Glires (rodents, lagomorphs and their fossil kin) is the most speciose and arguably most diversified clade of living placentals. Different lineages within the Glires evolved basically opposite chewing movements: a mostly transversal power stroke in lagomorphs, and a mostly proal power stroke in rodents, but the ancestral condition for Glires is still unclear. To address this knowledge gap, we studied the mandibles of Chinese Paleocene Glires representing the duplicidentate (lagomorph-like; Mimotona) and simplicidentate (rodent-like; Eomylus...

Sihailongwan Maar Lake, located in Northeast China, is a candidate Global boundary Stratotype Section and Point (GSSP) for demarcation of the Anthropocene. The lake’s varved sediments are formed by alternating allogenic atmospheric inputs and authigenic lake processes and store a record of environmental and human impacts at a continental-global scale. Varve counting and radiometric dating provided a precise annual-resolution sediment chronology for the site. Time series records of radioactive (239,240Pu, 129I and soot 14C), chemical...

Spontaneous intracerebral hemorrhage (ICH) is a devastating disease with high morbidity and mortality worldwide. We have previously shown that ferroptosis contributes to neuronal loss in ICH mice. The overload of iron and dysfunction of glutathione peroxidase 4 (GPx4) promote neuronal ferroptosis post-ICH. However, how epigenetic regulatory mechanisms affect the ferroptotic neurons in ICH remains unclear. In the current study, hemin was used to induce ferroptosis in N2A and SK-N-SH neuronal cells to mimic ICH. The...

Background: It remains controversial whether the application of chemotherapy has an impact on recurrent nasopharyngeal carcinoma (rNPC) patients with salvage radiotherapy. Here, we aimed to evaluate treatment outcomes of rNPC patients and derive a prognostic model to assess the benefit of chemotherapy in patients with re-radiotherapy. Methods: This study was conducted as a retrospective study. In total, 340 rNPC patients treated with salvage intensity-modulated radiotherapy (IMRT) or radiochemotherapy (RCT) from October 2006 to September 2019...

Abstract Background Compared to other healthcare workers, nurses are more vulnerable to the potentially devastating effects of pandemic-related stressors. Studies have not yet investigated the deeper characteristics of the relationship between team resilience and team performance among nurses during the COVID-19 pandemic. This study aimed to elucidate the characteristics of team resilience and performance networks among nurses during the pandemic. Methods A cross-sectional study involving 118 nursing teams comprising 1627 practice nurses from four tertiary-A...

Abstract Background Gestational weight gain (GWG) criteria recommended by the Institute of Medicine may not be appropriate for Asians. Our aims are to investigate the association between GWG and adverse pregnancy outcomes, and to propose optimal total GWG and rates of GWG for Chinese women. Methods Prospective data of 51,125 mother-child pairs from 27 hospitals and community health care centers from Guizhou, Yunnan and Sichuan provinces in China between 2014 and 2018 were analyzed. Generalized...

Abstract N6-methyladenosine (m6A) modification has been shown to regulate RNA metabolism. Here, we investigate m6A dynamics during maternal-to-zygotic transition (MZT) in mice through multi-omic analysis. Our results show that m6A can be maternally inherited or de novo gained after fertilization. Interestingly, m6A modification on maternal mRNAs not only correlates with mRNA degradation, but also maintains the stability of a small group of mRNAs thereby promoting their translation after fertilization. We identify Ythdc1 and Ythdf2 as...

Abstract Background Rheumatoid arthritis patients usually suffer from arthritic chronic pain. However, due to an incomplete understanding of the mechanisms underlying autoimmune disorders, the management of arthritic pain is unsatisfactory. Here, we investigated the analgesic effect and underlying mechanism of the natural flavonoid naringenin (NAR) in collagen-induced arthritis (CIA) pain. Methods NAR was injected (i.p.) once per day for 42 days after initial immunization, and rats were sacrificed on the 28th (the 21st day after...

Abstract We recently identified CD46 as a novel prostate cancer cell surface antigen that shows lineage independent expression in both adenocarcinoma and small cell neuroendocrine subtypes of metastatic castration resistant prostate cancer (mCRPC), discovered an internalizing human monoclonal antibody YS5 that binds to a tumor selective CD46 epitope, and developed a microtubule inhibitor-based antibody drug conjugate that is in a multi-center phase I trial for mCRPC (NCT03575819). Here we report the development of a novel...

Abstract Background Geranylgeranyl pyrophosphate synthase (GGPS) is a structural enzyme of the terpene biosynthesis pathway that is involved in regulating plant photosynthesis, growth and development, but this gene family has not been systematically studied in cotton. Results In the current research, genome-wide identification was performed, and a total of 75 GGPS family members were found in four cotton species, Gossypium hirsutum, Gossypium barbadense, Gossypium arboreum and Gossypium raimondii. The GGPS genes were divided into three...

Abstract Background Sepsis is a leading cause of preventable death around the world. Population-based estimation of sepsis incidence is lacking in China. In this study, we aimed to estimate the population-based incidence and geographic variation of hospitalized sepsis in China. Methods We retrospectively identified hospitalized sepsis from the nationwide National Data Center for Medical Service (NDCMS) and the National Mortality Surveillance System (NMSS) by ICD-10 codes for the period from 2017 to 2019. In-hospital sepsis...

Abstract Background Intrahepatic cholestasis of pregnancy (ICP) is strongly associated with an increased risk of adverse perinatal outcomes. Total bile acid (TBA) levels in the late second or third trimester are a major factor in the diagnosis. Here, we sought to establish the miRNA expression profile of plasm exosomes of ICP and identify possible biomarkers for the diagnosis of ICP. Methods This case–control study involved 14 ICP patients as the experimental group and 14 healthy...

Abstract Background Anaplastic lymphoma kinase (ALK)-positive histiocytosis, a novel rare histiocytic proliferation, was first described in 2008; it occurs in early infancy with liver and hematopoietic involvement. The spectrum was subsequently broadened to include localized diseases in older children and young adults. However, its full clinicopathological features and molecular lineage have not been fully elucidated. Results Here, we report four cases of multisystem ALK-positive histiocytosis without hematopoietic involvement. Clinically, three patients were adults aged between...

Abstract Background Dealing with the giant pheochromocytomas (maximum diameter ≥ 6 cm) has long been a tough challenge for urologists. We introduced a new retroperitoneoscopic adrenalectomy method modified with renal-rotation techniques to treat giant pheochromocytomas. Methods 28 diagnosed patients were prospectively recruited as the intervention group. Meanwhile, by referring to the historical records in our database, matched patients who had undergone routine retroperitoneoscopic adrenalectomy (RA), transperitoneal laparoscopic adrenalectomy (TA), or open adrenalectomy (OA) for giant...

Abstract Antigen self-assembly nanovaccines advance the minimalist design of therapeutic cancer vaccines, but the issue of inefficient cross-presentation has not yet been fully addressed. Herein, we report a unique approach by combining the concepts of “antigen multi-copy display” and “calcium carbonate (CaCO3) biomineralization” to increase cross-presentation. Based on this strategy, we successfully construct sub-100 nm biomineralized antigen nanosponges (BANSs) with high CaCO3 loading (38.13 wt%) and antigen density (61.87%). BANSs can be effectively uptaken by...

Abstract Antigen self-assembly nanovaccines advance the minimalist design of therapeutic cancer vaccines, but the issue of inefficient cross-presentation has not yet been fully addressed. Herein, we report a unique approach by combining the concepts of “antigen multi-copy display” and “calcium carbonate (CaCO3) biomineralization” to increase cross-presentation. Based on this strategy, we successfully construct sub-100 nm biomineralized antigen nanosponges (BANSs) with high CaCO3 loading (38.13 wt%) and antigen density (61.87%). BANSs can be effectively uptaken by...

Abstract Background The incidence and mortality of gastric cancer ranks fifth and fourth worldwide among all malignancies, respectively. Accumulating evidences have revealed the close relationship between mitochondrial dysfunction and the initiation and progression of stomach cancer. However, rare prognostic models for mitochondrial-related gene risk have been built up in stomach cancer. Methods In current study, the expression and prognostic value of mitochondrial-related genes in stomach adenocarcinoma (STAD) patients were systematically analyzed to establish a mitochondrial-related...

Abstract Background Cross breeding is an important way to improve livestock performance. As an important livestock and poultry resource in Henan Province of China, Bohuai goat was formed by crossing Boer goat and Huai goat. After more than 20 years of breeding, BoHuai goats showed many advantages, such as fast growth, good reproductive performance, and high meat yield. In order to better develop and protect Bohuai goats, we sequenced the whole genomes of 30 BoHuai...

Abstract Background Hepatitis B virus (HBV) reactivation impact negatively the prognosis of patients with HBV-related hepatocellular carcinoma (HCC). This study aimed to observe the effect of antiviral therapy (AVT) on viral reactivation and long-term outcomes after percutaneous radiofrequency ablation (PRFA) for HBV-related HCC. Methods Data on 538 patients between 2009 and 2013 were reviewed. Propensity score matching (PSM) analysis was used to adjust for differences in baseline features between patients who received AVT (AVT group)...

Abstract Background Fine particulate matter (PM2.5) is associated with increased incidence and severity of asthma. PM2.5 exposure disrupts airway epithelial cells, which elicits and sustains PM2.5-induced airway inflammation and remodeling. However, the mechanisms underlying development and exacerbation of PM2.5-induced asthma were still poorly understood. The aryl hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1) is a major circadian clock transcriptional activator that is also extensively expressed in peripheral tissues and plays a crucial role in organ...

Abstract Background Ginsenoside compound K (GC-K) potentially alleviates ulcerative colitis involved in gut microbiota, which is significantly associated with the occurrence and development of colitis. However, the effect and mechanism of GC-K on anti-colitis in relation to gut microbiota are not clear. This study focused on the prevention and mechanism of GC-K on Dextran sulfate sodium (DSS)-induced colitis of mice pertinent to gut microbiota. Methods DSS was used to establish a chronic colitis mouse model....

Abstract Background Ginsenoside compound K (GC-K) potentially alleviates ulcerative colitis involved in gut microbiota, which is significantly associated with the occurrence and development of colitis. However, the effect and mechanism of GC-K on anti-colitis in relation to gut microbiota are not clear. This study focused on the prevention and mechanism of GC-K on Dextran sulfate sodium (DSS)-induced colitis of mice pertinent to gut microbiota. Methods DSS was used to establish a chronic colitis mouse model....

Abstract Background Individuals born very low birthweight (VLBW) are at increased risk of impaired cardiovascular and respiratory function in adulthood. To identify markers to predict future risk for VLBW individuals, we analyzed DNA methylation at birth and at 28 years in the New Zealand (NZ) VLBW cohort (all infants born < 1500 g in NZ in 1986) compared with age-matched, normal birthweight controls. Associations between neonatal methylation and cardiac structure and function (echocardiography), vascular function...

Abstract Background Pancreatic beta cell dysfunction and activated macrophage infiltration are early features in type 1 diabetes pathogenesis. A tricarboxylic acid cycle metabolite that can strongly activate NF-E2-related factor 2 (Nrf2) in macrophages, itaconate is important in a series of inflammatory-associated diseases via anti-inflammatory and antioxidant properties. However, its role in type 1 diabetes is unclear. We used 4-octyl itaconate (OI), the cell-permeable itaconate derivate, to explore its preventative and therapeutic effects in mouse models...

Abstract Background Circulating tumor DNA (ctDNA) detection following curative-intent surgery could directly reflect the presence of minimal residual disease, the ultimate cause of clinical recurrence. However, ctDNA is not postoperatively detected in ≥ 50% of patients with stage I-III colorectal cancer (CRC) who ultimately recur. Herein we sought to improve recurrence risk prediction by combining ctDNA with clinicopathological risk factors in stage I-III CRC. Methods Two independent cohorts, both consisting of early-stage CRC patients who...