Effect of proton pump inhibitors versus histamine-2 receptor antagonists on acute kidney injury in septic patients at high risk for developing stress ulcers.

BACKGROUND: To compare the effects of proton pump inhibitor (PPI) and histamine-2 receptor antagonist (H2RA) use on the occurrence of acute kidney injury (AKI) in septic patients at high risk for developing stress ulcers. METHODS: Using the Medical Information Mart for Intensive Care IV version 2.2 database, septic patients with high-risk factors for stress ulcers (i.e., shock, coagulopathy, invasive mechanical ventilation, or chronic liver diseases) were included. Exposures included PPIs and H2RAs within 24 h of intensive care unit (ICU) admission or prior to ICU admission. The primary end point was severe sepsis-associated AKI as defined by the Kidney Disease Improving Global Outcomes criteria stage 3 (KDIGO-3). Propensity score matching (PSM) was performed to balance baseline characteristics. Multivariable Cox proportional hazards regression was used to estimate the effect size. RESULTS: 4731 PPI users and 4903 H2RA users were included. After PSM, there were 1785 pairs exposed to PPIs and H2RAs. In the PSM cohort, the cumulative incident KDIGO-3 rate was higher in the PPI group than in the H2RA group (log-rank test, p = 0.009). Regression analyses showed that PPI exposure [adjusted hazard ratio 1.32, 95% confidence interval (CI) 1.11-1.58, p = 0.002] was associated with incident KDIGO-3 compared with H2RA use. This association remained consistent in sensitivity analyses. Additionally, the PPI group had a higher need for kidney replacement therapy compared with the H2RA group (3.6% vs. 2.1%, P = 0.012). CONCLUSIONS: Among septic patients at high risk for developing stress ulcers, PPI exposure was associated with incident KDIGO-3 AKI compared with H2RA use.

Antifungal bioactivity of Sarcococca hookeriana var. digyna Franch. against fluconazole-resistant Candida albicans in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Sarcococca hookeriana var. digyna Franch. has been widely utilized in folk medicine by the Miao people in the southwestern region of China for treating skin sores which may be associated with microbial infection. AIM OF THE STUDY: To investigate the antifungal bioactivity of S. hookeriana var. digyna against fluconazole-resistant Candida albicans in vitro and in vivo, as well as its underlying mechanism and the key bioactive component. MATERIALS AND METHODS: The antifungal bioactivity of 80% ethanol extract of S. hookeriana var. digyna (SHE80) was investigated in vitro using the broth microdilution method, time-growth curve, and time-kill assay. Its key functional component and antifungal mechanism were explored with combined approaches including UPLC-Q-TOF-MS, network pharmacology and metabolomics. The antifungal pathway was further supported via microscopic observation of fungal cell morphology and examination of its effects on fungal biofilm and cell membranes using fluorescent staining reagents. In vivo assessment of antifungal bioactivity was conducted using a mouse model infected with C. albicans on the skin. RESULTS: S. hookeriana var. digyna suppressed fluconazole-resistant C. albicans efficiently (MIC = 16 µg/mL, MFC = 64 µg/mL). It removed fungal biofilm, increased cell membrane permeability, induced protein leakage, reduced membrane fluidity, disrupted mitochondrial membrane potential, induced the release of reactive oxygen species, promoted cell apoptosis, and inhibited the transformation of fungi from the yeast state to the hyphal state significantly. In terms of mechanism, it affected sphingolipid metabolism and signaling pathway. Moreover, the predicted bioactive component, sarcovagine D, was supported by antifungal bioactivity evaluation in vitro (MIC = 4 µg/mL, MFC = 16 µg/mL). Furthermore, S. hookeriana var. digyna promoted wound healing, reduced the number of colony-forming units, and reduced inflammation effectively in vivo. CONCLUSIONS: The traditional use of S. hookeriana var. digyna for fungal skin infections was supported by antifungal bioactivity investigated in vitro and in vivo. Its mechanism and bioactive component were predicted and confirmed by experiments, which also provided a new antifungal agent for future research.

Antibody-secreting cells as a source of NR1-IgGs in N-methyl-D-aspartate receptor-antibody encephalitis.

BACKGROUND: The pathogenicity of NR1-IgGs in N-methyl-D-aspartate receptor (NMDAR)-antibody encephalitis is known, but the immunobiological mechanisms underlying their production remain unclear. METHODS: For the first time, we explore the origin of NR1-IgGs and evaluate the contribution of B-cells to serum NR1-IgGs levels. Peripheral blood mononuclear cells (PBMCs) were obtained from patients and healthy controls (HCs). Naïve, unswitched memory (USM), switched memory B cells (SM), antibody-secreting cells (ASCs), and PBMC depleted of ASCs were obtained by fluorescence-activated cell sorting and cultured in vitro. RESULTS: For some patients, PBMCs spontaneously produced NR1-IgGs. Compared to the patients in PBMC negative group, the positive group had higher NR1-IgG titers in cerebrospinal fluid and Modified Rankin scale scores. The proportions of NR1-IgG positive wells in PBMCs cultures were correlated with NR1-IgGs titers in serum and CSF. The purified ASCs, SM, USM B cells produced NR1-IgGs in vitro. Compared to the patients in ASCs negative group, the positive group exhibited a worse response to second-line IT at 3-month follow-up. Naïve B cells also produce NR1-IgGs, implicating that NR1-IgGs originate from naïve B cells and a pre-germinal centres defect in B cell tolerance checkpoint in some patients. For HCs, no NR1-IgG from cultures was observed. PBMC depleted of ASCs almost eliminated the production of NR1-IgGs. CONCLUSIONS: These collective findings suggested that ASCs might mainly contribute to the production of peripheral NR1-IgG in patients with NMDAR-antibody encephalitis in the acute phase. Our study reveals the pathogenesis and helps develop tailored treatments (eg, anti-CD38) for NMDAR-antibody encephalitis.

Self-shedding MOF-nanocarriers modulated CdS/MoSe2 heterojunction activity through in-situ ion exchange: An enhanced split-type photoelectrochemical sensor for deoxynivalenol.

Deoxynivalenol (DON), a mycotoxin produced by Fusarium, poses a significant risk to human health and the environment. Therefore, the development of a highly sensitive and accurate detection method is essential to monitor the pollution situation. In response to this imperative, we have devised an advanced split-type photoelectrochemical (PEC) sensor for DON analysis, which leverages self-shedding MOF-nanocarriers to modulate the photoelectric response ability of PEC substrate. The PEC sensing interface was constructed using CdS/MoSe2 heterostructures, while the self-shedding copper peroxide nanodots@ZIF-8 (CPNs@ZIF-8) served as the Cu2+ source for the in-situ ion exchange reaction, which generated a target-related signal reduction. The constructed PEC sensor exhibited a broad linear range of 0.1 pg mL-1 to 500 ng mL-1 with a low detection limit of 0.038 pg mL-1, demonstrating high stability, selectivity, and proactivity. This work not only introduces innovative ideas for the design of photosensitive materials, but also presents novel sensing strategies for detecting various environmental pollutants.

[Effect of metabolic reprogramming on abdominal aortic aneurysm].

Abdominal aortic aneurysm (AAA) is a life-threatening disease that remains undetected until it acutely ruptures. Due to lack of effective pharmaceutic therapies, it is urgent to explore new prevention and treatment strategies. Metabolic reprogramming is a cellular process through which cells change their metabolic patterns to meet material and energy requirements, including glucose metabolism, lipid metabolism and amino acid metabolism. Recently, the regulatory role of metabolic reprogramming in cardiovascular diseases, especially AAA, has attracted significant attention. This review article focuses on the research progress regarding the effects of metabolic reprogramming of vascular smooth muscle cells (VSMCs) and macrophages on the occurrence and development of AAA, especially their roles in major pathological processes such as VSMCs apoptosis and phenotype transformation, extracellular matrix remodeling, oxidative stress, and inflammatory response. The aim is to provide new clues for the mechanism research and clinical treatment of AAA from the perspective of metabolism.

RNA m5C methylation: a potential modulator of innate immune pathways in hepatocellular carcinoma.

RNA 5-methylcytosine (m5C) methylation plays a crucial role in hepatocellular carcinoma (HCC). As reported, aberrant m5C methylation is closely associated with the progression, therapeutic efficacy, and prognosis of HCC. The innate immune system functions as the primary defense mechanism in the body against pathogenic infections and tumors since it can activate innate immune pathways through pattern recognition receptors to exert anti-infection and anti-tumor effects. Recently, m5C methylation has been demonstrated to affect the activation of innate immune pathways including TLR, cGAS-STING, and RIG-I pathways by modulating RNA function, unveiling new mechanisms underlying the regulation of innate immune responses by tumor cells. However, research on m5C methylation and its interplay with innate immune pathways is still in its infancy. Therefore, this review details the biological significance of RNA m5C methylation in HCC and discusses its potential regulatory relationship with TLR, cGAS-STING, and RIG-I pathways, thereby providing fresh insights into the role of RNA methylation in the innate immune mechanisms and treatment of HCC.

Screening and rational identification of a novel angiotensin-converting enzyme C-domain inhibitory peptide from Fabaceae food peptide library.

Angiotensin-converting enzyme (ACE), consisting of N-domain and C-domain, is a key regulator of blood pressure. The use of cACE-specific inhibitors helps minimize side effects in clinical applications. Legumes are a good source of proteins containing ACE inhibitory peptides; however, no studies have reported the identification of cACE-specific inhibitory peptides from Fabaceae. In this study, thermal hydrolysates from seeds, sprouts, pods, seedlings, and flowers of legumes were analyzed. Flowers of legumes exhibited a C-domain-preference ACE inhibition and anti-hypertensive effect in rats. Screening the legume peptide library identified a novel cACE inhibitory peptide, SJ-1. This study reported the first identification of cACE inhibitory peptide from Fabaceae foods. SJ-1, identified from the legume flowers, interacted with active site residues of cACE, leading to the inhibition of ACE activity, downregulation of bradykinin levels, and reduction of blood pressure. These findings also suggested the potential of legume proteins as a source of cACE inhibitory peptides.

Environmental-friendly extraction of di(2-ethylhexyl) phthalate from poly(vinyl chloride) using liquefied dimethyl ether.

Poly(vinyl chloride) (PVC) is one of the most widely used plastics. However, a major challenge in recycling PVC is that there is no economical method to separate and remove its toxic phthalate plasticizers. This research made a breakthrough by extracting PVC with liquefied dimethyl ether (DME) and successfully separating the plasticizer components. Nearly all (97.1 %) of the di(2-ethylhexyl) phthalate plasticizer was extracted within 30 min by passing liquefied DME (285 g) through PVC at 25 °C. The compatibility of PVC with organic solvents, including liquefied DME, was derived theoretically from their Hansen solubility parameters (HSP), and actual dissolution experiments were conducted to determine the optimal PVC solvents. A liquefied DME mixture was used to dissolve PVC, and the extract was diluted with ethanol to precipitate the dissolved PVC. We demonstrated that liquefied DME is a promising method for producing high quality recycled products and that the process retains the fundamental properties of plasticizers and PVC without inducing degradation or depolymerization. Because of its low boiling point, DME can be easily separated from the solute after extraction, allowing for efficient reuse of the solvent, extracted plasticizer, and PVC. DME does not require heat and produces little harmful wastewater, which significantly reduces the energy consumption of the plasticizer additive separation process.

Fucoidan-hybrid hydroxyapatite nanoparticles promote the osteogenic differentiation of human periodontal ligament stem cells under inflammatory condition.

Inflammation-related bone defects often lead to poor osteogenesis. Therefore, it is crucial to reduce the inflammation response and promote the osteogenic differentiation of stem/progenitor cells to revitalize bone physiology. Here, a kind of hybrid nano-hydroxyapatite was prepared using the confined phosphate ion release method with the participation of fucoidan, a marine-sourced polysaccharide with anti-inflammation property. The physicochemical analyses confirmed that the fucoidan hybrid nano-hydroxyapatite (FC/n-HA) showed fine needle-like architectures. With a higher amount of fucoidan, the crystal size and crystallinity of the FC/n-HA reduced while the liquid dispersibility was improved. Cell experiences showed that FC/n-HA had an optimal cytocompatibility at concentration of 50 µg/mL. Moreover, the lipopolysaccharide-induced cellular inflammatory model with PDLSCs was established and used to evaluate the anti-inflammatory and osteogenic properties. For the 1%FC/n-HA group, the expression levels of TNF-α and IL-1ß were significantly reduced at 24 h, while the expression of alkaline phosphatase of PDLSCs was significantly promoted at days 3 and 7, and calcium precipitates was enhanced at 21 days. In this study, the FC/n-HA particles showed effective anti-inflammatory properties and facilitated osteogenic differentiation of PDLSCs, indicating which has potential application in treating bone defects associated with inflammation, such as periodontitis.

Targeting Therapeutic Windows for Rheumatoid Arthritis Prevention.

Rheumatoid arthritis (RA) is a worldwide public health problem. Interventions to delay or prevent the onset of RA have attracted much attention in recent years, and researchers are now exploring various prevention strategies. At present, there is still no unified consensus for RA prevention, but targeting therapeutic windows and implementing interventions for at-risk individuals are extremely important. Due to the limited number of clinical trials on pharmacologic interventions, further studies are needed to explore and establish optimal intervention regimens and effective measures to prevent progression to RA. In this review, we introduce the RA disease process and risk factors, and present research on the use of both Western and Chinese medicine from clinical perspectives regarding RA prevention. Furthermore, we describe several complete and ongoing clinical studies on the use of Chinese herbal formulae for the prevention of RA.

Construction of the chronic temporomandibular disorder patients: the association between neural and psychological pathways.

Chronic temporomandibular disorder (cTMD) as a term based on the diagnostic criteria for temporomandibular disorders (DC/TMD) classification refers, in this paper, to the condition listed that has a non-mechanical association without any obvious organic cause. Specifically, this is the condition that falls under the International Classification of Diseases 11th revision (ICD-11) classification of chronic primary and chronic secondary pains. This implies that there is increased responsiveness of nociceptive neurons in the central nervous system, a phenomenon known as central sensitisation. cTMD patients may have their beginning with genetic susceptibility to pain. Although no single gene is exclusively linked to cTMD, various genes associated with nervous and musculoskeletal systems are believed to play a role. Environmental triggers and epigenetic changes are also thought to contribute to cTMD development. The biopsychosocial model emphasises the need to comprehensively address biological, psychological and social factors in cTMD assessment and management. In this study, we leverage the cyclic causation framework within the biopsychosocial model to illuminate the intricate interplay between biological and psychosocial factors in the context of cTMD. The conceptualisation of cTMD involves the dynamic evolution of genetic predispositions, influenced by life events and other biological susceptibilities. These factors collectively contribute to the emergence of nociplastic changes, ultimately manifesting as the distinctive features observed in individuals afflicted with cTMD.

A Review of the Evidence for Tryptophan and the Kynurenine Pathway as a Regulator of Stem Cell Niches in Health and Disease.

Stem cells are ubiquitously found in various tissues and organs in the body, and underpin the body's ability to repair itself following injury or disease initiation, though repair can sometimes be compromised. Understanding how stem cells are produced, and functional signaling systems between different niches is critical to understanding the potential use of stem cells in regenerative medicine. In this context, this review considers kynurenine pathway (KP) metabolism in multipotent adult progenitor cells, embryonic, haematopoietic, neural, cancer, cardiac and induced pluripotent stem cells, endothelial progenitor cells, and mesenchymal stromal cells. The KP is the major enzymatic pathway for sequentially catabolising the essential amino acid tryptophan (TRP), resulting in key metabolites including kynurenine, kynurenic acid, and quinolinic acid (QUIN). QUIN metabolism transitions into the adjoining de novo pathway for nicotinamide adenine dinucleotide (NAD) production, a critical cofactor in many fundamental cellular biochemical pathways. How stem cells uptake and utilise TRP varies between different species and stem cell types, because of their expression of transporters and responses to inflammatory cytokines. Several KP metabolites are physiologically active, with either beneficial or detrimental outcomes, and evidence of this is presented relating to several stem cell types, which is important as they may exert a significant impact on surrounding differentiated cells, particularly if they metabolise or secrete metabolites differently. Interferon-gamma (IFN-γ) in mesenchymal stromal cells, for instance, highly upregulates rate-limiting enzyme indoleamine-2,3-dioxygenase (IDO-1), initiating TRP depletion and production of metabolites including kynurenine/kynurenic acid, known agonists of the Aryl hydrocarbon receptor (AhR) transcription factor. AhR transcriptionally regulates an immunosuppressive phenotype, making them attractive for regenerative therapy. We also draw attention to important gaps in knowledge for future studies, which will underpin future application for stem cell-based cellular therapies or optimising drugs which can modulate the KP in innate stem cell populations, for disease treatment.

Bone fracture is associated with incident myocardial infarction in long-term follow-up.

BACKGROUND: The association between bone fracture and cardiovascular diseases is examined in this study. While basic research has established a connection between fractures and heart attacks through the linkage between bones and arteries, population studies have not provided clear evidence. The aim of the present study is to investigate the association between bone fracture and the occurrence of myocardial infarction in a natural population during long-term follow-up. METHODS: A total of 13,196 adult participants with bone fracture history at baseline from the China Health and Nutrition Survey (CHNS) prospective cohort were included in this study. Baseline investigation was performed in 1997-2009 and the outcome was followed up till 2015. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. RESULTS: From 1997 to 2015, a total of 329 incident myocardial infarction cases were identified. In univariate and multivariate Cox regression analysis, a history of bone fracture was associated with an increased risk of myocardial infarction incidence in the total population (for the crude model: HR = 2.56, 95% CI 1.83-3.53, P < 0.001; for the multivariate model: HR = 1.43, 95% CI 1.02-1.99, P = 0.036). In the stratified analysis, bone fracture was not associated with an increased risk of incident myocardial infarction in subjects with age < 50 years (HR = 0.71, 95% CI 0.34-1.47, P = 0.356), but significantly associated with an increased risk of incident myocardial infarction in subjects with age ≥ 50 years (HR = 1.80, 95% CI 1.23-2.63, P = 0.003). CONCLUSIONS: It is suggested by the present study that bone fracture may be associated with an increased risk of incident myocardial infarction in the elderly population during long-term follow-up.

Dual amplification for PEC ultrasensitive aptasensing of biomarker HER-2 based on Z-scheme UiO-66/CdIn2S4 heterojunction and flower-like PtPdCu nanozyme.

As an important prognostic indicator in breast cancer, human epithelial growth factor receptor-2 (HER-2) is of importance for assessing prognosis of breast cancer patients, whose accurate and facile analysis are imperative in clinical diagnosis and treatment. Herein, photoactive Z-scheme UiO-66/CdIn2S4 heterojunction was constructed by a hydrothermal method, whose optical property and photoactivity were critically investigated by a range of techniques, combined by elucidating the interfacial charge transfer mechanism. Meanwhile, PtPdCu nanoflowers (NFs) were fabricated by a simple aqueous wet-chemical method, whose peroxidase (POD)-mimicking catalytic activity was scrutinized by representative tetramethylbenzidine (TMB) oxidation in H2O2 system. Taken together, the UiO-66/CdIn2S4 based photoelectrochemical (PEC) aptasensor was established for quantitative analysis of HER-2, where the detection signals were further magnified through catalytic precipitation reaction towards 4-chloro-1-naphthol (4-CN) oxidation (assisted by the PtPdCu NFs nanozyme). The PEC aptasensor presented a broader linear range within 0.1 pg mL-1-0.1 µg mL-1 and a lower limit of detection of 0.07 pg mL-1. This work developed a new PEC aptasensor for ultrasensitive determination of HER-2, holding substantial promise for clinical diagnostics.

MOF-derived sandwich-structured dual Z-Scheme Co9S8@ZnIn2S4/CdSe hollow nanocages heterojunction: Target-induced ultrasensitive photoelectrochemical sensing of chlorpyrifos.

Exploring efficient photoactive material presents an intriguing opportunity to enhance the analytical performance of photoelectrochemical (PEC) sensor in the environmental analysis. In this work, a sandwich-structured multi-interface Co9S8@ZnIn2S4/CdSe QDs dual Z-Scheme heterojunction, derived from metal-organic framework (MOF), was synthesized as a sensing platform for chlorpyrifos detection, by integrating with enzyme-induced in situ insoluble precipitates strategy. The meticulously designed Co9S8@ZnIn2S4/CdSe QDs exhibited enhanced charge separation efficiency and was proved to be a highly effective sensing platform for the immobilization of biomolecules, attributing to the intrinsic dual Z-Scheme heterojunction and the distinctive hollow structure. The proposed PEC sensing platform combined with enzyme-induced in situ precipitate signal amplification strategy achieved superior performance for sensing of chlorpyrifos (CPF), showing in wide linear range (1.0 pg mL-1-100 ng mL-1), with a limit of detection (0.6 pg mL-1), excellent selectivity, and stability. This work offers valuable insights for the design of novel advanced photoactive materials aimed at detecting environmental pollutants with low level concentration.

Transmission characteristics in Tuberculosis by WGS: nationwide cross-sectional surveillance in China.

China, with the third largest share of global tuberculosis cases, faces a substantial challenge in its healthcare system as a result of the high burden of multidrug-resistant and rifampicin-resistant tuberculosis (MDR/RR-TB). This study employs a genomic epidemiological approach to assess recent tuberculosis transmissions between individuals, identifying potential risk factors and discerning the role of transmitted resistant isolates in the emergence of drug-resistant tuberculosis in China. We conducted a population-based retrospective study on 5052 Mycobacterium tuberculosis (MTB) isolates from 70 surveillance sites using whole genome sequencing (WGS). Minimum spanning tree analysis identified resistance mutations, while epidemiological data analysis pinpointed transmission risk factors. Of the 5052 isolates, 23% (1160) formed 452 genomic clusters, with 85.6% (387) of the transmissions occurring within the same counties. Individuals with younger age, larger family size, new cases, smear positive, and MDR/RR were at higher odds for recent transmission, while higher education (university and above) and occupation as a non-physical workers emerged as protective factors. At least 61.4% (251/409) of MDR/RR-TB were likely a result of recent transmission of MDR/RR isolates, with previous treatment (crude OR = 2.77), smear-positive (cOR = 2.07) and larger family population (cOR = 1.13) established as risk factors. Our findings highlight that local transmission remains the predominant form of TB transmission in China. Correspondingly, drug-resistant tuberculosis is primarily driven by the transmission of resistant tuberculosis isolates. Targeted interventions for high-risk populations to interrupt transmission within the country will likely provide an opportunity to reduce the prevalence of both tuberculosis and drug-resistant tuberculosis.

High blood pressure is associated with increased risk of future fracture, but not vice versa.

The association between high blood pressure and fracture showed obvious discrepancies and were mostly between hypertension with future fracture, but rarely between fracture and incident hypertension. The present study aims to investigate the associations of hypertension with future fracture, and fracture with incident hypertension. We included adult participants from the China Health and Nutrition Survey (CHNS) prospective cohort in 1997-2015 (N = 10,227), 2000-2015 (N = 10,547), 2004-2015 (N = 10,909), and 2006-2015 (N = 11,121) (baseline in 1997, 2000, 2004, 2006 respectively and outcome in 2015). Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs. In the analysis of the association between hypertension and future fracture, the adjusted HRs (95% CIs) were 1.34 (0.95-1.90) in 1997-2015, 1.40 (1.04-1.88) in 2000-2015, 1.32 (0.98-1.78) in 2004-2015, and 1.38 (1.01-1.88) in 2006-2015. In the analysis of the association between fracture and incident hypertension, the adjusted HRs (95% CIs) were 1.28 (0.96-1.72) in 1997-2015, 1.18 (0.94-1.49) in 2000-2015, 1.12 (0.89-1.40) in 2004-2015, and 1.09 (0.85-1.38) in 2006-2015. The present study showed that hypertension history was associated with increased risk of future fracture, but not vice versa.

Identifying Potential Sources of Phthalate Contamination in the Leaves of Stevia Rebaudiana (Bertoni) and the Development of Removal Technology.

Steviosides extracted from the leaves of the plant Stevia rebaudiana are increasingly used in the food industry as natural low-calorie sweeteners. Phthalates in food are often assumed to arise from food containers or packaging materials. Here, experiments were carried out to identify the potential sources of DMP, DBP, DIBP, and DEHP in the leaves of stevioside through investigation of their content in native stevioside tissues, soils, and associated agronomic materials. The results show that phthalate contamination was present in all the samples tested, and the influence of regional factors at the provincial level on the content of plasticizers in stevia leaves was not significant. Phthalates in stevia leaves can be absorbed into the plant body through leaves and roots. Using resin removal, the phthalate content in stevioside glycosides was reduced to less than 0.05 ppm, and some indicators were far lower than the limit standard in EU food.

Hybridization, polyploidization, and morphological convergence make dozens of taxa into one chaotic genetic pool: a phylogenomic case of the Ficus erecta species complex (Moraceae).

The Ficus erecta complex, characterized by its morphological diversity and frequent interspecific overlap, shares pollinating fig wasps among several species. This attribute, coupled with its intricate phylogenetic relationships, establishes it as an exemplary model for studying speciation and evolutionary patterns. Extensive researches involving RADseq (Restriction-site associated DNA sequencing), complete chloroplast genome data, and flow cytometry methods were conducted, focusing on phylogenomic analysis, genetic structure, and ploidy detection within the complex. Significantly, the findings exposed a pronounced nuclear-cytoplasmic conflict. This evidence, together with genetic structure analysis, confirmed that hybridization within the complex is a frequent occurrence. The ploidy detection revealed widespread polyploidy, with certain species exhibiting multiple ploidy levels, including 2×, 3×, and 4×. Of particular note, only five species (F. abelii, F. erecta, F. formosana, F. tannoensis and F. vaccinioides) in the complex were proved to be monophyletic. Species such as F. gasparriniana, F. pandurata, and F. stenophylla were found to encompass multiple phylogenetically distinct lineages. This discovery, along with morphological comparisons, suggests a significant underestimation of species diversity within the complex. This study also identified F. tannoensis as an allopolyploid species originating from F. vaccinioide and F. erecta. Considering the integration of morphological, molecular systematics, and cytological evidences, it is proposed that the scope of the F. erecta complex should be expanded to the entire subsect. Frutescentiae. This would redefine the complex as a continuously evolving group comprising at least 33 taxa, characterized by blurred species boundaries, frequent hybridization and polyploidization, and ambiguous genetic differentiation.

Effect of dissolved oxygen and ammonia nitrogen on Culter alburnus: Physiology, biochemistry, and molecular analyses.

Culter alburnus (topmouth culter)is an economically valuable freshwater fish. However, its insufficient tolerance to dissolved oxygen (DO) and ammonia nitrogen (AN) hinders its industrialisation. 360 experimental fish (4.87 ± 1.10 g) were placed in breathing chambers (oxygen level was 0.70-6.50 mg/L) or water tanks (control AN, 0 mg/L; low AN, 8 mg/L; high AN, 16 mg/L). This study analysed the effects of DO and AN on C. alburnus at physiological, biochemical, and molecular levels. (1) Physiology level: the floating point, coma critical point, and coma point at 20 °C group were significantly higher than those at 30 °C. The oxygen consumption rate of C. alburnus at 20 °C, 25 °C, and 30 °C was (256.65 ± 25.87), (470.47 ± 83.84), and (520.87 ± 55.40) mg/kg.h. The LC50 of AN after 96 h was 24.13 mg/L, and the safe concentration was 2.41 mg/L. The survival rate in the high AN group was significantly lower than that in the other two groups. (2) Biochemistry level: The change curves of antioxidant enzyme activity in the liver tissue under hypoxic stress reached a maximum at 12 h and then decreased. In addition, the increase and decrease in enzyme activity (except malondialdehyde) in the high AN group was lower than that in the low AN group. (3) Molecular level: the angiotensin-converting enzyme and carboxypeptidase genes were the major differentially expressed genes (DEGs) in hypoxic stress, and the DEGs were mainly enriched in the ABC transporter signal transduction pathway. In addition, the serum/glucocorticoid-regulated kinase, stearoyl-CoA desaturase, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase genes were among the major DEGs under high AN stress. The DEGs were mainly enriched in steroid biosynthesis or glycine, serine, and threonine metabolism transporter signal transduction pathways. In summary, it is necessary to focus on the DO and AN during C. alburnus breeding.