Associations of uric acid with the risk of cardiovascular disease and all-cause mortality among individuals with chronic kidney disease: the Kailuan Study.

AIMS: The relationship between uric acid (UA) concentrations and the risk of cardiovascular disease (CVD), especially for subtypes of CVD among individuals with chronic kidney disease (CKD) is not well understood. This study aimed to investigate whether uric acid concentration was associated with subtypes of CVD and all-cause mortality among individuals with CKD. METHODS: A total of 27,707 individuals with CKD, free of CVD at recruitment from the Kailuan Study, were included. Cox proportional hazards regression models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Over a median follow-up of 11-12 years, we documented 674 myocardial infarctions, 1197 heart failures, 2406 strokes, and 5676 total deaths. Among participants with CKD, compared with those in the lowest tertile of UA, the HRs (95% CIs) of participants in the highest UA tertile were 1.38 (1.13-1.67) for myocardial infarction, 1.60 (1.38-1.85) for heart failure, 1.01 (0.91-1.12) for stroke, and 1.29 (1.21-1.38) for all-cause mortality. Subgroup analyses showed that the associations between UA and heart failure and all-cause mortality were stronger in individuals with eGFR <45 mL/min/1.73m2 compared to their counterparts (Pinteraction<0.05). Additionally, the association between UA and all-cause mortality was stronger among individuals without diabetes than those with diabetes (Pinteraction<0.05). CONCLUSIONS: In individuals with CKD, a higher concentration of UA was associated with a higher risk of myocardial infarction, heart failure, and all-cause mortality, following a dose-response relationship. Our data underscore the importance of UA screening among individuals with CKD for CVD and premature death prevention.

This study investigated the relationship between uric acid (UA) concentrations and the risk of cardiovascular disease and all-cause mortality in individuals with chronic kidney disease (CKD) using the Kailuan Study. A higher concentration of UA was associated with a higher risk of myocardial infarction, heart failure, and all-cause mortality among individuals with CKD, following a dose-response manner.The associations between concentrations of UA and the risk of heart failure and all-cause mortality were more pronounced in individuals with severe kidney impairment (estimated glomerular filtration rate <45 mL/min/1.73m2). Furthermore, the association between UA and all-cause mortality was stronger among individuals without diabetes compared to those with the condition.

Serum Mac-2 binding protein glycosylation isomer dynamics in patients achieving sustained virologic response for hepatitis C virus.

BACKGROUND AND AIM: Understanding the dynamics of serum Mac-2 binding protein glycosylation isomer (M2BPGi) remains pivotal for hepatitis C virus (HCV) patients' post-sustained virologic response (SVR12) through direct-acting antivirals (DAAs). METHODS: We compared areas under receiver operating characteristic curves (AUROCs) of M2BPGi, FIB-4, and APRI and assess M2BPGi cutoff levels in predicting fibrosis stages of ≥F3 and F4 utilizing transient elastography in 638 patients. Variations in M2BPGi levels from pretreatment to SVR12 and their association with pretreatment alanine transaminase (ALT) levels and fibrosis stage were investigated. RESULTS: The AUROCs of M2BPGi were comparable to FIB-4 in predicting ≥F3 (0.914 vs 0.902, P = 0.48) and F4 (0.947 vs 0.915, P = 0.05) but were superior to APRI in predicting ≥F3 (0.914 vs 0.851, P = 0.001) and F4 (0.947 vs 0.857, P < 0.001). Using M2BPGi cutoff values of 2.83 and 3.98, fibrosis stages of ≥F3 and F4 were confirmed with a positive likelihood ratio ≥10. The median M2BPGi change was -0.55. Patients with ALT levels ≥5 times ULN or ≥F3 demonstrated more pronounced median decreases in M2BPGi level compared to those with ALT levels 2-5 times ULN and <2 times ULN (-0.97 vs -0.68 and -0.44; P < 0.001) or with < F3 (-1.52 vs -0.44; P < 0.001). CONCLUSIONS: Serum M2BPGi is a reliable marker for advanced hepatic fibrosis. Following viral clearance, there is a notable M2BPGi decrease, with the extent of reduction influenced by ALT levels and fibrosis stage.

Several major herb pairs containing Coptidis rhizoma: a review of key traditional uses, constituents and compatibility effects.

Herb compatibility is the soul of traditional Chinese Medicine prescriptions. Coptidis rhizoma (CR) (Coptis chinensis Franch., Coptis deltoidea C.Y.Cheng et Hsiao, or Coptis teeta Wall.; family Ranunculaceae), is a well-known herb. The bitter and cold nature of CR can irritate the spleen and stomach, and certain ingredients in CR may trigger allergic reactions. Herb combinations can help alleviate the side effects caused by CR. Through data analysis and literature research, there are many herbs combined with CR have a high frequency, but only a few are currently used as formulae in clinical practice. The results showed that these six herb pairs are usually widely studied or used as prescriptions in the clinic. This paper describes the six herb pairs from the key traditional uses, changes in bioactive constituents, and compatibility effects, especially with Euodiae fructus (family Rutaceae), Scutellariae radix (family Lamiaceae), Magnoliae Officinalis cortex (family Magnoliaceae), Glycyrrhizae radix et rhizoma (family Fabaceae), Ginseng radix et rhizoma (family Araliaceae), and Aucklandiae radix (family Asteraceae), and found that herbs are more effective when used in combination. Therefore, it is feasible to establish some methods to study herb pairs comprehensively from different perspectives. This paper aims to provide the latest and most comprehensive information on the six herb pairs and summarize the pattern of CR compatibility effects. It aims to attract more attention, and further experimental studies will be conducted to investigate and evaluate the effects of herb pairs containing CR. These data can also provide valuable references for researchers and also provide more possibilities for future applications in clinical practice and new drug development.

Mechanism and treatment of secondary glaucoma after corneal transplantation: a review.

Corneal transplantation is a common treatment for corneal diseases. Secondary glaucoma after corneal transplantation is the second leading cause of failure of keratoplasty. This article reviews the mechanism and treatment of secondary glaucoma after corneal transplantation.

Synonymous variant at the terminal nucleotide in exon 3 of F7 causes abnormal splicing: A case report.

BACKGROUND: Synonymous variants are non-pathogenic due to non-substitution of amino acids. However, synonymous exonic terminal nucleotide substitutions may affect splicing. Splicing variants are easily analyzed at RNA level for genes expressed in blood cells. Minigene analysis provides another method for splicing variant analysis of genes that are poorly or not expressed in peripheral blood. METHODS: Whole exome sequencing was performed to screen for potential pathogenic mutations in the proband, which were validated within the family by Sanger sequencing. The pathogenicity of the synonymous mutation was analyzed using the minigene technology. RESULTS: The proband harbored the compound heterogeneous variants c. [291G >A; 572-50C >T] and c.681 + 1G >T in F7, of which the synonymous variant c.291G >A was located at the terminal position of exon 3. Minigene analysis revealed exon3 skipping due to this mutation, which may have subsequently affected protein sequence, structure, and function. CONCLUSION: Our finding confirmed the pathogenicity of c.291G >A, thus extending the pathogenic mutation spectrum of F7, and providing insights for effective reproductive counseling.

Bidirectional effects of the tryptophan metabolite indole-3-acetaldehyde on colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) has a high incidence and mortality. Recent studies have shown that indole derivatives involved in gut microbiota metabolism can impact the tumorigenesis, progression, and metastasis of CRC. AIM: To investigate the effect of indole-3-acetaldehyde (IAAD) on CRC. METHODS: The effect of IAAD was evaluated in a syngeneic mouse model of CRC and CRC cell lines (HCT116 and DLD-1). Cell proliferation was assessed by Ki-67 fluorescence staining and cytotoxicity tests. Cell apoptosis was analysed by flow cytometry after staining with Annexin V-fluorescein isothiocyanate and propidium iodide. Invasiveness was investigated using the transwell assay. Western blotting and real-time fluorescence quantitative polymerase chain reaction were performed to evaluate the expression of epithelial-mesenchymal transition related genes and aryl hydrocarbon receptor (AhR) downstream genes. The PharmMapper, SEA, and SWISS databases were used to screen for potential target proteins of IAAD, and the core proteins were identified through the String database. RESULTS: IAAD reduced tumorigenesis in a syngeneic mouse model. In CRC cell lines HCT116 and DLD1, IAAD exhibited cytotoxicity starting at 24 h of treatment, while it reduced Ki67 expression in the nucleus. The results of flow cytometry showed that IAAD induced apoptosis in HCT116 cells but had no effect on DLD1 cells, which may be related to the activation of AhR. IAAD can also increase the invasiveness and epithelial-mesenchymal transition of HCT116 and DLD1 cells. At low concentrations (< 12.5 µmol/L), IAAD only exhibited cytotoxic effects without promoting cell invasion. In addition, predictions based on online databases, protein-protein interaction analysis, and molecular docking showed that IAAD can bind to matrix metalloproteinase-9 (MMP9), angiotensin converting enzyme (ACE), poly(ADP-ribose) polymerase-1 (PARP1), matrix metalloproteinase-2 (MMP2), and myeloperoxidase (MPO). CONCLUSION: Indole-3-aldehyde can induce cell apoptosis and inhibit cell proliferation to prevent the occurrence of CRC; however, at high concentrations (≥ 25 µmol/L), it can also promote epithelial-mesenchymal transition and invasion in CRC cells. IAAD activates AhR and directly binds MMP9, ACE, PARP1, MMP2, and MPO, which partly reveals why it has a bidirectional effect.

Intensive Versus Moderate Statin-Based Therapies in Patients With Mild Ischemic Stroke: A Prospective Multicenter Cohort Study.

BACKGROUND: Statins are widely used for treating patients with ischemic stroke at risk of secondary cerebrovascular events. It is unknown whether Asian populations benefit from more intensive statin-based therapy for stroke recurrence. Therefore, in the present study we evaluated the effectiveness and safety of high-dose and moderate-dose statins for patients who had experienced mild ischemic stroke during the acute period. METHODS AND RESULTS: This multicenter prospective study included patients with mild ischemic stroke who presented within 72 hours of symptom onset. The outcomes of patients in the high-intensity and moderate-intensity statin treatment groups were compared, with the main efficacy outcome being stroke recurrence and the primary safety end point being intracranial hemorrhage. The propensity score matching method was employed to control for imbalances in baseline variables. Subgroup analyses were conducted to evaluate group differences. In total, the data of 2950 patients were analyzed at 3 months, and the data of 2764 patients were analyzed at 12 months due to loss to follow-up. According to the multivariable Cox analyses adjusted for potential confounders, stroke recurrence occurred similarly in the high-intensity statin and moderate-intensity statin groups (3 months: adjusted hazard ratio [HR], 1.12 [95% CI, 0.85-1.49]; P=0.424; 12 months: adjusted HR, 1.08 [95% CI, 0.86-1.34]; P=0.519). High-intensity statin therapy was associated with an increased risk of intracranial hemorrhage (3 months: adjusted HR, 1.81 [95% CI, 1.00-3.25]; P=0.048; 12 months: adjusted HR, 1.86 [95% CI, 1.10-3.16]; P=0.021). The results from the propensity score-matched analyses were consistent with those from the Cox proportional hazards analysis. CONCLUSIONS: Compared with moderate-intensity statin therapy, high-dose statin therapy may not decrease the risk of mild, noncardiogenic ischemic stroke recurrence but may increase the risk of intracranial hemorrhage. REGISTRATION: URL: www.chictr.org.cn/. Unique Identifier: ChiCTR1900025214.

Effects of different afforestation years on soil moisture and nutrient content in Maxian Mountain of the Loess Plateau.

In the area of "returning farmland to forest" on the Loess Plateau in China, it is difficult to cultivate artificially planted trees into forests. In the current study, abandoned cultivated land after 10 years of natural restoration served as controls (CK), while the treatments included afforestation periods of 2, 4, 6, 8, and 10 years. Soil samples were collected from various depths: 0-20, 20-40, 40-60, 60-80, to 80-100 cm. The findings revealed that with increasing years of artificial afforestation, soil pH gradually increased, and soil moisture content rose in the 0-20 cm layer while declining in deeper layers (20-100 cm) in the Maxian Mountain region of the Loess Plateau. Moreover, the total carbon, nitrogen, phosphorus, and potassium content initially increased and then decreased with the duration of artificial afforestation, reaching peak values after 8 years. Contents of organic matter, ammonium nitrogen, nitrate nitrogen, available phosphorus, and available potassium in the same soil layer increased with each year of afforestation. However, upon reaching 10 years of artificial afforestation, the effective nutrient content in the 60-80 and 80-100 cm soil layers exhibited a decrease. The values of Integrated Fertility Index (IFI) in different afforestation years were ranked as follows: 8 years > 6 years > 10 years > 4 years > 2 year, but all of them were significantly smaller than those of natural restoration plot CK (P < 0.05). Overall, soil fertility in the Maxian Mountain area of the Loess Plateau increases with each additional year of artificial afforestation. However, when the artificial afforestation period is 10 years, soil fertility decreases and marking a shift from enhancement to decline beyond this duration.

Effect of Pretreatments on the Chemical, Bioactive and Physicochemical Properties of Cinnamomum camphora Seed Kernel Extracts.

Cinnamomum camphora seed kernels (CCSKs) are rich in phytochemicals, especially plant extracts. Phytochemicals play a vital role in therapy due to their strong antioxidant and anti-inflammatory activities. Extracts from CCSK can be obtained through multiple steps, including pretreatment, extraction and purification, and the purpose of pretreatment is to separate the oil from other substances in CCSKs. However, C. camphora seed kernel extracts (CKEs) were usually considered as by-products and discarded, and their potential bioactive values were underestimated. Additionally, little has been known about the effect of pretreatment on CKE. This study aimed to investigate the effects of pretreatment methods (including the solvent extraction method, cold pressing method, aqueous extraction method and sub-critical fluid extraction method) on the extraction yields, phytochemical profiles, volatile compounds and antioxidant capacities of different CKE samples. The results showed that the CKE samples were rich in phenolic compounds (15.28-20.29%) and alkaloids (24.44-27.41%). The extraction yield, bioactive substances content and in vitro antioxidant capacity of CKE pretreated by the sub-critical fluid extraction method (CKE-SCFE) were better than CKEs obtained by other methods. CKE pretreated by the solvent extraction method (CKE-SE) showed the best lipid emulsion protective capacity. Moreover, the volatile substances composition of the CKE samples was greatly influenced by the pretreatment method. The results provided a fundamental basis for evaluating the quality and nutritional value of CKE and increasing the economic value of by-products derived from CCSK.

A Deep Dynamic Causal Learning Model to Study Changes in Dynamic Effective Connectivity during Brain Development.

OBJECTIVE: Brain dynamic effective connectivity (dEC), characterizes the information transmission patterns between brain regions that change over time, which provides insight into the biological mechanism underlying brain development. However, most existing methods predominantly capture fixed or temporally invariant EC, leaving dEC largely unexplored. METHODS: Herein we propose a deep dynamic causal learning model specifically designed to capture dEC. It includes a dynamic causal learner to detect time-varying causal relationships from spatio-temporal data, and a dynamic causal discriminator to validate these findings by comparing original and reconstructed data. RESULTS: Our model outperforms established baselines in the accuracy of identifying dynamic causalities when tested on the simulated data. When applied to the Philadelphia Neurodevelopmental Cohort, the model uncovers distinct patterns in dEC networks across different age groups. Specifically, the evolution process of brain dEC networks in young adults is more stable than in children, and significant differences in information transfer patterns exist between them. CONCLUSION: This study highlights the brain's developmental trajectory, where networks transition from undifferentiated to specialized structures with age, in accordance with the improvement of an individual's cognitive and information processing capability. SIGNIFICANCE: The proposed model consists of the identification and verification of dynamic causality, utilizing the spatio-temporal fusing information from fMRI. As a result, it can accurately detect dEC and characterize its evolution over age.

Risks of anxiety disorders, depressive disorders, and sleep disorders in patients with dengue fever: A nationwide, population-based cohort study.

BACKGROUND: Dengue virus (DENV) infection, a common mosquito-borne disease, has been linked to several mental disorders like depression and anxiety. However, the temporal risk of these disorders after DENV infection is not well studied. METHODS: This population-based cohort study encompassed 45,334 recently lab-confirmed dengue patients in Taiwan spanning 2002 to 2015, matched at a 1:5 ratio with non-dengue individuals based on age, gender, and residence (n = 226,670). Employing subdistribution hazard regression analysis, we assessed the immediate (<3 months), intermediate (3-12 months), and prolonged (>12 months) risks of anxiety disorders, depressive disorders, and sleep disorders post DENV infection. Corrections for multiple comparisons were carried out using the Benjamini-Hochberg procedure. RESULTS: A significant increase in depressive disorder risk across all timeframes post-infection was observed (<3 months [aSHR 1.90, 95% CI 1.20-2.99], 3-12 months [aSHR 1.68, 95% CI 1.32-2.14], and >12 months [aSHR 1.14, 95% CI 1.03-1.25]). Sleep disorder risk was higher only during 3-12 months (aSHR 1.55, 95% CI 1.18-2.04). No elevated anxiety disorder risk was found. Subgroup analysis of hospitalized dengue patients showed increased risk of anxiety disorders within 3 months (aSHR 2.14, 95% CI 1.19-3.85) and persistent risk of depressive disorders across all periods. Hospitalized dengue patients also had elevated sleep disorder risk within the first year. CONCLUSION: Dengue patients exhibited significantly elevated risks of depressive disorders in both the short and long term. However, dengue's impact on sleep disorders and anxiety seems to be short-lived. Further research is essential to elucidate the underlying mechanisms.

Psychosocial Characteristics by Pain Presence and Limitations Among Older Adults.

PURPOSE: To compare psychosocial outcomes of older adults according to pain experience. METHOD: Using cross-sectional 2021 data from the National Health and Aging Trends Study, we examined psychosocial characteristics in older adults (N = 3,376) divided into three groups: no pain, pain without activity limitations, and activity-limiting pain. RESULTS: In multiple regression models, older adults with activity-limiting pain compared to those without pain had significantly higher depression, anxiety, and fear of falling, as well as reduced positive affect, self-realization, self-efficacy, resilience, and social participation. Older adults with non-activity-limiting pain had significantly higher social participation than those without pain, but no differences in self-realization, self-efficacy, or resilience. CONCLUSION: Pain is strongly associated with all psychosocial outcomes, especially in older adults with activity-limiting pain. Future research should examine the impact of self-realization, self-efficacy, resilience, and social participation on activity limitations. [Journal of Gerontological Nursing, 50(7), 27-34.].

Effects of endogenous testosterone on oscillatory activity during verbal working memory in youth.

Testosterone levels sharply rise during the transition from childhood to adolescence and these changes are known to be associated with changes in human brain structure. During this same developmental window, there are also robust changes in the neural oscillatory dynamics serving verbal working memory processing. Surprisingly, whereas many studies have investigated the effects of chronological age on the neural oscillations supporting verbal working memory, none have probed the impact of endogenous testosterone levels during this developmental period. Using a sample of 89 youth aged 6-14 years-old, we collected salivary testosterone samples and recorded magnetoencephalography during a modified Sternberg verbal working memory task. Significant oscillatory responses were identified and imaged using a beamforming approach and the resulting maps were subjected to whole-brain ANCOVAs examining the effects of testosterone and sex, controlling for age, during verbal working memory encoding and maintenance. Our primary results indicated robust testosterone-related effects in theta (4-7 Hz) and alpha (8-14 Hz) oscillatory activity, controlling for age. During encoding, females exhibited weaker theta oscillations than males in right cerebellar cortices and stronger alpha oscillations in left temporal cortices. During maintenance, youth with greater testosterone exhibited weaker alpha oscillations in right parahippocampal and cerebellar cortices, as well as regions across the left-lateralized language network. These results extend the existing literature on the development of verbal working memory processing by showing region and sex-specific effects of testosterone, and are the first results to link endogenous testosterone levels to the neural oscillatory activity serving verbal working memory, above and beyond the effects of chronological age.

Non-contact elasticity contrast imaging using photon counting.

Significance: Tissues' biomechanical properties, such as elasticity, are related to tissue health. Optical coherence elastography produces images of tissues based on their elasticity, but its performance is constrained by the laser power used, working distance, and excitation methods. Aim: We develop a new method to reconstruct the elasticity contrast image over a long working distance, with only low-intensity illumination, and by non-contact acoustic wave excitation. Approach: We combine single-photon vibrometry and quantum parametric mode sorting (QPMS) to measure the oscillating backscattered signals at a single-photon level and derive the phantoms' relative elasticity. Results: We test our system on tissue-mimicking phantoms consisting of contrast sections with different concentrations and thus stiffness. Our results show that as the driving acoustic frequency is swept, the phantoms' vibrational responses are mapped onto the photon-counting histograms from which their mechanical properties-including elasticity-can be derived. Through lateral and longitudinal laser scanning at a fixed frequency, a contrast image based on samples' elasticity can be reliably reconstructed upon photon level signals. Conclusions: We demonstrated the reliability of QPMS-based elasticity contrast imaging of agar phantoms in a long working distance, low-intensity environment. This technique has the potential for in-depth images of real biological tissue and provides a new approach to elastography research and applications.

Traditional uses, botany, phytochemistry, pharmacology and applications of Labisia pumila: A comprehensive review.

ETHNOPHARMACOLOGICAL RELEVANCE: Labisia pumila (Blume) Fern.-Vill, also known as Kacip Fatimah, is a traditional medicinal herb common throughout Southeast Asia. It is primarily used to facilitate childbirth and postpartum recovery in women. Additionally, it can also be used to treat dysentery, rheumatism, gonorrhea, and as an anti-flatulent. AIM OF THIS REVIEW: This article aims to provide a comprehensive review of the traditional uses, botany, cultivation, phytochemistry, pharmacological effects, practical applications, and potential uses of L. pumila (LP). Furthermore, we also explore the safety of this plant and its potential prospects for application. MATERIALS AND METHODS: The keywords "Labisia pumila," "Kacip Fatimah," and "Marantodes pumilum" were used to collect relevant information through electronic searches (including Elsevier, PubMed, Google Scholar, Baidu Scholar, CNKI, ScienceDirect, and Web of Science). RESULTS: This review summarizes 102 chemical components from different parts of the plant, including flavonoids, phenolic acids, saponins, and other chemical components. In addition, we also address the associated cultivation conditions, traditional uses, pharmacological effects and toxicity. A large number of reports indicate that LP has various pharmacological effects such as antioxidant, phytoestrogenic, antiinflammtory, antimicrobial, anti-osteoporosis and anti-obesity properties. These results provide valuable references for future research on LP. In addition, LP is also a potential medicinal and edible plant, and is currently sold on the market as a dietary supplement. CONCLUSIONS: LP is a renowned traditional ethnic medicine with numerous pharmacological activities attributed to its bioactive components. Therefore, isolation and identification of the chemical components in LP can be a focus of our future research. Current studies have focused only on the effects of LP on estrogen deficiency-related diseases in women and bone diseases. There is no scientific evidence for other traditional uses. Therefore, it is important to further explore its pharmacological activities and fill the research gaps related to other traditional uses. Furthermore, research on its safety should be expanded to prepare clinical applications.

Enhancing the production of L-proline in recombinant Escherichia coli BL21 by metabolic engineering.

L-proline is widely used in the fields of food, medicine and agriculture, and is also an important raw material for the synthesis of trans-4-hydroxy-L-proline. In this study, enhancing the production of L-proline by metabolic engineering was investigated. Three genes, proB, proA and proC, were introduced into Escherichia coli BL21 by molecular biology technology to increase the metabolic flow of L-proline from glucose. The genes putP and proP related to the proline transfer were knocked out by CRISPR/Cas9 gene editing technology to weaken the feedback inhibition of proB to increase the production of L-proline. The fermentation curves of the engineered strain at different glucose concentrations were determined, and a glucose concentration of 10 g/L was chosen to expand the batch culture to 1 L shake flask. Ultimately, through these efforts, the titer of L-proline reached 832.19 mg/L in intermittent glucose addition fermentation in a 1 L shake flask.

Moss differentiating the fluxes and sources of nitrogen deposition between 1984 and 2021 in a mountain area of Northern China.

Anthropogenic reactive nitrogen (N) deposition has increased significantly since the industrial revolution. Northern China has become a global hotspot for N deposition. However, few studies have been conducted to quantify the historical changes of atmospheric N deposition fluxes and source contributions in Northern China. By investigating N contents and δ15N values of mosses at Mount Tai (Northern China) in 1984 and 2021, we reconstructed fluxes and source contributions of wet inorganic N deposition and evaluated their historical changes. Compared with 1984, moss N contents (from 1.7 ± 0.3% to 2.1 ± 0.4%) showed a significant increase in 2021, which was mainly attributed to a significant increase in nitrate N deposition fluxes at Mount Tai. Moss δ15N values (from -5.9 ± 0.9‰ to -5.2 ± 2.4‰) showed a slight increase from 1984 to 2021 at Mount Tai. The importance of combustion-related NH3 (including vehicle exhaust, coal combustion, and biomass burning) in 2021 (51.2%) were higher than those in 1984 (43.9%), while the importance of volatilization NH3 sources (including waste and fertilizers) in 2021 (48.8%) were lower than those in 1984 (56.1%). It was fossil-fuel NOx (from vehicle exhaust and coal combustion) (54.1%) rather than non-fossil fuel NOx (from biomass burning and microbial N cycles) (45.9%) dominated NOx emissions in both 1984 and 2021. Our results revealed significant contributions of combustion-related NH3 and fossil-fuel NOx sources emissions to the elevation of N deposition at Mount Tai in Northern China, which are beneficial for mitigating N emissions and conducting ecological benefit assessments in Northern China.

Engineered plants provide a photosynthetic platform for the production of diverse human milk oligosaccharides.

Human milk oligosaccharides (HMOs) are a diverse class of carbohydrates which support the health and development of infants. The vast health benefits of HMOs have made them a commercial target for microbial production; however, producing the approximately 200 structurally diverse HMOs at scale has proved difficult. Here we produce a diversity of HMOs by leveraging the robust carbohydrate anabolism of plants. This diversity includes high-value and complex HMOs, such as lacto-N-fucopentaose I. HMOs produced in transgenic plants provided strong bifidogenic properties, indicating their ability to serve as a prebiotic supplement with potential applications in adult and infant health. Technoeconomic analyses demonstrate that producing HMOs in plants provides a path to the large-scale production of specific HMOs at lower prices than microbial production platforms. Our work demonstrates the promise in leveraging plants for the low-cost and sustainable production of HMOs.

Microglia Caspase11 non-canonical inflammasome drives fever.

AIM: Animals exhibit physiological changes designed to eliminate the perceived danger, provoking similar symptoms of fever. However, a high-grade fever indicates poor clinical outcomes. Caspase11 (Casp11) is involved in many inflammatory diseases. Whether Casp11 leads to fever remains unclear. In this study, we investigate the role of the preoptic area of the hypothalamus (PO/AH) microglia Casp11 in fever. METHODS: We perform experiments using a rat model of LPS-induced fever. We measure body temperature and explore the functions of peripheral macrophages and PO/AH microglia in fever signaling by ELISA, immunohistochemistry, immunofluorescence, flow cytometry, macrophage depletion, protein blotting, and RNA-seq. Then, the effects of macrophages on microglia in a hyperthermic environment are observed in vitro. Finally, adeno-associated viruses are used to knockdown or overexpress microglia Casp11 in PO/AH to determine the role of Casp11 in fever. RESULTS: We find peripheral macrophages and PO/AH microglia play important roles in the process of fever, which is proved by macrophage and microglia depletion. By RNA-seq analysis, we find Casp11 expression in PO/AH is significantly increased during fever. Co-culture and conditioned-culture simulate the induction of microglia Casp11 activation by macrophages in a non-contact manner. Microglia Casp11 knockdown decreases body temperature, pyrogenic factors, and inflammasome, and vice versa. CONCLUSION: We report that Casp11 drives fever. Mechanistically, peripheral macrophages transmit immune signals via cytokines to microglia in PO/AH, which activate the Casp11 non-canonical inflammasome. Our findings identify a novel player, the microglia Casp11, in the control of fever, providing an explanation for the transmission and amplification of fever immune signaling.