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Fast radio bursts (FRBs) are highly dispersed, millisecond-duration radio bursts 1-3 . Recent observations of a Galactic FRB 4-8 suggest that at least some FRBs originate from magnetars, but the origin of cosmological FRBs is still not settled. Here we report the detection of 1,863 bursts in 82 h over 54 days from the repeating source FRB 20201124A (ref.  9 ). These observations show irregular short-time variation of the Faraday rotation measure (RM), which scrutinizes the density-weighted line-of-sight magnetic field strength, of individual bursts during the first 36 days, followed by a constant RM. We detected circular polarization in more than half of the burst sample, including one burst reaching a high fractional circular polarization of 75%. Oscillations in fractional linear and circular polarizations, as well as polarization angle as a function of wavelength, were detected. All of these features provide evidence for a complicated, dynamically evolving, magnetized immediate environment within about an astronomical unit (AU; Earth-Sun distance) of the source. Our optical observations of its Milky-Way-sized, metal-rich host galaxy 10-12 show a barred spiral, with the FRB source residing in a low-stellar-density interarm region at an intermediate galactocentric distance. This environment is inconsistent with a young magnetar engine formed during an extreme explosion of a massive star that resulted in a long gamma-ray burst or superluminous supernova., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

The major function of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is to regulate cell metabolism. However, emerging evidence indicates that IGF2BP2 plays a role in cancer, but the underlying mechanism is largely unknown. Here we showed that upregulation of IGF2BP2 is associated with poor outcomes of pancreatic cancer patients and suppression of IGF2BP2 inhibits cell proliferation. We further showed that IGF2BP2 regulates lncRNA DANCR. Ectopic expression IGF2BP2 enhances, whereas knockdown (KD) or knockout (KO) of IGF2BP2 suppresses DANCR expression. Moreover, in vivo RNA precipitation and reciprocal RNA immunoprecipitation revealed that IGF2BP2 interacts with DANCR. DANCR promotes cell proliferation and stemness-like properties. Experiments with xenograft models revealed that while ectopic expression of DANCR promotes, DANCR KO suppresses tumor growth. Mechanistically, DANCR is modified at N6-methyladenosine (m6A) and mutagenesis assay identified that adenosine at 664 of DANCR is critical to the interaction between IGF2BP2 and DANCR where IGF2BP2 serves a reader for m6A modified DANCR and stabilizes DANCR RNA. Together, these results suggest that DANCR is a novel target for IGF2BP2 through m6A modification, and IGF2BP2 and DANCR work together to promote cancer stemness-like properties and pancreatic cancer pathogenesis.

Although multiple factors are known to contribute to pancreatic ductal adenocarcinoma (PDAC) progression, the role of long non-coding RNAs (lncRNAs) in PDAC remains largely unknown. In this study, we present data that long intergenic non-coding RNA 346 (LINC00346) functions as a promoting factor for PDAC development. We first show that LINC00346 is highly expressed in pancreatic tumor specimens as compared to normal pancreatic tissue based on interrogation of The Cancer Genome Atlas (TCGA) pancreatic adenocarcinoma dataset. Of significance, this upregulation of LINC00346 is associated with overall survival (OS) and disease-free survival (DFS), respectively. We further show that knockout (KO) of LINC00346 impairs pancreatic cancer cell proliferation, tumorigenesis, migration, and invasion ability. Importantly, these phenotypes can be restored by LINC00346 re-expression in KO cells (i.e., rescue experiment). RNA precipitation assays combined with mass spectrometry analysis indicate that LINC00346 interacts with CCCTC-binding factor (CTCF), a known transcriptional repressor of c-Myc. This interaction between LINC00346 and CTCF prevents the binding of CTCF to c-Myc promoter, relieving the CTCF-mediated repression of c-Myc. Thus, LINC00346 functions as a positive transcriptional regulator of c-Myc. Together, these results suggest that LINC00346 contributes to PDAC pathogenesis by activating c-Myc, and as such, LINC00346 may serve as a potential biomarker and therapeutic target for PDAC.

Factors associated with infections after spinal cord surgery were not fully understood. This study aimed to evaluate whether preoperative pressure ulcers was a risk factor of infections after spinal cord operation. A 1:1 matched follow-up study was performed in a tertiary referral center in southwest China between 2010 and 2015. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression analysis. A total of 334 patients with spinal cord surgery were recruited (167 patients with preoperative pressure ulcers and 167 patients without preoperative pressure ulcers). Participants previously exposed to pressure ulcers had an elevated risk of infections post spinal cord operation including surgical site infection (RR: 2.3, 95% CI: 1.1, 4.7), pneumonia (RR: 2.4, 95% CI: 1.1,5.3), urinary tract infection (RR: 2.8, 95% CI: 1.1, 7.3), any kinds of postoperative infections (RR: 3.4, 95% CI: 2.1, 5.6) and 30-day postoperative hospitalization for infections (RR: 2.6, 95% CI: 1.1, 6.0). The associations between preoperative pressure ulcers in stage III to IV and postoperative infections were also pronounced, but towards null in stage I to II. The study showed an increased risk of infections after spinal cord surgery in patients with preoperative pressure ulcers, indicative of an urgent need for monitoring postoperative infections and medical treatment for patients with pressure sores.

To date, a large number of long non-coding RNAs (lncRNAs) have been recently discovered through functional genomics studies. Importantly, lncRNAs have been shown, in many cases, to function as master regulators for gene expression and thus, they can play a critical role in various biological functions and disease processes including cancer. Although the lncRNA-mediated gene expression involves various mechanisms, such as regulation of transcription, translation, protein modification, and the formation of RNA-protein or protein-protein complexes, in this review, we discuss the latest developments primarily in important cell signaling pathways regulated by lncRNAs in cancer.

Aim: To study the multiple dose pharmacokinetics of quetiapine and its sulfoxide-, 7-hydroxy-, 7-hydroxy-N-dealkyl-metabolites in Chinese suffering from schizophrenia., Methods: Twenty-one patients (11 females and 10 males) were given quetiapine twice daily to control the symptoms. After the dose reached 200 mg twice daily, blood were sampled to study the pharmacokinetics. The plasma concentrations of quetiapine and its metabolites were assayed by HPLC-MS., Results: The main pharmacokinetic parameters of quetiapine, 7-hydroxy-N-dealkyl-quetiapine, quetiapine sulfoxide, and 7-hydroxy-quetiapine were as follows: tmax were 2.0 (0.3-5.0), 4.0 (1.5-6.0), 3.0 (0.5-5.0), and 3.0 (0.5-5.0) h respectively; t1/2 were (7+/-3), (9.4+/-2.7), (7+/-3), and (8+/-5) h, respectively; Cmax(SS) were (678+/-325), (19+/-5), (451+/-216), and (58+/-22) microg/L, respectively; Cmin(SS) were (51+/-68), (3.3+/-1.6), (35+/-36), and (5+/-4) microg/L, respectively; Cav(SS) were (295+/-144), (13+/-4), (209+/-71), and (28+/-9) micro/L, respectively; AUC(0-12)(SS) were (3,538+/-1 728), (153+/-44), (2,512+/-854), and (335+/-104) microg.h.L(-1), respectively; AUC(0-infinite)(SS) were (5,534+/-4 198), (287+/-107), (3,858+/-2 012), and (529+/-262) microg.h.L(-1), respectively; Ke were (0.11+/-0.03), (0.079+/-0.019), (0.11+/-0.03), and (0.103+/-0.028) h(-1), respectively; CL/F and V/F of quetiapine were (67+/-25) L.h(-1) and (672+/-394) L, respectively. The plasma concentrations for the four compounds reached a steady state within 48 h at the dose of 200 mg initiation. These parameters were not statistically different between genders., Conclusions: Quetiapine was absorbed quickly, distributed widely, and metabolized mainly to be quetiapine sulfoxide. The elimination speeds of quetiapine and its three metabolites were similar. Gender had no effect on the pharmacokinetics of quetiapine and its metabolites. The clinical dosage regime caused no drug accumulation.