Interferon regulated factor 5 (IRF5) is a key regulator of inflammatory responses in human and mammals; however, its role in teleost remains largely unknown. In this study, IRF5 homologue of black carp (Mylopharyngodon piceus) has been cloned and characterized, which possesses conservation in structure and sequence to its mammalian counterparts. Black carp IRF5 (bcIRF5) was characterized as a predominantly cytosolic protein by immunofluorescent staining and showed little IFN promoter-inducing ability in reporter assay. The direct association between bcIRF5 and black carp TBK1 (bcTBK1) were identified through co-immunoprecipitation assay, and co-expressed bcIRF5 in EPC cells suppressed bcTBK1-mediated IFN promoter transcription in reporter assay. Surprisingly, the titer of grass carp reovirus (GCRV) in the media of EPC cells co-expressing bcIRF5 and bcTBK1 was obviously lower than that of EPC cells expressing bcTBK1 alone. It was interesting that expression of bcIRF5 and/or bcTBK1 in EPC cells showed little effect on cell growth; however, the survival ratio of EPC cells co-expressing bcTBK1 and bcIRF5 post GCRV infection was much lower than that of EPC cells expressing bcIRF5 or bcTBK1 alone. These results indicate that bcIRF5 negatively regulates bcTBK1-mediated IFN signaling in healthy cells; however, it correlates with bcTBK1 and triggers cell death to inhibit the virus replication during the innate immune activation.

Sexually immature male mice exhibit parenting behavior toward unfamiliar pups; however, the percentage of males that engage in infanticidal behavior gradually increases with age. We previously reported that excitatory synaptic transmission of the rhomboid nucleus of the bed nucleus of the stria terminalis (BSTrh), a brain region implicated in infanticidal behavior, is reinforced during pubertal development. However, it remains unclear how gonadal steroid hormones mediate this behavioral transition and neural plastic change during pubertal development. Here we revealed that administration of either 17β-estradiol (E2) or 5α-dihydrotestosterone (DHT) to gonadectomized mice during pubertal development induced infanticidal behavior in adulthood (about 7 weeks old). Next, we performed whole-cell patch clamp recording in the BSTrh to study the effect of gonadal steroid hormones on neural synaptic transmission. We found that E2 but not DHT administration during pubertal development considerably enhanced excitatory synaptic transmission in the BSTrh by increasing the probability of excitatory neurotransmitter release from the presynaptic terminalis. These data suggest that reinforcement of excitatory synaptic transmission by estrogen-receptor-dependent signaling in the BSTrh during puberty may contribute to the development of infanticidal behavior.

Ameliorating cardiac microvascular injury is the most effective means to mitigate diabetes-induced cardiovascular complications. Inositol-requiring 1α (IRE1α), a sensor of endoplasmic reticulum stress, is activated by Toll like receptors (TLRs), and then promotes cardiac microvascular injury. Peli1 is a master regulator of TLRs and activates IRE1α. This study aims to investigate whether Peli1 in endothelial cells promotes diabetes-induced cardiac microvascular injury through activating IRE1α. Here we found that Peli1 was markedly up-regulated in cardiac endothelial cells of both diabetic mice and in AGEs-treated cardiac microvascular endothelial cells (CMECs). Peli1 deficiency in endothelial cells significantly alleviated diabetes-induced cardiac microvascular permeability, promoted microvascular regeneration, and suppressed apoptosis, accompanied by the attenuation of adverse cardiac remodeling. Furthermore, Peli1 deletion in CMECs ameliorated AGEs-induced damages in vitro. We identified heat shock protein 90 (Hsp90) as a potential binding partner for Peli1, and the Ring domain of Peli1 directly bound with Hsp90 to enhance IRE1α phosphorylation. Our study suggests that blocking Peli1 in endothelial cells may protect against diabetes-induced cardiac microvascular injury by restraining ER stress.

Disturbed mitochondrial function and energy crisis serve as key mechanisms for the development of liver injury. Hence, targeting cellular mitochondria in liver diseases might serve as a therapeutic option. Tapinanthus globifer (A.Rich.) Tiegh. has been used in traditional medicine in the management of liver disease. However, there is no scientific evidence supporting such use.

Humans and animals frequently experience dysmetabolism induced by inflammation. Zinc-α2-glycoprotein (ZAG), a newly identified adipokine, is potentially involved in lipid metabolism. Our previous study revealed that the ZAG content increased after lipopolysaccharide (LPS) treatment. To clarify ZAG's possible effects on inflammatory responses and lipid metabolism, we used gene overexpression and knockout mice as models to investigate the function of ZAG during inflammation. The results showed that LPS increased plasma triglyceride, non-esterified fatty acid and hepatic triglyceride, while ZAG overexpression decreased these effects. Furthermore, ZAG overexpression weakened inflammatory responses, suppressed lipogenesis, and improved mitochondrial function during inflammation. ZAG overexpression also increased β3-adrenoreceptor, protein kinase A, and phosphorylated cyclic adenosine monophosphate-response element binding protein (CREB), promoted the combination of CREB and CREB-binding protein (CBP), and competitively inhibited the combination of nuclear factor-κB and CBP. After ZAG knockout, LPS-induced the hyperlipidemia worsened. ZAG knockout aggravated inflammatory responses, promoted lipogenesis, and weakened mitochondrial function during inflammation. ZAG knockout also decreased β3-adrenoreceptor and protein kinase A. The present study demonstrated that ZAG alleviated lipid metabolism disorders by weakening inflammatory responses. The β3-adrenoreceptor/protein kinase A/CREB pathway mediated the effects of ZAG on inflammation. These results will provide new insight for research on anti-inflammation.

Alpha 7 nicotinic acetylcholine receptor (α7nAChR) stimulation can regulate acute inflammation, and lack of α7nAChR accelerates atherosclerosis in mice. In this study, we aimed to investigate the effects of the novel α7nAChR agonist, AZ6983, on atherosclerosis and assess its possible immunomodulating effects.

Breast cancer is characterized by high aggression, poor prognosis, and high recurrence rate. Early detection and specific targeted treatment with less toxicity are the ultimate goals for breast cancer therapy. To improve antitumor therapeutic effects, we developed a novel polypyrrole nanoparticle using the near infrared dye IRDye800CW with camptothecin (CPT)-conjugated hyaluronic acid (HA) shell (PPy@CPT-HA-IRDye800CW) and performed a photothermal therapy (PTT), along with chemotherapy, guided by fluorescence and photoacoustic dual-modality imaging, in combination with immunotherapy. Irradiation with near infrared (NIR) light offered a strong PTT effect and promoted CPT drug release in tumors. Moreover, we found that chemo-photothermal therapy with PPy@CPT-HA-IRDye800CW NPs, in combination with immune checkpoint inhibitor anti-PD-L1 immunotherapy, synergistically enhanced the anti-tumor immune response, thereby eliminating primary breast cancer and preventing tumor metastases and recurrences in 4T1 tumor-bearing mice. This approach may provide important clues for the clinical management of breast cancer and other malignant tumors.

To investigate the effect that a diet supplemented with KetoCal 4:1, a commercially available dietary formula consisting of a 4:1 ratio of fats to carbohydrates plus proteins, had on the seizure-like activity (SLA) and paralysis normally exhibited by the Drosophila Bang-sensitive (BS) paralytic mutants following mechanical shock.

Orthobunyaviruses of the Simbu serogroup are transmitted by insects (primarily biting midges) and infect mammals and/or birds. Many have been associated with disease in livestock or humans. The orthobunyavirus genome comprises three negative-sense RNA segments (L, M and S). We report the complete coding sequences of 57 isolates of Simbu serogroup viruses collected in Australia during 1968-1984. Phylogenetic analysis identified novel genogroups of Akabane virus (AKAV), Aino virus (AINOV) and Peaton virus, and provided evidence of constrained movement of AKAV between epidemiological systems in the northern and eastern regions of the continent. Differential clustering of AKAV isolates in trees inferred from L, M and S segments was indicative of intratypic segment reassortment. Similarly, intertypic segment reassortment was detected between AKAV and Tinaroo virus, and between AINOV and Douglas virus. L segments representing novel genogroups were detected in AINOV reassortants, suggesting the presence of unidentified Simbu group viruses in the episystem.

Acute kidney injury (AKI) is a serious and fatal complication of acute myocardial infarction (AMI). It has high short- and long-term mortality rates and a poor prognosis but is potentially preventable. However, the current incidence, risk factors, and outcomes of AKI in the Chinese population are not well understood and would serve the first step to identify high-risk patients who could receive preventative care.

Endoscopic approaches to the craniovertebral junction (CVJ) have been established as viable and effective surgical treatments in the past decade. One of the major complications is leakage of the cerebrospinal fluid (CSF). This study aimed to investigate the efficacy and feasibility of suture closure at the nasopharyngeal mucosa upon durotomy.

Vitamin D hydroxylation-deficient rickets type 1A (VDDR1A, OMIM 264700) is a rare autosomal recessive inherited disorder. Pathogenic variants in the CYP27B1 gene lead to loss of 1α-hydroxylase activity. We report the case of a 22-month-old toddler who presented with growth retardation and delayed development. The patient exhibited the typical laboratory findings of VDDR1A, including hypocalcemia (calcium: 5.2 mg/dL), elevated serum level of alkaline phosphatase (2,600 U/L), elevated serum level of intact-parathyroid hormone (238 pg/mL), low 1,25(OH)2D3 level (11.2 pg/mL), and normal 25(OH)D3 level (40.7 ng/mL). His height and weight were 76.5 cm and 9.5 kg, respectively (both <3rd percentile). The Bayley Scales of Infant and Toddler Development II indicated significantly delayed development (mental development index <50, psychomotor development index <50). The patient was a compound heterozygous for two novel pathogenic variants in the CYP27B1 gene: c.57_69del (p.Glu20Profs*2) and c.171dupG (p.Leu58Alafs*275), inherited from his mother and father, respectively. The patient showed remarkable improvement after treatment with calcitriol and calcium carbonate.

Human epidermal growth factor receptor 2-positive (HER2+) breast cancer accounts for ∼20% of invasive breast cancers and is associated with poor prognostics. The recent outcome of HER2+ breast cancer treatment has been vastly improved owing to the application of antibody-targeted therapies. Trastuzumab (Herceptin) is a monoclonal antibody designed to target HER2+ breast cancer cells. In addition to improved survival in the adjuvant treatment of HER2+ breast cancer, trastuzumab treatment has also been associated with cardiotoxicity side effect. However, the molecular mechanisms of trastuzumab action and trastuzumab-mediated cardiotoxicity are still not fully understood. Previous research utilized bulk transcriptomics analysis to study the underlining mechanisms, which relied on averaging molecular signals from bulk tumor samples and might have overlooked key expression features within breast cancer tumor. In contrast to previous research, we compared the single cancer cell level transcriptome profile between trastuzumab-treated and nontreated patients to reveal a more in-depth transcriptome profile. A total of 461 significantly differential expressed genes were identified, including previously defined and novel gene expression signatures. In addition, we found that trastuzumab-enhanced MGP gene expression could be used as prognostics marker for longer patient survival in breast invasive carcinoma patients, and validated our finding using TCGA (The Cancer Genome Atlas) breast cancer dataset. Moreover, our study revealed a 48-gene expression signature that is associated with cell death of cardiomyocytes, which could be used as early biomarkers for trastuzumab-mediated cardiotoxicity. This work is the first study to look at single cell level transcriptome profile of trastuzumab-treated patients, providing a new understanding of the molecular mechanism(s) of trastuzumab action and trastuzumab-induced cardiotoxicity side effects.

New-onset atrial fibrillation (NOAF) remains common arrhythmia in acute myocardial infarction (AMI), and is closely associated with increased subsequent cardiovascular mortality. Our meta-analysis aims to summarize more clinical risk factors for NOAF.Comprehensive systematic search of MEDLINE, EMBASE, and the Cochrane Library were carried out to find relevant studies inception to December 2017. Pooled mean difference (MD) and 95% confidence interval (CI) were calculated to evaluate the value of clinical risk factors in the prediction of NOAF after AMI.Eleven studies containing 9570 patients were included in the meta-analysis. Overall, older age and increased heart rate (HR) levels had a significant positive association with NOAF in patients with AMI. The MD in age between the patients with, and those without NOAF, was 8.22 units (95% confidence interval [CI]: 7.44-9.01), test for overall effect z score = 20.51 (P < .00001, I = 0%). Moreover, the MD in a subgroup analysis for HR levels between the patients with, and those without NOAF was 4.34 units (95% Cl: 2.56-6.11), test for overall effect z score = 4.78 (P < .00001, I = 31%).In patient with AMI, our meta-analysis demonstrated that older age and increased HR levels on admission are related to greater risk of NOAF.

MiR-101 plays an important role in tumorigenesis. The aim of this study was to estimate diagnostic potential of serum miR-101 in bladder cancer.Serum level of miR-101 in 122 bladder cancer patients and 110 healthy volunteers was detected using quantitative real-time polymerase chain reaction method. The association between miR-101 expression and clinicopathological characteristic was analyzed via χ test. Then receiver operating characteristic (ROC) curve was plotted to evaluate diagnostic value of serum miR-101 in bladder cancer.MiR-101 expression was statistically down-regulated in bladder cancer patients compared to healthy controls. MiR-101 expression was significantly associated with TNM stage (P = .019), pathological grade (P = .006) and lymph node metastasis (P = .010). ROC analysis suggested that miR-101 had high value in discriminating between bladder cancer patients and healthy individuals with an AUC value of 0.884. The cut-off value for serum miR-101 in bladder cancer diagnosis was 1.645, with a sensitivity of 82.0% and a specificity of 80.9%.MiR-101 is decreased in bladder cancer patients, and shows negative association with aggressive clinical characteristics. MiR-101 may serve as a bio-marker in diagnosing bladder cancer.

Osteoporosis is a common problem, especially among postmenopausal women. Postmenopausal women with osteoporosis have major risk factors for osteoporotic fractures. The abuse of epidural steroid injections (ESIs) or the misunderstanding of their proper use could cause osteoporotic fractures. Therefore, we aimed to investigate whether ESIs are associated with osteoporotic fractures in postmenopausal women with low back pain and osteoporosis. Furthermore, we aimed to provide evidence on whether ESIs could be used in postmenopausal women with osteoporosis who are at high risk for osteoporotic fractures.We reviewed the medical records of postmenopausal women with osteoporosis but no fractures. A total of 172 postmenopausal women were divided into 2 groups. Group 1 comprised patients receiving medications and Group 2 comprised patients receiving ESIs. All participants received medications for treating osteoporosis. Each patient's age, bone mineral density, body mass index, medical history, and status with respect to smoking, drinking, physical activity, and exercise were obtained using a questionnaire and medical records.The mean total number of ESIs was 6.2, and the mean cumulative administered dose of glucocorticoids (dexamethasone) was 31 mg. The incidences of fractures in the medication and ESI groups were 22% and 24%, respectively, in the thoracolumbar spine, and 2% and 5%, respectively, in the hip joint.There was no significant difference in the incidences of osteoporotic fractures at the thoraco-lumbar spine and hip joint in postmenopausal women with osteoporosis between those who received ESIs (a mean of 6.2 ESIs, a cumulative dexamethasone dose of 31 mg) and those who did not, with both groups taking anti-osteoporotic medications for low back pain. Our data suggest that ESI treatment using a mean of 6.2 ESIs to deliver a maximum cumulative dexamethasone dose of 31 mg could be safely used in postmenopausal women with osteoporosis, without any significant impact on the their risk for osteoporotic fractures.

Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease with increasing morbidity and mortality that cause huge social and economic loss. Although recommended by guidelines, pulmonary rehabilitation has not been widely applied in clinics because of its inherent limitations. Free from restrictions of specific training venues and equipment, Tai Chi, as a kind of pulmonary rehabilitation, has been used to cure the COPD, yet the efficacy and safety of Tai Chi remains to be assessed. In this study, we aim to draw up a protocol for systematic review to evaluate the efficacy and safety of Tai Chi for COPD.

Non-syndromic cleft of the lip and/or palate (NSCL/P) is one of the most common polygenic diseases. In this study, both case-control and family-based association study were used to confirm whether the Single Nucleotide Polymorphisms (SNPs) were associated with NSCL/P.

Health education during pregnancy is important to improve maternal and children outcomes. However, the strategies must be specifically designed for each context and demographic characteristics. Our objective was identify health education strategies targeting pregnant women with the intention of improving results of pregnancy at an urban level.

It is not clear whether age has any influence on the outcomes for sperm used for assisted reproductive technology in cryptozoospermic men. We evaluated intracytoplasmic sperm injection (ICSI) outcomes using ejaculated or testicular sperm in men with cryptozoospermia from different paternal age ranges.We conducted a retrospective observational study of 35 men with cryptozoospermia who underwent ICSI from 2010 to 2018. They were classified into 2 groups based on male age, namely < 35 years and ≥ 35 years. Each group was further divided into 2 subgroups according to the origin of sperm (ejaculated or testicular).In the <35 years group, the normal fertilization and high-quality embryo rates for ejaculated sperm were significantly higher than with testicular sperm (74.7% vs. 62.4%, P = .02; 50.5% vs. 36.6%, P = .03, respectively). However, in the ≥35 years group, the high-quality embryo and clinical pregnancy rates were significantly lower in the ejaculated sperm subgroup than in the testicular sperm subgroup (26.2% vs. 63%, P = .002; 12.5% vs. 71.4%, P = .04, respectively).This study indicates that ICSI should be performed as soon as possible for men with cryptozoospermia. When the paternal age ≥35 years, testicular sperm should be used for ICSI, as this offers better high-quality embryo and clinical pregnancy rates.