity synchronized with nitrogen removal by actinomycetes: Algicidal mechanism, stress response of algal cells, denitrification performance, and indigenous bacterial community co-occurrence.

The harmful algal blooms (HABs) can damage the ecological equilibrium of aquatic ecosystems and threaten human health. The bio-degradation of algal by algicidal bacteria is an environmentally friendly and economical approach to control HABs. This study applied an aerobic denitrification synchronization algicidal strain Streptomyces sp. LJH-12-1 (L1) to control HABs. The cell-free filtrate of the strain L1 showed a great algolytic effect on bloom-forming cyanobacterium, Microcystis aeruginosa (M. aeruginosa). The optimal algicidal property of strain L1 was indirect light-dependent algicidal with an algicidal rate of 85.0%. The functional metabolism, light-trapping, light-transfer efficiency, the content of pigments, and inhibition of photosynthesis of M. aeruginosa decreased after the addition of the supernatant of the strain L1 due to oxidative stress. Moreover, 96.05% nitrate removal rate synchronized with algicidal activity was achieved with the strain L1. The relative abundance of N cycling functional genes significantly increased during the strain L1 effect on M. aeruginosa. The algicidal efficiency of the strain L1 in the raw water was 76.70% with nitrate removal efficiency of 81.4%. Overall, this study provides a novel route to apply bacterial strain with the property of denitrification coupled with algicidal activity in treating micro-polluted water bodies.

Network pharmacology analysis and clinical efficacy of the traditional Chinese medicine Bu-Shen-Jian-Pi. Part 3: Alleviation of hypoxia, muscle-wasting, and modulation of redox functions in amyotrophic lateral sclerosis.

OBJECTIVE: The aim of this clinical study is to obtain evidence for the clinical efficacy of Bu-Shen-Jian-Pi formula (BSJP), a traditional Chinese medicine, used for the treatment of amyotrophic lateral sclerosis, a relatively rare, progressive and usually fatal disease possibly associated with alterations in tissue redox status, hypoxia, and muscular injury. BACKGROUND: The active agents in BSJP formula† causing apoptosis, modulation of redox changes, and alterations in the immune status have been studied previously by us using cell cultures. The findings from these investigations have been incorporated into pharmacology databases employed in our analysis of BSJP using network pharmacology analysis/artifical intelligence. This information has been used here in the design of the investigation and to optimize evaluation of the clinical efficacy and usefulness of this herbal medicine, as far as possible using evidence-based medicine criteria. MATERIALS AND METHODS: The design of the study was a randomized multi-center, controlled clinical trial in 127 patients with confirmed diagnoses of amyotrophic lateral sclerosis. Patients and investigator were double-blinded. Clinical efficacy was determined using the Amyotrophic Lateral Sclerosis Symptom Score in Integrative Treatment Scale (ALS-SSIT) and the Amyotrophic Lateral Sclerosis Rating Scale-Revised (ALSFRS-R), together with tests of limb muscle strength using the manual muscle test (MMT), forced vital capacity (FVC), and clinical chemistry laboratory tests over a 20-week observation period. RESULTS: The scores of ALS-SSIT in the BSJP group increased significantly (22%) after treatment. The ALSFRS-R score in the BSJP group decreased significantly after treatment (19%). The rate of decrease in muscle function (MMT score) in most BSJP patients was lower than that in the control group, where the differences in the scores for the trapezius and triceps brachii were statistically significant compared to the control group. The fall in FVC in the BJSP group was significantly slower than in the control group. There were no marked differences observed in the frequency of side effects. Serum vitamin D3 levels in the BSJP group showed greater increases compared to the control group. CONCLUSION: BSJP treatment reduced the rate of progression of amyotrophic lateral sclerosis according to the ALS-SSITS and ALSFRS scores and significantly reduced the rate of deterioration in muscle function in the limbs of amyotrophic lateral sclerosis patients. The modes of action of BSJP in treating amyotrophic lateral sclerosis are probably diverse and multi targeted, some of which may involve regulation of serum vitamin D3 and alleviation of the impairments in liver and kidney function.

Different seasonal dynamics, ecological drivers, and assembly mechanisms of algae in southern and northern drinking water reservoirs.

The role of environmental factors on the community structure of algae has been intensively studied, but there are few analyses on the assembly mechanism of the algal community structure. Here, changes in the community structure of algae in different seasons, the effects of environmental variables on the algal community structure, and the assembly mechanism of the algal community structure in northern and southern reservoirs were investigated in this study. The study revealed that Bacillariophyta, Cyanophyta, and Chlorophyta were the predominant algal species in the reservoirs, with Bacillariophyta and Cyanophyta exhibiting seasonal outbreaks. Compared to the northern reservoirs, the algal diversity in the southern reservoirs was greater. The diversity and algal community structure could be significantly impacted by variations in water temperature and nitrogen level. According to the ecological model, the interaction among algal communities in reservoirs was primarily cooperation. The key taxa in the northern reservoirs was Aphanizomenon sp., while the outbreak in the southern reservoirs was Coelosphaerium sp. The community formation pattern of reservoirs was stochastic, with a higher degree of explanation observed in the southern reservoirs compared to the northern reservoirs. This study preliminarily explored the assembly mechanism of the algal community, providing a theoretical basis for the control of eutrophication in drinking water reservoirs.

Ecological evolution of algae in connected reservoirs under the influence of water transfer: Algal density, community structure, and assembly processes.

Reservoir connectivity provides a solution for regional water shortages. Understanding the water quality of reservoirs and the response of algal communities to water transfer could provide the basis for a long-term evolutionary model of reservoirs. In this study, a water-algal community model was established to study the effects of water transfer on water quality and algal communities in reservoirs. The results showed that water transfer significantly decreased total nitrogen and nitrate concentrations. However, the water transfer resulted in an increase in the CODMn concentration and conductivity in the receiving reservoir. Additionally, the algal density and chlorophyll-a (chl-a) concentration showed an increase with water transfer. Bacillariophyta, Cyanophyta, and Chlorophyta were the dominant algal phyllum in all three reservoirs. Water transfer induced the evolution of the algal community by driving changes in the chemical parameters of the receiving reservoir and led to more complex relationships within the algal community. The effects of stochastic processes on algal communities were also enhanced in the receiving reservoirs. These results provide specific information for water quality safety management and eutrophication prevention in connected reservoirs.

Performance of aerobic denitrifying fungal community for promoting nitrogen reduction and its application in drinking water reservoirs.

The effect of mix-cultured aerobic denitrifying microorganisms on the water remediation has been extensively explored, but little is known about the performance of mix-cultured low efficiency fungi on denitrification. In this study, two kinds of aerobic denitrifying fungi (Trichoderma afroharzianum H1 and Aspergillus niger C1) were isolated from reservoirs, improved the capacity by mix-cultured. The results showed a difference between northern and southern reservoirs, the dominants of genera were Cystobasidium and Acremonium. The removals of total nitrogen (TN) was 12.00%, 7.53% and 69.33% in Trichoderma afroharzianum H1, Aspergillus niger C1 and mix-cultured (C1 and H1) under the denitrification medium. The contents of ATP and electron transport system activity in mix-cultured amendment were increased by 42.54% and 67.52%, 1.72 and 2.91 times, respectively. Besides, the raw water experiment indicated that TN removals were 24.05%, 12.66% and 73.42% in Trichoderma afroharzianum H1, Aspergillus niger C1 and mix-cultured. The removals of dissolved organic carbon in mix-cultured were increased 35.02% and 50.46% compared to Trichoderma afroharzianum H1 and Aspergillus niger C1. Therefore, mix-cultured of two low efficiency aerobic denitrifying fungi has been considered as a novelty perspective for mitigation of drinking water source.

Aerobic Denitrification Promoting by Actinomycetes Coculture: Investigating Performance, Carbon Source Metabolic Characteristic, and Raw Water Restoration.

The coculture theory that promotes denitrification relies on effectively utilizing the resources of low-efficiency denitrification microbes. Here, the strains Streptomyces sp. PYX97 and Streptomyces sp. TSJ96 were isolated and showed lower denitrification capacity when cultured individually. However, the coculture of strains PYX97 and TSJ96 enhanced nitrogen removal (removed 96.40% of total nitrogen) and organic carbon reduction (removed 92.13% of dissolved organic carbon) under aerobic conditions. Nitrogen balance analysis indicated that coculturing enhanced the efficiency of nitrate converted into gaseous nitrogen reaching 70.42%. Meanwhile, the coculturing promoted the cell metabolism capacity and carbon source metabolic activity. The coculture strains PYX97 and TSJ96 thrived in conditions of C/N = 10, alkalescence, and 150 rpm shaking speed. The coculturing reduced total nitrogen and CODMn in the raw water treatment by 83.32 and 84.21%, respectively. During this treatment, the cell metabolic activity and cell density increased in the coculture strains PYX97 and TSJ96 reactor. Moreover, the coculture strains could utilize aromatic protein and soluble microbial products during aerobic denitrification processes in raw water treatment. This study suggests that coculturing inefficient actinomycete strains could be a promising approach for treating polluted water bodies.

Magnolol supplementation alleviates diquat-induced oxidative stress via PI3K-Akt in broiler chickens.

This experiment was conducted to investigate the effects of magnolol on the oxidative parameters and jejunum injury induced by diquat in broiler chickens. This test adopts a 2 × 2 factors design, a total of 288 one-day-old male AA broiler chicks randomly allocated to four groups, consisting of six replicates of 12 birds each, which was then denoted as CON group, diquat (DIQ) group (16 mg/kg BW diquat was injected into birds at the age of 21 days), magnolol (MAG) group (basic bird diet supplemented with 300 mg/kg magnolol), and MAG + DIQ group. At 21 days of age, broilers in the DIQ group and the MAG + DIQ group were intraperitoneally injected with 16 mg/kg BW diquat. Results showed that diet supplementing with MAG could alleviate the decrease of ADG to a certain extent after exposure to DIQ. Addition of magnolol to the diet alleviated the decrease of ADG during injection, antioxidant enzymes, and gene expression and increased the markers of oxidative damage induced by diquat induction. Magnolol supplement reversed the increase of apoptotic cells in the diquat-induced chicken jejunum. RNA sequencing showed that PI3K-Akt, calcium, and NF-kappa B signaling pathways were the main enrichment pathways between the DIQ group and the MAG + DIQ group. Our findings revealed that magnolol may improve antioxidant enzyme activity and expression of related genes through the PI3K-Akt pathway to alleviate oxidative stress.

Retrospective pharmacogenetic study of psoriasis highlights the role of KLK7 in tumour necrosis factor signalling.

BACKGROUND: Multiple treatment options are available for the management of psoriasis, but clinical response varies among individual patients and no biomarkers are available to facilitate treatment selection for improved patient outcomes. OBJECTIVES: To utilize retrospective data to conduct a pharmacogenetic study to explore the potential genetic pathways associated with drug response in the treatment of psoriasis. METHODS: We conducted a retrospective pharmacogenetic study using self-evaluated treatment response from 1942 genotyped patients with psoriasis. We examined 6 502 658 genetic markers to model their associations with response to six treatment options using linear regression, adjusting for cohort variables and demographic features. We further utilized an integrative approach incorporating epigenomics, transcriptomics and a longitudinal clinical cohort to provide biological implications for the topmost signals associated with drug response. RESULTS: Two novel markers were revealed to be associated with treatment response: rs1991820 (P = 1.30 × 10-6) for anti-tumour necrosis factor (TNF) biologics; and rs62264137 (P = 2.94 × 10-6) for methotrexate, which was also associated with cutaneous mRNA expression levels of two known psoriasis-related genes KLK7 (P = 1.0 × 10-12) and CD200 (P = 5.4 × 10-6). We demonstrated that KLK7 expression was increased in the psoriatic epidermis, as shown by immunohistochemistry, as well as single-cell RNA sequencing, and its responsiveness to anti-TNF treatment was highlighted. By inhibiting the expression of KLK7, we further illustrated that keratinocytes have decreased proinflammatory responses to TNF. CONCLUSIONS: Our study implicates the genetic regulation of cytokine responses in predicting clinical drug response and supports the association between pharmacogenetic loci and anti-TNF response, as shown here for KLK7.

Enhanced nitrogen removal of micropolluted source waterbodies using an iron activated carbon system with siliceous materials: Insights into metabolic activity, biodiversity, interactions of core genus and co-existence.

Aerobic denitrification technology can effectively abate the nitrogen pollution of water source reservoirs. In this study, 40% siliceous material was used as the carrier to replace the activated carbon in Fe/C material to enhance denitrification and purify water. The removal efficiency of new material for target pollutants were nitrate nitrogen (95.68%), total phosphorus (68.23%) and chemical oxygen demand (46.20%). Aerobic denitrification of water samples and anaerobic denitrification of sediments in three systems jointly assisted nitrogen removal. In a reactor with new material, diversity and richness of denitrifying bacterial communities were enhanced, and the symbiotic structure of aerobic denitrifying bacteria was more complex (Bacillus and Mycobacteria as the dominant bacteria); the microbial distribution better matched the Zif and Mandelbrot models. This system significantly increased the abundance of key enzymes in water samples. The new material effectively removed pollutants and represents a promising and innovative in-situ remediation method for reservoirs.

Activation of indigenous denitrifying bacteria and enhanced nitrogen removal via artificial mixing in a drinking water reservoir: Insights into gene abundance, community structure, and co-existence model.

Nitrogen pollution poses a severe threat to aquatic ecosystems and human health. This study investigated the use of water lifting aerators for in situ nitrogen reduction in a drinking water reservoir. The reservoir was thoroughly mixed and oxygenated after using water-lifting aerators for 42 days. The average total nitrogen concentration, nitrate nitrogen, and ammonium nitrogen-in all water layers-decreased significantly (P < 0.01), with a reduction efficiency of 35 ± 3%, 34 ± 2%, and 70 ± 6%, respectively. Other pollutants, including organic matter, phosphorus, iron, and manganese, were also effectively removed. Quantitative polymerase chain reactions indicated that bacterial nirS gene abundance was enhanced 26.34-fold. High-throughput sequencing, phylogenetic tree, and network analysis suggested that core indigenous nirS-type denitrifying bacteria, such as Dechloromonas, Simplicispira, Thauera, and Azospira, played vital roles in nitrogen and other pollutant removal processes. Furthermore, structural equation modeling revealed that nitrogen removal responded positively to WT, DO, and nirS gene abundance. Our findings provide a promising strategy for nitrogen removal in oligotrophic drinking water reservoirs with carbon deficiencies.

Occurrence, fate and potential health risks of antibiotic resistomes in a constructed wetlands-reservoir ecosystem for drinking water source improvement.

The development of effective and feasible engineering technologies to control the transmission of antibiotic resistance genes (ARGs) and pathogenic antibiotic-resistant bacteria (PARB) form drinking water sources is urgently needed for ensuring drinking water safety. In this study, metagenomic analysis was applied to systematically explore the full profiles, removal, and potential health risks of antibiotic resistomes in a large constructed wetlands-reservoir ecosystem (CWs-R) for drinking water source improvement. A total of 343 ARG subtypes belonging to 18 ARG types were identified from water and sediment samples in the CWs-R ecosystem, with an average abundance of 0.339 copies/cell, and bacitracin and multidrug resistance genes were the predominant ARG types in the water and sediment, respectively. The CWs-R ecosystem showed an excellent removal efficiency of ARGs and mobile genetic elements (MGEs) in water, with the total removal rate reaching 64.82 % and 77.09 %, respectively, among which the emergent plant zone and ecological storage unit played major roles. The metagenomic assembly tracked many mobile ARGs and opportunistic pathogens in the CWs-R ecosystem and identified 19 contigs as ARG-carrying pathogens, including Staphylococcus aureus, Salmonella enterica, Escherichia coli, and Klebsiella pneumonia. Overall, the CWs-R ecosystem has an important role in reducing the potential public health risks posed by antibiotic resistomes in drinking water sources but still cannot fully eliminate them. Therefore, we further classified water and sediment samples in the CWs-R ecosystem and identified potential ARGs and PARB indicators based on the metagenomic analysis results by considering the potential for horizontal transfer of ARGs to opportunistic pathogens. Taken together, this work demonstrates the CWs-R ecosystem as an economical and feasible engineering technology to reduce the dissemination of antibiotic resistomes in the drinking water source, provides useful information for monitoring and controlling antibiotic resistance in similar water sources, and ensures biosafety of drinking water.

MUC13 promotes the development of esophageal cancer by upregulating the expression of O-glycan process-related molecules.

BACKGROUND: Esophageal cancer is one of the most common malignant tumors in the world, which is characterized by poor prognosis, aggressiveness, and poor survival. Mucin 13 (MUC13) is a member of the membrane-bound mucin and located on chromosome 3q21.2 and consists of α and ß subunits. It has been found that MUC13 is overexpressed in a variety of tumor cells and acts a vital role in the invasiveness and malignant progression of several types of tumors. However, the role and regulatory mechanism of MUC13 in the progression of esophageal cancer remain unclear. METHODS: The expression level of MUC13 was detected in 15 esophageal cancer tissues and 15 pairs of adjacent nontumor tissues by immunohistochemistry (IHC). In addition, the expression of MUC13 mRNA level in human esophageal cancer cell lines (EC9706 and ECA109 and TE-1) was measured by qRT-PCR. In vitro, after silencing MUC13 with lentiviral interference technology, CCK8 assay, clone formation assay, and flow cytometry were applied to investigate the proliferation activity, clone formation ability and anti-apoptosis ability of EC9706 and ECA109 cells. The tumor xenograft growth assay was used to confirm the influence of MUC13 knockdown on the growth of esophageal tumors in vivo. The qRT-PCR assay and western blot experiments were taken to study the mechanism of MUC13 regulating the proproliferation and antiapoptotic of esophageal cancer. RESULTS: The results showed that MUC13 was overexpressed in esophageal cancer tissues and cell lines (EC9706 and ECA109 and TE-1), especially in EC9706 and ECA109 cells, but low expressed in human esophageal epithelial cell line (HEEC). Next, silencing MUC13 inhibits proliferation, blocks cell cycle progression, and promotes cell apoptosis in vitro, and restrains the growth of esophageal cancer tissues in vivo. Finally, MUC13 affects the proproliferation and antiapoptotic by regulating the expression of GLANT14, MUC3A, MUC1, MUC12, and MUC4 that closely related to O-glycan process. CONCLUSIONS: This study proved that MUC13 is an important molecule that regulates the O-glycan process and then affects the progress of esophageal cancer. MUC13 may be a novel therapeutic target for patients with esophageal cancer.

Temporal patterns of algae in different urban lakes and their correlations with environmental variables in Xi'an, China.

Urban lakes were critical in aquatic ecology environments, but how environmental factors affected the distribution and change characteristics of algal communities in urban lakes of Xi'an city was not clearly. Here, we investigated the algal community structure of six urban lakes in Xi'an and evaluated the effects of water quality parameters on algae. The results indicated that the significant differences on physicochemical parameters existed in different urban lakes. The maximum concentration of total phosphorus in urban lakes was (0.18 ± 0.01) mg/L and there was a phenomenon of phosphorus limitation. In addition, 51 genera of algae were identified and Chlorella sp. was the dominant algal species, which was affiliated with Chlorophyta. Network analysis elucidated that each lake had a unique algal community network and the positive correlation was dominant in the interaction between algae species, illustrating that mature microbial communities existed or occupied similar niches. Redundancy analysis illustrated that environmental factors explained 47.35% variance of algal species-water quality correlation collectively, indicating that water quality conditions had a significant influence on the temporal variations of algae. Structural equation model further verified that algal community structure was directly or indirectly regulated by different water quality conditions. Our study shows that temporal patterns of algal communities can reveal the dynamics and interactions of different urban ecosystem types, providing a theoretical basis for assessing eutrophication levels and for water quality management.

Pollutants reduction via artificial mixing in a drinking water reservoir: Insights into bacterial metabolic activity, biodiversity, interactions and co-existence of core genera.

Endogenous pollution due to long periods of hypolimnetic anoxia in stratified reservoirs has become a worldwide concern, which can threaten metabolic activity, biodiversity, water quality security, and ultimately human health. In the present study, an artificial mixing system applied in a drinking water reservoir was developed to reduce pollutants, and the biological mechanism involved was explored. After approximately 44 days of system operation, the reservoir content was completely mixed resulting in the disappearance of anoxic layers. Furthermore, the metabolic activity estimated by the Biolog-ECO microplate technique and biodiversity was enhanced. 16S rRNA gene sequencing indicated a great variability on the composition of bacterial communities. Co-occurrence network analysis showed that interactions among bacteria were significantly affected by the proposed mixing system. Bacteria exhibited a more mutualistic state and >10 keystone genera were identified. Pollutants, including nitrogen, phosphorus, organic matter, iron, and manganese decreased by 30.63-80.15 %. Redundancy discriminant analysis revealed that environmental factors, especially the temperature and dissolved oxygen, were crucial drivers of the bacterial community structure. Furthermore, Spearman's correlation analysis between predominant genera and pollutants suggested that core genus played a vital role in pollutant reduction. Overall, our findings highlight the importance and provide insights on the artificial mixing systems' microbial mechanisms of reducing pollutants in drinking water reservoirs.

Promoted aerobic denitrification through denitrifying fungal communities: Co-occurrence patterns and treatment of low C/N micro-polluted water.

Despite the growing interest in using mixed-culture aerobic denitrifying fungal flora (mixed-CADFF) for water remediation, there is limited research on their nitrogen removal performance in low C/N polluted water bodies. To address this knowledge gap, we isolated three mixed-CADFFs from overlying water in urban lakes to evaluate their removal performance. The total nitrogen (TN) removal efficiencies were 93.60 %, 94.64 %, and 95.18 %, while the dissolved organic carbon removal efficiencies were 96.64 %, 95.12 %, and 96.70 % for mixed-CADFF LN3, LN7, and LN15, respectively in the denitrification medium under aerobic conditions at 48 h cultivation. The three mixed-CADFFs could utilize diverse types of low molecular weight carbon sources to drive the aerobic denitrification processes efficiently. The optimal C/N ratio for the mixed-CADFFs were C/N = 10, and then C/N = 15, 7, 5, and 2. The high-throughput sequencing analysis of three mixed-CADFFs indicated that Eurotiomycetes, Cystobasidiomycetes, and Sordariomycetes were the dominant class in the communities at class level. The network analysis showed that the rare fungal species, such as Scedosporium dehoogii Saitozyma, and Candida intermedia presented positively co-occurred with the TN removal and organic matter reduction capacity. Immobilization mixed-CADFFs treatment raw water experiments indicated that three mixed-CADFFs could reduce nearly 62.73 % of TN in the low C/N micro-polluted raw water treatment. Moreover, the cell density and cell metabolism indexes were also increased during the raw water treatment. This study will provides new insight into resource utilization of the mixed-culture aerobic denitrifying fungal community in field of environment restoration.

Actinobacteria produce taste and odor in drinking water reservoir: Community composition dynamics, co-occurrence and inactivation models.

Taste and odor (T&O) has become a significant concern for drinking water safety. Actinobacteria are believed to produce T&O during the non-algal bloom period; however, this has not been widely investigated. In this study, the seasonal dynamics of the actinobacterial community structure and inactivation of odor-producing actinobacteria were explored. The results indicated that the diversity and community composition of actinobacteria exhibited significant spatiotemporal distribution. Network analysis and structural equation modeling showed that the actinobacterial community occupied a similar environmental niche, and the major environmental attributes exhibited spatiotemporal dynamics, which affected the actinobacterial community. Furthermore, the two genera of odorous actinobacteria were inactivated in drinking water sources using chlorine. Amycolatopsis spp. have a stronger chlorine resistance ability than Streptomyces spp., indicating that chlorine inactivates actinobacteria by first destroying cell membranes and causing the release of intracellular compounds. Finally, we integrated the observed variability in the inactivation rate of actinobacteria into an expanded Chick-Watson model to estimate its effect on inactivation. These findings will deepen our understanding of the seasonal dynamics of actinobacterial community structure in drinking water reservoirs and provide a foundation for reservoir water quality management strategies.

Effects of copper sulfate algaecide on the cell growth, physiological characteristics, the metabolic activity of Microcystis aeruginosa and raw water application.

Harmful cyanobacteria blooms (HCBs) occurred frequently and become a serious scientific challenge. Copper sulfate (CuSO4) is a broad-spectrum chemical algaecide to control algae blooms. Herein, the Microcystis aeruginosa was exposed to different CuSO4 (0.0, 0.2 and 0.5 mg/L) to assess the variations in algal physiological process and metabolic profiles. The results indicated that exposure to CuSO4 of 0.5 mg/L at 72 h could significantly inhibit the cell growth and photosynthetic capacity of M. aeruginosa, including chl-a content and chlorophyll fluorescence parameters. Plasma membrane damage causing cell lysis of M. aeruginosa increased the K+ release. The increase of SOD and CAT suggested that CuSO4 treatment caused oxidative stress in algal cells. Different doses of CuSO4 modified the carbon metabolic potential, algal cells had their unique metabolic mode thereby. Moreover, the research further verified that CuSO4 would also inhibit algal growth and change algal community structure in site-collected water application. Overall, laboratory results of M. aeruginosa to CuSO4 and site-collected water application of algal responses to CuSO4 might be conducive to uncovering the controlling mechanism of algae and the potential effect of carbon cycling in an ecological environment.