The multifaceted role of RNA-based regulation in plant stress memory.

Plants have evolved interconnected regulatory pathways which enable them to respond and adapt to their environments. In plants, stress memory enhances stress tolerance through the molecular retention of prior stressful experiences, fostering rapid and robust responses to subsequent challenges. Mounting evidence suggests a close link between the formation of stress memories and effective future stress responses. However, the mechanism by which environmental stressors trigger stress memory formation is poorly understood. Here, we review the current state of knowledge regarding the RNA-based regulation on stress memory formation in plants and discuss research challenges and future directions. Specifically, we focus on the involvement of microRNAs (miRNAs), small interfering RNAs (siRNAs), long non-coding RNAs (lncRNAs), and alternative splicing (AS) in stress memory formation. miRNAs regulate target genes via post-transcriptional silencing, while siRNAs trigger stress memory formation through RNA-directed DNA methylation (RdDM). lncRNAs guide protein complexes for epigenetic regulation, and AS of pre-mRNAs is crucial to plant stress memory. Unraveling the mechanisms underpinning RNA-mediated stress memory formation not only advances our knowledge of plant biology but also aids in the development of improved stress tolerance in crops, enhancing crop performance and global food security.

Triglyceride-glucose index and health outcomes: an umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Numerous meta-analyses have explored the association between the triglyceride-glucose (TyG) index and diverse health outcomes, yet the comprehensive assessment of the scope, validity, and quality of this evidence remains incomplete. Our aim was to systematically review and synthesise existing meta-analyses of TyG index and health outcomes and to assess the quality of the evidence. METHODS: A thorough search of PubMed, EMBASE, and Web of Science databases was conducted from their inception through to 8 April 2024. We assessed the quality of reviews using A Measurement Tool to Assess Systematic Reviews (AMSTAR) and the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. This study was registered with PROSPERO (CRD: 42024518587). RESULTS: Overall, a total of 95 associations from 29 meta-analyses were included, investigating associations between TyG index and 30 health outcomes. Of these, 83 (87.4%) associations were statistically significant (P < 0.05) according to the random effects model. Based on the AMSTAR tool, 16 (55.2%) meta-analyses were high quality and none was low quality. The certainty of the evidence, assessed by the GRADE framework, showed that 6 (6.3%) associations were supported by moderate-quality evidence. When compared with the lowest category of the TyG index, the risk of contrast-induced nephropathy (CIN) [relative risk (RR) = 2.25, 95%CI 1.82, 2.77], the risk of stroke in patients with diabetes mellitus (RR = 1.26, 95%CI 1.18, 1.33) or with acute coronary syndrome disease (RR = 1.56, 95%CI 1.06, 2.28), the prognosis of coronary artery disease (CAD)-non-fatal MI (RR = 2.02, 95%CI 1.32, 3.10), and the severity of CAD including coronary artery stenosis (RR = 3.49, 95%CI 1.71, 7.12) and multi-vessel CAD (RR = 2.33, 95%CI 1.59, 3.42) increased with high TyG index. CONCLUSION: We found that the TyG index was positively associated with many diseases including the risk of CIN and stroke, the prognosis of CAD, and the severity of CAD which were supported by moderate-quality evidence. TyG index might be useful to identify people at high-risk for developing these diseases.

Human papillomavirus infection and the risk of cancer at specific sites other than anogenital tract and oropharyngeal region: an umbrella review.

BACKGROUND: Despite numerous studies having evaluated the associations between human papillomavirus (HPV) infection and risk of specific cancers other than anogenital tract and oropharyngeal, the findings are inconsistent and the quality of evidence has not been systematically quantified. We aimed to summarise the existing evidence as well as to evaluate the strength and credibility of these associations. METHODS: We conducted an umbrella review of systematic reviews and meta-analyses of observational studies. PubMed, EMBASE, and Web of Science were searched from inception to March 2024. Studies with systematic reviews and meta-analyses that examined associations between HPV or HPV-associated genotypes infection and specific cancers were eligible for this review. The quality of the methodology was evaluated using A Measurement Tool to Assess systematic Reviews (AMSTAR). The credibility of the evidence was assessed using GRADE. The protocol was preregistered with PROSPERO (CRD42023439070). FINDINGS: The umbrella review identified 31 eligible studies reporting 87 associations with meta-analytic estimates, including 1191 individual studies with 336,195 participants. Of those, 29 (93.5%) studies were rated as over moderate quality by AMSTAR. Only one association indicating HPV-18 infection associated with an increased risk of breast cancer (odds ratio [OR] = 3.48, 95% confidence interval [CI] = 2.24-5.41) was graded as convincing evidence. There were five unique outcomes identified as highly suggestive evidence, including HPV infection increased the risk of oral squamous cell carcinoma (OR = 7.03, 95% CI = 3.87-12.76), oesophageal cancer (OR = 3.32, 95% CI = 2.54-4.34), oesophageal squamous cell carcinoma (OR = 2.69, 95% CI = 2.05-3.54), lung cancer (OR = 3.60, 95% CI = 2.59-5.01), and breast cancer (OR = 6.26, 95% CI = 4.35-9.00). According to GRADE, one association was classified as high, indicating that compared with the controls in normal tissues, HPV infection was associated with an increased risk of breast cancer. INTERPRETATION: The umbrella review synthesised up-to-date observational evidence on HPV infection with the risk of breast cancer, oral squamous cell carcinoma, oesophageal cancer, oesophageal squamous cell carcinoma, and lung cancer. Further larger prospective cohort studies are needed to verify the associations, providing public health recommendations for prevention of disease. FUNDING: National Key Research and Development Program of China, Natural Science Foundation of China, Outstanding Scientific Fund of Shengjing Hospital of China Medical University, and 345 Talent Project of Shengjing Hospital of China Medical University.

Unraveling the structure-chirality sensing relationship between achiral anthracene-based tetracationic nanotubes and nucleosides in aqueous host-guest complexation.

In biological systems, nucleosides play crucial roles in various physiological processes. In this study, we designed and synthesized four achiral anthracene-based tetracationic nanotubes (1-4) as artificial hosts and chiroptical sensors for nucleosides in aqueous media. Notably, different nanotubes exhibit varied chirality sensing on circular dichroism (CD)/circularly polarized luminescence (CPL) spectra through the host-guest complexation, which prompted us to explore the factors influencing their chiroptical responses. Through systematic host-guest experiments, the structure-chirality sensing relationship between achiral anthracene-based tetracationic nanotubes and nucleosides in the host-guest complexation was unraveled. Firstly, the CD response originates from the anthracene rings situated at the side-wall position, resulting from the right-handed (P)- or left-handed (M)-twisted conformation of the macrocyclic structure. Secondly, the CPL signal is influenced by the presence of anthracene rings at the linking-wall position, which results from intermolecular chiral twisted stacking between these anthracene rings. Therefore, these nanotubes can serve as chiroptical sensor arrays to enhance the accuracy of nucleotide recognition through principal component analysis (PCA) analysis based on the diversified CD spectra. This study provides insights for the construction of adaptive chirality from achiral nanotubes with dynamic conformational nature and might facilitate further design of chiral functional materials for several applications.

Blue ZnSeTe quantum dot light-emitting diodes with low efficiency roll-off enabled by an in situ hybridization of ZnMgO nanoparticles and amino alcohol molecules.

ZnSeTe quantum dots (QDs) have been employed as promising emitters for blue QD-based light-emitting diodes (QLEDs) due to their unique optoelectronic properties and environmental friendliness. However, such QLEDs usually suffer from serious efficiency roll-off primarily stemming from exciton loss at the interface of the QD layer and the ZnMgO (ZMO) electron transport layer (ETL), which remarkably hinders their application in flat-panel displays. Herein, we propose an in situ hybridization strategy that involves the pre-introduction of amino alcohols into the reaction solution. This strategy effectively suppresses the nucleophilic condensation process by facilitating the coordination of ammonium and hydroxyl groups with metal cations (M2+, i.e. Zn2+ and Mg2+). It slows down the growth rate of ZMO nanoparticles (NPs) while simultaneously facilitating M-O coordination, resulting in the synthesis of small-sized and low-defect ZMO NPs. Notably, this in situ hybridization approach not only alleviates emission quenching at the QDs/ETL interface but also elevates the energy level of the ETL for enhancing carrier injection. We further investigated the impact of amino alcohols with varying carbon-chain lengths on the performance of ZMO NPs and the corresponding LED devices. The optimal blue ZnSeTe QLED demonstrates an impressive EQE of 8.6% with only an ∼11% drop when the current density is increased to 200 mA cm-2, and the device operating lifetime extends to over 1300 h. Conversely, the device utilizing traditionally post-treated ZMO NPs as the ETL exhibits 45% efficiency roll-off and device lifetime of merely 190 h.

Coumarin-Furoxan Hybrid Suppressed the Proliferation and Metastasis of Triple-Negative Breast Cancer by Activating Mitochondrial Stress and Cell Apoptosis.

Triple-negative breast cancer (TNBC) typically manifests as higher invasive carcinoma correlated with a worse prognosis that primarily relies on chemotherapy. There is growing evidence that nitric oxide (NO) donor drugs have the potential for anticancer therapy. On this basis, we constructed and evaluated a novel coumarin-furoxan hybrid 4A93 as an effective antitumor candidate drug. 4A93 exhibits low IC50 values in three TNBC cell lines and inhibits colony formation and DNA synthesis, probably due to the release of high concentrations of NO in mitochondria, which induces oxidative stress, mitochondrial dysfunction, and apoptosis. Further research suggests that 4A93 might destroy mitochondria by opening the mitochondrial permeability transition pore (mPTP), depolarizing the mitochondrial membrane potential (MMP), and promoting the release of cytochrome c into the cytoplasm. Intrinsic apoptosis is induced finally, along with Akt/Erk signaling suppression. Additionally, 4A93 underregulates the Epithelial-mesenchymal transition process to inhibit cell migration and invasion. In 4T1 subcutaneous and hematogenous models of mice, 4A93 therapy suppresses the tumor growth and prevented lung metastasis with favorable biosafety. Our results provide insights into 4A93 in TNBC treatment and validate the contribution of NO donors in tumor therapy.

Phenylspirodrimane with Moderate Reversal Effect of Multidrug Resistance Isolated from the Deep-Sea Fungus Stachybotrys sp. 3A00409.

Two new phenylspirodrimanes, stachybotrins K and L (1 and 2), together with eight known analogues (3-10), were isolated from deep-sea-derived Stachybotrys sp. MCCC 3A00409. Their structures were determined by extensive NMR data and mass spectroscopic analysis. Absolute configurations of new compounds were determined through a comparison of their circular dichroism (CD) spectra with other reported compounds. The possible reversal effects of all compounds were assayed in the resistant cancer cell lines. Stachybotrysin B (8) can reverse multidrug resistance (MDR) in ABCB1-overexpression cells (KBv200, Hela/VCR) at the non-cytotoxic concentration. Doxorubicin accumulation assay and molecular-docking analysis reveal that the mechanism of its reversal MDR effect may be related to the increase in the intracellular concentration of substrate anticancer drugs.

New anti-inflammatory limonoids from the fruits of Melia azedarach.

The phytochemical study of the fruits of Melia azedarach (Meliaceae) led to the isolation and characterisation of two novel natural limonoids1-deoxy- 3, 20-dicinnamoyl-11-methoxy-meliacarpinin (1) and 12ß- O- methyl nimbolinin A (2), along with twelve known limonoids. Its structure was identified by 1D- and 2D-NMR, HR-ESI-MS and comparison with published data. The anti-inflammatory effect of the compounds was measured in vitro in RAW 264.7 cells by evaluating the production of NO stimulated by LPS. Compounds 1, 8 and 14 indicated significant anti-inflammatory effect with inhibition rate of 11.76, 8.45 and 6.59 µM, respectively. Limonoid 1 significantly inhibited the production of NO, TNF-α and IL-1ß in RAW 264.7 cells. Therefore, limonoid derivative may be a promising source of bioactive metabolite for inflammatory diseases.

High-Efficiency and Stable Colloidal One-Dimensional Core/Shell Nanorod Light-Emitting Diodes.

Anisotropic nanocrystals such as nanorods (NRs) display unique linearly polarized emission, which is expected to break the external quantum efficiency (EQE) limit of quantum dot-based light-emitting diodes (LEDs). However, the progress in achieving a higher EQE using NRs encounters several challenges, primarily involving a low photoluminescence quantum yield (PLQY) of NRs and imbalanced charge injection in NR-LEDs. In this work, we investigated NR-LEDs based on CdSe/CdZnS/ZnS rod-in-rod NRs with a high PLQY and higher linear polarization compared to those of dot-in-rod NRs. The balanced charge injection is achieved using ZnMgO nanoparticles as the electron transport layer and poly-TPD {poly[N,N'-bis(4-butylphenyl)-N,N'-bis(phenyl)benzidine]} as the hole transport layer. Therefore, the NR-LEDs exhibit a maximum EQE of 21.5% and a maximum luminance of >120 000 cd/m2 owing to the high level of in-plane transitions with a dipole moment of 90%. The NR-LEDs also have greatly inhibited droop in EQE under a high current density as well as outstanding operation lifetime and cycle stability.

Recent Advances in the Application of P(III)-Nucleophiles to Create New P-C Bonds through Michaelis-Arbuzov-Type Rearrangement.

Organophosphorus compounds have long been considered valuable in both organic synthesis and life science. P(III)-nucleophiles, such as phosphites, phosphonites, and diaryl/alkyl phosphines, are particularly noteworthy as phosphorylation reagents for their ability to form new P-C bonds, producing more stable, ecofriendly, and cost-effective organophosphorus compounds. These nucleophiles follow similar phosphorylation routes as in the functionalization of P-H bonds and P-OH bonds. Activation can occur through photocatalytic, electrocatalytic, or thermo-driven reactions, often in coordination with a Michaelis-Arbuzov-trpe rearrangement process, to produce the desired products. As such, this review offers a thorough overview of the phosphorylated transformation and potential mechanisms of P(III)-nucleophiles, specifically focusing on developments since 2010. Notably, this review may provide researchers with valuable insights into designing and synthesizing functionalized organophosphorus compounds from P(III)-nucleophiles, guiding future advancements in both research and practical applications.

Intermittent fasting and health outcomes: an umbrella review of systematic reviews and meta-analyses of randomised controlled trials.

Background: Benefits of Intermittent fasting (IF) on health-related outcomes have been found in a range of randomised controlled trials (RCTs). Our umbrella review aimed to systematically analyze and synthesize the available causal evidence on IF and its impact on specific health-related outcomes while evaluating its evidence quality. Methods: We comprehensively searched the PubMed, Embase, Web of Science, and Cochrane databases (from inception up to 8 January 2024) to identify related systematic reviews and meta-analyses of RCTs investigating the association between IF and human health outcomes. We recalculated the effect sizes for each meta-analysis as mean difference (MD) or standardized mean difference (SMD) with corresponding 95% confidence intervals (CIs). Subgroup analyses were performed for populations based on three specific status: diabetes, overweight or obesity, and metabolic syndrome. The quality of systematic reviews was evaluated using A Measurement Tool to Assess Systematic Reviews (AMSTAR), and the certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system. This study is registered with PROSPERO (CRD42023382004). Findings: A total of 351 associations from 23 meta-analyses with 34 health outcomes were included in the study. A wide range of outcomes were investigated, including anthropometric measures (n = 155), lipid profiles (n = 83), glycemic profiles (n = 57), circulatory system index (n = 41), appetite (n = 9), and others (n = 6). Twenty-one (91%) meta-analyses with 346 associations were rated as high confidence according to the AMSTAR criteria. The summary effects estimates were significant at p < 0.05 in 103 associations, of which 10 (10%) were supported by high certainty of evidence according to GRADE. Specifically, compared with non-intervention diet in adults with overweight or obesity, IF reduced waist circumference (WC) (MD = -1.02 cm; 95% CI: -1.99 to -0.06; p = 0.038), fat mass (MD = -0.72 kg; 95% CI: -1.32 to -0.12; p = 0.019), fasting insulin (SMD = -0.21; 95% CI: -0.40 to -0.02; p = 0.030), low-density lipoprotein cholesterol (LDL-C) (SMD = -0.20; 95% CI: -0.38 to -0.02; p = 0.027), total cholesterol (TC) (SMD = -0.29; 95% CI: -0.48 to -0.10; p = 0.003), and triacylglycerols (TG) (SMD = -0.23; 95% CI: -0.39 to -0.06; p = 0.007), but increased fat free mass (FFM) (MD = 0.98 kg; 95% CI: 0.18-1.78; p = 0.016). Of note, compared with the non-intervention diet, modified alternate-day fasting (MADF) reduced fat mass (MD = -0.70 kg; 95% CI: -1.38 to -0.02; p = 0.044). In people with overweight or obesity, and type 2 diabetes, IF increases high-density lipoprotein cholesterol (HDL-C) levels compared to continuous energy restriction (CER) (MD = 0.03 mmol/L; 95% CI: 0.01-0.05; p = 0.010). However, IF was less effective at reducing systolic blood pressure (SBP) than a CER diet in adults with overweight or obesity (SMD = 0.21; 95% CI: 0.05-0.36; p = 0.008). Interpretation: Our findings suggest that IF may have beneficial effects on a range of health outcomes for adults with overweight or obesity, compared to CER or non-intervention diet. Specifically, IF may decreased WC, fat mass, LDL-C, TG, TC, fasting insulin, and SBP, while increasing HDL-C and FFM. Notably, it is worth noting that the SBP lowering effect of IF appears to be weaker than that of CER. Funding: This work was supported by the National Key Research and Development Program of China (Q-JW), the Natural Science Foundation of China (Q-JW and T-TG), Outstanding Scientific Fund of Shengjing Hospital of China Medical University (Q-JW), and 345 Talent Project of Shengjing Hospital of China Medical University (T-TG).

A coumarin-furoxan hybrid as novel nitric oxide donor induced cell apoptosis and ferroptosis in NSCLC by promoting S-nitrosylation of STAT3 and negative regulation of JAK2-STAT3 pathway.

Non-small cell lung cancer (NSCLC) still lacks effective treatment because of its extensive mutation diversity and frequent drug resistance. Therefore, it is urgent to develop new therapeutic strategies for NSCLC. In this study, we evaluated the inhibitory effect of a new coumarin-furoxan hybrid compound 9, a nitric oxide (NO) donor drug, on NSCLC proliferation and its mechanism. Our results show that compound 9 can inhibit the growth of four NSCLC cell lines and H1975 xenograft model in a dose-dependent manner. Compound 9 effectively releases high concentrations of NO within the mitochondria, leading to cellular oxidative stress, mitochondrial dysfunction, and apoptosis. Moreover, compound 9 inhibits JAK2/STAT3 protein phosphorylation and induces S-nitrosylation modification of STAT3, ultimately resulting in endogenous apoptosis in NSCLC. Additionally, compound 9 significantly induces NSCLC ferroptosis by depleting intracellular GSH, elevating MDA levels, inhibiting SLC7A11/GSH protein expression, and negatively regulating the JAK2/STAT3 pathway. In summary, this study elucidates the inhibitory effects of compound 9 on NSCLC proliferation and provides insights into the underlying mechanisms, offering new possibilities for NSCLC treatment strategies.

Zn-Catalyzed Dehydroxylative Phosphorylation of Allylic Alcohols with P(III)-Nucleophiles.

A novel and efficient protocol for the synthesis of diarylallyl-functionalized phosphonates, phosphinates, and phosphine oxides through the zinc-catalyzed dehydroxylative phosphorylation of allylic alcohols with P(III)-nucleophiles via a Michaelis-Arbuzov-type rearrangement is reported. A broad range of allylic alcohols and P(III)-nucleophiles (P(OR)3, ArP(OR)2, and Ar2P(OR)) are well tolerated in this reaction, and the expected dehydroxylative phosphorylation products could be synthesized with good to excellent yields under the optimal reaction conditions. The reaction can be easily scaled up at a gram-synthesis level. Furthermore, through the step-by-step control experiments, kinetic study experiments, and 31P NMR tracking experiments, we acquired insights into the reaction and proposed the possible mechanism for this transformation.

SH3RF2 contributes to cisplatin resistance in ovarian cancer cells by promoting RBPMS degradation.

Platinum-based chemotherapy remains one of the major choices for treatment of ovarian cancer (OC). However, primary or acquired drug resistance severely impairs their efficiency, thereby causing chemotherapy failure and poor prognosis. SH3 domain containing ring finger 2 (SH3RF2) has been linked to the development of cancer. Here we find higher levels of SH3RF2 in the tumor tissues from cisplatin-resistant OC patients when compared to those from cisplatin-sensitive patients. Similarly, cisplatin-resistant OC cells also express higher levels of SH3RF2 than normal OC cells. Through in vitro and in vivo loss-of-function experiments, SH3RF2 is identified as a driver of cisplatin resistance, as evidenced by increases in cisplatin-induced cell apoptosis and DNA damage and decreases in cell proliferation induced by SH3RF2 depletion. Mechanistically, SH3RF2 can directly bind to the RNA-binding protein mRNA processing factor (RBPMS). RBPMS has been reported as an inhibitor of cisplatin resistance in OC. As a E3 ligase, SH3RF2 promotes the K48-linked ubiquitination of RBPMS to increase its proteasomal degradation and activator protein 1 (AP-1) transactivation. Impairments in RBPMS function reverse the inhibitory effect of SH3RF2 depletion on cisplatin resistance. Collectively, the SH3RF2-RBPMS-AP-1 axis is an important regulator in cisplatin resistance and inhibition of SH3RF2 may be a potential target in preventing cisplatin resistance.

Global, regional and national temporal trends in prevalence for musculoskeletal disorders in women of childbearing age, 1990-2019: an age-period-cohort analysis based on the Global Burden of Disease Study 2019.

OBJECTIVES: To provide an overview and in-depth analysis of temporal trends in prevalence of musculoskeletal (MSK) disorders in women of childbearing age (WCBA) at global, regional and national levels over the last 30 years, with a special focus on their associations with age, period and birth cohort. METHODS: Estimates and 95% uncertainty intervals (UIs) for MSK disorders prevalence in WCBA were extracted from the Global Burden of Diseases, Injuries and Risk Factors Study 2019. An age-period-cohort model was adopted to estimate the overall annual percentage change of prevalence (net drift, % per year), annual percentage change of prevalence within each age group (local drift, % per year), fitted longitudinal age-specific rates adjusted for period deviations (age effects) and period/cohort relative risks (period/cohort effects) from 1990 to 2019. RESULTS: In 2019, the global number of MSK disorders prevalence in WCBA was 354.57 million (95% UI: 322.64 to 387.68). Fifty countries had at least one million prevalence, with India, China, the USA, Indonesia and Brazil being the highest accounting for 51.03% of global prevalence. From 1990 to 2019, a global net drift of MSK disorders prevalence in WCBA was -0.06% (95% CI: -0.07% to -0.05%) per year, ranging from -0.09% (95% CI: -0.10% to -0.07%) in low-middle sociodemographic index (SDI) region to 0.10% (95% CI: 0.08% to 0.12%) in high-middle SDI region, with 138 countries presenting increasing trends, 24 presenting decreasing trends and 42 presenting relatively flat trends. As reflected by local drift, higher SDI regions had more age groups showing rising prevalence whereas lower SDI regions had more declining prevalence. Globally, an increasing occurrence of MSK disorders prevalence in WCBA beyond adolescent and towards the adult stage has been prominent. Age effects illustrated similar patterns across different SDI regions, with risk increasing with age. High SDI region showed generally lower period risks over time, whereas others showed more unfavourable period risks. High, high-middle and middle SDI regions presented unfavourable prevalence deteriorations, whereas others presented favourable prevalence improvements in successively birth cohorts. CONCLUSIONS: Although a favourable overall temporal trend (net drift) of MSK disorders prevalence in WCBA was observed over the last 30 years globally, there were 138 countries showing unfavourable rising trends, coupled with deteriorations in period/cohort risks in many countries, collectively raising concerns about timely realisation of the Targets of Sustainable Development Goal. Improvements in the MSK disorders-related prevention, management and treatment programmes in WCBA could decline the relative risk for successively younger birth cohorts and for all age groups over period progressing.

Effects of Huzhangoside C on Dextran Sodium Sulfate-Stimulated Colitis in Mice.

Chronic inflammation is a major risk factor for cancer. Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, ultimately leading to a breakdown of intestinal barrier function. Clematis florida var. plena is a folk prescription used to treat inflammation and rheumatism in She pharmacy. The bioactivity of C. florida var. plena is primarily due to triterpene saponins. Huzhangoside C (HZ) is an active component of C. florida var. plena. In this study, the anti-inflammatory effect of HZ on a mouse colitis model induced by dextran sulfate sodium (DSS) was investigated. Result indicated a notable reduction in body weight loss and colon length shortening in HZ-mediated mice compared to DSS-stimulated control mice. Furthermore, inflammatory signaling mechanisms involving interleukin-6 and tumor necrosis factor-α were suppressed in HZ-treated mice. HZ treatment significantly suppressed the expression of nuclear factor kappa B (NF-κB), STAT3, and iNOS in colon tissue. After HZ treatment, malondialdehyde and nitric oxide levels were significantly decreased, while Nrf-2, superoxide dismutase, and glutathione expression levels were notably improved. The result indicated that HZ could activate the Nrf-2 signal cascade, inhibit the expression of NF-κB, eNOS, and STAT3, and enhance the intestinal barrier function of DSS stimulated ulcerative colitis intestinal injury. The results suggest that HZ is potential anti-inflammatory agent for treating IBD.

Serum albumin mediates the associations between heavy metals and two novel systemic inflammation indexes among U.S. adults.

BACKGROUND: The effects of heavy metal exposure on immunological function have sparked widespread concern, but unequivocal evidence on the association between mixed metal exposure and novel systemic inflammatory indexes remains scarce. OBJECTIVES: This study aimed to analyze the associations of heavy metals with two novel systemic inflammation indexes and the mediated effects of serum albumin. METHODS: Nineteen metals were detected among 4082 U.S. adults based on the NHANES. A linear regression, restricted cubic splines (RCS) regression, weighted quantile sum (WQS), Quantile-based Gcomputation (qgcomp), and Bayesian kernel machine regression (BKMR) were conducted to evaluate the associations of single metal and mixed metals with systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) levels, respectively. A series of subgroup analyses were used to identify potentially vulnerable populations. Furthermore, we conducted mediation analyses to investigate the mediated effects of serum albumin on the associations of metals with SII and SIRI. RESULTS: In the single-exposure model, exposure to various metals such as urinary Co, As, and serum Zn, Cu was associated with SII and SIRI (PFDR<0.05). Simultaneously, the above metals were linear positively correlated with SII and SIRI. Mixed-exposure analyses consistently showed that overall mixed urinary metal levels were positively pertinent for SII and SIRI levels, and the metal Co played a significant role in the urinary metal mixtures. Subgroup analyses showed that exposure to urinary Cd in men and elderly people increased SII and SIRI levels. The results of mediation analyses suggested the association of urinary metal mixture with SII and SIRI was mediated by albumin, and the proportion of mediation was 14.45% and 9.49%, respectively. CONCLUSIONS: Our findings suggested that metal exposure is strongly associated with the levels of system inflammation indexes and that serum albumin is, in part, a mediator of this association.

Brain changes with Chinese reading development in typical and atypical readers.

Reading is a high-order cognitive process that is unique in human beings. There is a prolonged developmental course and a wide range of proficiency levels associated with reading. In this review, I focus on brain changes underlying Chinese reading development in both typical readers and readers with reading disability. Reading development in typical readers is characterized by a shift from dorsal phonological reading to ventral orthographic reading in the brain and increased interactive specialization in the reading network. Even though some individuals with reading disability may be able to catch up with typical readers on phonological reading by adulthood, they cannot reach fluent orthographic reading. In the brain, the reduction of brain activation in the left inferior frontal gyrus associated with reading disability disappears by adulthood, suggesting that this is a developmental delay, while there is a greater reduction of brain activation in the left inferior temporal gyrus in adults than children with reading disability. It suggests a greater deficit in the dorsal phonological reading pathway in children and a greater deficit in the ventral orthographic reading pathway in adults with reading disability. This review provides insights about the developmental trajectories in typical and atypical reading.

Integration of Magnetic-Field-Directed Self-Assembly-Based Cell Culture and Biosensing Platform for Improving hPSCs-Derived Neurons and Quantitative Detection of Neurotransmitter.

Despite the fact that human neural cell models have played significant roles in both research and cell replacement therapies for neurological diseases, the existing techniques for obtaining neurons from human pluripotent stem cells (hPSCs) are arduous and intricate. Additionally, the evaluation of neuron quality in the natural environment remains deficient. Consequently, we have developed a comprehensive platform utilizing magnetic-field-directed self-assembly (MDSA) of MXenes@Fe3O4 (M/F) nanocomposites. This platform facilitates the cultivation and in situ analysis of differentiated dopaminergic (DA) neurons. Our results showed that the introduction of M/F enhances neurite outgrowth and leads to the development of more intricate ramifications. Moreover, with the increase of magnetic field intensity, neurite outgrowth is further enhanced, and the proportion of differentiated mature neurons from hPSCs increases. This suggests that our platform promotes the maturation of neurons, emphasizing the crucial role of biophysical cues in expediting the differentiation process. The homogenization platform formed by MDSA of M/F nanocomposites exhibits high conductivity, leading to its exceptional performance in the real-time monitoring of the release of dopamine neurotransmitter from hPSC-derived DA neurons. Hence, this platform demonstrates significant potential for monitoring cell quality. In conclusion, our integrated platform, based on MDSA of M/F nanocomposites, offers a reliable and efficient means for the in vitro generation of human neurons with a controllable quality. The as-prepared platform holds potential for enhancing neuronal maturation and ensuring consistent cell quality, showing significant implications for in vitro biological research, disease modeling, and cell replacement therapy.