DDX5 inhibits inflammation by modulating m6A levels of TLR2/4 transcripts during bacterial infection.

DExD/H-box helicases are crucial regulators of RNA metabolism and antiviral innate immune responses; however, their role in bacteria-induced inflammation remains unclear. Here, we report that DDX5 interacts with METTL3 and METTL14 to form an m6A writing complex, which adds N6-methyladenosine to transcripts of toll-like receptor (TLR) 2 and TLR4, promoting their decay via YTHDF2-mediated RNA degradation, resulting in reduced expression of TLR2/4. Upon bacterial infection, DDX5 is recruited to Hrd1 at the endoplasmic reticulum in an MyD88-dependent manner and is degraded by the ubiquitin-proteasome pathway. This process disrupts the DDX5 m6A writing complex and halts m6A modification as well as degradation of TLR2/4 mRNAs, thereby promoting the expression of TLR2 and TLR4 and downstream NF-κB activation. The role of DDX5 in regulating inflammation is also validated in vivo, as DDX5- and METTL3-KO mice exhibit enhanced expression of inflammatory cytokines. Our findings show that DDX5 acts as a molecular switch to regulate inflammation during bacterial infection and shed light on mechanisms of quiescent inflammation during homeostasis.

From Gatekeeper to Facilitator: Balancing Between Sexual Rights and Protection From Harm in Dementia Adults.

OBJECTIVE: The assessment of sexual consent capacity has been a challenge due to its dynamic nature, influenced by factors such as time, environment, individuals involved, and the nature of activities. Particularly in people living with dementia, the complexity is intensified with the interplay of the disease's impact, residential care setting, and legal constraints. This amplifies the dilemma faced by practitioners-whether to prioritize protection or encourage and support sexual expression. This article aims to provide a sensible approach to uphold the sexual autonomy of people living with dementia while mitigating the potential risks of them being involved as either perpetrators or victims. METHODS: In this narrative review, a literature search spanning from 1990 to 2023 was carried out on PubMed. Relevant articles on people living with dementia and topics related to sexuality were scrutinized. RESULTS: 41 relevant articles identified themes related to the impact of cognitive impairment on sexuality, challenges in residential care facilities, sexual consent capacity assessment models, and ethical frameworks regarding sexual rights and law. CONCLUSION: Discussions highlight the often neglected influence of prolonged suppression of sexual expression and the benefits of actualization of sexual autonomy, especially in people living with dementia, whose sense of identity is fading. It scrutinizes the limitations of existing sexual consent capacity evaluation models, emphasizing ethical concerns, practical challenges, and the need for a more balanced approach. Proposed strategies advocate for a shift from a gatekeeper to a facilitator role, offering principles for setting educational programs and policies to mitigate obstacles, supporting sexual rights, and safeguarding vulnerable groups.

Imbalance of multiple neurotransmitter pathways leading to depression-like behavior and cognitive dysfunction in the triple transgenic mouse model of Alzheimer disease.

Depression is among the most frequent psychiatric comorbid conditions in Alzheimer disease (AD). However, pharmacotherapy for depressive disorders in AD is still a big challenge, and the data on the efffcacy of current antidepressants used clinically for depressive symptoms in patients with AD remain inconclusive. Here we investigated the mechanism of the interactions between depression and AD, which we believe would aid in the development of pharmacological therapeutics for the comorbidity of depression and AD. Female APP/PS1/Tau triple transgenic (3×Tg-AD) mice at 24 months of age and age- and sex-matched wild-type (WT) mice were used. The shuttle-box passive avoidance test (PAT) were implemented to assess the abilities of learning and memory, and the open field test (OFT) and the tail suspension test (TST) were used to assess depression-like behavior. High-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) was used to detect the level of neurotransmitters related to depression in the hippocampus of mice. The data was identified by orthogonal projections to latent structures discriminant analysis (OPLS-DA). Most neurotransmitters exert their effects by binding to the corresponding receptor, so the expression of relative receptors in the hippocampus of mice was detected using Western blot. Compared to WT mice, 3×Tg-AD mice displayed significant cognitive impairment in the PAT and depression-like behavior in the OFT and TST. They also showed significant decreases in the levels of L-tyrosine, norepinephrine, vanillylmandelic acid, 5-hydroxytryptamine, and acetylcholine, in contrast to significant increases in 5-hydroxyindoleacetic acid, L-histidine, L-glutamine, and L-arginine in the hippocampus. Moreover, the expression of the alpha 1a adrenergic receptor (ADRA1A), serotonin 1 A receptor (5HT1A), and γ-aminobutyric acid A receptor subunit alpha-2 (GABRA2) was significantly downregulated in the hippocampus of 3×Tg-AD mice, while histamine H3 receptor (H3R) expression was significantly upregulated. In addition, the ratio of phosphorylated cAMP-response element-binding protein (pCREB) and CREB was significantly decreased in the hippocampus of 3×Tg-AD mice than WT mice. We demonstrated in the present study that aged female 3×Tg-AD mice showed depression-like behavior accompanied with cognitive dysfunction. The complex and diverse mechanism appears not only relevant to the imbalance of multiple neurotransmitter pathways, including the transmitters and receptors of the monoaminergic, GABAergic, histaminergic, and cholinergic systems, but also related to the changes in L-arginine and CREB signaling molecules.

First report of leaf spot on Ilex verticillata caused by Alternaria alternata in China.

Ilex verticillata (L.) A. Gray (Winter Red) is a deciduous shrub and native to North America with high ornamental value, which was introduced into China in 2006. In Oct. 2020, leaf spots occurred on I. verticillata at the nursery of Baima Base for Teaching and Scientific Research of Nanjing Forestry University (31°36'51"N, 119°11'8"E). In the early stage, there were small black spots occurred on the leaves. Then, these spots enlarged and coalesced into regular or irregular gray necrotic lesions with dark margins (Fig. S1A). The incidence of this disease was ca. 93%. Infected leaves were collected and surface-sterilized with 75% ethanol. Pieces cut from the margin of the lesions of ca. 5×5 mm were placed on potato dextrose agar (PDA) Petri plates and incubated at 25±2°C for 7 days. Ten Alternaria fungal isolates were single-spore isolated. Since these isolates shared similar morphological characters, isolates 9-1 and 15-2-2 were randomly chosen for further experiments. 2-yr-old potted I. verticillata were used for pathogenicity test in vivo. Leaves were surface-sterilized using 75% ethanol and wounded using a sterilized needle and inoculated with mycelial plugs or 10 µL of conidial suspensions (105 spores mL-1), respectively. The inoculated plants were kept in a growth chamber at 25°C and 85% RH under a 12-h photoperiod. PDA plugs without fungus or sterilized H2O were used as controls, respectively. The experiment was repeated 2 times. Each treatment had 3 replicates. By day 7, necrotic lesions were observed on the leaves inoculated with the fungal isolates 9-1 or 15-2-2. No lesions were found on the plants inoculated with PDA discs or dH2O (Fig. S1). To complete Koch's postulates, the pathogen was re-isolated from the infected leaves and shared similar morphological characteristics of colonies and conidia with the original inoculated isolates. Conidiophores of the 2 isolates were pale brown, erect or curved, (20.1-)21.4-29.9(-39.9) × (8.4-)10.6-14.9(-18.3) µm, (n = 30). Conidia were dictyospores, nearly ovoid or clubbed, brown or grayish brown, (25.2-)27.5-42.8(-47.9) × (5.7-)6-7.7(-8.7) µm, (n = 30), in branched or unbranched chains (Fig. S1). These morphological characteristics matched A. alternata (Woudenberg et al. 2013). The internal transcribed spacer (ITS), glyceraldehyde-3-phosphate dehydrogenase gene (GAPDH), endopolygalacturonase gene (endoPG), anonymous noncoding region (OPA10-2), small subunit gene (SSU), and large subunit gene (LSU) of isolates 9-1 and 15-2-2 were amplified using primer sets of Woudenberg et al. (2013). The SSU (OK428540, OK428541), LSU (OK428538, OK428539), ITS (OK316966, OK316967), GAPDH (OK428542, OK428543), endoPG (OK428544, OK428545), and OPA10-2 (OK428536, OK428537) of isolates 9-1 and 15-2-2 showed 99, 99, 99, 99, 100, and 100% similarity to the sequences of A. alternata ex-type CBS 916.96, respectively. Phylogenetic analyses using concatenated sequences of ITS, GAPDH, OPA10-2, LSU, SSU, and endOPG also showed that the isolates of 9-1 and 15-2-2 clustered with A. alternata ex-type and was supported with a 100% bootstrap value (Fig. S2). Based on the morphological and phylogenetic results, these fungal isolates were identified as A. alternata. A. alternata was reported as the pathogen of leaf spot and other diseases on more than 380 hosts (Farr & Rossman, 2022). To our knowledge, this was the first report of A. alternata causing leaf spot on I. verticillata in China. This report is important because the discovery is related to the management strategies of the new pathogen on I. verticillata. The monitoring and control of the disease needs to be emphasized in the future.

Bioinformatic Analysis Identifying PSMB 1/2/3/4/6/8/9/10 as Prognostic Indicators in Clear Cell Renal Cell Carcinoma.

Renal cancer incidence has been increasing across the world, clear cell renal cell carcinoma (ccRCC) represents the major subtype of renal cancer. The proteasome is involved in onset, metabolism and survival of tumor and has been recognized as a therapeutic target for various malignancies, while the role of ß subunits of proteasome, PSMB gene family, in ccRCC has not been fully unveiled. Herein we investigated the expression and the prognostic role of PSMBs in ccRCC by analyzing a series of databases, including ONCOMINE, UALCAN, cBioPortal, STRING, GEPIA, GO and KEGG. Over-expressions of PSMB1/2/4/7/8/9/10 mRNA were found in ccRCC tissues compared to normal tissues, transcriptional levels of PSMB2/3/4/6/8/9/10 were significantly positively associated with patients' individual cancer stages and grades. Similar or higher levels of proteins encoded by PSMB1/2/3/7/8/9/10 were observed in tumor tissues compared to normal renal tissues. Further, high mRNA levels of PSMB1/2/3/4/6/10 were correlated with shorter overall survival in univariate analysis. Taken together, the results of our analysis implied that overexpression of PSMB1/2/3/4/6/8/9/10 were indicative of worse prognosis of ccRCC. However, further researches were required to validate our findings.

Effects of 5.8 GHz microwave on hippocampal synaptic plasticity of rats.

OBJECTIVE: 5.8 GHz spectrum is gaining more attention in wireless technology. To explore the potential hazards, we investigated the effect of exposure to 5.8 GHz microwave on learning and memory ability of rats. Methods: Morris Water maze (MWM), Novel object recognition (NOR) and Fear conditioning test (FCT) were used to evaluate the ability of spatial and non-spatial memory of rats. The hippocampal morphology, the level of brain injury factors in serum and the mitochondrial membrane potential of hippocampal neurons was examined to evaluate the damage of hippocampal neurons. The density of dendritic spines, the ultrastructure of synapses and the level of PSD95, Synaptophysin, p-CREB and CREB were detected to evaluate the hippocampal synaptic plasticity. RESULTS: Compared with Sham group, there was no significant difference in the performance of ethology (in MWM, NOR, FCT) in Microwave 2 h group or Microwave 4 h group. The hippocampal morphology, the serum level of brain injury factors and the content of mitochondrial JC-1 monomer in Microwave 2 h group or Microwave 4 h group did not change obviously, compared with Sham group. The density of dendritic spines, the ultrastructure of synapse and the level of PSD95, Synaptophysin, p-CREB and CREB in hippocampus in Microwave 2 h group or Microwave 4 h group did not significantly change, compared with Sham group. CONCLUSION: Under this experimental condition, exposure to 5.8 GHz microwave could not affect the hippocampal synaptic plasticity of rats.

Involvement of noradrenergic and serotonergic systems in risk-based decisions between options of equivalent expected value in rats.

Risk perception is an important factor that may mediate risk-based decision-making processes regulated by noradrenergic (NA) and serotonergic (5-HT) systems. Most risk-based decision-making models involve complex factors, such as risk perception or reward value, such that the final decision is the result of the interactions among these factors. However, the contribution of risk perception per se in risk decisions has remained unclear. Therefore, in the present study, we made some modifications to the classical probabilistic discounting task (PDT) to focus on the impact of risk perception and noradrenergic/serotonergic systems on decision-making behavior. Meanwhile, we conducted an elevated plus-maze (EPM) test to detect the correlation between anxiety and choice behavior. In the current study, rats had to choose between a "certain" lever that delivered a certain number of pellets and a "risky" lever that delivered eight pellets in a probabilistic manner (descending: 50%, 25%, 12.5% or ascending 12.5%, 25%, 50% of the time). The long-term rewarding values of the two levers were always identical in each block within each session. According to their baseline performances in choosing the risky lever, rats were divided into the risk-prefer group and risk-averse group. The results showed that there was a significant correlation between open arm time in EPM and risky choice for both descending order and ascending order, indicating that highly anxious rats more often preferred the safe option under risk. Pharmacological stimulation of α2-adrenergic receptors via dexmedetomidine (0.01 mg/kg) decreased the preference of probabilistic rewards in the risk-prefer group, while blocking α2 receptors by atipamezole (0.3 mg/kg) also reduced risky choices. The NA reuptake inhibitor, atomoxetine, increased the preference for risky choices in the risk-prefer group, the effect of which was attained via multiple superimposed doses. Administration of the 5-HT2A receptor agonist, DOI (0.1 mg/kg), increased risk-taking behavior in the risk-prefer group. Taken together, these results suggest that NA may be more inclined to process negative information such as loss or uncertainty in the regulation of risk-related decision making, whereas 5-HT may function primarily to increase risk-taking behavior. Our findings may help to further elucidate how noradrenergic and serotonergic systems differentially affect individuals with different risk preferences in terms of regulating risk perception in risk-related decision making.

Differential Gene Profiling of the Heartwood Formation Process in Taiwania cryptomerioides Hayata Xylem Tissues.

Taiwania (Taiwania cryptomerioides) is an important tree species in Taiwan because of the excellent properties of its wood and fascinating color qualities of its heartwood (HW), as well as the bioactive compounds therein. However, limited information is available as to the HW formation of this species. The objective of this research is to analyze the differentially expressed genes (DEGs) during the HW formation process from specific Taiwania xylem tissues, and to obtain genes that might be closely associated with this process. The results indicated that our analyses have captured DEGs representative to the HW formation process of Taiwania. DEGs related to the terpenoid biosynthesis pathway were all up-regulated in the transition zone (TZ) to support the biosynthesis and accumulation of terpenoids. Many DEGs related to lignin biosynthesis, and two DEGs related to pinoresinol reductase (PrR)/pinoresinol lariciresinol reductase (PLR), were up-regulated in TZ. These DEGs together are likely involved in providing the precursors for the subsequent lignan biosynthesis. Several transcription factor-, nuclease-, and protease-encoding DEGs were also highly expressed in TZ, and these DEGs might be involved in the regulation of secondary metabolite biosynthesis and the autolysis of the cellular components of ray parenchyma cells in TZ. These results provide further insights into the process of HW formation in Taiwania.

Dicer interacts with SIRT7 and regulates H3K18 deacetylation in response to DNA damaging agents.

Dicer participates in heterochromatin formation in fission yeast and plants. However, whether it has a similar role in mammals remains controversial. Here we showed that the human Dicer protein interacts with SIRT7, an NAD(+)-dependent H3K18Ac (acetylated lysine 18 of histone H3) deacetylase, and holds a proportion of SIRT7 in the cytoplasm. Dicer knockdown led to an increase of chromatin-associated SIRT7 and simultaneously a decrease of cytoplasmic SIRT7, while its overexpression induced SIRT7 reduction in the chromatin-associated fraction and increment in the cytoplasm. Furthermore, DNA damaging agents promoted Dicer expression, leading to decreased level of chromatin-associated SIRT7 and increased level of H3K18Ac, which can be alleviated by Dicer knockdown. Taken together with that H3K18Ac was exclusively associated with the chromatin, our findings suggest that Dicer induction by DNA damaging treatments prevents H3K18Ac deacetylation, probably by trapping more SIRT7 in the cytoplasm.

Dicer regulates non-homologous end joining and is associated with chemosensitivity in colon cancer patients.

DNA double-strand break (DSB) repair is an important mechanism underlying chemotherapy resistance in human cancers. Dicer participates in DSB repair by facilitating homologous recombination. However, whether Dicer is involved in non-homologous end joining (NHEJ) remains unknown. Here, we addressed whether Dicer regulates NHEJ and chemosensitivity in colon cancer cells. Using our recently developed NHEJ assay, we found that DSB introduction by I-SceI cleavage leads to Dicer upregulation. Dicer knockdown increased SIRT7 binding and decreased the level of H3K18Ac (acetylated lysine 18 of histone H3) at DSB sites, thereby repressing the recruitment of NHEJ factors to DSB sites and inhibiting NHEJ. Dicer overexpression reduced SIRT7 binding and increased the level of H3K18Ac at DSB sites, promoting the recruitment of NHEJ factors to DSBs and moderately enhancing NHEJ. Dicer knockdown and overexpression increased and decreased, respectively, the chemosensitivity of colon cancer cells. Dicer protein expression in colon cancer tissues of patients was directly correlated with chemoresistance. Our findings revealed a function of Dicer in NHEJ-mediated DSB repair and the association of Dicer expression with chemoresistance in colon cancer patients.

A New Type of Signaling Pathways as Pilomotor Lines along Skin for Transmitting Acupuncture Signals to Produce Acupuncture Effects.

In our previous study, we observed a linear system consisted of sympathetic endings in the arrector pili muscles (AP muscles) along the rat skin termed sympathetic substance lines, or SSLs. After shaving the hair of the rats, the first wave of hair re-growth was not evenly distributed, but followed specific hair loop lines (HLLs). The patterns of HLL and SSL correspond with each other and also with the "Meridians" described in Chinese traditional medicine (CTM). Here I investigated in rabbits and rats whether the acupuncture signals are transmitted via the SSL/HLL, and whether the acupuncture analgesia (AA) is dependent on any peripheral mechanism. Firstly, when acupuncture was operated or phenylephrine, an agonist for α receptor, was injected into the dermis at an acupoint, a pilomotor line occurred. The course of the pilomotor line coincided with the SSL/HLL. When the skin was incised or regitin, an antagonist for α receptor, was injected into the dermis, the pilomotor line did not cross the site of incision or injection. These results directly demonstrated the process of transmission of acupuncture signals involving the pilomotor line and the sympathetic. Secondly, AA produced by acupuncture at an acupoint was significantly blocked when the skin was incised or regitin was injected into the dermis along the SSL/HLL or the Meridians. [corrected]. These results suggest that the factor that blocked the pilomotor line also blocked the AA and the pilomotor line related to the AA. Lastly, noradrenaline was shown to be released from the skin along the Meridian line after acupuncture; when phenylephrine was injected into an acupoint, AA was strongly simulated. All these results indicate that: 1. the transmission pathway of acupuncture signals exists in the skin, just as the Meridians described in the CTM; 2. these pathways are the SSLs/HLLs and the pilomotor lines; and 3. the pilomotor line is just for the transmission of acupuncture signals and the transmission is dependent on the α receptor in the AP muscles, specifically the contraction of the AP muscles. Moreover, these findings suggest a new system and a new type of signal transmission in the physiology.

Breast cancer awareness among women in Eastern China: a cross-sectional study.

BACKGROUND: High breast cancer mortality has been attributed to lack of public awareness, which leads to late diagnoses. As little is known about the level of knowledge and awareness of breast cancer in China, this study was designed to explore it among women in Eastern China. METHODS: We conducted a cross-sectional survey covering 122,058 females around Shandong, Hebei, Jiangsu and Tianjin, in Eastern China, using in-person interviews based on a self-designed structured questionnaire. Student's t-test, Pearson's χ2 test, reliability analysis, exploratory factor analysis, univariate and multivariate logistic regression analyses were performed in the statistical analysis. RESULTS: The results showed poor awareness of breast cancer among women aged 25-70 years in Eastern China. Only 18.6% of women were highly aware in the study, whereas 81.4% were poorly aware. Among all participants, family history of breast cancer was the best accepted risk factor for breast cancer (awareness rate 31.5%), followed by menarche at age before 12 (11.2%), no parity or late childbirth (13.9%), menopause at a late age (13.7%), high-fat diets (19.1%), long time drinking (19.5%) and long-term use of estrogen drugs (20.7%). Multivariate logistic regression analysis (α = 0.05) identified nine variables that predicted awareness of breast cancer: age (OR = 0.975, 95% CI: 0.960-0.990), location (OR = 1.675, 95% CI: 1.602-1.752), occupation (OR = 4.774, 95% CI: 4.316-5.281), family history of breast cancer (OR = 1.234, 95% CI: 1.073-1.420), household annual income (OR = 0.418, 95% CI: 0.400-0.436), behavioral prevention score (OR = 4.137, 95% CI: 3.991-4.290), no smoking (OR = 2.113, 95% CI: 1.488-2.999), no drinking (OR = 1.427, 95% CI: 1.018-2.000), overall life satisfaction (OR = 0.707, 95% CI: 0.683-0.731). CONCLUSIONS: Our study indicates insufficient awareness of breast cancer among women in Eastern China, and an urgent need for health education programs on this subject.

Phenolation to Improve Hardwood Kraft Lignin for Wood Adhesive Application.

Lignins, naturally occurring aromatic polymers with phenylpropane units, are promising bio-based alternatives for petroleum-based products. Resole-type phenol formaldehyde (PF) adhesive is commonly used in wood composites requiring durability and weather-proofness. However, PF adhesive is a petroleum-based product. The objective of this study is to transform the low-reactivity hardwood kraft lignin (KL) as the phenol substitute in the PF adhesive formulation by acidic phenolation. The variations in the molecular weights, chemical structures, and functional groups in lignins were investigated before and after the phenolation. The results indicate that the KL can be cleaved, and phenols are crosslinked onto KL to produce phenolated kraft lignin (PKL) under the suitable phenolation condition, heating 3/5 (w/w) of KL/phenol at 90 °C for 2 h with 5% H2SO4 as the catalyst. Resole-type PKL-PF adhesives can be directly synthesized after the phenolation in the same reactor. Plywood laminated with this adhesive obtains satisfactory strength and low formaldehyde emission. This not only reduces the usage of petroleum-based phenol but also increases the reactivity and applications for hardwood KL.

Obesity, diabetes mellitus, and the risk of female breast cancer in Eastern China.

BACKGROUND: This study was designed to explore the relationship between obesity, diabetes mellitus (DM), and female breast cancer in Eastern China. METHODS: A 1:3 matched case-control study was carried out, comprising 123 women with breast cancer and 369 controls. All of the 492 subjects were selected from a previous epidemiological survey of 122,058 women in Eastern China. RESULTS: There were significant differences between the case and control groups in waist circumference and body mass index (BMI), but not in waist to hip ratio or hip circumference. There was a significant difference between the two groups in BMI for post-menopausal women, and a significant difference in waist circumference for pre-menopausal women. After adjustment for other factors, BMI was still significantly associated with breast cancer (odds ratio (OR) = 1.58, 95% confidence interval (CI) 1.14 to 2.19). DM was significantly associated with breast cancer (OR = 3.35, 95% CI 1.02 to 11.01) in the univariate analysis but not in the multivariate analysis (P = 0.059). CONCLUSIONS: Obesity might be a risk factor for female breast cancer. We found different strengths of association for women with different menopausal status when we examined the relationship between obesity and breast cancer. The association between DM and female breast cancer should be further confirmed with larger sample sizes.

The changes in female physical and childbearing characteristics in China and potential association with risk of breast cancer.

BACKGROUND: There has been a sharp increase in the incidence of breast cancer in China in recent years. A number of female physical characteristics, such as age at menarche, menopause, first birth and the duration of breastfeeding, have been linked to breast cancer, yet data on these factors in Chinese women is largely missing both for aggregate and age-specific data. Thus, the objective of this study was to explore changes in female menstrual and childbearing characteristics as a possible explanation for increasing rates of breast cancer in this country. METHOD: From July to September 2008, a population based cross-sectional breast cancer survey covering 124,758 females from 4 provinces or cities in Eastern China was carried out, using multi-stage and cluster methods. In-person interviews based on a self-designed structured questionnaire were performed, in which female physiological and reproductive factors, such as age at menarche and menopause, menstrual cycle history, childbearing history, breastfeeding methods, abortions or miscarriage, were included. For every 10-year age category, the subjects were divided, and across those age groups, all the above factors were compared respectively and changes in physical and childbearing characteristics were evaluated. ANOVA was used to compare the differences across the groups. RESULTS: A total of 122058 subjects were included in the final analysis. The mean age at menarche was 15.39 years, the mean number of full-term pregnancies was 1.58, the mean duration of breastfeeding was 22.68 months, the mean age at first birth was 23.75 years, the mean frequency of miscarriage was 0.36, and the mean age at menopause was 48.63 years. Significant differences across the several age groups were noted for the age at menarche, number of full-term pregnancies, accumulated duration of breastfeeding, age at first birth, number of miscarriages, and age at menopause. These data clearly showed a gradual shift towards an earlier age at menarche, fewer pregnancies and shorter breastfeeding lengths. CONCLUSIONS: Significant changes in female physical and childbearing characteristics across a number of different age ranges were detected. These changes may be related to the increasing trend of breast cancer in China.

The preventive and therapeutic effect of repetitive transcranial magnetic stimulation on radiation-induced brain injury in mice.

PURPOSE: To clarify the preventive and therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) on brain injury induced by X-ray cranial irradiation, preliminarily identify the mechanism and provide a novel clinical approach for the prevention and treatment of radiation-induced brain injury (RBI). MATERIALS AND METHODS: Male C57BL/6 mice were randomly divided into the sham group, large fractionated dose (5 Gy × 4 d) group, large fractionated dose + rTMS (5 Gy × 4 d + rTMS) group, conventional fractionated dose (2 Gy × 10 d) group and conventional fractionated dose + rTMS (2 Gy × 10 d + rTMS) group. After cranial irradiation and rTMS, behavioral experiments, morphological staining and molecular biology experiments were performed. We further determined the mechanism of rTMS on the prevention and treatment of RBI, including changes in hippocampal neuronal apoptosis, neural stem cell (NSC) proliferation and differentiation, and neuronal synaptic plasticity. RESULTS: rTMS alleviated the negative effects of cranial radiation on the general health of mice and promoted their recovery. rTMS ameliorated the impairment of spatial learning and memory induced by cranial radiation, and this beneficial effect was more robust in the conventional fractionated dose group than the large fractionated dose group. Moreover, rTMS alleviated the alterations in hippocampal structure and neuronal death and had preventive and therapeutic effects against RBI. In addition, rTMS reduced hippocampal cell apoptosis, promoted NSC proliferation and differentiation in the hippocampus after cranial irradiation, and enhanced neuronal synaptic plasticity in the hippocampus. Subsequent studies showed that rTMS upregulated the expression of learning- and memory-related proteins. CONCLUSION: rTMS could alleviate learning and memory impairment caused by RBI, and the preventive and therapeutic effects of rTMS were better for the conventional fraction radiation paradigms.

Potential and functional prediction of six circular RNAs as diagnostic markers for colorectal cancer.

Background: Circular RNAs (circRNAs) have been discovered in colorectal cancer (CRC), but there are few reports on the expression distribution and functional mining analysis of circRNAs. Methods: Differentially expressed circRNAs in CRC tissues and adjacent normal tissues were screened and identified by microarray and qRT-PCR. ROC curves of the six circRNAs were analyzed. A series of bioinformatics analyses on differentially expressed circRNAs were performed. Results: A total of 207 up-regulated and 357 down-regulated circRNAs in CRC were screened, and three top up-regulated and down-regulated circRNAs were chosen to be verified in 33 pairs of CRCs by qRT-PCR. 6 circRNAs showed high diagnostic values (AUC = 0.6860, AUC = 0.8127, AUC = 0.7502, AUC = 0.9945, AUC = 0.9642, AUC = 0.9486 for hsa_circRNA_100833, hsa_circRNA_103828, hsa_circRNA_103831 and hsa_circRNA_103752, hsa_circRNA_071106, hsa_circRNA_102293). A circRNA-miRNA-mRNA regulatory network (cirReNET) including six candidate circRNAs, 19 miRNAs and 210 mRNA was constructed, and the functions of the cirReNET were predicted and displayed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses on these mRNAs and protein-protein interaction (PPI) network of the hub genes acquired by string and CytoHubba. Conclusion: A cirReNET containing potential diagnostic and predictive indicators of CRCs and several critical circRNA-miRNA-mRNA regulatory axes (cirReAXEs) in CRC were mined, and may provide a novel route to study the mechanism and clinical targets of CRC.

Comprehensive silk gland multi-omics comparison illuminates two alternative mechanisms in silkworm heterosis.

Heterosis is a common phenomenon in plants and animals with diverse underlying mechanisms. Here, we applied two widely used silkworm hybrid systems and performed multi-omics analysis to identify possible intrinsic associations between different hybrid strategies and epigenetic mechanisms with silkworm heterosis. We found significant differences in the silk gland transcriptomic landscape between the two systems, including differentially expressed genes and expression patterns in the hybrid offspring compared to their parents. In the quaternary hybrid system, hybrid vigor was primarily due to up-regulated genes and the parent-dominant up-regulated expression pattern, involving multiple transport processes, cellular nitrogen compound catabolism, glucose metabolism, and tricarboxylic acid cycle. In the binary system, hybrid vigor was mainly due to the down-regulated genes and transgressively down-regulated expression pattern, mainly involving basic nitrogen synthesis metabolism and body function. We also demonstrated that DNA methylation may affect hybrid vigor by regulating the expression of several heterosis-related genes. Thus, this study revealed two alternative mechanisms that may contribute to silkworm heterosis, both of which facilitate the efficient utilization of energy and nitrogen for silk production.