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.

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.

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.

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.

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.

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.

Worldwide review with meta-analysis of women's awareness about breast cancer.

OBJECTIVE: To summarize the awareness levels of breast cancer (BC) worldwide and investigate factors associated with BC awareness to determine differences in awareness between China and other countries. METHODS: This systematic review followed the PRISMA guidelines and included 92 articles up to July, 2021. We calculated percentages for BC awareness levels and conducted subgroup analysis and cumulative meta-analysis. RESULTS: A total 84% (95% confidence interval [95%CI]: 78-90%) of women knew about BC; however, only 51% (95%CI: 37-66%) and 40% (95%CI: 24-56%) of women were aware of BC symptoms and BC risk factors, respectively. The most commonly known BC symptom was breast lump (71%, 95%CI: 62-80%), and BC family history was the most well-known BC risk factor (61%, 95%CI: 54-69%). Subgroup analysis showed lower awareness levels among Chinese and Asian women than women from other countries. Cumulative meta-analysis showed no obvious progress in BC awareness levels over time. We investigated 15 awareness-related factors, the most frequent of which were education level (61.8%), occupation (29.4%), and age (26.5%). CONCLUSION: BC awareness levels remain low. Improving BC awareness is critical, especially in developing countries. PRACTICE IMPLICATIONS: Effective education programs are urgently needed to improve women's BC awareness.

The Abscopal Effects of Cranial Irradiation Induce Testicular Damage in Mice.

To investigate whether the abscopal effects of cranial irradiation (C-irradiation) cause testicular damage in mice, male C57BL/6 mice (9weeks of age) were randomly divided into a sham irradiation group, a shielded group and a C-irradiation group and administered sham/shielded irradiation or C-irradiation at a dose rate of 2.33Gy/min (5Gy/d for 4 d consecutively). All mice were sacrificed at 4weeks after C-irradiation. We calculated the testis index, observed testicular histology by haematoxylin-eosin (HE) staining and observed testicular ultrastructure by transmission electron microscopy. Western blotting was used to determine the protein levels of Bax, Bcl-2, Cleaved caspase 3, glial cell line-derived neurotrophic factor (GDNF) and stem cell factor (SCF) in the testes of mice. Immunofluorescence staining was performed to detect the expression of Cleaved caspase 3 and 3ß hydroxysteroid dehydrogenase (3ßHSD), and a TUNEL assay was used to confirm the location of apoptotic cells. The levels of testosterone (T), GDNF and SCF were measured by ELISA. We also evaluated the sperm quality in the cauda epididymides by measuring the sperm count, abnormality, survival rate and apoptosis rate. The results showed that there was no significant difference in testicular histology, ultrastructure or sperm quality between the shielded group and sham group. Compared with the sham/shielded group, the C-irradiation group exhibited a lower testis index and severely damaged testicular histology and ultrastructure at 4weeks after C-irradiation. The levels of apoptosis in the testes increased markedly in the C-irradiation group, especially in spermatogonial stem cells. The levels of serum T and testicular 3ßHSD did not obviously differ between the sham group and the C-irradiation group, but the levels of GDNF and SCF in the testes increased in the C-irradiation group, compared with the sham group. In addition, the sperm count and survival rate decreased in the C-irradiation group, while the abnormality and apoptosis rate increased. Under these experimental conditions, the abscopal effects of C-irradiation induced testicular damage with regard to both structure and function and ultimately decreased sperm quality in mice. These findings provide novel insights into prevention and treatment targets for male reproductive damage induced by C-irradiation.

3×Tg-AD Mice Overexpressing Phospholipid Transfer Protein Improves Cognition Through Decreasing Amyloid-ß Production and Tau Hyperphosphorylation.

BACKGROUND: Phospholipid transfer protein (PLTP) belongs to the lipid transfer glycoprotein family. Studies have shown that it is closely related to Alzheimer's disease (AD); however, the exact effect and mechanism remain unknown. OBJECTIVE: To observe the effect of PLTP overexpression on behavioral dysfunction and the related mechanisms in APP/PS1/Tau triple transgenic (3×Tg-AD) mice. METHODS: AAV-PLTP-EGFP was injected into the lateral ventricle to induce PLTP overexpression. The memory of 3×Tg-AD mice and wild type (WT) mice aged 10 months were assessed using Morris water maze (MWM) and shuttle-box passive avoidance test (PAT). Western blotting and ELISA assays were used to quantify the protein contents. Hematoxylin and eosin, Nissl, and immunochemistry staining were utilized in observing the pathological changes in the brain. RESULTS: 3×Tg-AD mice displayed cognitive impairment in WMW and PAT, which was ameliorated by PLTP overexpression. The histopathological hallmarks of AD, senile plaques and neurofibrillary tangles, were observed in 3×Tg-AD mice and were improved by PLTP overexpression. Besides, the increase of amyloid-ß42 (Aß42) and Aß40 were found in the cerebral cortex and hippocampus of 3×Tg-AD mice and reversed by PLTP overexpression through inhibiting APP and PS1. PLTP overexpression also reversed tau phosphorylation at the Ser404, Thr231 and Ser199 of the hippocampus in 3×Tg-AD mice. Furthermore, PLTP overexpression induced the glycogen synthase kinase 3ß (GSK3ß) inactivation via upregulating GSK3ß (pSer9). CONCLUSION: These results suggest that PLTP overexpression has neuroprotective effects. These effects are possibly achieved through the inhibition of the Aß production and tau phosphorylation, which is related to GSK3ß inactivation.

XRCC5/6 polymorphisms and their interactions with smoking, alcohol consumption, and sleep satisfaction in breast cancer risk: A Chinese multi-center study.

BACKGROUND: X-ray repair cross-complementary 5 (XRCC5) and 6 (XRCC6) are critical for DNA repair. Few studies have assessed their association with breast cancer risk, and related gene-environment interactions remain poorly understood. This study aimed to determine the influence of XRCC5/6 polymorphisms on breast cancer risk, and their interactions with cigarette smoking, alcohol consumption, and sleep satisfaction. METHODS: The study included 1039 patients with breast cancer and 1040 controls. Four single-nucleotide polymorphisms of XRCC5 and two of XRCC6 were genotyped. Information about smoking, alcohol consumption, and sleep satisfaction was collected through questionnaires. Odds ratios (OR) and related 95% confidence intervals (95% CI) were assessed using unconditional logistic regression models. Gene-environment interactions were analyzed using logistic regression with multiplicative interaction models. RESULTS: XRCC5 rs16855458 was associated with increased breast cancer risk in the co-dominant (ptrend  = 0.003) and dominant (CA + AA vs. CC, OR = 1.29, 95% CI = 1.07-1.56, p = 0.008) genetic models after Bonferroni correction. The CG + GG genotype of XRCC6 rs2267437 was associated with an increased risk of estrogen receptor-negative/progesterone receptor-negative (ER-/PR-) breast cancer (CG + GG vs. CC: OR = 1.54, 95% CI = 1.12-2.13, p = 0.008) after Bonferroni correction. Moreover, an antagonistic interaction between XRCC5 rs16855458 and alcohol consumption (pinteraction  = 0.017), and a synergistic interaction between XRCC6 rs2267437 and sleep satisfaction were associated with breast cancer risk (pinteraction  = 0.0497). However, these interactions became insignificant after Bonferroni correction. CONCLUSION: XRCC5 rs16855458 was associated with breast cancer risk, and XRCC6 rs2267437 was associated with the risk of ER-/PR- breast cancer. Breast cancer risk associated with XRCC5 and XRCC6 polymorphisms might vary according to alcohol consumption and sleep satisfaction, respectively, and merit further investigation.

The detection rate of methylene blue combined with another tracer in sentinel lymph node biopsy of early-stage breast cancer: a systematic review and network meta-analysis.

BACKGROUND: Methylene blue (MB) alone or combined with 99mtechnetium-labeled sulphur colloid (Tc99m) or indocyanine green (ICG) is widely used for sentinel lymph node biopsy (SLNB) of early-stage breast cancer in developing countries and regions. However, studies investigating the effectiveness of MB combined with another tracer have produced heterogeneous results. The purpose of this network meta-analysis (NMA) was to evaluate the detection rate of MB alone, MB + Tc99m, and MB + ICG, and to examine the differences between the 3 methods. METHODS: We conducted a comprehensive electronic literature search on the PubMed, Embase, Web of Science, CNKI, and Wanfang Data databases from inception to October 2021. The meta-analysis included 7,498 patients in 49 studies. The risk of bias for each study was independently assessed as low, moderate, or high using criteria adapted from the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Fixed- and random-effects models were used to calculate pooled estimates. Mixed-comparison analysis using random-effects models. We assessed statistical heterogeneity by I2 statistics and evaluated publication bias using Begg's test. RESULTS: The identification rate (IR), false-negative rate (FNR), sensitivity (SEN), and accuracy rate (AR) using MB + Tc99m were 96%, 7%, 93%, and 96%, respectively; the IR, FNR, SEN, and AR using MB + ICG were 97%, 7%, 93%, and 97%, respectively. The NMA found that IR and AR between MB + ICG and MB + Tc99m was OR =1.37 (95% CI: 0.41-4.20) and OR =1.33 (95% CI: 0.56-3.32), respectively. DISCUSSION: Our results are similar to those of most previous studies, and meta-analysis showed that the MB + Tc99m or MB + ICG mapping methods can be used to obtain higher IR and lower FNR than MB alone. Our NMA showed no statistical significance between MB + Tc99m and MB + ICG with IR and AR. Both MB + Tc99m and MB + ICG can be used as effective mapping methods in SLNB of early-stage breast cancer to improve the detection rate.

Relationship Between Lifestyle Habits and Health-Related Quality of Life of Recently Diagnosed Breast Cancer Patients: A Comparison Between Younger and Older Women in China.

Objective: The aim of this study was to evaluate the relationship between lifestyle habits and health-related quality of life (HRQoL) among different ages who were initially diagnosed with breast cancer (within the first 2 weeks) and to determine the contribution of lifestyle habits factors on HRQoL. Methods: Patients with breast cancer were recruited from 22 hospitals in 11 provinces or municipalities in northern and eastern China. The Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) was used to measure HRQoL. Chi-square test, ANOVA, and multivariable generalized linear models were conducted to identify the differences in HRQoL between two age groups (age <50 years and ≥50 years) and to evaluate the contribution of lifestyle habits factors on HRQoL of patients with breast cancer. Results: About 1,199 eligible patients with breast cancer were used for analysis. Younger women (aged <50 years) appeared to show lower scores than older women (aged ≥50 years) in HRQoL subscales, including emotional well-being (p = 0.003), functional well-being (p = 0.006), breast cancer subscale (p = 0.038), and FACT-B Total scores (p = 0.028). Tea and alcohol consumption and being very satisfied with sleep and current life were the strongest predictors of higher HRQoL in younger group. Meanwhile, no coffee consumption, frequent participation in physical activities, high sleep satisfaction, and current life satisfaction were the key predictors of higher HRQoL in older women with breast cancer. Conclusion: The relationship of the nine lifestyle habit items with HRQoL differed among younger and older women. The associated variable of low HRQoL can help clinicians take intervention early in order to improve the prognosis of patients with breast cancer.

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.

Molecular fingerprint of precancerous lesions in breast atypical hyperplasia.

OBJECTIVE: To identify atypical hyperplasia (AH) of the breast by shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS), and to explore the molecular fingerprinting characteristics of breast AH. METHODS: Breast hyperplasia was studied in 11 hospitals across China from January 2015 to December 2016. All patients completed questionnaires on women's health. The differences between patients with and without breast AH were compared. AH breast lesions were detected by Raman spectroscopy followed by the SHINERS technique. RESULTS: There were no significant differences in clinical features and risk-related factors between patients with breast AH (n = 37) and the control group (n = 2576). Fifteen cases of breast AH lesions were detected by Raman spectroscopy. The main different Raman peaks in patients with AH appeared at 880, 1001, 1086, 1156, 1260, and 1610 cm-1, attributed to the different vibrational modes of nucleic acids, ß-carotene, and proteins. Shell-isolated nanoparticles had different enhancement effects on the nucleic acid, protein, and lipid components in AH. CONCLUSION: Raman spectroscopy can detect characteristic molecular changes in breast AH lesions, and may thus be useful for the non-invasive early diagnosis and for investigating the mechanism of tumorigenesis in patients with breast AH.

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.

[Parameters and connotations of quantity of mild moxibustion stimulation].

The quantity of mild moxibustion stimulation is an important factor affecting clinical therapeutic effect. In the present study, we collected related literature by using key word "moxibustion stimulation quantity" from CNKI Database and make a summary about its concept. The quantity of mild moxibustion stimulation has two common characters, namely thermal intensity and cumulative stimulating quantity, and contains 6 components (parameters), including thermal energy, thermal stimulus, heated area of the skin, and stimulating duration, intensity and frequency. According to the facts mentioned above, we hold that the mild moxibustion quantity actually has 3 dimensions, i．e., the duration of stimulation, the stimulating quantity of one treatment session, and the total stimulating quantity of multiple treatment sessions. Accurately grasping and rationally using the basic term of the quantity of mild moxibustion is not only conductive to control clinical moxibustion operation, but also conforms to the basic requirements for quantitative control of intervention measures in experimental researches.

[Could Huatuo Jiaji (EX-B 2) Acupoint Be Assigned to the Governor Vessel ?]

The meridian tropism of acupoints is an important academic way to recognize and deal with the relationship between acupoints and meridians in acupuncture medicine. The Huatuo Jiaji (EX-B 2) (Jiaji for short) acupoint family consisting of 34 points has long been considered to be an important extra-acupoint since the ancient times of China and is widely employed in clinical practice through continuous development in Chinese past generations. The present paper introduces 1) historical origin and development of EX-B 2, and 2) intercorrelation among the EX-B 2, spine and the Governor Vessel in anatomical positions. On the basis of these, we also discuss the possibility of that EX-B 2 is assigned to the Governor Vessel, its academic significance including common features and actions in physiological and pathological aspects and clinical significance in diagnosis and treatment of disorders.