Influence of large open-pit mines on the construction and optimization of urban ecological networks: A case study of Fushun City, China.

Under the long-term effect of mineral resource exploitation, especially open-pit mining, ecosystems are severely disturbed. Constructing and optimizing urban ecological networks influenced by open-pit mines based on mine-city coordination helps integrate ecological restoration and the construction of urban ecological environments. We applied an InVEST model to Fushun City to evaluate urban ecosystem services under the influence of large open-pit mines. Twenty-one key patches important for maintaining landscape connectivity were screened as the ecological sources in the network, from which ecological resistance surfaces were constructed by combining the impacts of mines on the environment. Minimum cumulative resistance (MCR) and gravity models were then used to extract and classify ecological corridors favorable to species migration and diffusion. Fushun City had large spatial differences in ecosystem service functions, with high-value areas concentrated in the forest-rich Dongzhou District and the northern Shuncheng District. Under the influence of open-pit mining, the ecosystem service capacity of the region south of the Hunhe River was poor and lacked ecological sources. Urban ecological resistance surfaces reached a maximum in the open-pit mining area, and 210 ecological corridors were estimated using the MCR model, of which 46 were important. Only two corridors crossed the West and East open pit, forming two "ecological fracture surfaces." The Dongzhou and eastern Shuncheng districts had complex network structures and stable ecological environments. In contrast, the central and southern parts of Fushun City lacked ecological corridors owing to the influence of mining pits and gangue mountains, had simple network structures, and low connectivities with other sources. Combined with Fushun City's development plan, we propose that ecological network optimization should add new ecological source sites, reconstruct and repair ecological corridors, and upgrade ecological breakpoints. This study provides reference and basis for ecological network research in mining cities influenced by open-pit mines.

Screening and analysis of the targeted compounds in Choerospondias axillaris extract by receptor chromatographic column with immobilized angiotensin II type 1 receptor.

As a result of the lack of modern techniques, the study of Tibetan medicine has been hindered in identifying bioactive compounds. Herein, we established a chromatographic approach using an immobilized angiotensin II type 1 receptor (AT1R) via a one-step method triggered by haloalkane dehalogenase. The bioactive compounds from Choerospondias axillaris (Guangzao) were screened and identified using the immobilized AT1R followed by MS. Frontal analysis (FA) and adsorption energy distribution (AED) were used to evaluate the association constants. Molecular docking was used to investigate the binding configurations, and the surface efficiency index, binding efficiency index, and ligand-lipophilicity efficiency (LLE) were calculated to assess the drug-like properties. The results identified naringenin, pinocembrin, and chrysin as the compounds that specifically bind to AT1R in Guangzao. FA and AED confirmed that there is only one type of binding site between these compounds and AT1R. The association constants were (2.40 ± 0.02) × 104 M-1 for naringenin (5.22 ± 0.26) × 104 M-1 for pinocembrin, and (4.27 ± 0.14) × 104 M-1 for chrysin, respectively. These compounds can bind with AT1R through the orthosteric binding pocket. Naringenin exhibited better LLE than pinocembrin and chrysin. These results confirmed the feasibility of using the immobilized AT1R column for screening and analyzing bioactive compounds in Tibetan medicines.

Correction: Cell Therapy: A Safe and Efficacious Therapeutic Treatment for Alzheimer's Disease in APP+PS1 Mice.

[This corrects the article DOI: 10.1371/journal.pone.0049468.].

Screening, identification and evaluation of an acidophilic strain of Bacillus velezensis B4-7 for the biocontrol of tobacco bacterial wilt.

Tobacco (Nicotiana tabacum L.) bacterial wilt, caused by Ralstonia solanacearum, is indeed a highly destructive plant disease, leading to substantial damage in tobacco production. While biological control is considered an effective measure for managing bacterial wilt, related research in this area has been relatively limited compared to other control methods. In order to discover new potential antagonistic bacteria with high biocontrol efficacy against tobacco bacterial wilt, we conducted an analysis of the microbial composition differences between disease-suppressive and disease-conducive soils using Illumina sequencing. As a result, we successfully isolated six strains from the disease-suppressive soil that exhibited antibacterial activity against Ralstonia solanacearum. Among these strains, B4-7 showed the strongest antibacterial activity, even at acidic conditions with a pH of 4.0. Based on genome analysis using Average Nucleotide Identity (ANI), B4-7 was identified as Bacillus velezensis. In greenhouse and field trials, strain B4-7 significantly reduced the disease index of tobacco bacterial wilt, with control efficiencies reaching 74.03% and 46.88% respectively. Additionally, B4-7 exhibited plant-promoting abilities that led to a 35.27% increase in tobacco production in field conditions. Quantitative real-time (qPCR) analysis demonstrated that strain B4-7 effectively reduced the abundance of R. solanacearum in the rhizosphere. Genome sequencing and Liquid Chromatography-Mass Spectrometry (LC-MS) analysis revealed that strain B4-7 potentially produces various lipopeptide metabolites, such as microlactin, bacillaene, difficidin, bacilysin, and surfactin. Furthermore, B4-7 influenced the structure of the rhizosphere soil microbial community, increasing bacterial abundance and fungal diversity, while also promoting the growth of different beneficial microorganisms. In addition, B4-7 enhanced tobacco's resistance to R. solanacearum by increasing the activities of defense enzymes, including superoxide dismutase (SOD), phenylalanine ammonia-lyase (PAL), peroxidase (POD), catalase (CAT), and polyphenol oxidase (PPO). Collectively, these findings suggest that B. velezensis B4-7 holds significant biocontrol potential and can be considered a promising candidate strain for eco-friendly management of tobacco bacterial wilt.

Friend or foe: The role of stress granule in neurodegenerative disease.

Stress granules (SGs) are dynamic membraneless organelles that form in response to cellular stress. SGs are predominantly composed of RNA and RNA-binding proteins that assemble through liquid-liquid phase separation. Although the formation of SGs is considered a transient and protective response to cellular stress, their dysregulation or persistence may contribute to various neurodegenerative diseases. This review aims to provide a comprehensive overview of SG physiology and pathology. It covers the formation, composition, regulation, and functions of SGs, along with their crosstalk with other membrane-bound and membraneless organelles. Furthermore, this review discusses the dual roles of SGs as both friends and foes in neurodegenerative diseases and explores potential therapeutic approaches targeting SGs. The challenges and future perspectives in this field are also highlighted. A more profound comprehension of the intricate relationship between SGs and neurodegenerative diseases could inspire the development of innovative therapeutic interventions against these devastating diseases.

Challenges and dynamics of public health reporting and data exchange during COVID-19: insights from US hospitals.

The US health care response during the early stages of the COVID-19 pandemic unveiled challenges in public health reporting systems and electronic clinical data exchange. Using data from the 2020 and 2022 American Hospital Association information technology supplement surveys, this study examined US hospitals' experiences in public health reporting, accessing clinical data from external providers for COVID-19 patient care, and their success in reporting vaccine-related adverse events to relevant state and federal agencies. Results showcase significant disparities in reporting practices across government levels due to inconsistent requirements. Although many hospitals leaned toward automated data transmission, a substantial portion continued to depend on manual processes. Pertaining to electronic clinical data, while entities like large commercial laboratories outperformed others, a considerable number were sluggish in delivering critical information. Moreover, a small percentage of hospitals reported challenges in recording vaccine-related adverse events, emphasizing the need for transparent reporting systems. The study underscores the necessity for standardized reporting protocols, explicit directives, and a pivot from manual to automated processes. Tackling these challenges is pivotal for ensuring prompt and reliable data, bolstering future public health responses, and rejuvenating public trust in health institutions.

Changes in physio-biochemical metabolism, phenolics and antioxidant capacity during germination of different wheat varieties.

Changes in physio-biochemical metabolism, phenolics and antioxidant capacity during germination were studied in eight different wheat varieties. Results showed that germination enhanced sprout growth, and caused oxidative damage, but enhanced phenolics accumulation. Ferulic acid and p-coumaric acid were the main phenolic acids in wheat sprouts, and dihydroquercetin, quercetin and vitexin were the main flavonoids. The phenolic acid content of Jimai 44 was the highest on the 2th and 4th day of germination, and that of Bainong 307 was the highest on the 6th day. The flavonoid content of Hei jingang was the highest during whole germination. The enzymes activities of phenylalanine ammonia lyase (PAL), cinnamic acid 4-hydroxylase (C4H) and 4-coumarate coenzyme A ligase (4CL) were up-regulated. The activities of catalase, polyphenol oxidase and peroxidase were also activated. Antioxidant capacity of wheat sprouts was enhanced. The results provided new ideas for the production of naturally sourced phenolic rich foods.

Dextran-based antibacterial hydrogel-derived fluorescent sensors for the visual monitoring of AgNPs.

The unpredictable release behavior of metal nanoparticles/metal ions from metal nanoparticle-loaded hydrogels, without a suitable in situ detection method, is resulting in serious cytotoxicity. To optimize the preparation and design of antibacterial hydrogels for in situ detection of metal nanoparticles, an in-situ detection platform based on the fluorescence signal change caused by the potential surface energy transfer of silver nanoparticles (AgNPs) and carbon dots (CD) through silver mirror reaction and Schiff base reaction was established. The antimicrobial test results show that the composite antimicrobial hydrogel, with lower dosages of AgNPs and CD, exhibited a higher inhibition rate of 99.1 % against E. coli and 99.8 % against S. aureus compared to the single antimicrobial component. This suggests a potential synergistic antimicrobial activity. Furthermore, the fluorescence detection platform was established with a difference of <3 µg between detected values and actual values over a period of 72 h. This demonstrates the excellent in situ detection capability of the hydrogel in antimicrobial-related applications.

Indobufen alleviates ischemic stroke injury by regulating transcription factor NRF2 and inhibiting ATG5 expression.

BACKGROUND: Ischemic stroke (IS) is a detrimental neurological disease and IS lacks valuable methods to recover body function. Indobufen (IND) could alleviate IS. However, the possible mechanism remains undefined. METHODS: SH-SY5Y cells were cultured under the oxygen-glucose deprivation/reoxygenation (OGD/R) environment and then were treated with small interfering RNA (siRNA) of NRF2 and ATG5. The influence of various concentrations of IND (50 µM, 100 µM, 200 µM, and 400 µM) was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide. Levels of superoxide dismutase (SOD) and malonaldehyde (MDA) were examined by ELISA. Reactive oxygen species (ROS) production was determined by DCFH-DA staining. The protein levels of LC3II/LC3I, Beclin1, p62, NRF2, and ATG5 were detected by western blot. RESULTS: IND increased cell viability, while depressed the rate of apoptosis in SH-SY5Y cells of OGD/R environment. IND inhibited autophagy by suppressing the levels of LC3II/LC3I, Beclin1 protein, and increasing p62 protein expression in SH-SY5Y cells of OGD/R environment. IND limited the contents of ROS and MDA, while amplifying the activity of SOD in SH-SY5Y cells with OGD/R exposure. IND also promoted NRF2 expression in OGD/R environment. CONCLUSION: IND could inhibit autophagy, oxidative stress, and apoptosis in SH-SY5Y cells with OGD/R exposure, further alleviating IS injury by regulating transcription factor NRF2 and inhibiting ATG5 expression.

Emergency Department Trauma Activation Fees by Payer Type.

This cross-sectional study examines the wide variations in prices of emergency medical services at US hospitals.

Bacterial antigens and asthma: a comparative study of common respiratory pathogenic bacteria.

Objective: In a previous study we have shown that, in the presence of interleukin (IL)-33, repeated, per-nasal challenge of murine airways with Streptococcus pneumoniae (S. pneumoniae) organisms induces human asthma-like airways inflammation. It is not clear, however, whether this effect is unique or manifest in response to other common respiratory pathogens.Methods: To explore this, airways of BALB/c mice were repeatedly challenged per-nasally with formaldehyde-inactivated bacterial bodies in the presence or absence of murine recombinant IL-33. Serum concentrations of S.pneumoniae, Moraxella catarrhalis (M.catarrhalis) and Haemophilus influenzae (H.influenzae) lysates-specific IgE were measured in patients with asthma and control subjects.Results: We showed that in the presence of IL-33, repeated, per-nasal airways exposure to the bodies of these bacteria induced airways hyperresponsiveness (AHR) in the experimental mice. This was accompanied by cellular infiltration into bronchoalveolar lavage fluid (BALF), eosinophilic infiltration and mucous hypertrophy of the lung tissue, with elevated local expression of some type 2 cytokines and elevated, specific IgG and IgE in the serum. The precise characteristics of the inflammation evoked by exposure to each bacterial species were distinguishable.Conclusions: These results suggest that in the certain circumstances, inhaled or commensal bacterial body antigens of both Gram-positive (S. pneumoniae) and Gram-negative (M. catarrhalis and H. influenzae) respiratory tract bacteria may initiate type 2 inflammation typical of asthma in the airways. In addition, we demonstrated that human asthmatic patients manifest elevated serum concentrations of M.catarrhalis- and H.influenzae-specific IgE.

Effects from medications on functional biomarkers of aging in three longitudinal studies of aging in Sweden.

Antihypertensive, lipid-lowering, and blood glucose-lowering drugs have slowed down the aging process in animal models. In humans, studies are limited, have short follow-up times, and show mixed results. Therefore, this study aimed to estimate the effects of commonly used medications on functional aging, cognitive function, and frailty. We included information on individuals from three Swedish longitudinal population-based studies collected between 1986 and 2014. Our exposures were the 21 most used groups of medications among individuals aged 65 years and older in the Swedish population in 2022. Functional aging index (n = 1191), cognitive function (n = 1094), and frailty index (n = 1361) were the outcomes of interest. To estimate the medication effects, we used a self-controlled analysis, where each individual is his/her own control, thereby adjusting for all time-stable confounders. The analysis was additionally adjusted for time-varying confounders (chronological age, Charlson Comorbidity Index, smoking, body mass index, and the number of drugs). The participants were 65.5-82.8 years at the first in-person assessment. Adrenergics/inhalants (effect size = 0.089) and lipid-modifying agents/plain (effect size = 0.082) were associated with higher values of cognitive function (improvement), and selective calcium channel blockers with mainly vascular effects (effect size = -0.129) were associated with lower values of the functional aging index (improvement). No beneficial effects were found on the frailty index. Adrenergics/inhalants, lipid-modifying agents/plain, and selective calcium channel blockers with mainly vascular effects may benefit functional biomarkers of aging. More research is needed to investigate their clinical value in preventing adverse aging outcomes.

ZNF468 inhibits irradiation-induced G2/M cell cycle arrest and apoptosis by facilitating AURKA transcription in Esophageal Squamous Cell Carcinoma.

BACKGROUND: ZNF468 is a relatively unexplored gene that has been implicated in potential oncogenic properties in various cancer types. However, the exact role of ZNF468 in radiotherapy resistance of esophageal squamous cell carcinomas (ESCCs) is not well understood. METHODS: Bioinformatic analysis was performed using the TCGA database to assess ZNF468 expression and prognostic significance in pan-cancer and ESCC. Functional experiments were conducted using ZNF468 overexpressing and knockdown cell lines to assess its impact on cell survival, DNA damage response, cell cycle, and apoptosis upon radiation. A luciferase reporter assay was utilized to validate ZNF468 binding to the AURKA promoter. RESULTS: ZNF468 was significantly upregulated in diverse cancer types, including ESCC, and its high expression correlated with adverse prognosis in specific tumors. In the ESCC cohort, ZNF468 exhibited substantial upregulation in post-radiotherapy tissues, indicating its potential role in conferring radiotherapy resistance. Functional experiments revealed that ZNF468 enhances cell viability and facilitates DNA damage repair in radiotherapy-treated ESCC cells, while dampening the G2/M cell cycle arrest and apoptosis induced by radiation. Moreover, ZNF468 facilitated AURKA transcription, resulting in upregulated Aurora A expression, and subsequently inhibited P53 expression, unveiling key molecular mechanisms underlying radiotherapy resistance in ESCC. CONCLUSION: ZNF468 plays an oncogenic role in ESCC and contributes to radiotherapy resistance. It enhances cell survival while dampening radiation-induced G2/M cell cycle arrest and apoptosis. By modulating AURKA and P53 expression, ZNF468 represents a promising therapeutic target for enhancing radiotherapy efficacy in ESCC.

Appropriately Reduced Nitrogen and Increased Phosphorus in Ratooning Rice Increased the Yield and Reduced the Greenhouse Gas Emissions in Southeast China.

Reducing greenhouse gas emissions while improving productivity is the core of sustainable agriculture development. In recent years, rice ratooning has developed rapidly in China and other Asian countries, becoming an effective measure to increase rice production and reduce greenhouse gas emissions in these regions. However, the lower yield of ratooning rice caused by the application of a single nitrogen fertilizer in the ratooning season has become one of the main reasons limiting the further development of rice ratooning. The combined application of nitrogen and phosphorus plays a crucial role in increasing crop yield and reducing greenhouse gas emissions. The effects of combined nitrogen and phosphorus application on ratooning rice remain unclear. Therefore, this paper aimed to investigate the effect of combined nitrogen and phosphorus application on ratooning rice. Two hybrid rice varieties, 'Luyou 1831' and 'Yongyou 1540', were used as experimental materials. A control treatment of nitrogen-only fertilization (187.50 kg·ha-1 N) was set, and six treatments were established by reducing nitrogen fertilizer by 10% (N1) and 20% (N2), and applying three levels of phosphorus fertilizer: N1P1 (168.75 kg·ha-1 N; 13.50 kg·ha-1 P), N1P2 (168.75 kg·ha-1 N; 27.00 kg·ha-1 P), N1P3 (168.75 kg·ha-1 N; 40.50 kg·ha-1 P), N2P1 (150.00 kg·ha-1 N; 13.50 kg·ha-1 P), N2P2 (150.00 kg·ha-1 N; 27.00 kg·ha-1 P), and N2P3 (150.00 kg·ha-1 N; 40.50 kg·ha-1 P). The effects of reduced nitrogen and increased phosphorus treatments in ratooning rice on the yield, the greenhouse gas emissions, and the community structure of rhizosphere soil microbes were examined. The results showed that the yield of ratooning rice in different treatments followed the sequence N1P2 > N1P1 > N1P3 > N2P3 > N2P2 > N2P1 > N. Specifically, under the N1P2 treatment, the average two-year yields of 'Luyou 1831' and 'Yongyou 1540' reached 8520.55 kg·ha-1 and 9184.90 kg·ha-1, respectively, representing increases of 74.30% and 25.79% compared to the N treatment. Different nitrogen and phosphorus application combinations also reduced methane emissions during the ratooning season. Appropriately combined nitrogen and phosphorus application reduced the relative contribution of stochastic processes in microbial community assembly, broadened the niche breadth of microbial communities, enhanced the abundance of functional genes related to methane-oxidizing bacteria and soil ammonia-oxidizing bacteria in the rhizosphere, and decreased the abundance of functional genes related to methanogenic and denitrifying bacteria, thereby reducing greenhouse gas emissions in the ratooning season. The carbon footprint of ratooning rice for 'Luyou 1831' and 'Yongyou 1540' decreased by 25.82% and 38.99%, respectively, under the N1P2 treatment compared to the N treatment. This study offered a new fertilization pattern for the green sustainable development of rice ratooning.

Telmisartan loading thermosensitive hydrogel repairs gut epithelial barrier for alleviating inflammatory bowel disease.

Inflammatory bowel disease (IBD) remains a global health concern with a complex and incompletely understood pathogenesis. In the course of IBD development, damage to intestinal epithelial cells and a reduction in the expression of tight junction (TJ) proteins compromise the integrity of the intestinal barrier, exacerbating inflammation. Notably, the renin-angiotensin system and angiotensin II receptor type 1 (AT1R) play a crucial role in regulating the pathological progression including vascular permeability, and immune microenvironment. Thus, Telmisartan (Tel), an AT1R inhibitor, loading thermosensitive hydrogel was constructed to investigate the potential of alleviating inflammatory bowel disease through rectal administration. The constructed hydrogel exhibits an advantageous property of rapid transformation from a solution to a gel state at 37°C, facilitating prolonged drug retention within the gut while mitigating irritation associated with rectal administration. Results indicate that Tel also exhibits a beneficial effect in ameliorating colon shortening, colon wall thickening, cup cell lacking, crypt disappearance, and inflammatory cell infiltration into the mucosa in colitis mice. Moreover, it significantly upregulates the expression of TJ proteins in colonic tissues thereby repairing the intestinal barrier damage and alleviating the ulcerative colitis (UC) disease process. In conclusion, Tel-loaded hydrogel demonstrates substantial promise as a potential treatment modality for IBD.

Health Insurance Coverage-Is Broader Always Better?

This Viewpoint discusses the traditional goals of health insurance and contrasts those with the current needs of insurance beneficiaries.

Do Insurers With Greater Market Power Negotiate Consistently Lower Prices for Hospital Care? Evidence From Hospital Price Transparency Data.

This study examined if greater insurer market power was associated with consistently lower negotiated prices within each hospital for 44 shoppable and emergency procedures, using price transparency data disclosed by 1,506 hospitals in metropolitan areas. We used multi-level fixed effects models to estimate the within-hospital variation in plan-level insurer-negotiated prices (from the largest insurer, the second largest insurer, other major insurers, and nonmajor insurers) and cash-pay prices as a function of insurer market power. For shoppable services, relative to nonmajor insurers, the largest, second largest, and other major insurers negotiated 23%, 16%, and 3% lower prices, respectively, while cash prices were 17% higher. For emergency room visits, while the largest insurers paid 5% less than nonmajor insurers, the second largest and other major insurers did not pay lower prices. Stratified analyses by type of shoppable services found varying magnitudes and patterns of price discounts associated with insurer market power.

Spending on Dual Over-the-Counter and Prescription Drugs in the Medicare Part D Program.

This study compares Medicare and patient spending for dual over-the-counter and prescription drugs with their over-the-counter cash prices.