Long noncoding RNA NONHSAT122636.2 attenuates myocardial inflammation and apoptosis in myocarditis.

OBJECTIVE: The main pathological change of myocarditis is an inflammatory injury of cardiomyocytes. Long noncoding RNAs (lncRNAs) are closely related to inflammation, and our previous study showed that differential expression of lncRNAs is associated with myocarditis. This study aimed to investigate the impact of lncRNAs on the onset of myocarditis. METHODS: RNA expression was measured by quantitative reverse-transcription polymerase chain reaction (RT-qPCR). Lipopolysaccharide (LPS) was used to induce inflammation in human cardiomyocytes (HCMs). The expression of inflammatory cytokines and myocardial injury markers was detected by enzyme-linked immunosorbent assay (ELISA) and RT-qPCR. Cell viability and apoptosis were measured by the cell counting kit-8 assay and flow cytometry. The binding force between lncRNA NONHSAT122636.2 and microRNA miRNA-2110 was detected using the dual-luciferase assay. RESULTS: NONHSAT122636.2 was dynamically expressed in patients with myocarditis and negatively correlated with inflammation severity. The overexpression of NONHSAT122636.2 improved inflammatory injury in LPS-stimulated HCMs. The study observed that there was a weak binding force between NONHSAT122636.2 and miR-2110. CONCLUSION: NONHSAT122636.2 attenuates myocardial inflammation and apoptosis in myocarditis. Additionally, its expression decreases in the peripheral blood of children suffering from myocarditis and in patients who are diagnosed for the first time showing higher diagnostic sensitivity and specificity. This decrease is negatively correlated with the degree of inflammation. Overall, the study suggests that NONHSAT122636.2 can be exploited as a potential diagnostic biomarker for pediatric myocarditis.

Gestational weight gain trajectories in patients with gestational diabetes mellitus: a retrospective cohort study.

Aims/Background Gestational diabetes mellitus is a common pregnancy complication that affects approximately 14% of pregnancies worldwide and can lead to adverse maternal and neonatal outcomes. This study aimed to investigate the trajectories of gestational weight gain among gestational diabetes mellitus patients and to inform the development of effective weight management strategies. Methods Demographic and antenatal examination data from 1421 pregnant women diagnosed with gestational diabetes mellitus were retrospectively analysed. Quantitative data comparisons were performed using Chi-square tests, Fisher's exact test, t-tests, and one-way analysis of variance. Group-based trajectory modelling was employed to identify the trajectories of gestational weight gain among patients with gestational diabetes mellitus. Results This study revealed that pre-pregnancy body mass index and types of gestational diabetes mellitus significantly influence gestational weight gain (p < 0.05). Group-based trajectory modelling identified three distinct gestational weight gain trajectories. Patients with gestational diabetes mellitus demonstrated a continuous weight gain throughout pregnancy, while women who were overweight or obese before pregnancy were more likely to follow a low-speed growth trajectory. Women in the rapid growth trajectory group were more inclined to deliver by caesarean section and were more likely to give birth to macrosomic infants. Conclusion Our research underscores the importance of identifying and distinguishing between different gestational weight gain trajectories in pregnant women, thereby identifying high-risk groups, which is crucial for improving the health conditions of both mothers and newborns.

Binder-Responsive DNA Strand Displacement Enables High-Throughput and High-Fidelity Discovering of Small Molecular DNA Binders.

High-throughput screening (HTS) is pivotal in the discovery of small molecules that bind to DNA, yet there are limited sensing mechanisms available for designing HTS assays for DNA binders. Herein, we introduce a binder-responsive toehold-mediated DNA strand displacement (BR-TMSD) technique featuring programmable reaction kinetics in response to DNA-binder interactions. When two DNA binders are used, BR-TMSD is initiated through a rapid binder displacement, followed by the DNA strand displacement. The orthogonal displacement reactions of BR-TMSD enables a high-fidelity, dual-channel HTS assay, returning 19 new DNA binders from a library of 1,170 compounds.

Pyrgos[n]cages: Redefining antibacterial strategy against drug resistance.

Amid rising antibiotic resistance, the quest for advanced antibacterial agents to surpass microbial adaptation is paramount. This study introduces Pyrgos[n]cages (n = 1 to 4), pioneering multidecker cationic covalent organic cages engineered to combat drug-resistant bacteria via a dual-targeting approach. Synthesized through successive photocatalytic bromination and cage-forming reactions, these architectures stand out for their dense positive charge distribution, exceptional stability, and substantial rigidity. Pyrgos[n]cages exhibit potent bactericidal activity by disrupting bacterial membrane potential and binding to DNA. Notably, these structures show unparalleled success in eradicating both extracellular and intracellular drug-resistant pathogens in diverse infection scenarios, with antibacterial efficiency markedly increasing over 100-fold as the decker number rises from 1 to 3. This study provides an advance in antibacterial tactics and underscores the transformative potential of covalent organic cages in devising enduring countermeasures against antibiotic-resistant microbial threats.

Ligand-Receptor Interaction-Induced Intracellular Phase Separation: A Global Disruption Strategy for Resistance-Free Lethality of Pathogenic Bacteria.

Addressing the global challenge of bacterial resistance demands innovative approaches, among which multitargeting is a widely used strategy. Current strategies of multitargeting, typically achieved through drug combinations or single agents inherently aiming at multiple targets, face challenges such as stringent pharmacokinetic and pharmacodynamic requirements and cytotoxicity concerns. In this report, we propose a bacterial-specific global disruption approach as a vastly expanded multitargeting strategy that effectively disrupts bacterial subcellular organization. This effect is achieved through a pioneering chemical design of ligand-receptor interaction-induced aggregation of small molecules, i.e., DNA-induced aggregation of a diarginine peptidomimetic within bacterial cells. These intracellular aggregates display affinity toward various proteins and thus substantially interfere with essential bacterial functions and rupture bacterial cell membranes in an "inside-out" manner, leading to robust antibacterial activities and suppression of drug resistance. Additionally, biochemical analysis of macromolecule binding affinity, cytoplasmic localization patterns, and bacterial stress responses suggests that this bacterial-specific intracellular aggregation mechanism is fundamentally different from nonselective classic DNA or membrane binding mechanisms. These mechanistic distinctions, along with the peptidomimetic's selective permeation of bacterial membranes, contribute to its favorable biocompatibility and pharmacokinetic properties, enabling its in vivo antimicrobial efficacy in several animal models, including mice-based superficial wound models, subcutaneous abscess models, and septicemia infection models. These results highlight the great promise of ligand-receptor interaction-induced intracellular aggregation in achieving a globally disruptive multitargeting effect, thereby offering potential applications in the treatment of malignant cells, including pathogens, tumor cells, and infected tissues.

Finer Particle Size Distribution and Potential Higher Toxicity of Elemental Carbon and Polycyclic Aromatic Hydrocarbons Emitted by Ships after Fuel Oil Quality Improvement.

Ship emissions are a significant source of air pollution, and the primary policy to control is fuel oil quality improvement. However, the impact of this policy on particle size distribution and composition characteristics remains unclear. Measurements were conducted on nine different vessels (ocean-going vessels, coastal cargo ships, and inland cargo ships) to determine the impact of fuel upgrading (S < 0.1% m/m marine gas oil (MGO) vs S < 0.5% m/m heavy fuel oil (HFO)) on elemental carbon (EC) and polycyclic aromatic hydrocarbons (PAHs) emitted by ships. (1) Fuel improvement significantly reduced EC and PAH emission, by 31 ± 25 and 45 ± 38%, respectively. However, particle size distributions showed a trend toward finer particles, with the peak size decreasing from DP = 0.38-0.60 µm (HFO) to DP = 0.15-0.25 µm (MGO), and the emission factor of DP < 100 nm increased. (2) Changes in emission characteristics led to an increase in the toxicity of ultrafine particulate matter. (3) Ship types and engine conditions affected the EC and PAH particle size distributions. Inland ships have a more concentrated particle size distribution. Higher loads result in higher emissions. (4) The composition and engine conditions of fuel oils jointly affected pollutant formation mechanisms. MGO and HFO exhibited opposite EC emissions when emitting the same level of PAHs.

DNA methylation patterns in patients with asthenospermia and oligoasthenospermia.

BACKGROUND: Spermatogenesis is a highly regulated and complex process in which DNA methylation plays a crucial role. This study aimed to explore the differential methylation profiles in sperm DNA between patients with asthenospermia (AS) and healthy controls (HCs), those with oligoasthenospermia (OAS) and HCs, and patients with AS and those with OAS. RESULTS: Semen samples and clinical data were collected from five patients with AS, five patients with OAS, and six age-matched HCs. Reduced representation bisulfite sequencing (RRBS) was performed to identify differentially methylated regions (DMRs) in sperm cells among the different types of patients and HCs. A total of 6520, 28,019, and 16,432 DMRs were detected between AS and HC, OAS and HC, and AS and OAS groups, respectively. These DMRs were predominantly located within gene bodies and mapped to 2868, 9296, and 9090 genes in the respective groups. Of note, 12, 9, and 8 DMRs in each group were closely associated with spermatogenesis and male infertility. Furthermore, BDNF, SMARCB1, PIK3CA, and DDX27; RBMX and SPATA17; ASZ1, CDH1, and CHDH were identified as strong differentially methylated candidate genes in each group, respectively. Meanwhile, the GO analysis of DMR-associated genes in the AS vs. HC groups revealed that protein binding, cytoplasm, and transcription (DNA-templated) were the most enriched terms in the biological process (BP), cellular component (CC), and molecular function (MF), respectively. Likewise, in both the OAS vs. HC and AS vs. OAS groups, GO analysis revealed protein binding, nucleus, and transcription (DNA-templated) as the most enriched terms in BP, CC, and MF, respectively. Finally, the KEGG analysis of DMR-annotated genes and these genes at promoters suggested that metabolic pathways were the most significantly associated across all three groups. CONCLUSIONS: The current study results revealed distinctive sperm DNA methylation patterns in the AS vs. HC and OAS vs. HC groups, particularly between patients with AS and those with OAS. The identification of key genes associated with spermatogenesis and male infertility in addition to the differentially enriched metabolic pathways may contribute to uncovering the potential pathogenesis in different types of abnormal sperm parameters.

Screening and verification of proteins that interact with the anthocyanin-related transcription factor PbrMYB114 in 'Yuluxiang' pear.

Despite extensive research highlighting the pivotal role of MYB transcription factors in regulating anthocyanin biosynthesis, the interactive regulatory network involving these MYB factors in pear fruits remains inadequately characterized. In this study, the anthocyanin-regulatory gene PbrMYB114 was successfully cloned from 'Yuluxiang' pear (Pyrus bretschneideri) fruits, and its influence on anthocyanin accumulation was confirmed through transient expression assays. Specifically, the co-transformation of PbrMYB114 with its partner PbrbHLH3 in pears served to validate the functional role of PbrMYB114. Subsequently, PbrMYB114 was employed as bait in a yeast two-hybrid screening assay, using a 'Yuluxiang' pear protein library, which led to the identification of 25 interacting proteins. Further validation of the interactions between PbrMYB114 and PbrMT2/PbrMT3 was conducted. Investigations into the role of PbrMT2 and PbrMT3 in 'Duli' seedlings (Pyrus betulaefolia) revealed their potential to enhance anthocyanin accumulation. The outcomes of these studies provide novel insights into the protein network that regulates pear anthocyanin biosynthesis, particularly the functional interactions among PbrMYB114 and associated proteins.

Rapid identification of peanut oil adulteration by near infrared spectroscopy and chemometrics.

Peanut oil, prized for its unique taste and nutritional value, grapples with the pressing issue of adulteration by cost-cutting vendors seeking higher profits. In response, we introduce a novel approach using near-infrared spectroscopy to non-invasively and cost-effectively identify adulteration in peanut oil. Our study, analyzing spectral data of both authentic and intentionally adulterated peanut oil, successfully distinguished high-quality pure peanut oil (PPEO) from adulterated oil (AO) through rigorous analysis. By combining near-infrared spectroscopy with factor analysis (FA) and partial least squares regression (PLS), we achieved discriminant accuracies exceeding 92 % (S > 2) and 89 % (S > 1) for FA models 1 and 2, respectively. The PLS model demonstrated strong predictive capabilities, with a prediction coefficient (R2) surpassing 93.11 and a root mean square error (RMSECV) below 4.43. These results highlight the effectiveness of NIR spectroscopy in confirming the authenticity of peanut oil and detecting adulteration in its composition.

Significance of immunoglobulins synthesis with central nervous system involvement in Neuro-Behçet's disease.

OBJECTIVES: Demyelination and immunocyte-infiltrated lesions have been found in neuro-Behçet's disease (NBD) pathology. Lacking satisfying laboratory biomarkers in NBD impedes standard clinical diagnostics. We aim to explore the ancillary indicators for NBD diagnosis unveiling its potential etiology. METHODS: 28 NBD with defined diagnosis, 29 patients with neuropsychiatric lupus erythematosus, 30 central nervous system idiopathic inflammatory demyelination diseases (CNS-IIDD), 30 CNS infections, 30 cerebrovascular diseases, and 30 noninflammatory neurological diseases (NIND) were retrospectively enrolled. Immunoglobulins (Ig) in serum and cerebral spinal fluid (CSF) were detected by immunonephelometry and myelin basic protein (MBP) by quantitative enzyme-linked immunosorbent assay. RESULTS: IgA index is almost twice enhanced in NBD than NIND with an accuracy of 0.8488 in differential diagnosis, the sensitivity and specificity of which were 75.00 % and 90.00 % when the cutoff was > 0.6814. The accuracy of CSF Ig and quotient of Ig all exceed 0.90 in discerning NBD with damaged and intact blood-brain barrier (BBB). Clustering analyses divided NBD into two different phenotypes: one with BBB damage has lower Ig synthesis, the other with extra-synthesis in parenchymal sites but with intact BBB. MBP index is significantly correlated with kappa (KAP) index and lambda (LAM) index (r = 0.358, 0.575, P < 0.001), hinting the NBD pathogenesis of CNS demyelination in triggering excessive intrathecal Ig productions and humoral responses. CONCLUSIONS: IgA index acts as a potential diagnostic indicator in differentiating NBD from NIND and CNS-IIDD. Excessive immunoglobulin production induced by CNS inflammation and demyelination might be latent immunopathogenesis of NBD.

The Physiological Response of Apricot Flowers to Low-Temperature Stress.

The growth and development of apricot flower organs are severely impacted by spring frosts. To better understand this process, apricot flowers were exposed to temperatures ranging from 0 °C to -8 °C, including a control at 18 °C, in artificial incubators to mimic diverse low-temperature environments. We aimed to examine their physiological reactions to cold stress, with an emphasis on changes in phenotype, membrane stability, osmotic substance levels, and antioxidant enzyme performance. Results reveal that cold stress induces significant browning and cellular damage, with a sharp increase in browning rate and membrane permeability below -5 °C. Soluble sugars and proteins initially rise as osmoprotectants, but their content decreases at lower temperatures. Proline content consistently increases, suggesting a protective role. Antioxidant enzyme activities, including catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), and ascorbate peroxidase (APX), exhibit a complex pattern, with initial increases followed by declines at more severe cold conditions. Correlation and principal component analyses highlight the interplay between these responses, indicating a multifaceted adaptation strategy. The findings contribute to the understanding of apricot cold tolerance and inform breeding efforts for improved crop resilience.

MicroRNA-542-3p targets Pten to inhibit the myoblasts proliferation but suppresses myogenic differentiation independent of targeted Pten.

BACKGROUND: Non-coding RNA is a key epigenetic regulation factor during skeletal muscle development and postnatal growth, and miR-542-3p was reported to be conserved and highly expressed in the skeletal muscle among different species. However, its exact functions in the proliferation of muscle stem cells and myogenesis remain to be determined. METHODS: Transfection of proliferative and differentiated C2C12 cells used miR-542-3p mimic and inhibitor. RT-qPCR, EdU staining, immunofluorescence staining, cell counting kit 8 (CCK-8), and Western blot were used to evaluate the proliferation and myogenic differentiation caused by miR-542-3p. The dual luciferase reporter analysis and rescued experiment of the target gene were used to reveal the molecular mechanism. RESULTS: The data shows overexpression of miR-542-3p downregulation of mRNA and protein levels of proliferation marker genes, reduction of EdU+ cells, and cellular vitality. Additionally, knocking it down promoted the aforementioned phenotypes. For differentiation, the miR-542-3p gain-of-function reduced both mRNA and protein levels of myogenic genes, including MYOG, MYOD1, et al. Furthermore, immunofluorescence staining immunized by MYHC antibody showed that the myotube number, fluorescence intensity, differentiation index, and myotube fusion index all decreased in the miR-542-3p mimic group, compared with the control group. Conversely, these phenotypes exhibited an increased trend in the miR-542-3p inhibitor group. Mechanistically, phosphatase and tensin homolog (Pten) was identified as the bona fide target gene of miR-542-3p by dual luciferase reporter gene assay, si-Pten combined with miR-542-3p inhibitor treatments totally rescued the promotion of proliferation by loss-function of miR-542-3p. CONCLUSIONS: This study indicates that miR-542-3p inhibits the proliferation and differentiation of myoblast and Pten is a dependent target gene of miR-542-3p in myoblast proliferation, but not in differentiation.

Acceptance, safety, and immunogenicity of a booster dose of inactivated SARS-CoV-2 vaccine in patients with primary biliary cholangitis.

Inactivated coronavirus disease 2019 (COVID-19) vaccines showed impaired immunogenicity in some autoimmune diseases, but it remains unclear in primary biliary cholangitis (PBC). This study aimed to explore the antibody response to the inactivated COVID-19 vaccine in individuals with PBC, as well as to evaluate coverage, safety, and attitudes toward the COVID-19 vaccine among them. Two cohorts of patients with PBC were enrolled in this study. One cohort was arranged to evaluate the immunogenicity of the inactivated COVID-19 vaccine, another cohort participated in an online survey. The titers of the anti-receptor-binding domain (RBD)-specific immunoglobulin G (IgG), neutralizing antibody (NAb) toward severe acute respiratory syndrome coronavirus 2 wild-type, and NAb toward Omicron BA.4/5 subvariants were detected to assess antibody response from the vaccine. After booster vaccination for more than six months, patients with PBC had significantly lowered levels of anti-RBD-specific IgG compared to HCs, and the inhibition rates of NAb toward wild-type also declined in individuals with PBC. The detected levels of NAb toward Omicron BA.4/5 were below the positive threshold in patients with PBC and HCs. Laboratory parameters did not significantly correlate with any of the three antibodies. The online survey revealed that 24% of patients with PBC received three COVID-19 vaccines, while 63% were unimmunized. Adverse effect rates after the first, second, and third vaccine doses were 6.1%, 10.3%, and 9.5%, respectively. Unvaccinated patients with PBC were more worried about the safety of the vaccine than those who were vaccinated (P = 0.004). As a result, this study fills the immunological assessment gap in patients with PBC who received inactivated COVID-19 vaccines.

Multi-targeting oligopyridiniums: Rational design for biofilm dispersion and bacterial persister eradication.

The development of effective antibacterial drugs to combat bacterial infections, particularly the biofilm-related infections, remains a challenge. There are two important features of bacterial biofilms, which are well-known critical factors causing biofilms hard-to-treat in clinical, including the dense and impermeable extracellular polymeric substances (EPS) and the metabolically repressed dormant and persistent bacterial population embedded. These characteristics largely increase the difficulty for regular antibiotic treatment due to insufficient penetration into EPS. In addition, the dormant bacteria are insensitive to the growth-inhibiting mechanism of traditional antibiotics. Herein, we explore the potential of a series of new oligopyridinium-based oligomers bearing a multi-biomacromolecule targeting function as the potent bacterial biofilm eradication agent. These oligomers were rationally designed to be "charge-on-backbone" that can offer a special alternating amphiphilicity. This novel and unique feature endows high affinity to bacterial membrane lipids, DNAs as well as proteins. Such a broad multi-targeting nature of molecules not only enables its penetration into EPS, but also plays vital roles in the bactericidal mechanism of action that is highly effective against dormant and persistent bacteria. Our in vitro, ex vivo, and in vivo studies demonstrated that OPc3, one of the most effective derivatives, was able to offer excellent antibacterial potency against a variety of bacteria and effectively eliminate biofilms in zebrafish models and mouse wound biofilm infection models.

Triphenylamine-Based Polythioacetal for Selective Sensing of Mercury(II) with High Specificity and Sensitivity.

Utilizing the mercury (Hg2+)-triggered deprotection of thioacetals to aldehyde groups, we constructed a water-soluble triphenylamine (TPA)-based polythioacetal PTA-TPA with thioacetal groups in the backbones for efficient sensing of Hg2+ in aqueous solutions. PTA-TPA is conveniently prepared by polycondensation of 3, 6-dioxa-1,8-octanedithiol (DODT) with 4-(N,N-diphenylamino) benzaldehyde (TPA-CHO) using thiol-terminated mPEG2k-SH as a capping agent. The interaction of Hg2+ with PTA-TPA activates the aggregation-induced emission (AIE) process of TPA-CHO molecules, which makes the emission enhanced, and the emission color changes to sky blue, while other metal ions do not interfere with the sensing process. PTA-TPA can be used as a highly selective and ultrafast detection system for Hg2+ with a low detection limit (LOD) of 9.88 nM and a fast response of less than 1 min. In addition, the prepared test strips report the presence of Hg2+ with an LOD as low as 1 × 10-5 M. Intracellular imaging applications have demonstrated that PTA-TPA acts as a biocompatible fluorescent probe for efficient Hg2+ sensing in HeLa cells. Overall, the PTA-TPA fluorescence probes have the characteristics of easy synthesis, cost-effective, ultrafast detection speed, high selectivity, and high sensitivity, which can be used in practical applications.

Transcutaneous electrical acupoint stimulation for prevention of postoperative urinary retention: A systematic review.

Introduction: Transcutaneous electrical acupoint stimulation (TEAS) has been proposed for postoperative urinary retention (POUR). This meta-analysis evaluated the effect of TEAS in preventing POUR. Methods: Databases were searched until February 6, 2023. Randomized controlled trials (RCTs) about TEAS for preventing POUR were included. The primary concern was the incidence of POUR, with post-void residual urine volume as a secondary outcome. Results: Fourteen studies with 2865 participants were identified. TEAS reduced the incidence of POUR (RR = 0.44, 95%CI = 0.33 to 0.58, P < 0.00001) and decreased the post-void residual urine volume (MD = -75.41 mL, 95%CI = -118.76 to -32.06, P = 0.0007). The preventive effect on POUR was found in patients receiving anorectal, gynecologic, orthopedic and biliary surgery, but not urinary surgery. Dilatational- and continuous-wave TEAS had a great outcome in preventing POUR. Intraoperative TEAS, preoperative and intraoperative TEAS, and postoperative TEAS were beneficial, and TEAS was more beneficial when compared with sham TEAS and blank control. It is nevertheless difficult to rule out publication bias. Conclusions: TEAS could prevent POUR. Due to insufficient evidence, multicenter, large-sample and high-quality RCTs should be conducted. (Registration:INPLASY202320095).

Pyrene-Based "Turn-On" Fluorescent Polymeric Probe with Thioacetal Units in the Main Chain for Mercury(II) Detection in Aqueous Solutions and Living Cells.

A water-soluble polymeric pyrene-based polythioacetal (PTA-Py) with thioacetal units in the main chain is simply synthesized by direct polycondensation of 3, 6-dioxa-1, 8-octanedithiol, 1-pyrene formaldehyde, and mPEG2k-SH. The probe PTA-Py shows a good fluorescence response to Hg2+ ions due to the Hg2+-promoted deprotection reaction of thioacetal groups to regenerate the original 1-pyrene formaldehyde compound. After adding Hg2+ to the PTA-Py solution, the fluorescence intensity (FI) gradually increases with increasing concentrations of Hg2+. Compared with other metal ions, the probe exhibits high sensitivity, good selectivity, and rapid response to Hg2+. The low detection limits are 12.3 nm in ethanol-PBS buffer and 13.3 nm in water, respectively. The results imply that the simply synthesized water-soluble polymeric probe had potential applications in the rapid detection of Hg2+ ions in aqueous solutions. Moreover, the polymeric PTA-Py shows high sensitivity for CH3Hg+ with detection limits of 26.5 nm in ethanol/PBS buffer. In addition, PTA-Py can efficiently detect Hg2+ ions in HeLa cells. The results demonstrate that a valuable method is developed for biocompatible polymeric sensors for Hg2+ ions in biological and environmental samples.

Dominant Contribution of NO3 Radical to NO3- Formation during Heavy Haze Episodes: Insights from High-Time Resolution of Dual Isotopes Δ17O and δ18O.

δ18O is widely used to track nitrate (NO3-) formation but overlooks NO3 radical reactions with hydrocarbons (HCs), particularly in heavily emitting hazes. This study introduces high-time resolution Δ17O-NO3- as a powerful tool to quantify NO3- formation during five hazes in three cities. Results show significant differences between Δ17O-NO3- and δ18O-NO3- in identifying NO3- formation. δ18O-NO3- results suggested N2O5 hydrolysis (62.0-88.4%) as the major pathway of NO3- formation, while Δ17O-NO3- shows the NO3- formation contributions of NO2 + OH (17.7-66.3%), NO3 + HC (10.8-49.6%), and N2O5 hydrolysis (22.9-33.3%), revealing significant NO3 + HC contribution (41.7-56%) under severe pollution. Furthermore, NO3- formation varies with temperatures, NOx oxidation rate (NOR), and pollution levels. Higher NO2 + OH contribution and lower NO3 + HC contribution were observed at higher temperatures, except for low NOR haze where higher NO2 + OH contributions were observed at low temperatures (T ← 10 °C). This emphasizes the significance of NO2 + OH in emission-dominated haze. Contributions of NO2 + OH and NO3 + HC relate to NOR as positive (fP1 = 3.0*NOR2 - 2.4*NOR + 0.8) and negative (fP2 = -2.3*NOR2 + 1.8*NOR) quadratic functions, respectively, with min/max values at NOR = 0.4. At mild pollution, NO2 + OH (58.1 ± 22.2%) dominated NO3- formation, shifting to NO3 + HC (35.5 ± 16.3%) during severe pollution. Additionally, high-time resolution Δ17O-NO3- reveals that morning-evening rush hours and high temperatures at noon promote the contributions of NO3 + HC and NO2 + OH, respectively. Our results suggested that the differences in the NO3- pathway are attributed to temperatures, NOR, and pollution levels. Furthermore, high-time resolution Δ17O-NO3- is vital for quantifying NO3 + HC contribution during severe hazes.

Analyzing Morphology, Metabolomics, and Transcriptomics Offers Invaluable Insights into the Mechanisms of Pigment Accumulation in the Diverse-Colored Labellum Tissues of Alpinia.

Alpinia plants are widely cherished for their vibrant and captivating flowers. The unique feature of this genus lies in their labellum, a specialized floral structure resulting from the fusion of two non-fertile staminodes. However, the intricate process of pigment formation, leading to distinct color patterns in the various labellum segments of Alpinia, remains a subject of limited understanding. In this study, labellum tissues of two Alpinia species, A. zerumbet (yellow-orange flowers) and A. oxyphylla (white-purple flowers), were sampled and analyzed through morphological structure observation, metabolite analysis, and transcriptome analyses. We found that hemispherical/spherical epidermal cells and undulate cell population morphology usually display darker flower colors, while flat epidermal cells and cell populations usually exhibit lighter flower colors. Metabolomic analysis identified a high concentration of anthocyanins, particularly peonidin derivatives, in segments with orange and purple pigments. Additionally, segments with yellow pigments showed significant accumulations of flavones, flavanols, flavanones, and xanthophylls. Furthermore, our investigation into gene expression levels through qRT-PCR revealed notable differences in several genes that participated in anthocyanin and carotenoid biosynthesis among the four pigmented segments. Collectively, these findings offer a comprehensive understanding of pigmentation in Alpinia flowers and serve as a valuable resource for guiding future breeding efforts aimed at developing Alpinia varieties with novel flower colors.

Chemical Biology Approach to Reveal the Importance of Precise Subcellular Targeting for Intracellular Staphylococcus aureus Eradication.

Intracellular bacterial pathogens, such as Staphylococcus aureus, that may hide in intracellular vacuoles represent the most significant manifestation of bacterial persistence. They are critically associated with chronic infections and antibiotic resistance, as conventional antibiotics are ineffective against such intracellular persisters due to permeability issues and mechanistic reasons. Direct subcellular targeting of S. aureus vacuoles suggests an explicit opportunity for the eradication of these persisters, but a comprehensive understanding of the chemical biology nature and significance of precise S. aureus vacuole targeting remains limited. Here, we report an oligoguanidine-based peptidomimetic that effectively targets and eradicates intracellular S. aureus persisters in the phagolysosome lumen, and this oligomer was utilized to reveal the mechanistic insights linking precise targeting to intracellular antimicrobial efficacy. The oligomer has high cellular uptake via a receptor-mediated endocytosis pathway and colocalizes with S. aureus persisters in phagolysosomes as a result of endosome-lysosome interconversion and lysosome-phagosome fusion. Moreover, the observation of a bacterium's altered susceptibility to the oligomer following a modification in its intracellular localization offers direct evidence of the critical importance of precise intracellular targeting. In addition, eradication of intracellular S. aureus persisters was achieved by the oligomer's membrane/DNA dual-targeting mechanism of action; therefore, its effectiveness is not hampered by the hibernation state of the persisters. Such precise subcellular targeting of S. aureus vacuoles also increases the agent's biocompatibility by minimizing its interaction with other organelles, endowing excellent in vivo bacterial targeting and therapeutic efficacy in animal models.