Genome-edited powdery mildew resistance in wheat without growth penalties.

Disruption of susceptibility (S) genes in crops is an attractive breeding strategy for conferring disease resistance1,2. However, S genes are implicated in many essential biological functions and deletion of these genes typically results in undesired pleiotropic effects1. Loss-of-function mutations in one such S gene, Mildew resistance locus O (MLO), confers durable and broad-spectrum resistance to powdery mildew in various plant species2,3. However, mlo-associated resistance is also accompanied by growth penalties and yield losses3,4, thereby limiting its widespread use in agriculture. Here we describe Tamlo-R32, a mutant with a 304-kilobase pair targeted deletion in the MLO-B1 locus of wheat that retains crop growth and yields while conferring robust powdery mildew resistance. We show that this deletion results in an altered local chromatin landscape, leading to the ectopic activation of Tonoplast monosaccharide transporter 3 (TaTMT3B), and that this activation alleviates growth and yield penalties associated with MLO disruption. Notably, the function of TMT3 is conserved in other plant species such as Arabidopsis thaliana. Moreover, precision genome editing facilitates the rapid introduction of this mlo resistance allele (Tamlo-R32) into elite wheat varieties. This work demonstrates the ability to stack genetic changes to rescue growth defects caused by recessive alleles, which is critical for developing high-yielding crop varieties with robust and durable disease resistance.

Polarity-Mediated Antisolvent Control Enables Efficient Lanthanide-Based near-Infrared Perovskite LEDs.

Alloying lanthanide ions (Yb3+) into perovskite quantum dots (Yb3+:CsPb(Cl1-xBrx)3) is an effective method to achieve efficient near-infrared (NIR) luminescence (>950 nm). Increasing the Yb3+ alloying ratio in the perovskite matrix enhances the luminescence intensity of Yb3+ emission at 990 nm. However, high Yb3+ alloying (>15%) results in vacancy-induced inferior material stability. In this work, we developed a polarity-mediated antisolvent manipulation strategy to resolve the incompatibility between a high Yb3+ alloying ratio and inferior stability of Yb3+:CsPb(Cl1-xBrx)3. Precise control of solution polarity enables increased uniformity of the perovskite matrix with fewer trap densities. Employing this strategy, we obtain Yb3+:CsPb(Cl1-xBrx)3 with the highest Yb3+ alloying ratio of 30.2% and a 2-fold higher electroluminescence intensity at 990 nm. We lever the engineered Yb3+:CsPb(Cl1-xBrx)3 to fabricate NIR-LEDs, achieving a peak external quantum efficiency (EQE) of 8.5% at 990 nm: this represents the highest among perovskite NIR-LEDs with an emission wavelength above 950 nm.

Vernalization promotes bolting in sugar beet by inhibiting the transcriptional repressors of BvGI.

Sugar beet (Beta vulgaris L.), a biennial sugar crop, contributes about 16% of the world's sugar production. The transition from vegetative growth, during which sugar accumulated in beet, to reproductive growth, during which sugar exhausted in beet, is determined by vernalization and photoperiod. GIGANTEA (GI) is a key photoperiodic flowering gene that is induced by vernalization in sugar beet. To identify the upstream regulatory factors of BvGI, candidate transcription factors (TF) that were co-expressed with BvGI and could bind to the BvGI promoter were screened based on weighted gene co-expression network analysis (WGCNA) and TF binding site prediction. Subsequently, their transcriptional regulatory role on the BvGI was validated through subcellular localization, dual-luciferase assays and yeast transformation tests. A total of 7,586 differentially expressed genes were identified after vernalization and divided into 18 co-expression modules by WGCNA, of which one (MEcyan) and two (MEdarkorange2 and MEmidnightblue) modules were positively and negatively correlated with the expression of BvGI, respectively. TF binding site predictions using PlantTFDB enabled the screening of BvLHY, BvTCP4 and BvCRF4 as candidate TFs that negatively regulated the expression of BvGI by affecting its transcription. Subcellular localization showed that BvLHY, BvTCP4 and BvCRF4 were localized to the nucleus. The results of dual-luciferase assays and yeast transformation tests showed that the relative luciferase activity and expression of HIS3 was reduced in the BvLHY, BvTCP4 and BvCRF4 transformants, which suggested that the three TFs inhibited the BvGI promoter. In addition, real-time quantitative reverse transcription PCR showed that BvLHY and BvTCP4 exhibited rhythmic expression characteristics similar to that of BvGI, while BvCRF4 did not. Our results revealed that vernalization crosstalked with the photoperiod pathway to initiate bolting in sugar beet by inhibiting the transcriptional repressors of BvGI.

Identification and exploration of aging-related subtypes and distinctive role of SERPINE1 in heart failure based on single-cell and bulk RNA sequencing data.

Aging is a major risk factor for heart failure (HF) and is the leading cause of death worldwide. Currently, the nature of the relationship between aging and HF is not entirely clear. Herein, this study aimed to explore new diagnostic biomarkers, molecular typing and therapeutic strategies for HF by investigating the biological significance of aging-related genes in HF. A total of 157 differentially expressed genes (DEGs) were screened totally between HF and normal samples, and functional enrichment analysis of DEGs revealed the strong association of HF progression with aging, immune processes and metabolism. Six HF-specific aging-related genes were further identified, and a diagnostic model was developed and validated for good diagnostic efficacy. In addition, we collected blood samples from 10 normal controls and 10 HF patients for RT-qPCR analysis to verify the bioinformation. We also identified two aging-associated subtypes with distinctly different immune infiltration and metabolic microenvironment. Further single-cell sequencing analysis conducted in the study identified SERPINE1 as a key gene in HF. The distinctive role of SERPINE1 fibroblasts was revealed, including three main findings: (I) fibroblasts had a higher proportion and expression of SERPINE1 levels in HF; (II) the ligand-receptor pair MDK-LRP1 made the most contributions in high interactions with other cell types in SERPINE1 fibroblasts; and (III) SERPINE1 fibroblasts were associated with the interaction of extracellular matrix and receptor and may be regulated by the transcription factor EGR1. In conclusion, this study highlights the importance of aging-related genes in diagnosing HF and regulating immune infiltration. We also identified different HF subtypes and a potentially crucial gene, which may provide a better understanding of the molecular-level mechanisms of aging-related HF and aid in developing effective therapeutic strategies.

Intratumoral microbial heterogeneity affected tumor immune microenvironment and determined clinical outcome of HBV-related HCC.

BACKGROUND AND AIMS: The intratumoral microbiome has been reported to regulate the development and progression of cancers. We aimed to characterize intratumoral microbial heterogeneity (IMH) and establish microbiome-based molecular subtyping of HBV-related HCC to elucidate the correlation between IMH and HCC tumorigenesis. APPROACH AND RESULTS: A case-control study was designed to investigate microbial landscape and characteristic microbial signatures of HBV-related HCC tissues adopting metagenomics next-generation sequencing. Microbiome-based molecular subtyping of HCC tissues was established by nonmetric multidimensional scaling. The tumor immune microenvironment of 2 molecular subtypes was characterized by EPIC and CIBERSORT based on RNA-seq and verified by immunohistochemistry. The gene set variation analysis was adopted to explore the crosstalk between the immune and metabolism microenvironment. A prognosis-related gene risk signature between 2 subtypes was constructed by the weighted gene coexpression network analysis and the Cox regression analysis and then verified by the Kaplan-Meier survival curve.IMH demonstrated in HBV-related HCC tissues was comparably lower than that in chronic hepatitis tissues. Two microbiome-based HCC molecular subtypes, defined as bacteria- and virus-dominant subtypes, were established and significantly correlated with discrepant clinical-pathologic features. Higher infiltration of M2 macrophage was detected in the bacteria-dominant subtype with to the virus-dominant subtype, accompanied by multiple upregulated metabolism pathways. Furthermore, a 3-gene risk signature containing CSAG4 , PIP4P2 , and TOMM5 was filtered out, which could predict the clinical prognosis of HCC patients accurately using the Cancer Genome Atlas data. CONCLUSIONS: Microbiome-based molecular subtyping demonstrated IMH of HBV-related HCC was correlated with a disparity in clinical-pathologic features and tumor microenvironment (TME), which might be proposed as a biomarker for prognosis prediction of HCC.

Relationship between triglyceride-glucose index baselines and trajectories with incident cardiovascular diseases in the elderly population.

BACKGROUND: The triglyceride-glucose (TyG) index is regarded as a sophisticated surrogate biomarker for insulin resistance, offering a refined means for evaluating cardiovascular diseases (CVDs). However, prospective cohort studies have not simultaneously conducted baseline and multi-timepoint trajectory assessments of the TyG index in relation to CVDs and their subtypes in elderly participants. METHODS: After excluding data deficiencies and conditions that could influence the research outcomes, this study ultimately incorporated a cohort of 20,185 participants, with data chronicles extending from 2016 to 2022. The TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Latent Class Trajectory Model (LCTM) was used to assess the change trends of the TyG index over multiple time points. Utilizing the Cox proportional-hazards models, we assessed the relationship between the baseline quartiles of the TyG index and various trajectories with CVDs and subtypes. RESULTS: During the mean follow-up time of 4.25 years, 11,099 patients experienced new CVDs in the elderly population. After stratifying by baseline TyG quartiles, the higher TyG level was associated with an increased risk of CVDs; the aHR and 95% CI for the highest quartile group were 1.28 (1.19-1.39). Five trajectory patterns were identified by the LCTM model. The low gradual increase group as the reference, the medium stable group, and the high gradual increase group exhibited an elevated risk of CVDs onset, aHR and 95%CIs were 1.17 (1.10-1.25) and 1.25 (1.15-1.35). Similar results were observed between the trajectories of the TyG index with subtypes of CVDs. CONCLUSION: Participants with high levels of baseline TyG index and medium stable or high gradual increase trajectories were associated with an elevated risk of developing CVDs in elderly populations.

DAHOS Study: Efficacy of dapagliflozin in treating heart failure with reduced ejection fraction and obstructive sleep apnea syndrome - A 3-month, multicenter, randomized controlled clinical trial.

BACKGROUND: The recent discovery of new therapeutic approaches to heart failure with reduced ejection fraction (HFrEF), including sodium-glucose cotransporter-2 (SGLT-2) inhibitors, as well as improved treatment of co-morbidities has provided much needed help to HFrEF. In addition, dapagliflozin, one of the SGLT-2 inhibitors, serves as a promising candidate in treating obstructive sleep apnea (OSA) of HFrEF patients due to its likely mechanism of countering the pathophysiology of OSA of HFrEF. METHODS: This 3-month multicenter, prospective, randomized controlled trial enrolled participants with left ventricular ejection fraction (LVEF) less than 40% and apnea-hypopnea index (AHI) greater than 15. Participants were randomized into two groups: the treatment group received optimized heart failure treatment and standard-dose dapagliflozin, while the control group only received optimized heart failure treatment. The primary endpoint was the difference in AHI before and after treatment between the two groups. Secondary endpoints included oxygen desaturation index (ODI), minimum oxygen saturation, longest apnea duration, inflammatory factors (CRP, IL-6), quality of life score, and LVEF. RESULTS: A total of 107 patients were included in the final analysis. AHI, LVEF and other baseline data were similar for the dapagliflozin and control groups. After 12 weeks of dapagliflozin treatment, the dapagliflozin group showed significant improvements in sleep parameters including AHI, HI, longest pause time, ODI, time spent with SpO2 < 90%, and average SpO2. Meanwhile, the control group showed no significant changes in sleep parameters, but did demonstrate significant improvements in left ventricular end-diastolic diameter, LVEF, and NT-proBNP levels at 12 weeks. In the experimental group, BMI was significantly reduced, and there were improvements in ESS score, MLHFQ score, and EQ-5D-3L score, as well as significant reductions in CRP and IL-6 levels, while the CRP and IL-6 levels were not improved in the control group. The decrease in LVEF was more significant in the experimental group compared to the control group. There were no significant differences in the magnitude of the decreases between the two groups. CONCLUSIONS: Dapagliflozin may be an effective treatment for heart failure complicated with OSA, and could be considered as a potential new treatment for OSA. (Trial registration  www.chictr.org.cn , ChiCTR2100049834. Registered 10 August 2021).

Insights into the removal of antibiotics from livestock and aquaculture wastewater by algae-bacteria symbiosis systems.

With the burgeoning growth of the livestock and aquaculture industries, antibiotic residues in treated wastewater have become a serious ecological threat. Traditional biological wastewater treatment technologies-while effective for removing conventional pollutants, such as organic carbon, ammonia and phosphate-struggle to eliminate emerging contaminants, notably antibiotics. Recently, the use of microalgae has emerged as a sustainable and promising approach for the removal of antibiotics due to their non-target status, rapid growth and carbon recovery capabilities. This review aims to analyse the current state of antibiotic removal from wastewater using algae-bacteria symbiosis systems and provide valuable recommendations for the development of livestock/aquaculture wastewater treatment technologies. It (1) summarises the biological removal mechanisms of typical antibiotics, including bioadsorption, bioaccumulation, biodegradation and co-metabolism; (2) discusses the roles of intracellular regulation, involving extracellular polymeric substances, pigments, antioxidant enzyme systems, signalling molecules and metabolic pathways; (3) analyses the role of treatment facilities in facilitating algae-bacteria symbiosis, such as sequencing batch reactors, stabilisation ponds, membrane bioreactors and bioelectrochemical systems; and (4) provides insights into bottlenecks and potential solutions. This review offers valuable information on the mechanisms and strategies involved in the removal of antibiotics from livestock/aquaculture wastewater through the symbiosis of microalgae and bacteria.

Aberrant METTL14 gene expression contributes to malignant transformation of benzene-exposed myeloid cells.

Benzene is a known contributor to human leukaemia through its toxic effects on bone marrow cells, and epigenetic modification is believed to be a potential mechanism underlying benzene pathogenesis. However, the specific roles of N6-methyladenosine (m6A), a newly discovered RNA post-transcriptional modification, in benzene-induced hematotoxicity remain unclear. In this study, we identified self-renewing malignant proliferating cells in the bone marrow of benzene-exposed mice through in vivo bone marrow transplantation experiments and Competitive Repopulation Assay. Subsequent analysis using whole transcriptome sequencing and RNA m6A methylation sequencing revealed a significant upregulation of RNA m6A modification levels in the benzene-exposed group. Moreover, RNA methyltransferase METTL14, known as a pivotal player in m6A modification, was found to be aberrantly overexpressed in Lin-Sca-1+c-Kit+ (LSK) cells of benzene-exposed mice. Further analysis based on the GEO database showed a positive correlation between the expression of METTL14, mTOR, and GFI and benzene exposure dose. In vitro cellular experiments, employing experiments such as western blot, q-PCR, m6A RIP, and CLIP, validated the regulatory role of METTL14 on mTOR and GFI1. Mechanistically, continuous damage inflicted by benzene exposure on bone marrow cells led to the overexpression of METTL14 in LSK cells, which, in turn, increased m6A modification on the target genes' (mTOR and GFI1) RNA. This upregulation of target gene expression activated signalling pathways such as mTOR-AKT, ultimately resulting in malignant proliferation of bone marrow cells. In conclusion, this study offers insights into potential early targets for benzene-induced haematologic malignant diseases and provides novel perspectives for more targeted preventive and therapeutic strategies.

Prediction of Pre-Loading Relaxation of Bolt Structure of Complex Equipment under Tangential Cyclic Load.

Bolts have the advantages of simple installation and easy removal. They are widely applied in aerospace and high-speed railway traffic. However, the loosening of bolts under mixed loads can lead to nonlinear decreases in pre-loading. This affects the safety performance of the structure and may lead to catastrophic consequences. Existing techniques cannot be used to monitor the bolt performance status in time. This has caused significant problems with the safety and reliability of equipment. In order to study the relaxation law of bolt pre-loading, this paper carries out an experimental analysis for 8.8-grade hexagonal bolts and calibrates the torque coefficient. We also studied different loading waveforms, nickel steel plate surface roughnesses, tangential displacement frequencies, four different strengths and bolt head contact areas of the bolt, the initial pre-loading, and the effects of tangential cyclic displacement on pre-loading relaxation. This was done in order to accurately predict the degree of bolt pre-loading loosening under external loads. The laws are described using the allometric model function and the nine-stage polynomial function. The least squares method is used to identify the parameters in the function. The results show that bolts with a smooth surface of the connected structure nickel steel flat plate, high-frequency working conditions, half-sine wave, and a high-strength have better anti-loosening properties. Taking 5-10 cycles of cyclic loading as a boundary, the pre-loading relaxation is divided into two stages. The first stage is a stage of rapid decrease in bolt pre-loading, and the second stage is the slow decrease process. The performance prediction study shows that the allometric model function is the worst fitted, at 71.7% for the small displacement condition. Other than that, the allometric model function and the nine-stage polynomial function can predict more than 85.5% and 90.4%, which require the use of least squares to identify two and ten unknown parameters, respectively. The complexity of the two is different, but both can by better indicators than the pre-loading relaxation law under specific conditions. It helps to improve the monitoring of bolt loosening and the system use cycle, and it can provide theoretical support for complex equipment working for a long time.

Heavy industrial aggregation area's green transformation optimisation pathways exploration with synergistic reduction pursue of CO2 and gaseous pollutants.

A profound green transformation of China's heavy industrial aggregation regions is required to conquer severe air pollution, and fulfill carbon peak pledge. Here, to clarify the coordinated mechanism and an optimal roadmap for the reduction of CO2 and gaseous pollutants, we integrated input-output modelling, system dynamics, and multi-objective programming to construct a CO2 and gaseous pollutants synergistic reduction model initially; investigated incentive approaches from 2020 to 2035; Hebei, with the largest steel production in China, was adopted as a demonstrative region. Results revealed that intensive dual control of efficiency and structure in energy and industry can accelerate achieving carbon peak in 2029. In optimal case, CO2 emission intensity can reach a 75.2% reduction compared to 2020, and gaseous pollutants continue decline simultaneously (SO2 and NOx can drop by 63% and 48%); and the synergistic reduction level is expected to improve. Thus, vigorously develop decoupling between economy-air pollution-carbon reduction in Hebei. As opposed to efficiency improvement, structural adjustments were demonstrated to be more effective than short-term efficiency improvements. In addition, the estimated development potential of traditional heavy industries such as steel and petrochemicals is limited, whereas the equipment manufacturing industry, closely linked to traditional industries, is expected to continue its development. Furthermore, although in the electrification process, coal consumption is still needed because of its indispensable role in the production process of heavy industries. The results can facilitate policy-making for heavy industrial aggregation areas' green transformation in shaping policies and actions with clear objectives, effective measures, and sound coordination.

Parental Autonomy Granting, Peer Attachment and Problematic Internet Use Among Chinese Adolescents: The Moderating Effect of School Climate.

While the correlation between parental autonomy granting and adolescents' problematic Internet use (PIU) has been confirmed, the processes underlying this connection have not been thoroughly investigated. Drawing on the ecological systems theory, this study sought to investigate the mediating mechanism of peer attachment and the moderating mechanism of school climate that link parental autonomy granting to PIU. A two-wave longitudinal design was employed with a time interval of six months. The participants were 852 adolescents who attended three middle schools located in Guangdong Province, China. Self-report questionnaires were used to obtain data on demographics, parental autonomy granting, peer attachment, school climate, and PIU. The findings indicated that peer attachment significantly mediated the link between parental autonomy granting and adolescent PIU. A positive school climate significantly moderated the influence of parental autonomy granting on peer attachment and the influence of peer attachment on PIU. Specifically, the association between parental autonomy granting and peer attachment and the association between peer attachment and PIU were more pronounced when the school climate was perceived to be positive. This research underscores the possible significance of peer attachment in the association between parental autonomy granting and PIU and offers valuable insights for mitigating the negative outcomes of PIU.

Fasting mimicking diet inhibits tumor-associated macrophage survival and pro-tumor function in hypoxia: implications for combination therapy with anti-angiogenic agent.

BACKGROUND: Recent research shows that tumor-associated macrophages (TAMs) are the primary consumers of glucose in tumor tissue, surpassing that of tumor cells. Our previous studies revealed that inhibiting glucose uptake impairs the survival and tumor-promoting function of hypoxic TAMs, suggesting that glucose reduction by energy restriction (calorie restriction or short-term fasting) may has a significant impact on TAMs. The purpose of this study is to verify the effect of fasting-mimicking diet (FMD) on TAMs, and to determine whether FMD synergizes with anti-angiogenic drug apatinib via TAMs. METHODS: The effect of FMD on TAMs and its synergistic effects with apatinib were observed using an orthotopic mouse breast cancer model. An in vitro cell model, utilizing M2 macrophages derived from THP-1 cell line, was intended to assess the effects of low glucose on TAMs under hypoxic and normoxic conditions. Bioinformatics was used to screen for potential mechanisms of action, which were then validated both in vivo and in vitro. RESULTS: FMD significantly inhibit the pro-tumor function of TAMs in vivo and in vitro, with the inhibitory effect being more pronounced under hypoxic conditions. Additionally, the combination of FMD-mediated TAMs inhibition with apatinib results in synergistic anti-tumor activity. This effect is partially mediated by the downregulation of CCL8 expression and secretion by the mTOR-HIF-1α signaling pathway. CONCLUSIONS: These results support further clinical combination studies of FMD and anti-angiogenic therapy as potential anti-tumor strategies.

ApoE4 associated with severe COVID-19 outcomes via downregulation of ACE2 and imbalanced RAS pathway.

BACKGROUND: Recent numerous epidemiology and clinical association studies reported that ApoE polymorphism might be associated with the risk and severity of coronavirus disease 2019 (COVID-19), and yielded inconsistent results. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection relies on its spike protein binding to angiotensin-converting enzyme 2 (ACE2) receptor expressed on host cell membranes. METHODS: A meta-analysis was conducted to clarify the association between ApoE polymorphism and the risk and severity of COVID-19. Multiple protein interaction assays were utilized to investigate the potential molecular link between ApoE and the SARS-CoV-2 primary receptor ACE2, ApoE and spike protein. Immunoblotting and immunofluorescence staining methods were used to access the regulatory effect of different ApoE isoform on ACE2 protein expression. RESULTS: ApoE gene polymorphism (ε4 carrier genotypes VS non-ε4 carrier genotypes) is associated with the increased risk (P = 0.0003, OR = 1.44, 95% CI 1.18-1.76) and progression (P < 0.00001, OR = 1.85, 95% CI 1.50-2.28) of COVID-19. ApoE interacts with both ACE2 and the spike protein but did not show isoform-dependent binding effects. ApoE4 significantly downregulates ACE2 protein expression in vitro and in vivo and subsequently decreases the conversion of Ang II to Ang 1-7. CONCLUSIONS: ApoE4 increases SARS-CoV-2 infectivity in a manner that may not depend on differential interactions with the spike protein or ACE2. Instead, ApoE4 downregulates ACE2 protein expression and subsequently the dysregulation of renin-angiotensin system (RAS) may provide explanation by which ApoE4 exacerbates COVID-19 disease.

(P)ppGpp synthetase Rsh participates in rifampicin tolerance of persister cells in Brucella abortus in vitro.

Brucella abortus is facultative intracellular pathogen that causes chronic persistent infections and results in abortion and infertility in food animals. Recurrent infections can be one of the results of persister cells formation that transiently displays phenotypic tolerance to high dose of antibiotics treatment. We examined persister cells formation of B. abortus strain A19 in stationary phase and investigated a potential role for the (p)ppGpp synthetase Rsh in this process. We found that B. abortus stationary phase cells can produce higher levels of multi-drugs tolerant persister cells in vitro under high dose of antibiotics (20 × MIC) exposure than do exponential phase cells. Persister cell formation was also induced with environmental stressors pH 4.5, 0.01 M PBS (pH7.0), 2% NaCl and 25 °C, upon exposure to ampicillin, enrofloxacin and rifampicin. Persister cells were not formed following exposure to 1 mM H2O2. The numbers of persister cells were significantly increased following uptake of B. abortus stationary phase cells by RAW264.7 macrophages in contrast with cultures in TSB liquid medium. Environmental stressors to B. abortus significantly increased expression of rsh mRNA level. The rsh null mutant (Δrsh) formed significantly fewer persister cells than the complemented (CΔrsh) and wildtype (WT) strains under high dose of rifampicin in vitro. These data for the first time demonstrate that B. abortus can produce multi-drug tolerant persister cells in stationary phase. The (p)ppGpp synthetase Rsh is necessary for persister cell formation in B. abortus in the presence of rifampicin. On this basis, a new understanding of the recurrent infections of Brucella was advanced, thus provided a new basis for revelation of pathogenic mechanism of the chronic persistent infection in Brucella.

The Effect of Increasing Concentrations of Omega-3 Fatty Acids from either Flaxseed Oil or Preformed Docosahexaenoic Acid on Fatty Acid Composition, Plasma Oxylipin, and Immune Response of Laying Hens.

BACKGROUND: There is a lack of nutrition guidelines for the feeding of omega-3 polyunsaturated fatty acids (PUFA) to laying hens. Knowledge as to whether the type and concentrations of α-linolenic acid (ALA) and/or docosahexaenoic acid (DHA) in the diet can make a difference to the birds' immune responses when subjected to a lipopolysaccharide (LPS) challenge is limited. OBJECTIVES: The study was designed to determine the potential nutritional and health benefits to laying hens when receiving dietary omega-3 PUFA from either ALA or DHA. METHODS: A total of 80 Lohmann LSL-Classic (white egg layer, 20 wk old) were randomly assigned to 1 of 8 treatment diets (10 hens/treatment), provided 0.2%, 0.4%, 0.6%, or 0.8% of total dietary omega-3 PUFA, provided as either ALA-rich flaxseed oil or DHA-enriched algal biomass. After an 8-wk feeding period, the birds were challenged with Escherichia coli-derived LPS (8 mg/kg; i.v. injection), with terminal sample collection 4 h after challenge. Egg yolk, plasma, liver, and spleen samples were collected for subsequent analyses. RESULTS: Increasing dietary omega-3 supplementation yielded predictable responses in egg yolk, plasma, and liver fatty acid concentrations. Dietary intake of ALA contributed mainly to ALA-derived oxylipins. Meanwhile, eicosapentaenoic acid- and DHA-derived oxylipins were primarily influenced by DHA dietary intake. LPS increased the concentrations of almost all the omega-6 PUFA-, ALA-, and DHA-derived oxylipins in plasma and decreased hepatic mRNA expression of COX-2 and 5-LOX (P < 0.001) involved in the biosynthesis of oxylipins. LPS also increased mRNA expression of proinflammatory cytokine IFN-γ and receptor TLR-4 (P < 0.001) in the spleen. CONCLUSIONS: These results revealed that dietary intake of ALA and DHA had unique impacts on fatty acid deposition and their derived oxylipins and inflammatory responses under the administration of LPS in laying hens.

Calcium Orthophosphate in Liposomes for Co-Delivery of Doxorubicin Hydrochloride/Paclitaxel in Breast Cancer.

Nanoparticles (NPs) show great advantages in cancer treatment by enabling controlled and targeted delivery of payloads to tumor sites through the enhanced permeability and retention (EPR) effect. In this study, highly effective pH-responsive and biodegradable calcium orthophosphate@liposomes (CaP@Lip) NPs with a diameter of 110 ± 20 nm were designed and fabricated. CaP@Lip NPs loaded with hydrophobic paclitaxel and hydrophilic doxorubicin hydrochloride achieved excellent drug loading efficiencies of 70 and 90%, respectively. Under physiological conditions, the obtained NPs are negatively charged. However, they switched to positively charged when exposed to weak acidic environments by which internalization can be promoted. Furthermore, the CaP@Lip NPs exhibit an obvious structural collapse under acid conditions (pH 5.5), which confirms their excellent biodegradability. The "proton expansion" effect in endosomes and the pH-responsiveness of the NPs facilitate the release of encapsulated drugs from individual channels. The effectiveness and safety of the drug delivery systems were demonstrated through in vitro and in vivo experiments, with a 76% inhibition of tumor growth. These findings highlight the high targeting ability of the drug-loaded NPs to tumor sites through the EPR effect, effectively suppressing tumor growth and metastasis. By combining CaP NPs and liposomes, this study not only resolves the toxicity of CaP but also enhances the stability of liposomes. The CaP@Lip NPs developed in this study have significant implications for biomedical applications and inspire the development of intelligent and smart drug nanocarriers and release systems for clinical use.

Association of Dietary Approaches to Stop Hypertension (DASH) diet with self-reported sleep-disordered breathing (SDB): a cross-sectional study from China.

Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet has been associated with sleep quality. However, its relationship with sleep-disordered breathing (SDB) remains unknown. This study aimed to explore the association between the DASH diet and SDB using data from a community-based survey among adults in Suzhou, Eastern China. We conducted a cross-sectional analysis of the Suzhou Food Consumption and Health Survey in 2018-2020. Dietary intake was measured by a validated FFQ. The association between the DASH diet and SDB was estimated by multivariable logistic regression analysis. In addition, subgroup analysis and sensitivity analysis were performed to reinforce our findings. A total of 3939 participants were included in the final analysis. Participants in the upper quintile of the DASH score consumed more fruits, vegetables, nuts and legumes, whole grains, and dairy products, and less Na, red/processed meats, and sweetened beverages. The OR for the highest compared with the lowest quintile of the DASH score was 0·68 (95 % CI 0·52, 0·88; Pfor trend = 0·004) for SDB after multivariable adjustment. Of the eight DASH components, vegetables, nuts and legumes, and dairy products were inversely associated with SDB. The associations were similar in subgroups by age, sex, BMI, smoking, alcohol drinking, hypertension, diabetes and hyperlipidaemia. Adherence to the DASH diet was independently associated with decreased odds of self-reported SDB. Our novel results expand previous findings on diet and sleep and suggest the possibility of improving SDB by enhancing diet quality.

Significant Effects of Associated Microorganisms on the Community of Photosynthetic Picoeukaryotes.

Photosynthetic picoeukaryotes (PPEs) form associations with other microorganisms. However, whether and how the associated microbes affect PPE communities remain unknown. We used flow cytometric cell sorting combined with parallel high-throughput sequencing of the 18S and 16S rRNA genes to simultaneously investigate PPEs and their associated microbial communities in the Yangtze-connected Lake Dongting. The lake harbors a great diversity of PPEs. PPE communities exhibited significant temporal rather than spatial variations. Two distinct PPE taxa affiliated with Discostella nipponica and Poterioochromonas malhamensis were dominant during winter/spring and summer, respectively. Parallel high-throughput sequencing revealed a great diversity of associated bacteria and non-pigmented eukaryotes (NPEs) in PPEs sorts. Proteobacteria, Actinobacteria, Bacteroidetes, and Cyanobacteria among the associated bacteria and fungi among the associated NPEs were dominant. PPEs were more apparently associated with bacteria than with NPEs. The co-occurrence network of PPEs and associated microbes formed five major modules, which exhibited distinct temporal patterns, being specific to a certain period. Variations in PPEs communities were significantly correlated with both environmental factors and associated microbial communities. In variation partitioning analysis, the associated bacteria explained the greatest variations in PPE communities, and associated bacteria and NPEs co-explained a large portion of environmental effects on PPE communities. Our results highlight the significance of associated microbes in shaping PPE communities.

Isotopic Constraints on Sources and Transformations of Nitrate in the Mount Everest Proglacial Water.

Glacier melting exports a large amount of nitrate to downstream aquatic ecosystems. Glacial lakes and glacier-fed rivers in proglacial environments serve as primary recipients and distributors of glacier-derived nitrate (NO3-), yet little is known regarding the sources and cycling of nitrate in these water bodies. To address this knowledge gap, we conducted a comprehensive analysis of nitrate isotopes (δ15NNO3, δ18ONO3, and Δ17ONO3) in waters from the glacial lake and river of the Rongbuk Glacier-fed Basin (RGB) in the mountain Everest region. The concentrations of NO3- were low (0.43 ± 0.10 mg/L), similar to or even lower than those observed in glacial lakes and glacier-fed rivers in other high mountain regions, suggesting minimal anthropogenic influence. The NO3- concentration decreases upon entering the glacial lake due to sedimentation, and it increases gradually from upstream to downstream in the river as a soil source is introduced. The analysis of Δ17ONO3 revealed a substantial contribution of unprocessed atmospheric nitrate, ranging from 34.29 to 56.43%. Denitrification and nitrification processes were found to be insignificant in the proglacial water of RGB. Our study highlights the critical role of glacial lakes in capturing and redistributing glacier-derived NO3- and emphasizes the need for further investigations on NO3- transformation in the fast-changing proglacial environment over the Tibetan Plateau and other high mountain regions.