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.

Effects of storm events on nutrient characteristics in a stratified drinking water reservoir: Behavior, transmission pathways and management strategy.

Storm events result in nutrient fluctuations and deterioration of reservoir water supply quality. Understanding of nutrient dynamics (e.g., concentration, composition, loads and transport pathways) and adoption of effective management strategies are critical for safeguarding water quality. A comprehensive monitoring was conducted for three storm events during the rainy season in 2023. Results showed nitrogen (N) and phosphorus (P) dynamics demonstrate a significant response to hydrological process. Rainfall resulted in the highest event mean concentrations (EMCs) of total nitrogen (TN), nitrate nitrogen (NO3--N), ammonia nitrogen (NH4+-N), total phosphorus (TP), and particulate phosphorus (PP) in the runoff being 1.97, 2.15, 2.30, 44.17, and 62.38 times higher than those observed in baseflow. On average, NO3--N/PP accounted for 82 %/96 % of N/P exports. Hysteresis analyses reveal that NH4+-N and PP were mainly transported by surface runoff from over-land sources, whereas TN and NO3--N were primarily delivered by subsurface runoff. Additionally, nutrient concentrations were significantly higher in the intrusive layer in reservoir compared to the pre-storm period, which gradually decreased from the tail to the head as particulate sedimentation and water column mixing occurred. Water-lifting-aerators (WLAs) were employed to alter the reservoir thermal stratification regime via artificial mixing to affect the intrusive layer of storm runoff. Comparison of the intrusive layer for three storms reveals that WLAs triggers the storm runoff to form an underflow via increasing the reservoir bottom water temperature above that the runoff, ensuring that water quality at the intake position remains unaffected by inflows. These findings serve as a reference for the response of reservoir eutrophication levels to storm events and present practical engineering experience for enhancing water quality safety during the rainy season.

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.

Direct to Patient Synchronous Teledermatology During COVID-19 Pandemic.

Background: During the COVID-19 pandemic, teledermatology became a popular mode of health care delivery. Thus, deciphering which diagnoses are best suited for synchronous video visits is important to guide providers on appropriate patient care. Methods: We conducted a retrospective study of 1,647 submitted synchronous video visits from September 1, 2020 to March 31, 2021 at a single, large academic institution. Results: Video visits' follow-up rate was significantly associated with diagnosis subtype (p < 0.001). Compared with patients with skin lesions and nonskin dermatologic conditions, patients with a rash had higher odds of being recommended to have their follow-up visit as a video visit (odds ratio [OR] = 0.222, p < 0.001; OR = 0.296, p < 0.001). Patients with a rash had lower odds of being recommended to have their follow-up visit as an in-person office visit when compared with skin lesions (OR = 9.679, p < 0.001), nonskin dermatologic conditions (OR = 4.055, p < 0.001), and other skin dermatologic conditions (OR = 2.23, p < 0.01). Demographically, employed, middle-aged patients with private insurance made up the majority of video visit usage. African American patients were less likely to utilize a video visit compared with Asian patients (OR = 2.06, p < 0.038). Conclusions: Certain dermatologic diagnoses, most notably rashes, are more conducive to video visit management. Rashes made up 86% of new patient video visits, were more likely to have video visit follow-up if needed and were more likely to not require further follow-up indicating that the management of rashes from initial diagnosis to completion in care is suitable for video visit management.

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 denitrifying bacterial community with low C/N ratio remove nitrate from micro-polluted water: Metagenomics unravels denitrification pathways.

The efficient nitrogen removal from micro-polluted source water is an international challenge to be solved urgently. However, the inner denitrification mechanism of native aerobic denitrifying bacterial communities in response to carbon scarcity remains relatively unclear. Here, the bacterial community XT6, screened from an oligotrophic reservoir, exhibited aerobic denitrifying capacity under low-carbon environments. Up to 76.79-81.64 % of total organic carbon (TOC) and 51.48-67.60 % of NO3--N were removed by XT6 within 48 h at C/N ratios of 2.0-3.0. Additionally, the nitrogen balance experiments further manifested that 26.27-38.13 % of NO3--N was lost in gaseous form. As the C/N ratio decreased, XT6 tended to generate more extracellular polymeric substances (EPS), with the tightly bound EPS showing the largest increase. Pseudomonas and Variovorax were quite abundant in XT6, constituting 59.69 % and 28.65 % of the total sequences, respectively. Furthermore, metagenomics analysis evidenced that XT6 removed TOC and nitrate mainly through the tricarboxylic acid cycle and aerobic denitrification. Overall, the abovementioned results provide a deeper understanding of the nitrogen metabolic pathways of indigenous aerobic denitrifying bacterial communities with low C/N ratios and offer useful guidance for controlling nitrogen pollution in oligotrophic ecosystems.

Phenotypic Identification, Genetic Characterization, and Selective Signal Detection of Huitang Duck.

The Huitang duck (HT), a long-domesticated elite local breed from Hunan Province, China, with excellent meat quality, has not had its population genetic structure and genomic selective sweeps extensively studied to date. This study measured the phenotypic characteristics of HT and conducted comparative analysis between HT and 16 different duck breeds, including wild, indigenous, and meat breeds, to characterize its population structure and genetic potential. The results revealed that HT is a dual-purpose indigenous breed with a genetic background closely related to the Youxian sheldrake and Linwu ducks. In the selective sweep analysis between HT and Linwu ducks, genes such as PLCG2, FN1, and IGF2BP2, which are associated with muscle growth and development, were identified near the 27 selection signals. The comparison between HT and Jinding ducks revealed 68 selective signals that contained important genes associated with ovarian development (GRIK4, MAP3K8, and TGIF1) and egg-laying behaviors (ERBB4). Selective sweep analysis between HT and Youxian sheldrake ducks found 93 selective regions covering genes related to both meat (IGF1R and IGFBP5) and egg-production (FOXO3 and ITPR1) traits. Our study may provide novel knowledge for exploring the population structure and genetic potential of HT, offering a theoretical basis for its breeding strategies in the future.

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.

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.

Ignored microbial-induced taste and odor in drinking water reservoirs: Novel insight into actinobacterial community structure, assembly, and odor-producing potential.

The presence of actinobacteria in reservoirs can lead to taste and odor issues, posing potential risks to the safety of drinking water supply. However, the response of actinobacterial communities to environmental factors in drinking water reservoirs remains largely unexplored. To address this gap, this study investigated the community structure and metabolic characteristics of odor-producing actinobacteria in water reservoirs across northern and southern China. The findings revealed differences in the actinobacterial composition across the reservoirs, with Mycobacterium sp. and Candidatus Nanopelagicus being the most prevalent genera. Notably, water temperature, nutrient levels, and metal concentrations were associated with differences in actinobacterial communities, with stochastic processes playing a major role in shaping the community assembly. In addition, three strains of odor-producing actinobacteria were cultured in raw reservoir water, namely Streptomyces antibioticus LJH21, Streptomyces sp. ZEU13, and Streptomyces sp. PQK19, with peak ATP concentrations of 51 nmol/L, 66 nmol/L, and 70 nmol/L, respectively, indicating that odor-producing actinobacteria could remain metabolically active under poor nutrient pressure. Additionally, Streptomyces antibioticus LJH21 produced the highest concentration of geosmin at 24.4 ng/L. These findings enhance our understanding of regional variances and reproductive metabolic mechanisms of actinobacteria in drinking water reservoirs, providing a solid foundation for improving drinking water quality control, especially for taste and odor.

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.

Mixotrophic aerobic denitrification facilitated by denitrifying bacterial-fungal communities assisted with iron in micro-polluted water: Performance, metabolic activity, functional genes abundance, and community co-occurrence.

Low-dosage nitrate pollutants can contribute to eutrophication in surface water bodies, such as lakes and reservoirs. This study employed assembled denitrifying bacterial-fungal communities as bio-denitrifiers, in combination with zero-valent iron (ZVI), to treat micro-polluted water. Immobilized bacterial-fungal mixed communities (IBFMC) reactors demonstrated their ability to reduce nitrate and organic carbon by over 43.2 % and 53.7 %, respectively. Compared to IBFMC reactors, IBFMC combined with ZVI (IBFMC@ZVI) reactors exhibited enhanced removal efficiencies for nitrate and organic carbon, reaching the highest of 31.55 % and 17.66 %, respectively. The presence of ZVI in the IBFMC@ZVI reactors stimulated various aspects of microbial activity, including the metabolic processes, electron transfer system activities, abundance of functional genes and enzymes, and diversity and richness of microbial communities. The contents of adenosine triphosphate and electron transfer system activities enhanced more than 5.6 and 1.43 folds in the IBFMC@ZVI reactors compared with IBFMC reactors. Furthermore, significant improvement of crucial genes and enzyme denitrification chains was observed in the IBFMC@ZVI reactors. Iron played a central role in enhancing microbial diversity and activity, and promoting the supply, and transfer of inorganic electron donors. This study presents an innovative approach for applying denitrifying bacterial-fungal communities combined with iron enhancing efficient denitrification in micro-polluted water.

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).