External stimuli-triggered photodynamic and sonodynamic therapies in combination with hybrid nanomicelles of ICG@PEP@HA: laser vs. ultrasound.

The concept of combining external medical stimuli with internal functional biomaterials to achieve cancer-oriented treatments is being emergingly developed. Optical and acoustical activations have shown particular promise as non-invasive regulation modalities in cancer treatment and intervention. It is always challenging to leverage the contributions of optical and acoustical stimuli and find appropriate biomaterials to optimally match them. Herein, a type of hybrid nanomicelle (ICG@PEP@HA) containing ICG as a photo/sonosensitizer, an amphiphilic peptide for membrane penetration and hyaluronic acid for cluster determinant 44 (CD44) targeting was fabricated. Triggered by the external stimuli of laser and US irradiation, their photo/sonothermal performance, in vitro reactive oxygen species (ROS) production capability and tumor-targeting efficiency have been systematically evaluated. It was interestingly found that the external stimulus of laser irradiation induced a greater quantity of ROS, which resulted in significant cell apoptosis and tumor growth inhibition in the presence of ICG@PEP@HA. The individual analyses and corresponding rationales have been investigated. Meanwhile, these hybrid nanomicelles were administered into MDA-MB-231 tumor-bearing nude mice for PDT and SDT therapies and their biocompatibility assessment, and a prevailing PDT efficacy and reliable bio-safety have been evidenced based on the hematological analysis and histochemical staining. In summary, this study has validated a novel pathway to utilize these hybrid nanomicelles for laser/US-triggered localized tumor treatment, and the treatment efficiency may be leveraged by different external stimuli sources. It is also expected to give rise to full accessibility to clinical translations for human cancer treatments by means of the as-reported laser/US-nanomicelle combination strategy.

Intracellular Zn2+ promotes extracellular matrix remodeling in dexamethasone-treated trabecular meshwork.

Given the widespread application of glucocorticoids in ophthalmology, the associated elevation of intraocular pressure (IOP) has long been a vexing concern for clinicians, yet the underlying mechanisms remain inconclusive. Much of the discussion focuses on the extracellular matrix (ECM) of trabecular meshwork (TM). It is widely agreed that glucocorticoids impact the expression of matrix metalloproteinases (MMPs), leading to ECM deposition. Since Zn2+ is vital for MMPs, we explored its role in ECM alterations induced by dexamethasone (DEX). Our study revealed that in human TM cells treated with DEX, the level of intracellular Zn2+ significantly decreased, accompanied by impaired extracellular Zn2+ uptake. This correlated with changes in several Zrt-, Irt-related proteins (ZIPs) and metallothionein. ZIP8 knockdown impaired extracellular Zn2+ uptake, but Zn2+ chelation did not affect ZIP8 expression. Resembling DEX's effects, chelation of Zn2+ decreased MMP2 expression, increased the deposition of ECM proteins, and induced structural disarray of ECM. Conversely, supplementation of exogenous Zn2+ in DEX-treated cells ameliorated these outcomes. Notably, dietary zinc supplementation in mice significantly reduced DEX-induced IOP elevation and collagen content in TM, thereby rescuing the visual function of the mice. These findings underscore zinc's pivotal role in ECM regulation, providing a novel perspective on the pathogenesis of glaucoma.NEW & NOTEWORTHY Our study explores zinc's pivotal role in mitigating extracellular matrix dysregulation in the trabecular meshwork and glucocorticoid-induced ocular hypertension. We found that in human trabecular meshwork cells treated with dexamethasone, intracellular Zn2+ significantly decreased, accompanied by impaired extracellular Zn2+ uptake. Zinc supplementation rescues visual function by modulating extracellular matrix proteins and lowering intraocular pressure, offering a direction for further exploration in glaucoma management.

Analysis of soil fertility and toxic metal characteristics in open-pit mining areas in northern Shaanxi.

The study specifically focused on the Hongliulin mining area, where a total of 40 soil samples were meticulously collected and analyzed from within a 1000 m radius extending from the tailings dam. The findings revealed that soil pH within the 0-1000 m range generally leaned towards the alkaline side. In terms of soil nutrient content, encompassing factors such as soil organic matter (SOM), total nitrogen (TN), total phosphorus (TP), total potassium (TK), alkali nitrogen (AK), available phosphorus (AP), and quick-acting potassium (AK), the variations fell within the following ranges: 2.23-13.58 g/kg, 0.12-0.73 g/kg, 0.18-1.15 g/kg, 9.54-35.82 g/kg, 2.89-6.76 mg/kg, 3.45-11.25 mg/kg, and 5.86-130.9 mg/kg. Collectively, these values indicate relatively low levels of soil nutrients. Within the 0-500 m range of soil samples, the average concentrations of Cd, Hg, Pb, and As were 0.778, 0.198, 24.87, and 17.92 mg/kg, respectively. These concentrations exceeded the established soil background values of Shaanxi Province and emerged as the primary pollutants in the study area. Within this same range, the mean values of eight toxic metals (Pi) were ranked in the following descending order: 1.726 (Hg), 1.400 (As), 1.129 (Cr), 1.109 (Pb), 0.623 (Zn), 0.536 (Cd), 0.309 (Cu), and 0.289 (Ni). With the exception of Hg, As, Cr, and Pb, which exhibited slight pollution, the other toxic metals were found to be within acceptable pollution limits for this sampling range, in line with the results obtained using the geo-accumulation index method. The average potential ecological risk index for the eight toxic metals in the study area stood at 185.0, indicating a moderate overall pollution level. When assessing individual elements, the proportions of ecological risk attributed to Hg, As, Pb, and Cd were 34.57%, 27.44%, 25.11%, and 23.11%, respectively. This suggests that the primary potential ecological risk elements in the study area are Hg and As, followed by Cd and Pb. Notably, toxic metals Hg and Pb, as well as As and Pb, exhibited significant positive correlations within the sampling area, suggesting a common source. An analysis of the relationship between soil physicochemical properties and toxic metals indicated that soil pH, SOM, TN, and TP were closely linked to toxic metal concentrations. The toxic metal elements in the research area's soil exhibit moderate variability (0.16 < CV < 0.36) to high variability (CV > 0.36). Within the range of 0-200 m, the CV values for Cd and Hg exceed 1, indicating a high level of variability. The coefficient of variation for SOM, TP, AP, AK and TK is relatively high with the of 2.93, 2.36, 2.36, 21.01, 7.54. The soil in the sampling area has undergone significant disturbances due to human activities, resulting in toxic metal pollution and nutrient deficiencies.

The effect and mechanism of Huangqin-Baishao herb pair in the treatment of dextran sulfate sodium-induced ulcerative colitis.

Background: The haungqing (Scutellariae Radix) and baishao (Paeoniae Radix Alba) herb pair (HBHP) is a common prescribed herbal formula or is added to other traditional Chinese medicine (TCM) prescriptions to treat ulcerative colitis (UC). However, the underlying mechanism is unclear. Purpose: Elucidate the efficacy and potential mechanism of HBHP against UC. Methods: First, The UC model of mice induced by dextran sulfate sodium (DSS) was established. The mice were randomly divided into Control group, DSS group, SASP group (390 mg/kg), and HPHP group (1.95 g/kg), with 8 mice per group. Drugs were administrated via oral gavage for 7 days. Then, Disease activity index (DAI), length of the colon, histopathology, and changes in inflammatory cytokines in colonic tissues were analyzed to assess the effect of HBHP on UC. Besides, Network pharmacology was applied to identify the active compounds, core targets of HBHP in the treatment of UC, and the corresponding signaling pathways to explore the underlying mechanisms. Finally, Western blot (WB), immunohistochemistry (IHC) and molecular docking were performed to validate the results. Results: HBHP significantly reduced DAI score and decreased colon length shortening in DSS-induced UC mice. The administration of HBHP was able to effectively alleviated mucosal ulceration and epithelial destruction. In addition, HBHP treatment obviously - reduced the expressions of TNF-α, IL-6, and IL-1ß in colon tissues (p < 0.05 or p < 0.01). 35 bioactive compounds and 290 HBHP targets related to UC were obtained. Among them 3 key active compounds (baicalein, panicolin, and norwogonin) with higher degree values in the drug-compound-target network and 21 hub genes (STAT3, JAK2, SRC, AKT1, PIK3CA, and VEGFA, etc.) were identified. KEGG enrichment analysis suggested that HBHP's mechanisms mainly involve the JAK-STAT pathway. Abnormal activation of JAK/STAT signaling is believed to be involved in the pathogeneses of UC. Notably, WB and IHC showed that HBHP significantly down-regulated the protein expression levels of p-JAK2 (p < 0.05) and p-STAT3 (p < 0.05 or p < 0.01). JAK2 and STAT3 might be core targets for the action of HBHP; this possibility was also supported by molecular docking. Conclusions: HBHP could alleviate DSS-induced UC, reduce tissue inflammation, and its mechanism might primarily be achieved by inhibiting JAK2/STAT3 signaling pathway. Meanwhile, our work revealed that network pharmacology combined with experimental verification is a cogent means of studying the mechanism of TCM.

Improving soil phosphorus availability in saline areas by marine bacterium Bacillus paramycoides.

The utilization of phosphate-solubilizing bacteria (PSB) in agriculture has long been proposed as an eco-friendly method to enhance soil phosphorus (P) availability, thereby reducing reliance on chemical P fertilizers. However, their application in saline soils is challenged by salt-induced stress on common PSB strains. In this study, we sourced bacterial strains from marine environments, aiming to identify robust PSB strains adaptable to saline conditions and assess their potential as P bio-fertilizers through a microcosm experiment. Our findings indicate that the inoculation of a selected marine PSB, Bacillus paramycoides 3-1a, increased soil available P content by 12.5% when applied alone and by 61.2% when combined with organic amendments. This enhancement results from improved inorganic P solubilization and organic P mineralization in soils. Additionally, these treatments raised soil nitrogen levels, reshaped microbial community structures, and significantly enhanced wheat (Triticum aestivum L.) growth, with P accumulation increasing by 24.2-40.9%. Our results underscore the potential of marine PSB in conjunction with organic amendments for the amelioration of saline agricultural soils.

Study on sewage characteristics in rural China and pollutants removal performance of biologically enhanced internal circulation treatment system.

With rapid economic development and urbanization in China, rural wastewater treatment has become an important issue. This study investigated 63 rural sewage treatment stations in northern, central and southern Shaanxi, China for a 1-year period, 2021 to 2022. The main purpose of the research was to investigate the quality and discharge characteristics of rural sewage, along with current problems in rural wastewater treatment, in order to provide evidence for the optimal construction and operation of rural sewage treatment stations. We found that the biodegradability of rural wastewater is adequate, and BOD5/COD ratio in sewage was 0.4, which is suitable for biological treatment. It has obvious intermittent flow cut-off characteristics, and the range of cut-off duration of sewage was 6-16 h/d, which leads to poor pollutant removal efficiency (COD: 50.0 ± 29.2%, NH4+-N: 46.0 ± 26.1%, TN: 38.5 ± 24.9% and TP: 38.3 ± 23.8%) in sewage treatment stations. In response to the above characteristics, the rural sewage biologically enhanced internal circulation treatment (BEICT) system was constructed. After 97 days of operation, the system has a stable removal effect on TN and TP with an average removal rate of 77.42% and 89.69%, respectively, under the condition of influent interruption for 12 h per day. The activated sludge of system maintained good activity and stable sedimentation performance during the whole experiment, with MLVSS/MLSS and SVI of 0.72 and 128 mL/g, respectively. This study can provide the basis and technical support for the accurate design of rural sewage treatment facilities, and has important significance for guiding the treatment of rural domestic sewage in China.

Enhanced degradation of petroleum in saline soil by nitrogen stimulation and halophilic emulsifying bacteria Bacillus sp. Z-13.

Remediation of petroleum-contaminated soil is a widely concerned challenge. As an ecofriendly method, the performance improvement of indigenous microbial degradation is facing the bottleneck. In this study, a strain with high efficiency of petroleum degradation was isolated from the petroleum-contaminated soil and identified and named as Bacillus sp. Z-13. The strain showed the ability to produce lipopeptide surfactant which could improve 66% more petroleum hydrocarbons eluted. Strain Z-13 and its biosurfactant exhibited broad environmental adaptability to salinity (0-8%), pH (6-9) and temperature (15-45 °C). With the addition of strain Z-13 and the stimulation of NH4Cl, up to 59% of the petroleum in the contaminated soil was removed at the carbon to nitrogen ratio of 10. Microbial community analysis showed that petroleum-degrading bacteria, represented by Bacillus, became the dominant species at genus level and played an important role in the remediation. Additionally, ammonium stimulation facilitated both pathways of ammonium assimilation and nitrification in native microorganisms to achieve efficient degradation of petroleum hydrocarbons. This study could provide a promising approach for stable, environmental-friendly and efficient remediation of petroleum-contaminated soil.

Traditional Chinese medicine in the era of immune checkpoint inhibitor: theory, development, and future directions.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer management and have been widely applied; however, they still have some limitations in terms of efficacy and toxicity. There are multiple treatment regimens in Traditional Chinese Medicine (TCM) that play active roles in combination with Western medicine in the field of oncology treatment. TCM with ICIs works by regulating the tumor microenvironment and modulating gut microbiota. Through multiple targets and multiple means, TCM enhances the efficacy of ICIs, reverses resistance, and effectively prevents and treats ICI-related adverse events based on basic and clinical studies. However, there have been few conclusions on this topic. This review summarizes the development of TCM in cancer treatment, the mechanisms underlying the combination of TCM and ICIs, existing studies, ongoing trials, and prospects for future development.

Integrated application of phosphorus-accumulating bacteria and phosphorus-solubilizing bacteria to achieve sustainable phosphorus management in saline soils.

The challenge of managing agricultural phosphorus (P) in saline regions entails both reducing leaching for environmental protection and maintaining soil available P levels for crop production, which could be achieved through functional microorganisms that can facilitate P transformation processes like P assimilation, inorganic P solubilization, and organic P mineralization. In this study, we proposed an integrated utilization of phosphorus-accumulating bacteria (PAB) and phosphorus-solubilizing bacteria (PSB) to reach the goal of alleviating P leaching while improving soil available P levels. The study conducted a microcosm experiment that combined a soil column test, soil incubation, and pot experiment to evaluate the effect of bacterial inoculants on soil P leaching, soil P availability, and plant P accumulation. The results showed that the application of PAB reduced 22.6 % of dissolved P leaching through the absorption of labile phosphate in the soil, and 17.3 % of particulate P leaching through the promoted soil aggregation. The integrated inoculation of PSB and PAB synergistically improved soil available P content by 18.3 % through the mineralization of soil organic P, and remarkably boosted wheat growth and its P accumulation. Microbial community analysis revealed that the integrated microbial treatment decreased the diversity of soil bacterial community and increased the abundance of native microbial species, i.g. Lysobacter and Ramlibacter, which were positively correlated with soil available P content and alkaline phosphatase level. In conclusion, the integrated microbial strategy based on halotolerant PAB and PSB has great potential for sustainable P management in saline areas and agricultural activities.

Enhanced phytoremediation of petroleum-contaminated soil by biochar and urea.

Application of bioremediation in petroleum-contaminated soils is limited by its low efficiency. Although biochar and urea are commonly used soil additives, their potential beneficial effect on the bioremediation of petroleum contamination have rarely been discussed. In this study, biochar and urea were combined to test their effects on the phytoremediation of petroleum-contaminated soil in pot experiments. Our results showed that the degradation rate of total petroleum hydrocarbons reached 49.6%, 38.3%, 42.5%, and 77.9% when the soil was treated with biochar, urea, ryegrass, and their integrated application treatment (PBCN), respectively. A number of soil physicochemical properties (e.g., pH, elements, aggregate distribution, and organic matter composition) altered by the treatments were found to be linked to the accelerated degradation of petroleum hydrocarbons. The activities of soil dehydrogenase, lipase, and urease, and the abundances of 16 s rRNA gene and alkane degradation-related genes could be increased simultaneously when biochar, urea, and ryegrass were co-applied. Furthermore, urea significantly reduced soil bacterial α-diversity, while soil bacterial community dissimilation was mainly driven by urea and ryegrass. Lysobacter, xanthomonadaceae, and longimicrobia could be biomarker species in the PBCN group. Soil bacterial network analysis showed that biochar and urea application decreased the network complexity and robustness, while ryegrass behaved inversely. Lastly, soil metabolomic analysis revealed that root soil metabolites were greatly affected by urea-addition during phytoremediation, and co-application of biochar and urea could activate the putative metabolism pathway of petroleum hydrocarbons in root soil (e.g., naphthalene and anthracene degradation, and pyruvate metabolism). In summary, this study confirmed the enhancement of biochar and urea application in the phytoremediation of petroleum-contaminated soil and explored the internal mechanism of the interactive effect, which can potentially improve the development of eco-friendly and cost-effective in-situ bioremediation technology for petroleum-contaminated soils.

Nano-selenium Antagonizes Heat Stress-Induced Apoptosis of Rainbow Trout (Oncorhynchus mykiss) Hepatocytes by Activating the PI3K/AKT Pathway.

The cold-water fish rainbow trout (Oncorhynchus mykiss) shows poor resistance to heat, which is the main factor restricting their survival and yield. With the advancement of nanotechnology, nano-selenium (nano-Se) has emerged as a key nano-trace element, showing unique advantages, including high biological activity and low toxicity, for studying the response of animals to adverse environmental conditions. However, little is still known regarding the potential protective mechanisms of nano-Se against heat stress-induced cellular damage. Herein, we aimed to investigate the mechanism underlying the antagonistic effects of nano-Se on heat stress. Four groups were assessed: CG18 (0 µg/mL nano-Se, 18 °C), Se18 (5.0 µg/mL nano-Se, 18 °C), CG24 (0 µg/mL nano-Se, incubated at 18 °C for 24 h and then transferred to 24 °C culture), and Se24 (5.0 µg/mL nano-Se, incubated at 18 °C for 24 h and then transferred to 24 °C culture). We found that after heat treatment (CG24 group), T-AOC, GPx, and CAT activities in rainbow trout hepatocytes showed a decrease of 36%, 33%, and 19%, respectively, while ROS and MDA levels showed an increase of 67% and 93%, respectively (P < 0.05). Meanwhile, the mRNA levels of the apoptosis-related genes caspase3, caspase9, Cyt-c, Bax, and Bax/Bcl-2 in the CG24 group were 41%, 47%, 285%, 65%, and 151% higher than those in the CG18 group, respectively, while those of PI3K and AKT were 31% and 17% lower, respectively (P < 0.05). Besides, flow cytometry analysis showed an increase in the level of apoptotic cells after heat exposure. More importantly, we observed that nano-Se cotreatment (Se24 group) remarkably attenuated heat stress-induced effects (P < 0.05). We conclude that heat stress induces oxidative stress and apoptosis in rainbow trout hepatocytes. Nano-Se ameliorates heat stress-induced apoptosis by activating the PI3K/AKT pathway. Our results provide a new perspective to improve our understanding of the ability of nano-Se to confer heat stress resistance.

miR-330 targeting BCO2 is involved in carotenoid metabolism to regulate skin pigmentation in rainbow trout (Oncorhynchus mykiss).

BACKGROUND: MicroRNAs (miRNAs) play a critical role in regulating skin pigmentation. As a key economic trait, skin color directly affects the market value of rainbow trout (Oncorhynchus mykiss), however, the regulatory mechanism of most miRNAs in fish skin color is still unclear. RESULTS: In this study, the full-length cDNA sequence of ß-carotene oxygenase 2 (BCO2, a key regulator of carotenoid metabolism) from the rainbow trout was obtained using rapid-amplification of cDNA ends (RACE) technology, and qRT-PCR was used to investigate the differential expression of miR-330 and BCO2 in 14 developmental stages and 13 tissues between wild-type rainbow trout (WTrt) and yellow mutant rainbow trout (YMrt). Additionally, the function of miR-330 was verified by overexpression and silencing in vitro and in vivo. The results showed that the complete cDNA sequence of BCO2 was 2057 bp with a 1707 bp ORF, encoding a 568 amino acid protein having a molecular weight of 64.07 kD. Sequence alignment revealed that higher conservation of BCO2 protein amongst fishes than amongst other vertebrates, which was further confirmed by phylogenetic analysis. The analysis of spatial and temporal expression patterns suggested that BCO2 and miR-330 were abundantly expressed from fertilized-stage to multi-cell as well as in the dorsal and ventral skin of WTrt and YMrt, and their expression patterns were opposite in most of the same periods and tissues. In vitro, luciferase reporter assay confirmed that BCO2 was a direct target of miR-330, and transfection of miR-330 mimics into rainbow trout liver cells resulted in a decrease in the expression of BCO2; conversely, miR-330 inhibitor had the opposite effect to the miR-330 mimics. In vivo, miR-330 agomir significantly decreased BCO2 expression in dorsal skin, tail fin, and liver. Furthermore, overexpression of miR-330 could suppress cell proliferation and induce apoptosis. CONCLUSION: Our results showed that miR-330 is involved in the regulation of skin pigmentation in rainbow trout by targeting BCO2 and shows its promise as a potential molecular target to assist the selection of rainbow trout with better skin color patterns.

Dietary nano-selenium alleviates heat stress-induced intestinal damage through affecting intestinal antioxidant capacity and microbiota in rainbow trout (Oncorhynchus mykiss).

Heat stress-induced intestinal damage is a key event in fish pathology. Nano-selenium (nano-Se) shows remarkably high biological activity and low toxicity, making it an ideal and ecological Se formulation; however, to date, the protective effects of nano-Se against heat stress-induced intestinal injury and pertinent molecular mechanisms remain unknown. Herein, rainbow trout (Oncorhynchus mykiss) were fed either a basal diet or basal diet + 5 mg/kg nano-Se. Samples were collected before (18 °C for 9 days; CG18 and Se18 groups) and after (24 °C for 8 h; CG24 and Se24 groups) heat stress treatment. On heat stress exposure, intestinal villus height, muscularis thickness, and goblet cell number decreased, and expression of tight junction proteins (ZO-1, occludin, and claudin-8d) was downregulated; dietary supplementation with nano-Se alleviated these effects. Furthermore, in the presence of nano-Se, catalase activity was elevated, and expression of diverse heat shock proteins (Hsp70b, Hsp90α, and Hsp30), selenoproteins (Gpx1a, Gpx1b1, and Trx), and anti-inflammatory cytokine (TGF-ß) was upregulated. In contrast, nano-Se supplementation significantly alleviated the increase of the expression of pro-inflammatory cytokines (IL-1ß and TNF-α) and the malondialdehyde content. We also observed that heat stress markedly increased the relative abundance of Actinobacteria, Firmicutes, Methylobacterium, Akkermansia, and Deinococcus and decreased that of Proteobacteria; nano-Se supplementation restored these changes, making their distribution similar to that in the control group. Overall, our findings suggest that nano-Se plays a protective role against heat stress-induced intestinal damage in rainbow trout by promoting the recovery of antioxidant enzyme activity, enhancing protein repair, alleviating inflammatory responses, and restoring intestinal microbiota composition.

Transcriptome sequencing reveals the effect of selenium nanoparticles on primary hepatocytes of rainbow trout.

Heat stress is one of the important threats in rainbow trout culture, and selenium nanoparticles (SeNPs) have an important role in combating heat stress and enhancing immunity. In this study, to enable rainbow trout to survive at higher temperatures, we added 5 µg/mL SeNPs to hepatocytes to study the resistance effect and immune effect of SeNPs against heat stress, thus enabling rainbow trout to adapt to summer temperatures (Average 26 °C) in Lanzhou, Gansu Province, China. Therefore, we investigated the transcriptome expression profile of hepatocytes spiked with SeNPs when exposed to heat stress. A total of 234 differentially expressed genes (DEGs) were firmly established in SeNPs-added group when exposed to heat stress compared to non-SeNPs-added group. Of these DEGs, 156 were up-regulated and 78 were down-regulated. These DEGs were grouped into different Gene Ontology (GO) functional terms and enriched in 75 significantly different Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, of which approximately-one-third (19) were associated with immunity. STRING was used to identify 39 key immune DEGs belonging to 5 immune pathways (C-type lectin receptor signaling pathway, FoxO signaling pathway, Toll-like receptor signaling pathway, RIG-I-like receptor signaling pathway, and Rachidonic acid metabolism). These pathways interact extensively and formed a complex network to regulate heat stress. These results provided an important basis for future elucidation of the role of SeNPs in heat stress resistance and immune enhancement in rainbow trout.

Effect of selenium nanoparticles on alternative splicing in heat-stressed rainbow trout primary hepatocytes.

Alternative splicing (AS) is a ubiquitous post-transcriptional regulatory mechanism in eukaryotes that generates multiple mRNA isoforms from a single gene, increasing diversity of mRNAs and proteins that are essential for eukaryotic developmental processes and responses to environmental stress. Results showed that a total of 37,463 AS events were identified in rainbow trout hepatocytes. In addition, a total of 364 differential alternative splicing (DAS) events were identified in hepatocytes under selenium nanoparticles (SeNPs) and 3632 DAS events were identified under a combination of SeNPs and heat stress (24 °C). Gene Ontology (GO) enrichment showed that some subcategories "immune effector processes", "response to stimuli" and "antioxidant activity" were associated with immunity, abiotic stimuli and antioxidants. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment showed that differentially expressed genes (DEGs) were significantly enriched in spliceosomes by adding SeNPs in heat-stressed hepatocytes. Splicing factor family (SRSF3, SRSF7, SRSF9, U2AF1 and U2AF2) and pre-RNA splicing factors (ACIN1 and PPRF18) were significantly upregulated and promoted AS. Furthermore, addition of SeNPs activated the phosphatidylinositol signaling system and upregulated the related genes PI4KA, DGKH, ITPK1 and Ocrl, and thus attenuated the inflammatory response to heat stress and enhanced resistance to heat stress by activating the adherent plaque kinase-PI3K-Akt signaling pathway and calcium channels. Those findings suggested that AS could be an essential regulatory mechanism in adaptation of rainbow trout to heat-stressed environments.

Response to roxadustat in a patient undergoing long-term dialysis and allergic to erythropoiesis-stimulating agents: A case report.

BACKGROUND: Hypoxia-inducible factor prolyl hydroxylase inhibitor is a new class of drugs for treating renal anemia. It is a second-generation hypoxia-inducible factor prolyl hydroxylase-2 (PHD2) inhibitor. Roxadustat can effectively increase hemoglobin in patients with dialysis-dependent chronic kidney disease, with an adverse events profile comparable to that of epoetin alfa. We administered roxadustat to a maintenance hemodialysis patient who was allergic to erythropoiesis-stimulating agents (ESAs) and depended on blood transfusion for five years. After applying Roxadustat, the patient's anemia improved significantly. CASE SUMMARY: A 77-year-old Chinese man had type 2 diabetes for 16 years, underwent maintenance hemodialysis for five years, and had fatigue for five years. Laboratory tests showed severe anemia (hemoglobin concentration of 42 g/L). The patient was administered a subcutaneous injection of ESAs before dialysis. He suffered an allergic shock immediately and fainted. His blood pressure dropped to undetectable levels. He was not administered ESAs henceforth. The patient was prescribed iron supplements and received blood transfusions occasionally for five years. His hemoglobin concentration ranged from 42-68 g/L. After taking six weeks of oral roxadustat three times weekly (100 mg TIW), the patient's hemoglobin concentration increased significantly, and his symptoms decreased. We adjusted the doses of roxadustat, and the hemoglobin concentration was maintained between 97 and 126 g/L. CONCLUSION: Oral roxadustat is effective in treating anemia in maintenance hemodialysis patients who cannot be administered ESAs.

Effects of autotoxicity and allelopathy on seed germination and seedling growth in Medicago truncatula.

Autotoxicity is a form of intraspecific allelopathy, in which a plant species inhibits the establishment or growth of the same species through the release of toxic chemical compounds into the environment. The phenomenon of autotoxicity in crops is best traced in alfalfa (Medicago sativa). A close relative of alfalfa, M. truncatula, has been developed into an excellent model species for leguminous plants. However, it is not known whether M. truncatula has autotoxicity. In this study, M. truncatula root exudates showed a negative impact on the growth of M. truncatula seedlings, indicating autotoxicity. Detailed analyses with plant extracts from M. truncatula and alfalfa revealed varying degrees of suppression effects in the two species. The extracts negatively affected seed germination potential, germination rate, radicle length, hypocotyl length, synthetic allelopathic effect index, plant height, root growth, fresh weight, dry weight, net photosynthetic rate, transpiration rate, and stomatal conductance in both M. truncatula and alfalfa. The results demonstrated that autotoxicity and allelopathic effects exist in M. truncatula. This opens up a new way to use M. truncatula as a model species to carry out in-depth studies of autotoxicity and allelopathy to elucidate biochemical pathways of allelochemicals and molecular networks controlling biosynthesis of the chemicals.

Comprehensive characterization of ingredients in Crocus sativus L. from different origins based on the combination of targeted and nontargeted strategies.

As a valuable medicinal and edible plant, Crocus sativus L. has had wide applications since ancient times. Herein, a comprehensive approach for characterization of constituents in saffron was established based on the combination of targeted and non-targeted strategies. A targeted UPLC-ESI/MSn strategy was applied for in-depth identification of crocins, and a non-targeted UPLC-ESI/MS2 approach characterized other components. This integration strategy was used to analyze ingredients in 21 batches of saffrons from 6 origins. Forty-seven crocins belonging to 8 types were identified including 32 new crocins. Among them, 6 new compounds with specific structures were reported for the first time, i.e. trans-6(G, 2G), trans-4(GT, g), trans-3(GT), cis-3(GT), methyl ester-trans-2(G) and methyl ester-cis-2(G). Besides, 91 non-crocin components were identified including 43 new compounds. Based on systematic investigation of crocins and non-crocins, we found that crocins were the critical components to distinguish saffrons from different origins, especially between domestic and foreign samples.

Association of Vitamin D Supplementation with Cardiovascular Events: A Systematic Review and Meta-Analysis.

BACKGROUND: low vitamin D status has been associated with an increased incidence of cardiovascular events. However, whether vitamin D supplementation would reduce the incidence of cardiovascular events remains unclear. PURPOSE: To perform a systematic review and meta-analysis of the effect of vitamin D supplementation on the mortality and incidence of cardiovascular events. DATA SOURCES: We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from their inception until 3 May 2022. STUDY SELECTION: Two authors searched for randomized clinical trials that reported vitamin D supplementation's effect on cardiovascular events outcomes. DATA EXTRACTION: Two authors conducted independent data extraction. DATA SYNTHESIS: We identified 41,809 reports; after exclusions, 18 trials with a total of 70,278 participants were eligible for analysis. Vitamin D supplementation was not associated with the mortality of cardiovascular events (RR 0.96, 95% CI 0.88-1.06, I2 = 0%), the incidence of stroke (RR 1.05, 95% CI 0.92-1.20, I2 = 0%), myocardial infarction (RR 0.97, 95% CI 0.87-1.09, I2 = 0%), total cardiovascular events (RR 0.97, 95% CI 0.91-1.04, I2 = 27%), or cerebrovascular events (RR 1.01, 95% CI 0.87-1.18, I2 = 0%). LIMITATION: Cardiovascular events were the secondary outcome in most trials and thus, might be selectively reported. CONCLUSION: In this meta-analysis of randomized clinical trials, vitamin D supplementation was not associated with a lower risk of cardiovascular events than no supplementation. These findings do not support the routine use of vitamin D supplementation in general.

Blending Technology Based on HPLC Fingerprint and Nonlinear Programming to Control the Quality of Ginkgo Leaves.

The breadth and depth of traditional Chinese medicine (TCM) applications have been expanding in recent years, yet the problem of quality control has arisen in the application process. It is essential to design an algorithm to provide blending ratios that ensure a high overall product similarity to the target with controlled deviations in individual ingredient content. We developed a new blending algorithm and scheme by comparing different samples of ginkgo leaves. High-consistency samples were used to establish the blending target, and qualified samples were used for blending. Principal component analysis (PCA) was used as the sample screening method. A nonlinear programming algorithm was applied to calculate the blending ratio under different blending constraints. In one set of calculation experiments, the result was blended by the same samples under different conditions. Its relative deviation coefficients (RDCs) were controlled within ±10%. In another set of calculations, the RDCs of more component blending by different samples were controlled within ±20%. Finally, the near-critical calculation ratio was used for the actual experiments. The experimental results met the initial setting requirements. The results show that our algorithm can flexibly control the content of TCMs. The quality control of the production process of TCMs was achieved by improving the content stability of raw materials using blending. The algorithm provides a groundbreaking idea for quality control of TCMs.