Establishment of a Posttraumatic Osteoarthritis Model in Mice Induced by Noninvasive Anterior Cruciate Ligament Tear.

BACKGROUND: Animal models that use open surgical transection of the anterior cruciate ligament (ACL) do not accurately simulate the clinical condition regarding the pivot-shift mechanism and the associated inflammatory response that occurs before reconstruction. PURPOSE/HYPOTHESIS: The purpose was to characterize a reproducible manual, nonsurgical method to mimic an isolated ACL tear in a clinically relevant model and to evaluate the development of progressive posttraumatic osteoarthritis due to ACL injury. It was hypothesized that the ACL could be reproducibly torn with minimal damage to other ligaments and that there would be progressive development of degenerative joint disease after ACL injury. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 37 mice (strain C57BL/6) were used to compare the manual procedure with sham surgery (sham group; n = 10) and with the established surgical ACL transection (ACLT) procedure (surgical group; n = 27). In the sham group, a closed manual procedure was performed on the right knee and sham surgery on the left knee. In the surgical group, the closed manual procedure was performed on the right knee and surgical ACLT on the left knee. Dissection using India ink, histological assessment with safranin O and hematoxylin-eosin staining, radiological evaluation through radiographs and microfocus computed tomography scans, and gait analyses were performed to assess cartilage/ligament status. Osteoarthritis Research Society International (OARSI) and synovitis scores, anterior tibial translation, range of motion, bone microstructure, osteophyte volume, and pain were assessed at 2, 4, and 8 weeks postoperatively. RESULTS: The manual procedure successfully resulted in an ACL rupture and associated meniscal injury. The posterior cruciate, lateral collateral, and medial collateral ligaments were intact in all dissected knees. Two weeks after ACL tear, the surgical group showed a significantly higher synovitis score, whereas 8 weeks after ACL tear, the manual group showed a significantly higher volume of osteophytes. No significant differences were found between the groups in terms of OARSI score, anterior tibial translation, range of motion, bone microstructure computed tomography values, and stride distance/irregularity. CONCLUSION: This procedure can be used to create an ACL tear model without causing grossly evident injuries to other ligaments and avoiding the risk of cartilage damage from surgical instruments. CLINICAL RELEVANCE: This procedure offers a more clinically relevant ACL tear model and facilitates simple, inexpensive, and reproducible development of posttraumatic osteoarthritis.

The trajectories of psychosocial adjustment among young to middle-aged women with breast cancer: A prospective longitudinal study.

PURPOSE: This study aims to explore heterogeneous trajectories of psychosocial adjustment among young to middle-aged women with breast cancer and determine the predictive factors influencing these trajectories. METHODS: This study was conducted from October 2019 to October 2022 across two hospitals in Guangzhou. Demographic and disease characteristics, psychosocial adjustment, self-efficacy, social support, and coping modes were collected at baseline. Follow-up evaluations of psychosocial adjustment occurred at 1, 3, and 6 months post-surgery. Latent class growth modeling identified distinct patterns of psychosocial adjustment trajectories. Logistic regression analysis determined the predictive factors. RESULTS: A total of 377 young to middle-aged women with breast cancer participated in this study, with 289 participants completing the 6-month follow-up. Three distinct trajectories of psychosocial adjustment were identified including a "sustained severe maladjustment" trajectory, comprising 22.5% of participants, a "sustained moderate maladjustment" trajectory, comprising 50.4% of participants, and a "well-adjusted class" trajectory, comprising 27.1% of participants. Predictors of psychosocial adjustment trajectories included affected side, surgical type, chemotherapy, self-efficacy, social support, and coping modes. CONCLUSIONS: This study revealed three distinct trajectories of psychosocial adjustment among young to middle-aged women with breast cancer. Those with right-sided breast cancer, undergoing total mastectomy, receiving chemotherapy, low self-efficacy, limited social support, and relying on confrontation or avoidance coping modes may experience sustained maladjustment.

Transcriptomic Analysis Reveals the Flavonoid Biosynthesis Pathway Involved in Rhizome Development in Polygonatum cyrtonema Hua.

Polygonatum cyrtonema Hua (P. cyrtonema) rhizomes are rich in flavonoids and other secondary metabolites, exhibiting remarkable antioxidant, anti-tumor, and immunomodulatory effects. Polygonatum flavonoid-biosynthesis-related genes have been characterized already. However, a comprehensive overview of Polygonatum flavonoid biosynthesis pathways is still absent. To articulate the accumulation of the flavonoid biosynthesis pathways, we examined transcriptome changes using Illumina HiSeq from five different tissues and the RNA-seq of 15 samples had over 105 Gb of a clean base, generating a total of 277,955 unigenes. The cDNA libraries of the fruits (F), leaves (L), roots (R), stems (S), and rhizomes (T) of three-year-old P. cyrtonema plants generated 57,591, 53,578, 60,321, 51,530, and 54,935 unigenes. Comparative transcriptome analysis revealed that 379 differentially expressed genes (DEGs) were in the group of F _vs_ T, L _vs_ T, R _vs_ T, and S _vs_ T, and the transcripts of flavonoid-biosynthesis-related DEGs were principally enriched in rhizomes. In addition, combined with WGCNA and the FPKM of five tissues' transcription, nine differentially expressed transcription factor families (MYB, WRKY, AP2/ERF, etc.) were characterized in the red module, the red module positively correlated with rhizome flavonoid accumulation. Quantitative real-time PCR (qRT-PCR) further indicated that BZIP1, C3H31, ERF114, and DREB21 are differentially expressed in rhizomes, accompanied in rhizome development in P. cyrtonema. Therefore, this study provides a foundation for further research into uncovering the accumulation of flavonoid biosynthesis in the rhizomes of P. cyrtonema.

Genome-wide identification and expression analysis of the GAD family reveal their involved in embryogenesis and hormones responses in Dimocarpus longan Lour.

Glutamate decarboxylase (GAD) is involved in GABA metabolism and plays an essential regulatory role in plant growth, abiotic stresses, and hormone response. This study investigated the expression mechanism of the GAD family during longan early somatic embryogenesis (SE) and identified 6 GAD genes based on the longan genome. Homology analysis indicated that DlGAD genes had a closer relationship with dicotyledonous plants. The analysis of cis-acting elements in the promoter region suggests that the GAD genes were associated with various stress responses and hormones. RNA sequencing (RNA-Seq) and the qRT-PCR data indicated that most DlGAD genes were highly expressed in the incomplete compact pro-embryogenic cultures (ICpEC) and upregulated in longan embryogenic callus (EC) after treatments with 2,4-D, high temperature (35 °C), IAA, and ABA. Moreover, the RNA-Seq analysis also revealed that DlGADs exhibit different expression patterns in various tissues and organs. The subcellular localization results showed that DlGAD5 was localized in the cytoplasm, suggesting that it played a role in the cytoplasm. Transient overexpression of DlGAD5 enhanced the expression levels of DlGADs and increased the activity of glutamate decarboxylase in longan embryogenic callus (EC), while the content of glutamic acid decreased. Thus, the DlGAD gene can play an important role in the early somatic embryogenesis of longan by responding to hormones such as IAA and ABA. DlGAD5 can affect the growth and development of longan by stimulating the expression of the DlGAD gene family, thereby increasing the GAD activity in the early SE of longan, participating in hormone synthesis and signaling pathways.

Genome-centric metagenomics and methanogenic pathway analysis for acclimated anaerobic digestion of chicken manure with high ammonia stressed under thermophilic condition.

Thermophilic anaerobic digestion (AD) of animal manure offers various environmental benefits but the process requires a microbial community acclimatized to high ammonia. In current study, a lab-scale continuous stirred tank reactor (CSTR) fed with chicken manure was operated under thermophilic condition for 450 days in total. Results showed that the volumetric methane production decreased from 445 to 328 and sharply declined to 153 mL L-1·d-1 with feeding total solid (TS) step increased from 5% to 7.5% and 10%, respectively. While, after a long-term stop feeding for 80 days, highly disturbed reactor was able to recover methane generation to 739 mL L-1·d-1 at feeding TS of 10%. Isotope analysis indicted acetate converted to methane through the syntrophic acetate oxidation and hydrogenotrophic methanogenesis (SAO-HM) pathway increased from 33% to 63% as the concentration of ammonium increased from 2493 to 6258 mg L-1. Significant different in the genome expression of the SAO bacterial from 0.09% to 1.23%, combining with main hydrogenotrophic partners (Methanoculleus spp. and Methanothermobacter spp.) contented of 2.1% and 99.9% during inhibitory and recovery stages, respectively. The highly expressed KEGG pathway in level 3 (enzyme genes) for the Recovery sludge combining with the extraordinary high abundance of genera Halocella sp. suggested that Halocella sp. might be a highly efficient hydrolytic and acidogenic microorganism and enhance the process of SAO during carbon metabolic flow to methane. This report will be a basis for further study of AD studies on high nitrogen content of poultry manure.

Ultrathin zigzag-surface copper nanowire assembled hierarchical microspheres to enhance oxygen reduction catalysis.

Ultrathin catalysts predominantly expose surface active atoms to deliver promising applications in oxygen reduction reactions (ORRs). However, they are commonly synthesized at high reaction temperatures, with tedious chemical routes involved. Herein, we report a low temperature (273 K) electric field driven route to synthesize zigzag-surface ultrathin copper nanowires. Interestingly, the ultrathin copper nanowires assemble into three-dimensional microspheres, which exhibit hydrophobic-aerophilic features, eventually resulting in good ORR activities. The aerophilicity and hydrophobicity of copper nanowires are related to their Cu2O active sites and hierarchical protuberances, respectively. Our findings open a new door to grow ultrathin catalysts for new energy storage systems.

Benefits and costs: Understanding the influence of heavy metal pollution on environmental adaptability in Strauchbufo raddei tadpoles through an energy budget perspective.

Understanding the impact of environmental pollution on organismal energy budgets is crucial for predicting adaptive responses and potential maladaptation to stressors. However, the regulatory mechanism governing the trade-off between energy intake and consumption remains largely unknown, particularly considering the diverse adaptations influenced by exposure history in realistic field conditions. In the present study, we conducted a simulated field reciprocal transplant experiment to compare the energy budget strategies of Strauchbufo raddei tadpoles exposed to heavy metal. The simulated heavy metal concentrations (0.29 mg/L Cu, 1.17 mg/L Zn, 0.47 mg/L Pb, 0.16 mg/L Cd) mirrored the actual environmental exposure concentrations observed in the field habitat. This allowed for a comparison between tadpoles with parental chronic exposure to heavy metal pollutants in their habitat and those without such exposure. Results revealed that under heavy metal exposure, tadpoles originating from unpolluted areas exhibited heightened vulnerability, characterized by reduced food intake, diminished nutrient absorption, increased metabolism cost, reduced energy reserves, and increased mortality rates. In contrast, tadpoles originating from areas with long-term heavy metal pollution demonstrated adaptive strategies, manifested through adjustments in liver and small intestine phenotypes, optimizing energy allocation, and reducing energy consumption to preserve energy, thus sustaining survival. However, tadpoles from polluted areas exhibited certain maladaptive such as growth inhibition, metabolic suppression, and immune compromise due to heavy metal exposure. In conclusion, while conserving energy consumption has proven to be an effective way to deal with long-term heavy metal stress, it poses a threat to individual survival and population development in the long run.

Heterologous Expression and Characterization of a pH-Stable Chitinase from Micromonospora aurantiaca with a Potential Application in Chitin Degradation.

To promote the bioconversion of marine chitin waste into value-added products, we expressed a novel pH-stable Micromonospora aurantiaca-derived chitinase, MaChi1, in Escherichia coli and subsequently purified, characterized, and evaluated it for its chitin-converting capacity. Our results indicated that MaChi1 is of the glycoside hydrolase (GH) family 18 with a molecular weight of approximately 57 kDa, consisting of a GH18 catalytic domain and a cellulose-binding domain. We recorded its optimal activity at pH 5.0 and 55 °C. It exhibited excellent stability in a wide pH range of 3.0-10.0. Mg2+ (5 mM), and dithiothreitol (10 mM) significantly promoted MaChi1 activity. MaChi1 exhibited broad substrate specificity and hydrolyzed chitin, chitosan, cellulose, soluble starch, and N-acetyl chitooligosaccharides with polymerization degrees ranging from three to six. Moreover, MaChi1 exhibited an endo-type cleavage pattern, and it could efficiently convert colloidal chitin into N-acetyl-D-glucosamine (GlcNAc) and (GlcNAc)2 with yields of 227.2 and 505.9 mg/g chitin, respectively. Its high chitin-degrading capacity and exceptional pH tolerance makes it a promising tool with potential applications in chitin waste treatment and bioactive oligosaccharide production.

Anxiety in adolescents and subsequent risk of suicidal behavior: A systematic review and meta-analysis.

BACKGROUND: Suicide is a major public health concern, and anxiety is a prevalent developmental challenge in adolescents closely linked to suicidal behavior. This study aimed to assess the association between anxiety in adolescents and subsequent risk of suicidal behavior through a meta-analysis, offering crucial insights for suicide prevention. METHODS: Six bibliographic databases were comprehensively searched to clarify the association between adolescents anxiety and subsequent risk of suicidal behavior. We used a fixed-effects model to determine the total pooled effect size estimate and reported odds ratios and the corresponding 95 % confidence intervals. Subgroup analysis, sensitivity analysis and publication bias analysis were conducted with Stata version 15.1. RESULTS: The findings revealed a significant association between anxiety in adolescents and subsequent suicidal behavior (OR = 2.33, 95 % CI [2.00, 2.71]). Subgroup analyses indicated differences in mean effect size estimates based on clinical diagnoses and self-reported measures used to assess anxiety. The correlation strength between adolescent anxiety and subsequent suicidal behavior increased with a longer follow-up period. Furthermore, adolescents anxiety was associated with increased risk of subsequent suicidal ideation (OR = 1.97, 95 % CI [1.72, 2.25]) and attempts (OR = 3.56, 95 % CI [2.49, 5.07]). Finally, boys (OR = 2.41, 95 % CI [1.67, 3.47]) with anxiety had a greater risk of subsequent suicidal behavior than girls (OR = 2.02, 95 % CI [1.47, 2.78]). CONCLUSION: This study revealed that adolescents anxiety increases the risk of suicidal behavior, including suicidal ideation and attempts. Consequently, there is a critical need for timely interventions tailored to adolescents with anxiety to prevent future instances of suicide.

Transcriptome and metabolome analyses reveal the regulatory role of MdPYL9 in drought resistance in apple.

BACKGROUND: The mechanisms by which the apple MdPYL9 gene mediates the response to drought stress remain unclear. Here, transcriptome and metabolome analyses of apple plants under drought were used to investigate the mechanisms by which MdPYL9 regulates the response to drought stress in apple. MdPYL9-overexpressed transgenic and non-transgenic apple histoculture seedlings were rooted, transplanted, and subjected to drought treatments to clarify the mechanisms underlying the responses of apples to drought stress through phenotypic observations, physiological and biochemical index measurements, and transcriptomic and metabolomic analyses. RESULTS: Under drought stress treatment, transgenic plants were less affected by drought stress than non-transgenic plants. Decreases in the net photosynthetic rate, stomatal conductance, and transpiration rate of transgenic apple plants were less pronounced in transgenic plants than in non-transgenic plants, and increases in the intercellular CO2 concentration were less pronounced in transgenic plants than in non-transgenic plants. The relative electrical conductivity and content of malondialdehyde, superoxide anion, and hydrogen peroxide were significantly lower in transgenic plants than in non-transgenic plants, and the chlorophyll content and activities of antioxidant enzymes (superoxide dismutase, peroxidase, and catalase) were significantly higher in transgenic plants than in non-transgenic plants. The number of differentially expressed genes (DEGs) involved in the response to drought stress was lower in transgenic plants than in non-transgenic plants, and the most significant and highly annotated DEGs in the transgenic plants were involved in the flavonoid biosynthesis pathway, and the most significant and highly annotated DEGs in control plants were involved in the phytohormone signal transduction pathway. The number of differentially accumulated metabolites involved in the response to drought stress was lower in transgenic plants than in non-transgenic plants, and up-regulated metabolites were significantly enriched in apigenin-7-O-glucoside in transgenic plants and in abscisic acid in non-transgenic plants. In the flavonoid biosynthetic pathway, the expression of genes encoding chalcone synthase (CHS) and chalcone isomerase (CHI) was more significantly down-regulated in non-transgenic plants than in transgenic plants, and the expression of the gene encoding 4-coumarate-CoA ligase (4CL) was more significantly up-regulated in transgenic plants than in non-transgenic plants, which resulted in the significant up-regulation of apigenin-7-O-glucoside in transgenic plants. CONCLUSIONS: The above results indicated that the over-expression of MdPYL9 increased the drought resistance of plants under drought stress by attenuating the down-regulation of the expression of genes encoding CHS and CHI and enhancing the up-regulated expression of the gene encoding 4CL, which enhanced the content of apigenin-7-O-glucoside.

Natural products in atherosclerosis therapy by targeting PPARs: a review focusing on lipid metabolism and inflammation.

Inflammation and dyslipidemia are critical inducing factors of atherosclerosis. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors and control the expression of multiple genes that are involved in lipid metabolism and inflammatory responses. However, synthesized PPAR agonists exhibit contrary therapeutic effects and various side effects in atherosclerosis therapy. Natural products are structural diversity and have a good safety. Recent studies find that natural herbs and compounds exhibit attractive therapeutic effects on atherosclerosis by alleviating hyperlipidemia and inflammation through modulation of PPARs. Importantly, the preparation of natural products generally causes significantly lower environmental pollution compared to that of synthesized chemical compounds. Therefore, it is interesting to discover novel PPAR modulator and develop alternative strategies for atherosclerosis therapy based on natural herbs and compounds. This article reviews recent findings, mainly from the year of 2020 to present, about the roles of natural herbs and compounds in regulation of PPARs and their therapeutic effects on atherosclerosis. This article provides alternative strategies and theoretical basis for atherosclerosis therapy using natural herbs and compounds by targeting PPARs, and offers valuable information for researchers that are interested in developing novel PPAR modulators.

Expression and potential molecular mechanism of TOP2A in metastasis of non-small cell lung cancer.

DNA topoisomerase II alpha (TOP2A) expression, gene alterations, and enzyme activity have been studied in various malignant tumors. Abnormal elevation of TOP2A expression is considered to be related to the development of non-small cell lung cancer (NSCLC). However, its association with tumor metastasis and its mode of action remains unclear. Bioinformatics, real-time quantitative PCR, immunohistochemistry and immunoblotting were used to detect TOP2A expression in NSCLC tissues and cells. Cell migration and invasion assays as well as cytoskeletal staining were performed to analyze the effects of TOP2A on the motility, migration and invasion ability of NSCLC cells. Cell cycle and apoptosis assays were used to verify the effects of TOP2A on apoptosis as well as cycle distribution in NSCLC. TOP2A expression was considerably upregulated in NSCLC and significantly correlated with tumor metastasis and the occurrence of epithelial-mesenchymal transition (EMT) in NSCLC. Additionally, by interacting with the classical ligand Wnt3a, TOP2A may trigger the canonical Wnt signaling pathway in NSCLC. These observations suggest that TOP2A promotes EMT in NSCLC by activating the Wnt/ß-catenin signaling pathway and positively regulates malignant events in NSCLC, in addition to its significant association with tumor metastasis. TOP2A promotes the metastasis of NSCLC by stimulating the canonical Wnt signaling pathway and inducing EMT. This study further elucidates the mechanism of action of TOP2A, suggesting that it might be a potential therapeutic target for anti-metastatic therapy.

Plasma-activated water improves the accessibility of chitinase to chitin by decreasing molecular weight and breaking crystal structure.

Chitooligosaccharides, the hydrolysis products of chitin, have superior biological activities and application value to those of chitin itself; however, the ordered and highly crystalline structure of chitin renders its degradation by chitinase difficult. Herein, the effects of plasma-activated water (PAW) pre-treatment on the physicochemical properties, crystal structure, and enzymatic hydrolysis of chitin were investigated. The hydrolysis of PAW-pre-treated chitin (PAW activation time of 5 min) using chitinase from Vibrio harveyi (VhChit2) yielded 71 % more reducing sugar, compared with that from untreated chitin, with the degree of chitin hydrolysis increasing from 13 % without pre-treatment to 23 % post-treatment. Moreover, the amount of VhChit2 adsorbed by chitin increased from 41.7 to 58.2 mg/g. Fourier transform infrared spectrometry revealed that PAW could break the ß-1,4-glycosidic bonds of chitin (but had no effects on the hydrogen and amido bonds), thereby decreasing the molecular weight and crystallinity of the polysaccharide, which caused its structural damage and enhanced its enzymatic hydrolysis by chitinase. Consequently, PAW pre-treatment can be considered a simple, effective, and environmentally-friendly method for the biotransformation of chitin as its easier hydrolysis yields high-value products.

A comparative study of the hypolipidemic effects and mechanisms of action of Laminaria japonica- and Ascophyllum nodosum-derived fucoidans in apolipoprotein E-deficient mice.

The structural characteristics of fucoidans exhibit species and regional diversity. Previous studies have demonstrated that Laminaria japonica- and Ascophyllum nodosum-derived fucoidans have type I and type II fucosyl chains, respectively. These chemical differences may contribute to distinct hypolipidemic effects and mechanisms of action. Chemical analysis demonstrated that the percentage contents of sulfate, glucuronic acid, and galactose were higher in L. japonica-derived fucoidans than those of A. nodosum-derived fucoidans. In hyperlipidemic apolipoprotein E-deficient mice, both A. nodosum- and L. japonica-derived fucoidans significantly decreased the plasma and hepatic levels of total cholesterol and triglyceride, leading to the reduction of atherosclerotic plaques. Western blotting experiments demonstrated that these fucoidans significantly enhanced the expression and levels of scavenger receptor B type 1, cholesterol 7 alpha-hydroxylase A1, and peroxisome proliferator-activated receptor (PPAR)-α, contributing to circulating lipoprotein clearance and fatty acid degradation, respectively. Differentially, L. japonica-derived fucoidan significantly increased the LXR/ATP-binding cassette G8 signaling pathway in the small intestine, as revealed by real-time quantitative PCR, which may lead to further cholesterol and other lipid excretion. Collectively, these data are useful for understanding the hypolipidemic mechanisms of action of seaweed-derived fucoidans, and their potential application for the prevention and/or treatment of atherosclerotic cardiovascular diseases.

Longitudinal and Reciprocal Effects in the Association Between School Bullying and Homicidal Ideation During Early Adolescence.

Several cross-sectional studies indicated a positive association between school bullying and homicidal ideation during early adolescence. However, few longitudinal studies investigated this association. This study examined whether a bi-directional relationship exists within the longitudinal association between bullying victimization or bullying perpetration and homicidal ideation among early adolescents using a Random Intercept Cross-Lagged Panel Model. A total of 1611 early adolescents (39.5% girls; Mage = 12.50 years, SD = 0.50) were recruited from the Chinese Early Adolescents Cohort study. Data on bullying victimization, bullying perpetration, and homicidal ideation collected during three time points (September 2019, September 2020, and September 2021) were used. Bullying victimization showed a significant positive association with homicidal ideation at the between-person level. Bullying victimization and bullying perpetration had a bi-directional relationship with homicidal ideation at the within-person level. Additionally, this study considered the impact of biological sex-based differences and bullying types on adolescents' homicidal ideation. Based on these findings, school bullying might exhibit unique reciprocal associations with homicidal ideation.

Dopamine Alleviates Phloridzin Toxicity in Apple by Modifying Rhizosphere Bacterial Community Structure and Function.

Phloridzin significantly influences apple plant growth, development, and resistance to environmental stresses by engaging in various metabolic processes. Its excessive accumulation in soil, attributed to continuous monoculture practices, not only inhibits plant growth but also disrupts the rhizosphere microbial community. This study aims to explore the remedial effects of dopamine, a known antioxidant and stress resistance modulator in plants, on the adverse impacts of phloridzin stress in apple. Through hydroponic and pot experiments, it was demonstrated that dopamine significantly mitigates the growth inhibition caused by phloridzin stress in apple by reducing reactive oxygen species levels and enhancing photosynthesis and nitrogen transport. Additionally, dopamine reduced phloridzin concentrations in both the rhizosphere and roots. Furthermore, dopamine positively influences the structure of the rhizosphere microbial community, enriching beneficial microbes associated with nitrogen cycling. It increases the potential for soil nitrogen degradation and fixation by upregulating the abundance of ureC, GDH, and nifH, as revealed by metagenomic analysis. This aids in alleviating phloridzin stress. The study reveals dopamine's pivotal roles in modulating rhizosphere ecology under phloridzin stress and suggests its potential in sustainable apple cultivation practices to counter ARD and enhance productivity.

The function of brown adipose tissue at different sites of the body in Brandt's voles during cold acclimation.

Ambient temperatures have great impacts on thermoregulation of small mammals. Brown adipose tissue (BAT), an obligative thermogenic tissue for small mammals, is localized not only in the interscapular depot (iBAT), but also in supraclavicular, infra/subscapular, cervical, paravertebral, and periaortic depots. The iBAT is known for its cold-induced thermogenesis, however, less has been paid attention to the function of BAT at other sites. Here, we investigated the function of BAT at different sites of the body during cold acclimation in a small rodent species. As expected, Brandt's voles (Lasiopodomys brandtii) consumed more food and reduced the body mass gain when they were exposed to cold. The voles increased resting metabolic rate and maintained a relatively lower body temperature in the cold (36.5 ± 0.27 °C) compared to those in the warm condition (37.1 ± 0.36 °C). During cold acclimation, the uncoupling protein 1 (UCP1) increased in aBAT (axillary), cBAT (anterior cervical), iBAT (interscapular), nBAT (supraclavicular), and sBAT (suprascapular). The levels of proliferating cell nuclear antigen (PCNA), a marker for cell proliferation, were higher in cBAT and iBAT in the cold than in the warm group. The pAMPK/AMPK and pCREB/CREB were increased in cBAT and iBAT during cold acclimation, respectively. These data indicate that these different sites of BAT play the cold-induced thermogenic function for small mammals.

Bisphenol AF exposure synergistically increases the risk for suicidality among early adolescents with child maltreatment: A prospective cohort study.

BACKGROUND: Child maltreatment (CM) is correlated with suicidality risk among adolescents. Additionally, exposure to bisphenol AF (BPAF) may increase this risk. However, the combined effect of CM and BPAF exposure remains unknown and should be further investigated. METHODS: In this study, 1,475 early adolescents (mean age = 12.48 years) from the Chinese Early Adolescents Cohort were enrolled. Data were collected at three time points with an interval of 12 months between 2019 and 2021. Participants' history of CM and suicidality (including suicidal ideation and suicidal attempts) were evaluated using a self-report questionnaire. Blood samples were obtained from participants to measure serum BPAF concentrations at baseline. Group-based trajectory modeling was employed to identify different developmental trajectories of suicidality across the three waves. After adjusting for potential confounders, the association between CM and BPAF exposure on suicidal ideation and suicidal attempts was assessed using logistic regression and Poisson regression analyses. RESULTS: Participants with CM were associated with a risk of one- and two-year incident suicidality (all ps < 0.05), and BPAF levels were positively associated with two-year incident suicidal ideation (adjusted OR = 1.68, 95% CI: 1.13-2.50). Additionally, middle and high levels of BPAF exposure synergistically increase the risk for one- and two-year incident suicidal ideation among participants with CM (adjusted ORs = 2.00-3.83). Similarly, participants exposed to high-level BPAF as well as CM were at a greater risk of one- and two-year incident suicidal attempts than those with low-level BPAF exposure and no CM (adjusted incidence rate ratio [IRRs] = 2.82-4.34). Moreover, compared with participants with a low developmental trajectory of suicidality across the three waves, high BPAF exposure exhibited a significant synergistic effect on participants with CM in the persistently high suicidal ideation trajectory and the increasing suicidal attempts trajectory (all ps < 0.05). Sex subgroup analysis revealed that females were more susceptible to the synergistic effect of BPAF and CM exposure on suicidality than males. CONCLUSIONS: Environmental factors and the psychological status of individuals may synergistically increase their susceptibility to suicidality. These results offer novel insights into enhancing our understanding of suicidality among adolescents.

Perceived discrimination and youth vaping: The role of intersectional identities.

INTRODUCTION: Electronic cigarettes (also termed e-cigarette or vapes) often contain nicotine, an addictive psychoactive substance, which can have harmful effects during adolescence. Frequent experiences of discrimination are one risk factor shown to increase susceptibility to tobacco use, especially for individuals that identify as a social minority. Applying Intersectionality Theory, this research examined the relationship between youth experiences of discrimination and vape use at the intersection of race/ethnicity and sexual orientation. METHOD: Cross-sectional survey data from 4747 youth (ages 12-17) that participated in the 2022 Teens, Nicotine, and Tobacco Project (TNT) online survey were used to evaluate the impact of discrimination on vape use for lesbian, gay, bisexual, and/or queer/questioning (LGBQ+) youth of color. RESULTS: Multivariable regression analyses showed that identifying as both a sexual and racial/ethnic minority was a risk factor for experiencing discrimination. Frequent discrimination and reporting discrimination due to sexual orientation was associated with a greater likelihood of ever and current vaping. Path models supported that discrimination mediated the relationship between intersectional identity and vape use. LGBQ+ youth of color reported more frequent discrimination, which was associated with a greater likelihood of ever/current vape use. CONCLUSIONS: Intersectionality Theory aids in understanding how discrimination can exacerbate tobacco-related disparities for youth with multiple minority identities. Findings corroborate the importance of measuring discrimination in public health surveys. Effective tobacco interventions could incorporate strategies to cope with discrimination-related stress.

Mesenchymal stem cells derived from adipose tissue and umbilical cord reveal comparable efficacy upon radiation-induced colorectal fibrosis in rats.

Chemoradiotherapy (CRT) and radiotherapy (RT) have served as anticancer treatments and neoadjuvant therapies for conquering multimodal rectal cancers including colorectal carcinoma (CRC), yet the concomitant radiation-induced colorectal fibrosis (RICF) has caused chronic toxicity and stenosis in the colorectal mucosa of patients. Mesenchymal stem/stromal cells (MSCs) with unique bidirectional immunoregulation and anti-fibrotic effect have been recognized as splendid sources for regenerative purposes including intestinal diseases. Herein, we are aiming to verify the feasibility and variations of MSC-based cytotherapy for the remission of RICF from the pathological features and the potential impact upon the transcriptomic signatures of RICF rats. For the purpose, we utilized our well-established RICF Sprague-Dawley (SD) rats by radiation for five weeks, and conducted consecutive intraperitoneal injection of two distinct MSCs for treatment, including MSCs derived from adult adipose tissue (AD-MSCs) and perinatal umbilical cord (UC-MSCs). On the one hand, the efficacy of AD-MSCs and UC-MSCs was assessed by diverse indicators, including weight change, pathological detections (e.g., H&E staining, Masson staining, EVG staining, IF staining, and IHC staining), and proinflammatory and fibrotic factor expression. On the other hand, we turned to RNA-sequencing (RNA-SEQ) and multifaceted bioinformatics analyses (e.g., GOBP, Venn Map, KEGG, and GSEA) to compare the impact of AD-MSC and UC-MSC treatment upon the gene expression profiling and genetic variations. RICF rats after consecutive AD-MSC and UC-MSC administration revealed comparable remission in histopathogenic features and significant suppression of diverse proinflammatory and fibrotic factors expression. Meanwhile, RICF rats after both MSC treatment revealed decrease and variations in the alterations in diverse gene expression and somatic mutations compared to RICF rats. Collectively, our data indicated the comparable therapeutic effect of AD-MSCs and UC-MSCs upon RICF in SD rats, together with the conservations in gene expression profiling and the diverse variations in genetic mutations. Our findings indicated the multifaceted impact of MSC infusion for the supervision of RICF both at the therapeutic and transcriptomic levels, which would provide novel references for the further evaluation and development of MSC-based regimens in future.