Associations between menopausal symptoms and cardiovascular disease in middle-aged Chinese women.

OBJECTIVE: This study aimed to examine the association between severity of menopausal symptoms and cardiovascular disease (CVD) risk among middle-aged Chinese women. METHODS: A cross-sectional study recruited 9679 women aged 40-70 years from three socioeconomic regions of China in 2018. Menopausal symptoms were assessed by the modified Kupperman Menopausal Index (KMI). The severity of individual symptoms was classified as none (0 points), mild (1 points) and moderate-to-severe symptoms (2-3 points), and overall menopausal symptoms were classified as none (<15 points), mild (15-24 points) or moderate-to-severe (≥25 points) according to the sum score of the KMI. Logistic regression models were used to examine associations of the severity of menopausal symptoms with CVD risk. RESULTS: A total of 5.6% of participants reported being diagnosed with CVD. Overall menopausal symptoms were more common in women aged 60-70 years than in women aged 40-59 years. After multiple adjustment, mild (odds ratio [OR] = 2.07, 95% confidence interval [CI]: 1.64-2.61) and moderate-to-severe (OR = 2.64, 95% CI: 1.92-3.63) overall menopausal symptoms were associated with increased risk of CVD compared with no symptoms. Significant positive associations between the severity of individual menopausal symptoms and CVD risk were observed for all 13 items. CONCLUSION: The severity of menopausal symptoms was positively associated with CVD risk in middle-aged Chinese women.

Short-term high-light intensity and low temperature improve the quality and flavor of lettuce grown in plant factory.

BACKGROUND: Lettuce holds a prominent position in the year-round supply of vegetables, offering a rich array of health-beneficial substances, such as dietary fiber, phenolic compounds, lactucopicrin and lactucin. As such, its flavor has garnered increasing attention. Balancing the enhancement of beneficial compounds with the reduction of undesirable taste is a key focus of scientific research. To investigate short-term management to improve the nutritional quality and flavor of lettuce, combinations of different light intensities (200, 500 and 800 µm ol m-2 s-1) and temperatures (10 and 22 °C) were applied separately to 'Lollo Rosso' and 'Little Butter Lettuce' for 7 days before harvest. RESULTS: The results obtained showed that increasing light intensity at low temperatures decreased nitrate content and increased soluble sugar, soluble protein, anthocyanin and phenolic compound content. In the case of lettuce flavor, the bitterness-related metabolites such as lactucin and lactucopicrin were reduced with high light intensity at a low temperature of 10 °C. With this combination, the fructose and glucose contents increased, significantly improving lettuce flavor. CONCLUSION: Higher light intensity combined with low temperature for 7 days before harvest effectively improved the nutritional quality and flavor of lettuce, suggesting its great potential for use in horticultural practices. © 2024 Society of Chemical Industry.

Responsive ß-Diketonate-europium(III) Complex-Based Probe for Time-Gated Luminescence Detection and Imaging of Hydrogen Sulfide In Vitro and In Vivo.

As a crucial biological gasotransmitter, hydrogen sulfide (H2S) plays important roles in many pathological and physiological processes. Highly selective and sensitive detection of H2S is significant for the precise diagnosis and evaluation of diverse diseases. Nevertheless, challenges remain in view of the interference of autofluorescence in organisms and the stronger reactivity of H2S itself. Herein, we report the design and synthesis of a novel H2S-responsive ß-diketonate-europium(III) complex-based probe, [Eu(DNB-Npketo)3(terpy)], for background-free time-gated luminescence (TGL) detection and imaging of H2S in autofluorescence-rich biological samples. The probe, consisting of a 2,4-dinitrobenzenesulfonyl (DNB) group coupled to a ß-diketonate-europium(III) complex, shows almost no luminescence owing to the existence of intramolecular photoinduced electron transfer. The cleavage of the DNB group by a H2S-triggered reaction results in the recovery of the long-lived luminescence of the Eu3+ complex, allowing the detection of H2S in complicated biological samples to be performed in TGL mode. The probe showed a fast response, high specificity, and high sensitivity toward H2S, which enabled it to be successfully used for the quantitative TGL detection of H2S in tissue homogenates of mouse organs. Additionally, the low cytotoxicity of the probe allowed it to be further used for the TGL imaging of H2S in living cells and mice under different stimuli. All of the results suggested the potential of the probe for the investigation and diagnosis of H2S-related diseases.

Differences in intestinal and renal Ca and P uptake in three different breeds of growing-finishing pigs.

This study investigated the differences in bone growth and turnover and calcium (Ca) and phosphorus (P) uptake among three different breeds of growing-finishing pigs. Ninety healthy Duroc, Xiangcun black (XCB), and Taoyuan black (TYB) pigs (30 pigs per breed) at 35 day-old (D) with the average body weight (BW) of their respective breed were assigned and raised to 185 D. The results showed that Duroc pigs had higher bone weight and length than the XCB and TYB pigs at 80, 125, and 185 D and the bone index at 185 D (p < 0.05). Duroc pigs had higher bone mineral densities (femur and tibia) compared with the other two breeds at 80 D and 125 D, whereas TYB pigs had higher mineral content and bone breaking load (rib) compared with the other two breeds at 185 D (p < 0.05). The bone morphogenetic protein-2 and osteocalcin concentrations were higher, and TRACP5b concentration was lower in serum of TYB pigs at 125 D (p < 0.05). Meanwhile, 1,25-dihydroxyvitamin D3, parathyroid hormone, thyroxine, and fibroblast growth factor 23 concentrations were higher in serum of TYB pigs at 185 D (p < 0.05). The TYB pigs had higher apparent total tract digestibility of P at 80 D and 185 D and bone Ca and P contents at 185 D in comparison to the Duroc pigs (p < 0.05). Furthermore, gene expressions related to renal uptake of Ca and P differed among the three breeds of pigs. Collectively, Duroc pigs have higher bone growth, whereas TYB pigs have a higher potential for mineral deposition caused by more active Ca uptake.

Elevated Fibrinogen-to-Albumin Ratio Correlates with Incident Stroke in Cerebral Small Vessel Disease.

Purpose: We aimed to explore the association between fibrinogen-to-albumin ratio (FAR) and the risk of incident stroke (IS) in a cohort of cerebral small vessel disease (CSVD) patients. Patients and Methods: Participants were screened from a prospective CSVD database. Clinical data, hematologic measures and imaging findings were collected. The primary outcome was IS during follow-up, with a secondary outcome of composite vascular events (CVE) including IS, myocardial infarction (MI), and vascular deaths. Univariate and multivariate COX proportional risk models, along with competing risk models, were employed to identify factors associated with outcomes. Restricted cubic spline (RCS) and subgroup analyses were conducted to assess the association between FAR and the risk of IS and CVE in CSVD patients. Results: In the final analysis of 682 CSVD patients over a median observation period of 34.0 [24.0-53.0] months, there were 33 cases of IS (4.84%, 1.55/100 person-years), 4 incidents of MI (0.59%, 0.19/100 person-years), 15 non-vascular deaths (2.20%, 0.70/100 person-years), and 37 occurrences of CVE (5.43%, 1.74/100 person-years). Multivariate Cox regression analysis revealed a significant positive correlation between elevated FAR and both IS (HR 1.146; 95% CI 1.043-1.259; P=0.004) and CVE (HR 1.156; 95% CI 1.063-1.257; P=0.001) in CSVD patients. Multivariate competing risk model showed the similar results (IS: HR 1.16; 95% CI 1.06-1.27; P=0.001, CVE: HR 1.15; 95% CI 1.05-1.26; P=0.003). RCS analysis indicated a linear relationship between FAR and the risks of both IS (P for non-linearity =0.7016) and CVE (P for non-linearity =0.6475), with an optimal cutoff value of 8.69, particularly in individuals over 60 years of age. Conclusion: Elevated FAR demonstrated an independent and linear association with IS and the development of CVE in CSVD patients.

Complete genome sequence of Erwinia amylovora PBI209 isolated from a necrotic flower of Pyrus sinkiangensis in China.

Here, we report the complete genome sequence of Erwinia amylovora PBI209 that causes fire blight isolated from a necrotic flower of Pyrus sinkiangensis in Xinjiang, China. The genome consists of 3,800,955 bp, with 3,403 protein-coding genes and a guanine-cytosine content of 53.61%.

A real-time epilepsy seizure detection approach based on EEG using short-time Fourier transform and Google-Net convolutional neural network.

Epilepsy is one of the most common brain disorders, and seizures of epilepsy have severe adverse effects on patients. Real-time epilepsy seizure detection using electroencephalography (EEG) signals is an important research area aimed at improving the diagnosis and treatment of epilepsy. This paper proposed a real-time approach based on EEG signal for detecting epilepsy seizures using the STFT and Google-net convolutional neural network (CNN). The CHB-MIT database was used to evaluate the performance, and received the results of 97.74 % in accuracy, 98.90 % in sensitivity, 1.94 % in false positive rate. Additionally, the proposed method was implemented in a real-time manner using the sliding window technique. The processing time of the proposed method just 0.02 s for every 2-s EEG episode and achieved average 9.85- second delay in each seizure onset.

Ephedra sinica polysaccharide regulate the anti-inflammatory immunity of intestinal microecology and bacterial metabolites in rheumatoid arthritis.

Introduction: Ephedra sinica polysaccharide (ESP) exerts substantial therapeutic effects on rheumatoid arthritis (RA). However, the mechanism through which ESP intervenes in RA remains unclear. A close correlation has been observed between enzymes and derivatives in the gut microbiota and the inflammatory immune response in RA. Methods: A type II collagen-induced arthritis (CIA) mice model was treated with Ephedra sinica polysaccharide. The therapeutic effect of ESP on collagen-induced arthritis mice was evaluated. The anti-inflammatory and cartilage-protective effects of ESP were also evaluated. Additionally, metagenomic sequencing was performed to identify changes in carbohydrate-active enzymes and resistance genes in the gut microbiota of the ESP-treated CIA mice. Liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry were performed to observe the levels of serum metabolites and short-chain fatty acids in the gut. Spearman's correlational analysis revealed a correlation among the gut microbiota, antibiotic-resistance genes, and microbiota-derived metabolites. Results: ESP treatment significantly reduced inflammation levels and cartilage damage in the CIA mice. It also decreased the levels of pro-inflammatory cytokines interleukin (IL)-6, and IL-1-ß and protected the intestinal mucosal epithelial barrier, inhibiting inflammatory cell infiltration and mucosal damage. Here, ESP reduced the TLR4, MyD88, and TRAF6 levels in the synovium, inhibited the p65 expression and pp65 phosphorylation in the NF-κB signaling pathway, and blocked histone deacetylase (HDAC1 and HDAC2) signals. ESP influenced the gut microbiota structure, microbial carbohydrate-active enzymes, and microbial resistance related to resistance genes. ESP increased the serum levels of L-tyrosine, sn-glycero-3-phosphocholine, octadecanoic acid, N-oleoyl taurine, and decreased N-palmitoyl taurine in the CIA mice. Conclusion: ESP exhibited an inhibitory effect on RA. Its action mechanism may be related to the ability of ESP to effectively reduce pro-inflammatory cytokines levels, protect the intestinal barrier, and regulate the interaction between mucosal immune systems and abnormal local microbiota. Accordingly, immune homeostasis was maintained and the inhibition of fibroblast-like synoviocyte (FLS) proliferation through the HDAC/TLR4/NF-κB pathway was mediated, thereby contributing to its anti-inflammatory and immune-modulating effects.

CRISPR-Cas9-mediated editing of GmARM improves resistance to multiple stresses in soybean.

The growth and development of soybean plants can be affected by both abiotic and biotic stressors, such as saline-alkali stress and Phytophthora root rot. In this study, we identified a stress-related gene-GmARM-whose promoter contained several hormone-response and stress-regulatory elements, including ABRE, TCA element, STRE, and MBS. qRT-PCR analysis showed that the expression of GmARM was the highest in seeds at 55 days after flowering. Furthermore, this gene was upregulated after exposure to saline-alkali stress and Phytophthora root rot infection at the seedling stage. Thus, we generated GmARM mutants using the CRISPR-Cas9 system to understand the role of this gene in stress response. T3 plants showed significantly improved salt tolerance, alkali resistance, and disease resistance, with a significantly higher survival rate than the wildtype plants. Moreover, mutations in GmARM affected the expression of related stress-resistance genes, indicating that GmARM mutants achieved multiple stress tolerance. Therefore, this study provides a foundation for further exploration of the genes involved in resistance to multiple stresses in soybean that can be used for breeding multiple stress-resistance soybean varieties.

Nitric Oxide-Activated Bioorthogonal Codelivery Nanoassembly for In Situ Synthesis of Photothermal Agent for Precise and Safe Anticancer Treatment.

The development of bioorthogonal activation in drug release represents a promising avenue for precise and safe anticancer treatment. However, two significant limitations currently hinder their clinical application: i) the necessity for separate administration of the drug precursor and its corresponding activator, leading to poor drug accumulation and potential side effects; ii) the reliance on exogenous metal or organic activators for triggering bioorthogonal activation, which often exhibit low efficiency and systemic toxicity when extending to living animals. To overcome these limitations, a nitric oxide (NO)-mediated bioorthogonal codelivery nanoassembly, termed TTB-NH2@PArg, which comprises a precursor molecular (TTB-NH2) and amphipathic polyarginine (PArg) is developed. In TTB-NH2@PArg, PArg serves as both self-assembled nanocarrier for TTB-NH2 and a NO generator. In tumor microenvironment (TME), the TME-specific generation of NO acts as a gas activator, triggering in situ bioorthogonal bond formation that transforms TTB-NH2 into TTB-AZO. This tumor-specific generation of TTB-AZO not only serves as a potential photothermal agent for effective tumor inhibition but also induces fluorescence change that enables real-time monitoring of bioorthogonal activation. This study presents a drug codelivery approach that enables precise and safe control of bioorthogonal activation for anticancer treatment, improving cancer therapy efficacy while minimizing side effects.

Plastid phylogenomics contributes to the taxonomic revision of taxa within the genus Sanicula L. and acceptance of two new members of the genus.

Introduction: The genus Sanicula L. is a taxonomically complicated taxa within Apiaceae, as its high variability in morphology. Although taxonomists have performed several taxonomic revisions for this genus, the interspecific relationships and species boundaries have not been satisfactorily resolved, especially for those endemic to China. This study mainly focused on S. giraldii var. ovicalycina, S. tienmuensis var. pauciflora, and S. orthacantha var. stolonifera and also described two new members of the genus. Methods: We newly sequenced sixteen plastomes from nine Sanicula species. Combined with eleven plastomes previously reported by us and one plastome downloaded, we performed a comprehensively plastid phylogenomics analysis of 21 Sanicula taxa. Results and Discussion: The comparative results showed that 21 Sanicula plastomes in their structure and features were highly conserved and further justified that two new species were indeed members of Sanicula. Nevertheless, eleven mutation hotspot regions were still identified. Phylogenetic analyses based on plastome data and the ITS sequences strongly supported that these three varieties were clearly distant from three type varieties. The results implied that these three varieties should be considered as three independent species, which were further justified by their multiple morphological characters. Therefore, revising these three varieties into three independent species was reasonable and convincing. Moreover, we also identified and described two new Sanicula species (S. hanyuanensis and S. langaoensis) from Sichuan and Shanxi, China, respectively. Based on their distinct morphological characteristics and molecular phylogenetic analysis, two new species were included in Sanicula. In summary, our study impelled the revisions of Sanicula members and improved the taxonomic system of the genus.

Generation of New ß-Conglycinin-Deficient Soybean Lines by Editing the lincRNA lincCG1 Using the CRISPR/Cas9 System.

Soybean ß-conglycinin is a major allergen that adversely affects the nutritional properties of soybean. Soybean deficient in ß-conglycinin is associated with low allergenicity and high nutritional value. Long intergenic noncoding RNAs (lincRNAs) regulate gene expression and are considered important regulators of essential biological processes. Despite increasing knowledge of the functions of lincRNAs, relatively little is known about the effects of lincRNAs on the accumulation of soybean ß-conglycinin. The current study presents the identification of a lincRNA lincCG1 that was mapped to the intergenic noncoding region of the ß-conglycinin α-subunit locus. The full-length lincCG1 sequence was cloned and found to regulate the expression of soybean seed storage protein (SSP) genes via both cis- and trans-acting regulatory mechanisms. Loss-of-function lincCG1 mutations generated using the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system led to the deficiency of the allergenic α'-, α-, and ß-subunits of soybean ß-conglycinin as well as higher content of proteins, sulfur-containing amino acids, and free arginine. The dominant null allele LincCG1, and consequently, the ß-conglycinin-deficient phenotype associated with the lincCG1-gene-edited line was stably inherited by the progenies in a Mendelian fashion. The dominant null allele LincCG1 may therefore be exploited for engineering/developing novel hypoallergenic soybean varieties. Furthermore, Cas9-free and ß-conglycinin-deficient homozygous mutant lines were obtained in the T1 generation. This study is the first to employ the CRISPR/Cas9 technology for editing a lincRNA gene associated with the soybean allergenic protein ß-conglycinin. Moreover, this study reveals that lincCG1 plays a crucial role in regulating the expression of the ß-conglycinin subunit gene cluster, besides highlighting the efficiency of employing the CRISPR/Cas9 system for modulating lincRNAs, and thereby regulating soybean seed components.

Construction and evaluation of a practical model for measuring health-adjusted life expectancy (HALE) in China.

BACKGROUND: HALE is now a regular strategic planning indicator for all levels of the Chinese government. However, HALE measurements necessitate comprehensive data collection and intricate technology. Therefore, effectively converting numerous diseases into the years lived with disability (YLD) rate is a significant challenge for HALE measurements. Our study aimed to construct a simple YLD rate measurement model with high applicability based on the current situation of actual data resources within China to address challenges in measuring HALE target values during planning. METHODS: First, based on the Chinese YLD rate in the Global Burden of Disease (GBD) 2019, Pearson correlation analysis, the global optimum method, etc., was utilized to screen the best predictor variables from the current Chinese data resources. Missing data for predictor variables were filled in via spline interpolation. Then, multiple linear regression models were fitted to construct the YLD rate measurement model. The Sullivan method was used to measure HALE. The Monte Carlo method was employed to generate 95% uncertainty intervals. Finally, model performances were assessed using the mean absolute error (MAE) and mean absolute percentage error (MAPE). RESULTS: A three-input-parameter model was constructed to measure the age-specific YLD rates by sex in China, directly using the incidence of infectious diseases, the incidence of chronic diseases among persons aged 15 and older, and the addition of an under-five mortality rate covariate. The total MAE and MAPE for the combined YLD rate were 0.0007 and 0.5949%, respectively. The MAE and MAPE of the combined HALE in the 0-year-old group were 0.0341 and 0.0526%, respectively. There were slightly fewer males (0.0197, 0.0311%) than females (0.0501, 0.0755%). CONCLUSION: We constructed a high-accuracy model to measure the YLD rate in China by using three monitoring indicators from the Chinese national routine as predictor variables. The model provides a realistic and feasible solution for measuring HALE at the national and especially regional levels, considering limited data.

A Review of Fucoxanthin Biomanufacturing from Phaeodactylum tricornutum.

Microalgae, compared to macroalgae, exhibit advantages such as rapid growth rates, feasible large-scale cultivation, and high fucoxanthin content. Among these microalgae, Phaeodactylum tricornutum emerges as an optimal source for fucoxanthin production. This paper comprehensively reviews the research progress on fucoxanthin production using Phaeodactylum tricornutum from 2012 to 2022, offering detailed insights into various aspects, including strain selection, media optimization, nutritional requirements, lighting conditions, cell harvesting techniques, extraction solvents, extraction methodologies, as well as downstream separation and purification processes. Additionally, an economic analysis is performed to assess the costs of fucoxanthin production from Phaeodactylum tricornutum, with a comparative perspective to astaxanthin production from Haematococcus pluvialis. Lastly, this paper discusses the current challenges and future opportunities in this research field, serving as a valuable resource for researchers, producers, and industry managers seeking to further advance this domain.

γ-Mangosteen, an autophagy enhancer, prevents skin-aging via activating KEAP1/NRF2 signaling and downregulating MAPKs/AP-1/NF-κB-mediated MMPs.

BACKGROUND: Mangosteens, a naturally occurring xanthones, found abundantly in mangosteen fruits. The anti-skin aging potential of γ-mangosteen (GM) remains unexplored; therefore, we investigated the UVB-induced anti-skin aging of GM via activation of autophagy. HYPOTHESIS: We hypothesized that GM exerts antioxidant and anti-aging capabilities both in vitro and in vivo through activation of autophagy as well as control of KEAP1/NRF2 signaling and MAPKs/AP-1/NF-κB-mediated MMPs pathways. METHODS: The anti-skin aging effects of GM were studied using HDF cells and a mice model. Various assays, such as DPPH, ABTS, CUPRAC, FRAP, and ROS generation, assessed antioxidant activities. Kits measured antioxidant enzymes, SA-ß-gal staining, collagen, MDA content, si-RNA experiments, and promoter assays. Western blotting evaluated protein levels of c-Jun, c-Fos, p-IκBα/ß, p-NF-κB, MAPK, MMPs, collagenase, elastin, KEAP1, NRF2, HO-1, and autophagy-related proteins. RESULTS: GM exhibited strong antioxidant, collagenase and elastase enzyme inhibition activity surpassing α- and ß-mangosteen. GM competitively inhibited elastase with a Ki value of 29.04 µM. GM orchestrated the KEAP1-NRF2 pathway, enhancing HO-1 expression, and suppressed UVB-induced ROS in HDF cells. NRF2 knockdown compromised GM's antioxidant efficacy, leading to uncontrolled ROS post-UVB. GM bolstered endogenous antioxidants, curbing lipid peroxidation in UVB-exposed HDF cells and BALB/c mice. GM effectively halted UVB-induced cell senescence, and reduced MMP-1/-9, while elevated TIMP-1 levels, augmented COL1A1, ELN, and HAS-2 expression in vitro and in vivo. Additionally, it suppressed UVB-induced MAPKs, AP-1, NF-κB phosphorylation. Pharmacological inhibitors synergistically enhanced GM's anti-skin aging potential. Moreover, GM inhibited UVB-induced mTOR activation, upregulated LC3-II, Atg5, Beclin 1, and reduced p62 in both UVB induced HDF cells and BALB/c mice, while blocking of autophagy successfully halt the GM effects against the UVB-induced increase of cell senescence, degradation of collagen through upregulation of MMP-1, underscoring GM's substantial anti-skin aging impact via autophagy induction in vitro and in vivo. CONCLUSION: Together, GM has potent antioxidant and anti-skin aging ingredients that can be used to formulate skin care products for both the nutraceutical and cosmeceutical industries.

Korea Nurses' Health Study and the health of reproductive-aged women: a cohort profile.

The Korea Nurses' Health Study (KNHS) is an ongoing, large-scale, prospective cohort study of female nurses, focusing on the effects of occupational, environmental, and lifestyle factors on the health of women. The first KNHS survey was performed in 2013-2014 (n=20,613). As of December 2023, 11 follow-up surveys have been conducted. Participants who were pregnant were asked to participate in the early pregnancy survey (n=2,179) and postpartum survey after giving birth (n=2,790). The main variables included sociodemographic, work-related, lifestyle, physical, mental, and women's health factors. Blood, urine, and toenail samples were collected from a participant subgroup of the first survey (n=1,983). The subgroups of the second survey completed a food frequency questionnaire in 2019 (n=300) and 2021 (n=871). In 2020, a subgroup of the first survey answered a coronavirus disease 2019 (COVID-19)-related survey (n=975). To examine various health-related factors in young adults, new participants were added to the KNHS cohort in the 11th (n=1,000) and 12th (n=1,002) surveys. The KNHS cohort will help identify health and illness determinants in Korean women. Data can be accessed at https://coda.nih.go.kr/frt/index.do.

Mitophagy Regulates the Circadian Rhythms by Degrading NR1D1 in Simulated Microgravity and Isolation Environments.

Long-term spaceflight is known to induce disruptions in circadian rhythms, which are driven by a central pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus, but the underlying molecular mechanisms remain unclear. Here, we developed a rat model that simulated microgravity and isolation environments through tail suspension and isolation (TSI). We found that the TSI environment imposed circadian disruptions to the core body temperature, heart rate, and locomotor-activity rhythms of rats, especially in the amplitude of these rhythms. In TSI model rats' SCNs, the core circadian gene NR1D1 showed higher protein but not mRNA levels along with decreased BMAL1 levels, which indicated that NR1D1 could be regulated through post-translational regulation. The autophagosome marker LC3 could directly bind to NR1D1 via the LC3-interacting region (LIR) motifs and induce the degradation of NR1D1 in a mitophagy-dependent manner. Defects in mitophagy led to the reversal of NR1D1 degradation, thereby suppressing the expression of BMAL1. Mitophagy deficiency and subsequent mitochondrial dysfunction were observed in the SCN of TSI models. Urolithin A (UA), a mitophagy activator, demonstrated an ability to enhance the amplitude of core body temperature, heart rate, and locomotor-activity rhythms by prompting mitophagy induction to degrade NR1D1. Cumulatively, our results demonstrate that mitophagy exerts circadian control by regulating NR1D1 degradation, revealing mitophagy as a potential target for long-term spaceflight as well as diseases with SCN circadian disruption.

[A multicenter study of neonatal stroke in Shenzhen, China]. / 深圳市新生儿脑卒中多中心现况调查.

OBJECTIVES: To investigate the incidence rate, clinical characteristics, and prognosis of neonatal stroke in Shenzhen, China. METHODS: Led by Shenzhen Children's Hospital, the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022. The incidence, clinical characteristics, treatment, and prognosis of neonatal stroke in Shenzhen were analyzed. RESULTS: The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137, 1/6 060, and 1/7 704, respectively. Ischemic stroke accounted for 75% (27/36); boys accounted for 64% (23/36). Among the 36 neonates, 31 (86%) had disease onset within 3 days after birth, and 19 (53%) had convulsion as the initial presentation. Cerebral MRI showed that 22 neonates (61%) had left cerebral infarction and 13 (36%) had basal ganglia infarction. Magnetic resonance angiography was performed for 12 neonates, among whom 9 (75%) had involvement of the middle cerebral artery. Electroencephalography was performed for 29 neonates, with sharp waves in 21 neonates (72%) and seizures in 10 neonates (34%). Symptomatic/supportive treatment varied across different hospitals. Neonatal Behavioral Neurological Assessment was performed for 12 neonates (33%, 12/36), with a mean score of (32±4) points. The prognosis of 27 neonates was followed up to around 12 months of age, with 44% (12/27) of the neonates having a good prognosis. CONCLUSIONS: Ischemic stroke is the main type of neonatal stroke, often with convulsions as the initial presentation, involvement of the middle cerebral artery, sharp waves on electroencephalography, and a relatively low neurodevelopment score. Symptomatic/supportive treatment is the main treatment method, and some neonates tend to have a poor prognosis.

Glycoprotein from Sargassum fusiforme exhibiting anti-inflammatory responses in vitro and in vivo via modulation of TLR4/MyD88 and NF-κB signaling.

This study focuses on the identification and characterization of a glycoprotein from Sargassum fusiforme (Harvey) Setchell (SFGP), as well as investigating its potential anti-inflammatory properties both in vitro and in vivo, along with the underlying mechanism. SDS-PAGE analysis revealed a prominent band with a molecular weight of <10 kDa, consisting of 58.39 % protein and 41.61 % carbohydrates, which was confirmed through glycoprotein staining and Coomassie blue staining. Various analytical techniques, including high-resolution mass spectrometry (HRMS), FTIR, amino acid analysis, and UV-visible spectrometry, provided evidence for the presence of monosaccharides (such as d-glucose and mannose) and 17 amino acids linked by an O-glycopeptide bond. In vitro and in vivo studies were conducted to assess the anti-inflammatory activities of SFGP. The results demonstrated that SFGP effectively attenuated nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions in LPS-treated RAW264.7 cells. Moreover, SFGP administration significantly and dose-dependently suppressed TLR4/MyD88 signaling as well as the phosphorylation of MAPKs, IκB, and NF-κB, leading to a reduction in the production of TNF-α, IL-1ß, and IL-6 in LPS-stimulated RAW264.7 cells. Furthermore, the anti-inflammatory efficacy of SFGP was validated in a carrageenan-induced inflammatory mouse model. These findings indicate that SFGP exhibits anti-inflammatory characteristics and has the potential to be utilized as a novel anti-inflammatory agent.

Unraveling paraquat-induced toxicity on mouse neural stem cells: Dose-response metabolomics insights and identification of sensitive biomarkers for risk assessment.

Exposure to pesticide could contribute to neurodevelopmental and neurodegenerative disorders. Notably, research suggests that prenatal or early postnatal exposure to paraquat (PQ), an herbicide, might trigger neurodevelopmental toxicity in neural stem cells (NSCs) via oxidative stress. However, the molecular mechanisms of PQ-induced perturbations in NSCs, particularly at the metabolite level, are not fully understood. Using a dose-response metabolomics approach, we examined metabolic changes in murine NSCs exposed to different PQ doses (0, 10, 20, 40 µM) for 24h. At 20 µM, PQ treatment led to significant metabolic alterations, highlighting unique toxic mechanisms. Metabolic perturbations, mainly affecting amino acid metabolism pathways (e.g., phenylalanine, tyrosine, arginine, tryptophan, and pyrimidine metabolism), were associated with oxidative stress, mitochondrial dysfunction, and cell cycle dysregulation. Dose-response models were used to identify potential biomarkers (e.g., Putrescine, L-arginine, ornithine, L-histidine, N-acetyl-L-phenylalanine, thymidine) reflecting early damage from low-dose PQ exposure. These biomarkers could be used as points of departure (PoD) for characterizing PQ exposure hazard in risk assessment. Our study offers insights into mechanisms and risk assessment related to PQ-induced neurotoxicity in NSCs.