Effects of Fe(III) on the formation and toxicity alteration of halonitromethanes, dichloroacetonitrile, and dichloroacetamide from polyethyleneimine during UV/chlorine disinfection.

Trace iron ions (Fe(III)) are commonly found in water and wastewater, where free chlorine is very likely to coexist with Fe(III) affecting the disinfectant's stability and N-DBPs' fate during UV/chlorine disinfection, and yet current understanding of these mechanisms is limited. This study investigates the effects of Fe(III) on the formation and toxicity alteration of halonitromethanes (HNMs), dichloroacetonitrile (DCAN), and dichloroacetamide (DCAcAm) from polyethyleneimine (PEI) during UV/chlorine disinfection. Results reveal that the maxima concentrations of HNMs, DCAN, and DCAcAm during UV/chlorine disinfection with additional Fe(III) were 1.39, 1.38, and 1.29 times higher than those without additional Fe(III), instead of being similar to those of Fe(III) inhibited the formation of HNMs, DCAN and DCAcAm during chlorination disinfection. Meanwhile, higher Fe(III) concentration, acidic pH, and higher chlorine dose were more favorable for forming HNMs, DCAN, and DCAcAm during UV/chlorine disinfection, which were highly dependent on the involvement of HO· and Cl·. Fe(III) in the aquatic environment partially hydrolyzed to the photoactive Fe(III)­hydroxyl complexes Fe(OH)2+ and [Fe(H2O)6]3+, which undergone UV photoactivation and coupling reactions with HOCl to achieve effective Fe(III)/Fe(II) interconversion, a process that facilitated the sustainable production of HO·. Extensive product analysis and comparison verified that the HO· production enhanced by the Fe(III)/Fe(II) internal cycle played a primary role in increasing HNMs, DCAN, and DCAcAm productions during UV/chlorine disinfection. Note that the incorporation of Fe(III) increased the cytotoxicity and genotoxicity of HNMs, DCAN, and DCAcAm formed during UV/chlorine disinfection, and yet Fe(III) did not have a significant effect on the acute toxicity of water samples before, during, and after UV/chlorine disinfection. The new findings broaden the knowledge of Fe(III) affecting HNMs, DCAN, and DCAcAm formation and toxicity alteration during UV/chlorine disinfection.

Organocatalytic Csp2-O Amination of Quinolin-4(1H)-ones with 3-Alkynyl-3-hydroxyisoindolinones.

The Brønsted acid catalytic Csp2-O amination of quinolin-4(1H)-ones with 3-alkynyl-3-hydroxyisoindolinones as animation reagents has been developed. The cascade dehydration/conjugate addition/intramolecular annulation/ring-opening reaction proceeded smoothly to afford a broad scope of aminated products with high efficiency. Furthermore, the enantioselective construction of Csp2-N atropisomers was also investigated in the presence of chiral phosphoric acid. Importantly, this work not only realized the organocatalytic Csp2-O amination of quinolin-4(1H)-ones but also laid the foundation for directly asymmetric synthesis of Csp2-N atropisomers.

Effect of temperature on anisotropic bending elasticity of dsRNA: an all-atom molecular dynamics simulation.

Employing all-atom molecular dynamics simulations, we examined the temperature-dependent behavior of bending elasticity in double-stranded RNA (dsRNA). Specifically, we focused on the bending persistence length and its constituent components, namely, the tilt and roll stiffness. Our results revealed a near-linear decrease in these stiffness components as a function of temperature, thereby highlighting the increased flexibility of dsRNA at elevated temperatures. Furthermore, our data revealed a significant anisotropy in dsRNA bending elasticity, which diminished with increasing temperature, attributable to marked disparities in tilt and roll stiffness components. We delineated the underlying biophysical mechanisms and corroborated our findings with extant literature. These observations offer salient implications for advancing our understanding of nucleic acid elasticity, and are pertinent to potential medical applications.

Prognostic Significance of Excision Repair Cross-Complementation Group 1 on Circulating Tumor Cells for Nasopharyngeal Carcinoma.

BACKGROUND: Liquid biopsy, including the detection of circulating tumor cells (CTCs), has emerged as a promising tool for cancer diagnosis and monitoring. However, the prognostic value of CTCs in nasopharyngeal carcinoma (NPC) remains unclear due to the lack of phenotypic characterization. The expression of Excision Repair Cross-Complementation Group 1 (ERCC1) and CTCs epithelial-mesenchymal transition (EMT) have been associated with treatment efficacy. In this study, we aimed to evaluate the prognostic significance of ERCC1 expression on CTCs and their EMT subtypes before treatment in NPC. METHODS: We retrospectively analyzed 108 newly diagnosed locally advanced NPC patients who underwent CanPatrol™ CTC testing between November 2018 and November 2021. CTCs were counted and classified into epithelial, epithelial-mesenchymal hybrid, and mesenchymal subtypes. ERCC1 expression was divided into negative and positive groups. Clinical features and survival outcomes were analyzed. RESULTS: The positive rate of CTCs was 92.6% (100/108), with an ERCC1 positivity rate of 74% (74/100). Further analysis of the subtypes showed that positive ERCC1 on mesenchymal CTCs was associated with a later N stage (P = .01). Positive ERCC1 expression was associated with poor overall survival (OS; P = .039) and disease-free survival (DFS; P = .035). Further analysis of subtypes showed that the positive ERCC1 on mesenchymal-type CTCs was associated with poor OS (P = .012) and metastasis-free survival (MFS; P = .001). CONCLUSION: Our findings suggest that ERCC1 expression on CTCs may serve as a new prognostic marker for NPC patients. Evaluating CTCs subtypes may become an auxiliary tool for personalized and precise treatment.

BackgroundLiquid biopsy, including the detection of circulating tumor cells (CTCs), has emerged as a promising tool for cancer diagnosis and monitoring. However, the prognostic value of CTCs in nasopharyngeal carcinoma (NPC) remains unclear due to the lack of phenotypic characterization. The expression of Excision Repair Cross-Complementation Group 1 (ERCC1) and CTCs epithelial-mesenchymal transition (EMT) have been associated with treatment efficacy. In this study, we aimed to evaluate the prognostic significance of ERCC1 expression on CTCs and their EMT subtypes before treatment in NPC.MethodsWe retrospectively analyzed 108 newly diagnosed locally advanced NPC patients who underwent CanPatrol™ CTC testing between November 2018 and November 2021. CTCs were counted and classified into epithelial, epithelial-mesenchymal hybrid, and mesenchymal subtypes. ERCC1 expression was divided into negative and positive groups. Clinical features and survival outcomes were analyzed.ResultsThe positive rate of CTCs was 92.6% (100/108), with an ERCC1 positivity rate of 74% (74/100). Further analysis of the subtypes showed that positive ERCC1 on mesenchymal CTCs was associated with a later N stage (P = .01). Positive ERCC1 expression was associated with poor overall survival (OS; P = .039) and disease-free survival (DFS; P = .035). Further analysis of subtypes showed that the positive ERCC1 on mesenchymal-type CTCs was associated with poor OS (P = .012) and metastasis-free survival (MFS; P = .001).ConclusionOur findings suggest that ERCC1 expression on CTCs may serve as a new prognostic marker for NPC patients. Evaluating CTCs subtypes may become an auxiliary tool for personalized and precise treatment.

Early-life tobacco smoke exposure and stroke risk: a prospective study of 341,783 and 352,737 UK Biobank participants.

INTRODUCTION: Stroke is a life-threatening condition that causes a major medical burden globally. The currently used methods for the prevention or prediction of stroke have certain limitations. Exposure to tobacco in early life, including smoking during adolescence and maternal smoking during pregnancy, can affect adolescent development and lead to several negative outcomes. However, the association between early-life tobacco exposure and stroke is not known. METHODS: In this prospective cohort study, for the analyses involving exposure to maternal smoking during pregnancy and age of smoking initiation, we included 304,984 and 342,893 participants, respectively., respectively from the UK Biobank. Cox proportional hazard regression model and subgroup analyses were performed to investigate the association between early-life tobacco exposure and stroke. Mediation analyses were performed to identify the mediating role of biological aging in the association between early tobacco exposure and stroke. RESULTS: Compared with participants whose mothers did not smoke during pregnancy, participants whose mothers smoked during pregnancy showed an 11% increased risk of stroke (HR: 1.11, 95% CI: 1.05-1.18, P < 0.001). Compared with participants who never smoked, participants who smoked during adulthood, adolescence and childhood showed a 22%, 24%, and 38% increased risk of stroke during their adulthood, respectively. Mediation analysis indicated that early-life tobacco exposure can cause stroke by increasing biological aging. CONCLUSION: This study reveals that exposure to tobacco during early life is associated with an increased risk of experiencing a stroke, and increased biological aging can be the underlying mechanism.

Formation and toxicity alteration of halonitromethanes from Chlorella vulgaris during UV/chloramination process involving bromide ion.

Frequent algal blooms cause algal cells and their algal organic matter (AOM) to become critical precursors of disinfection by-products (DBPs) during water treatment. The presence of bromide ion (Br-) in water has been demonstrated to affect the formation laws and species distribution of DBPs. However, few researchers have addressed the formation and toxicity alteration of halonitromethanes (HNMs) from algae during disinfection in the presence of Br-. Therefore, in this work, Chlorella vulgaris was selected as a representative algal precursor to investigate the formation and toxicity alteration of HNMs during UV/chloramination involving Br-. The results showed that the formation concentration of HNMs increased and then decreased during UV/chloramination. The intracellular organic matter of Chlorella vulgaris was more susceptible to form HNMs than the extracellular organic matter. When the Br-: Cl2 mass ratio was raised from 0.004 to 0.08, the peak of HNMs total concentration increased 33.99%, and the cytotoxicity index and genotoxicity index of HNMs increased 67.94% and 22.80%. Besides, the formation concentration and toxicity of HNMs increased with increasing Chlorella vulgaris concentration but decreased with increasing solution pH. Possible formation pathways of HNMs from Chlorella vulgaris during UV/chloramination involving Br- were proposed based on the alteration of nitrogen species and fluorescence spectrum analysis. Furthermore, the formation laws of HNMs from Chlorella vulgaris in real water samples were similar to those in deionized water samples. This study contributes to a better comprehension of HNMs formation from Chlorella vulgaris and provides valuable information for water managers to reduce hazards associated with the formation of HNMs.

Systems genetics analyses reveals key genes related to behavioral traits in the striatum of CFW mice.

The striatum plays a central role in directing many complex behaviors ranging from motor control to action choice and reward learning. In our study, we used 55 CFW mice with rapid decay linkage disequilibrium to systematically mine the striatum-related behavioral functional genes by analyzing their striatal transcriptomes and 79 measured behavioral phenotypic data. By constructing a gene co-expression network, we clustered the genes into 13 modules, with most of them being positively correlated with motor traits. Based on functional annotations as well as Fisher's exact and hypergeometric distribution tests, brown and magenta modules were identified as core modules. They were significantly enriched for striatal-related functional genes. Subsequent Mendelian randomization analysis verified the causal relationship between the core modules and dyskinesia. Through the intra-modular gene connectivity analysis, Adcy5 and Kcnma1 were identified as brown and magenta module hub genes, respectively. Knockouts of both Adcy5 and Kcnma1 lead to motor dysfunction in mice, and KCNMA1 acts as a risk gene for schizophrenia and smoking addiction in humans. We also evaluated the cellular composition of each module and identified oligodendrocytes in the striatum to have a positive role in motor regulation.Significance Statement The striatum plays a central role in guiding many complex behaviours from motor control to action selection and reward learning. Clinically, striatal dysfunction contributes to a variety of neurodegenerative diseases, including the well-known Alzheimer's disease and Huntington's disease. In our study, we systematically mined striatum-associated behavioural function genes using 55 CFW mice. And we validated our findings in multiple ways. We found that Adcy5 and Kcnma1 knockouts in mice lead to motor dysfunction in mice and that Kcnma1 is associated with schizophrenia, a finding that holds true in humans. Finally, we also assessed the role of different cells in the regulation of striatal behaviour and found that oligodendrocytes in the striatum play an active role in movement regulation.

Tannic acid and quaternized chitosan mediated puerarin-loaded octacalcium phosphate /sodium alginate scaffold for bone tissue engineering.

Current limitations in mechanical performance and foreign body reactions (FBR) often lead to implant failure, restricting the application of bioceramic scaffolds. This study presents a novel 3D-printed scaffold that combines the release of anti-inflammatory drugs with osteogenic stimulation. Initially, the inorganic and organic phases were integrated to ensure the scaffold's mechanical integrity through catechol chemistry and the electrostatic interactions between tannic acid and quaternary ammonium chitosan. Subsequently, layers of polydopamine-encapsulated puerarin-loaded zeolitic imidazolate framework-8 (ZIF-8) were self-assembled onto the stent's surface, creating the drug-loaded scaffold that improved drug release without altering the scaffold's structure. Compared with unloaded scaffolds, the puerarin-loaded scaffold demonstrated excellent osteogenic differentiation properties along with superior anti-inflammatory and osteogenic effects in a range of in vitro and in vivo studies. RNA sequencing clarified the role of the TNF and NF/κB signaling pathways in these effects, further supporting the scaffold's osteogenic potential. This study introduces a novel approach for creating drug-loaded scaffolds, providing a unique method for treating cancellous bone defects.

Association of physical activity pattern and risk of Parkinson's disease.

Increasing evidence suggests an association between exercise duration and Parkinson's disease. However, no high-quality prospective evidence exists confirming whether differences exist between the two modes of exercise, weekend warrior and equal distribution of exercise duration, and Parkinson's risk. Hence, this study aimed to explore the association between different exercise patterns and Parkinson's risk using exercise data from the UK Biobank. The study analyzed data from 89,400 UK Biobank participants without Parkinson's disease. Exercise data were collected using the Axivity AX3 wrist-worn triaxial accelerometer. Participants were categorized into three groups: inactive, regularly active, and engaged in the weekend warrior (WW) pattern. The relationship between these exercise patterns and Parkinson's risk was assessed using a multifactorial Cox model. During a mean follow-up of 12.32 years, 329 individuals developed Parkinson's disease. In a multifactorial Cox model, using the World Health Organization-recommended threshold of 150 min of moderate-to-vigorous physical activity per week, both the active WW group [hazard ratio (HR) = 0.58; 95% confidence interval (CI) = 0.43-0.78; P < 0.001] and the active regular group (HR = 0.44; 95% CI = 0.34-0.57; P < 0.001) exhibited a lower risk of developing Parkinson's disease compared with the inactive group. Further, no statistically significant difference was observed between the active WW and the active regular groups (HR = 0.77; 95% CI = 0.56-1.05; P = 0.099). In conclusion, in this cohort study, both the WW exercise pattern and an equal distribution of exercise hours were equally effective in reducing Parkinson's risk.

Exploring the Diagnostic and Prognostic Significance of Alkaline Phosphatase on Neutrophil Surface Membrane in Patients with Sepsis.

Background: Sepsis, characterized by life-threatening organ dysfunction, stems from an unregulated host response. Timely identification is pivotal for enhancing the prognosis of sepsis patients. Objective: This study aims to explore the diagnostic and prognostic values of alkaline phosphatase on the surface membrane of neutrophils (mNAP) in peripheral blood among sepsis patients. Design: The study employed a retrospective design. Setting: This study was conducted at Donghai County People's Hospital. Participants: A total of 180 sepsis patients were selected and categorized into the sepsis shock group (n=45) and the sepsis non-shock group (n=135). Additionally, 35 patients with non-infectious systemic inflammatory response syndrome served as the control group. Interventions: mNAP was assessed via flow cytometry, while serum procalcitonin (PCT) and C-reactive protein (CRP) levels were measured through immunoassay. Primary Outcome Measures: (1) Changes in mNAP, PCT, and CRP. (2) Correlation of mNAP with CRP and PCT in sepsis patients. (3) Diagnostic values of mNAP, PCT, and CRP in sepsis. Results: Statistically significant differences in mNAP, PCT, and CRP were observed between the sepsis shock group, the sepsis non-shock group, and the control group (P = .000). The median value of mNAP (22627 Ab/c) in the 28-day death group was significantly higher than that (5100 Ab/c) in the survival group (P = .000). Spearman rank correlation analysis indicated a positive correlation between mNAP, PCT, and CRP in sepsis patients (P < .01). Conclusions: Both mNAP and PCT exhibit superior diagnostic specificity and sensitivity compared to CRP. While mNAP demonstrates similar sensitivity to PCT in diagnosing sepsis, its diagnostic specificity surpasses that of PCT. mNAP holds promise as a novel marker for the diagnosis and prognosis of sepsis.

A mini review of reinfection with the SARS-CoV-2 Omicron variant.

Background: COVID-19 has caused severe morbidity and mortality worldwide. After the end of the dynamic zero-COVID policy in China in December, 2022, concerns regarding reinfection were raised while little was known due to the lack of surveillance data in this country. Aims: This study reviews the probability, risk factors, and severity of severe acute respiratory syndrome coronavirus 2 Omicron variant reinfection, as well as the interval between infections, risk of onward transmission by reinfected cases, and the role of booster vaccination against reinfection. Sources: References for this review were identified through searches of PubMed and Web of Science up to September 24, 2023. Results: The rate of reinfection ranges from 3.1% to 13.0%. Factors associated with a higher risk of reinfection include being female, having comorbidities, and being unvaccinated. Reinfection with the BA.4 or BA.5 variant occurs approximately 180 days after the initial infection. Reinfections are less clinically severe than primary infections, and there is evidence of lower transmissibility. The debate surrounding the effectiveness and feasibility of booster vaccinations in preventing reinfection continues. Conclusions: The reinfection rate during the Omicron epidemic is significantly higher than in previous epidemic periods. However, the symptoms and infectivity of reinfection were weaker than those of the prior infection. Medical staff and individuals at high risk of reinfection should be vigilant. The efficacy of booster vaccinations in reducing reinfection is currently under debate.

Identification of Mycobacterium tuberculosis Resistance to Common Antibiotics: An Overview of Current Methods and Techniques.

Multidrug-resistant tuberculosis (MDR-TB) is an essential cause of tuberculosis treatment failure and death of tuberculosis patients. The rapid and reliable profiling of Mycobacterium tuberculosis (MTB) drug resistance in the early stage is a critical research area for public health. Then, most traditional approaches for detecting MTB are time-consuming and costly, leading to the inappropriate therapeutic schedule resting on the ambiguous information of MTB drug resistance, increasing patient economic burden, morbidity, and mortality. Therefore, novel diagnosis methods are frequently required to meet the emerging challenges of MTB drug resistance distinguish. Considering the difficulty in treating MDR-TB, it is urgently required for the development of rapid and accurate methods in the identification of drug resistance profiles of MTB in clinical diagnosis. This review discussed recent advances in MTB drug resistance detection, focusing on developing emerging approaches and their applications in tangled clinical situations. In particular, a brief overview of antibiotic resistance to MTB was present, referred to as intrinsic bacterial resistance, consisting of cell wall barriers and efflux pumping action and acquired resistance caused by genetic mutations. Then, different drug susceptibility test (DST) methods were described, including phenotype DST, genotype DST and novel DST methods. The phenotype DST includes nitrate reductase assay, RocheTM solid ratio method, and liquid culture method and genotype DST includes fluorescent PCR, GeneXpert, PCR reverse dot hybridization, ddPCR, next-generation sequencing and gene chips. Then, novel DST methods were described, including metabolism testing, cell-free DNA probe, CRISPR assay, and spectral analysis technique. The limitations, challenges, and perspectives of different techniques for drug resistance are also discussed. These methods significantly improve the detection sensitivity and accuracy of multidrug-resistant tuberculosis (MRT) and can effectively curb the incidence of drug-resistant tuberculosis and accelerate the process of tuberculosis eradication.

Establishment of reference intervals for plasma IL-2, IL-4, IL-5, and IL-17A in healthy adults from the Jiangsu region of eastern China using flow cytometry: A single-center study.

BACKGROUND: Cytokines are of utmost importance in both the physiological and pathological immune responses of the human body. This study utilized flow cytometry to measure the levels of plasma interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-5 (IL-5) and interleukin-17A (IL-17A) and established their reference intervals, aiming to provide data support for the diagnosis and treatment of clinical diseases. METHODS: According to the inclusion and exclusion criteria, a total of 728 reference individuals were included in this study from January 2023 to June 2023. The Kolmogorov-Smirnov test was used to analyse the distributions of plasma IL-2, IL-4, IL-5 and IL-17A. The reference intervals of plasma IL-2, IL-4, IL-5 and IL-17A were established by the unilateral percentile method (95th percentile) based on the guidelines of C28-A 3 and WS/T 402-2012. RESULTS: In this study, the levels of plasma IL-2, IL-4, IL-5 and IL-17A were nonnormally distributed. The concentrations of plasma IL-2, IL-4, IL-5 and IL-17A in healthy adults were not significantly different by sex or age (all P > 0.05). Therefore, all the reference individuals were combined into one group, and the reference intervals of plasma IL-2, IL-4, IL-5 and IL-17 were established by flow cytometry (IL-2 ≤ 10.25 pg/mL, IL-4 ≤ 9.87 pg/mL, IL-5 ≤ 3.36 pg/mL and IL-17A ≤ 9.46 pg/mL). CONCLUSIONS: We first established the reference intervals of plasma IL-2, IL-4, IL-5 and IL-17A in healthy adults based on a single-center population in the Jiangsu region in eastern China, which will provide an important reference value for evaluating human immune status and the diagnosis and treatment of clinical diseases.

Cytochrome P450 Mining for Bufadienolide Diversification.

Bufadienolides are a class of steroids with a distinctive α-pyrone ring at C17, mostly produced by toads and consisting of over 100 orthologues. They exhibit potent cardiotonic and antitumor activities and are active ingredients of the traditional Chinese medicine Chansu and Cinobufacini. Direct extraction from toads is costly, and chemical synthesis is difficult, limiting the accessibility of active bufadienolides with diverse modifications and trace content. In this work, based on the transcriptome and genome analyses, using a yeast-based screening platform, we obtained eight cytochrome P450 (CYP) enzymes from toads, which catalyze the hydroxylation of bufalin and resibufogenin at different sites. Moreover, a reported fungal CYP enzyme Sth10 was found functioning in the modification of bufalin and resibufogenin at multiple sites. A total of 15 bufadienolides were produced and structurally identified, of which six were first discovered. All of the compounds were effective in inhibiting the proliferation of tumor cells, especially 19-hydroxy-bufalin (2) and 1ß-hydroxy-bufalin (3), which were generated from bufalin hydroxylation catalyzed by CYP46A35. The catalytic efficiency of CYP46A35 was improved about six times and its substrate diversity was expanded to progesterone and testosterone, the common precursors for steroid drugs, achieving their efficient and site-specific hydroxylation. These findings elucidate the key modification process in the synthesis of bufadienolides by toads and provide an effective way for the synthesis of unavailable bufadienolides with site-specific modification and active potentials.

Illness Perception and Benefit Finding of Thyroid Cancer Survivors: A Chain Mediating Model of Sense of Coherence and Self-disclosure.

BACKGROUND: Benefit finding is gaining attention as a strong predictor of quality of life, but few studies have addressed the mechanisms of its development. OBJECTIVE: The purpose of this study was to determine the relationship between illness perception and benefit finding in female thyroid cancer survivors and to further elucidate the mechanisms by which illness perception contributes to benefit finding through sense of coherence and self-disclosure. METHODS: A total of 280 female thyroid cancer survivors completed the questionnaire between January and August 2023. The study investigated participants' baseline information, illness perception, sense of coherence, self-disclosure, and benefit finding. The bootstrap method was used to test the chain mediation effect. RESULTS: The findings showed that in the chain-mediated model, illness perception negatively predicted sense of coherence (ß = -.475, P < .001) and self-disclosure (ß = -.335, P < .001). Sense of coherence positively predicted self-disclosure (ß = .272, P < .001) and benefit finding (ß = .251, P < .001). Self-disclosure positively predicted benefit finding (ß = .213, P < .001). The separate mediating roles of sense of coherence and self-disclosure between illness perception and benefit finding were both significant, as were the chained mediating roles of sense of coherence, and self-disclosure. CONCLUSION: This study provides a theoretical basis for elucidating the mechanisms of benefit finding and provides precise targets for clinical intervention. IMPLICATIONS FOR PRACTICE: Healthcare professionals can improve mental health outcomes by improving cancer survivors' disease awareness, fostering their sense of coherence, and encouraging moderate self-disclosure to achieve benefit finding.

Effect of microwave alone and microwave-assisted modification on the physicochemical properties of starch and its application in food.

Native starch has poor stability and usually requires modification to expand its industrial application range. Commonly used methods are physical, chemical, enzymatic and compound modification. Microwave radiation, as a kind of physical method, is promising due to its uniform energy radiation, greenness, safety, non-toxicity. It can meet the demand of consumers for safe food. Microwave-assisted modification with other methods can directly or indirectly affect the structure of starch granules to obtain modified starch with high degree of substitution and low viscosity, and the modification efficiency is greatly improved. This paper reviews the effect of microwave radiation on the physicochemical properties of starch, such as granule morphology, crystallization characteristics, and gelatinization characteristics, as well as the application of microwave radiation in starch modification and starch food processing. It provides theoretical references and suggestions for the research of microwave heating modified starch and the deep processing of starchy foods.

Integrative omics studies revealed synergistic link between sucrose metabolic isogenes and carbohydrates in poplar roots infected by Fusarium wilt.

Advances in carbohydrate metabolism prompted its essential role in defense priming and sweet immunity during plant-pathogen interactions. Nevertheless, upstream responding enzymes in the sucrose metabolic pathway and associated carbohydrate derivatives underlying fungal pathogen challenges remain to be deciphered in Populus, a model tree species. In silico deduction of genomic features, including phylogenies, exon/intron distributions, cis-regulatory elements, and chromosomal localization, identified 59 enzyme genes (11 families) in the Populus genome. Spatiotemporal expression of the transcriptome and the quantitative real-time PCR revealed a minuscule number of isogenes that were predominantly expressed in roots. Upon the pathogenic Fusarium solani (Fs) exposure, dynamic changes in the transcriptomics atlas and experimental evaluation verified Susy (PtSusy2 and 3), CWI (PtCWI3), VI (PtVI2), HK (PtHK6), FK (PtFK6), and UGPase (PtUGP2) families, displaying promotions in their expressions at 48 and 72 h of post-inoculation (hpi). Using the gas chromatography-mass spectrometry (GC-MS)-based non-targeted metabolomics combined with a high-performance ion chromatography system (HPICS), approximately 307 metabolites (13 categories) were annotated that led to the quantification of 46 carbohydrates, showing marked changes between three compared groups. By contrast, some sugars (e.g., sorbitol, L-arabitol, trehalose, and galacturonic acid) exhibited a higher accumulation at 72 hpi than 0 hpi, while levels of α-lactose and glucose decreased, facilitating them as potential signaling molecules. The systematic overview of multi-omics approaches to dissect the effects of Fs infection provides theoretical cues for understanding defense immunity depending on fine-tuned Suc metabolic gene clusters and synergistically linked carbohydrate pools in trees.

A three-level regulatory mechanism of the aldo-keto reductase subfamily AKR12D.

Modulation of protein function through allosteric regulation is central in biology, but biomacromolecular systems involving multiple subunits and ligands may exhibit complex regulatory mechanisms at different levels, which remain poorly understood. Here, we discover an aldo-keto reductase termed AKRtyl and present its three-level regulatory mechanism. Specifically, by combining steady-state and transient kinetics, X-ray crystallography and molecular dynamics simulation, we demonstrate that AKRtyl exhibits a positive synergy mediated by an unusual Monod-Wyman-Changeux (MWC) paradigm of allosteric regulation at low concentrations of the cofactor NADPH, but an inhibitory effect at high concentrations is observed. While the substrate tylosin binds at a remote allosteric site with positive cooperativity. We further reveal that these regulatory mechanisms are conserved in AKR12D subfamily, and that substrate cooperativity is common in AKRs across three kingdoms of life. This work provides an intriguing example for understanding complex allosteric regulatory networks.

Salmonella Enteritidis antitoxin DinJ inhibits NLRP3-dependent canonical inflammasome activation in macrophages.

The inflammasome is a pivotal component of the innate immune system, acting as a multiprotein complex that plays an essential role in detecting and responding to microbial infections. Salmonella Enteritidis have evolved multiple mechanisms to regulate inflammasome activation and evade host immune system clearance. Through screening S. Enteritidis C50336ΔfliC transposon mutant library, we found that the insertion mutant of dinJ increased inflammasome activation. In this study, we demonstrated the genetic connection between the antitoxin DinJ and the toxin YafQ in S. Enteritidis, confirming their co-transcription. The deletion mutant ΔfliCΔdinJ increased cell death and IL-1ß secretion in J774A.1 cells. Western blotting analysis further showed elevated cleaved Caspase-1 product (p10 subunits) and IL-1ß secretion in cells infected with ΔfliCΔdinJ compared to cells infected with ΔfliC. DinJ was found to inhibit canonical inflammasome activation using primary bone marrow-derived macrophages (BMDMs) from Casp-/- C57BL/6 mice. Furthermore, DinJ specifically inhibited NLRP3 inflammasome activation, as demonstrated in BMDMs from Nlrp3-/- and Nlrc4-/- mice. Fluorescence resonance energy transfer (FRET) experiments confirmed the translocation of DinJ into host cells during infection. Finally, we revealed that DinJ could inhibit the secretion of IL-1ß and IL-18 in vivo, contributing to S. Enteritidis evading host immune clearance. In summary, our findings provide insights into the role of DinJ in modulating the inflammasome response during S. Enteritidis infection, highlighting its impact on inhibiting inflammasome activation and immune evasion.

Organocatalytic enantioselective synthesis of Csp2-N atropisomers via formal Csp2-O bond amination.

Compared with well-developed construction of Csp2-Csp2 atropisomers, the synthesis of Csp2-N atropisomers remains in its infancy, which is recognized as both appealing and challenging. Herein, we achieved the first organocatalyzed asymmetric synthesis of Csp2-N atropisomers by formal Csp2-O amination. With the aid of a suitable acid, 3-alkynyl-3-hydroxyisoindolinones reacted smoothly with 1-methylnaphthalen-2-ols to afford a wide range of atropisomers by selective formation of the Csp2-N axis. Particularly, both the kinetic (Z)-products and the thermodynamic (E)-products could be selectively formed. Furthermore, the rarely used combination of two chiral Brønsted acid catalysts achieved excellent enantiocontrol, which is intriguing and unusual in organocatalysis. Based on control experiments and DFT calculations, a cascade dehydration/addition/rearrangement process was proposed. More importantly, this work provided a new plat-form for direct atroposelective construction of the chiral Csp2-N axis.