Notes

Rounded RNA circPRKDC helps bring about tumorigenesis associated with gastric cancer by means of modulating the hormone insulin receptor substrate Two (IRS2) and mediating microRNA-493-5p.
Fe-N-C catalysts offer excellent performance for the oxygen reduction reaction (ORR) in alkaline media. With a view toward boosting the intrinsic ORR activity of Fe single-atom sites in Fe-N-C catalysts, fine-tuning the local coordination of the Fe sites to optimize the binding energies of ORR intermediates is imperative. Herein, a porous FeN4 -O-NCR electrocatalyst rich in catalytically accessible FeN4 -O sites (wherein the Fe single atoms are coordinated to four in-plane nitrogen atoms and one subsurface axial oxygen atom) supported on N-doped carbon nanorods (NCR) is reported. Fe K-edge X-ray absorption spectroscopy (XAS) verifies the presence of FeN4 -O active sites in FeN4 -O-NCR, while density functional theory calculations reveal that the FeN4 -O coordination offers a lower energy and more selective 4-electron/4-proton ORR pathway compared to traditional FeN4 sites. Electrochemical tests validate the outstanding intrinsic activity of FeN4 -O-NCR for alkaline ORR, outperforming Pt/C and almost all other M-N-C catalysts reported to date. A primary zinc-air battery constructed using FeN4 -O-NCR delivers a peak power density of 214.2 mW cm-2 at a current density of 334.1 mA cm-2 , highlighting the benefits of optimizing the local coordination of iron single atoms.The fetal to adult switch in hematopoietic stem cell (HSC) behavior is characterized by alterations in lineage output and entry into deep quiescence. Here we identify the emergence of megakaryocyte (Mk) biased HSCs as an event coinciding with this developmental switch. Single-cell chromatin accessibility analysis reveals a ubiquitous acquisition of Mk lineage priming signatures in HSCs during the fetal to adult transition. These molecular changes functionally coincide with an increased amplitude of early Mk differentiation events following acute inflammatory insult. Importantly, we identify LIN28B - known for its role in promoting fetal-like self-renewal, as an insulator against the establishment of a Mk biased HSC pool. LIN28B protein is developmentally silenced in the third week of life and its prolonged expression delays emergency platelet output in young adult mice. We propose that developmental regulation of Mk priming may represent a switch for HSCs to toggle between prioritizing self-renewal in the fetus and increased host protection in postnatal life.Autophagy plays a vital role in maintaining intracellular homeostasis through a lysosome-dependent intracellular degradation pathway, which is closely related to the polarity and ATP. Herein, the first example of the dual-response fluorescent probe Lyso-NRB was reported for visualizing the fluctuation of polarity and ATP in lysosomes during autophagy. Probe Lyso-NRB is non-fluorescent. After the decrease of polarity, Lyso-NRB exhibits significant green emission due to the unique intramolecular charge transfer (ICT) effect. Upon the addition of ATP, the probe can react with ATP to rapidly open the spirocycle of rhodamine and a strong red emission can be observed. Moreover, Lyso-NRB exhibits a high sensitivity and selectivity toward polarity and ATP. Most importantly, the probe possesses a good lysosome-targeting ability and is used for the real-time monitoring of lysosome polarity and ATP fluctuations during H2O2 or starvation induced autophagy in living cells. Interestingly, it is found that that ATP deficiency can induce autophagy to increase lysosome polarity. Furthermore, the probe is applied for imaging the change of polarity and ATP under oxidative stress induced autophagy in zebrafish. Therefore, this work holds great potential for tracking the autophagy procedure by detecting the changes of lysosome polarity and ATP, which makes it a potentially powerful tool for understanding the roles of autophagy in diverse biological processes.
Azathioprine (AZA)-induced pancreatitis (AIP) is a common, idiosyncratic adverse effect whose incidence and risk factors data in inflammatory bowel disease (IBD) patients are not fully clarified. We aimed to establish the incidence, clinical course and identify risk factors for AIP.

A retrospective study including all IBD patients on AZA between January 2013 and July 2020 was conducted. Patients with AIP were considered.

Azathioprine-induced pancreatitis occurred in 33 patients (7.5%; 442 patients on AZA). The mean time receiving AZA until AIP was 25 days, with a mean dose of 88 mg. All patients had a mild course of disease, which resolved with suspension of AZA and with no complications. Smoking (P = 0.02), single daily dose of AZA (P < 0.001), and concomitant budesonide (P = 0.001) were risk factors for AIP. In multivariate analysis, concomitant treatment with budesonide (odds ratio, 5.3; P = 0.002) and single daily dose of AZA (odds ratio, 3.8; P = 0.002) were the only predictors of AIP.

Although AIP was a relatively common adverse effect, it presented a mild course in all patients. Smoking, concomitant use of budesonide, and single-dose regimen of AZA should be avoided in IBD patients treated with AZA.
Although AIP was a relatively common adverse effect, it presented a mild course in all patients. Smoking, concomitant use of budesonide, and single-dose regimen of AZA should be avoided in IBD patients treated with AZA.
During the last decades, significant progress has been made in the management of patients with pancreatic neuroendocrine tumors (pNETs). It is unclear how the type of the treating health care facility alters patient outcomes.

Data from pNETs reported to the National Cancer Database between 2004 and 2016 were examined. Types of institutions were as follows academic/research cancer program (ARP), comprehensive community cancer program (CCCP), integrated network cancer program (INCP), and community cancer program (CCP).

A total of 17,887 patients with pNETs were analyzed. Treatment at ARPs was significantly associated with receipt of surgery (ARP, 61.9%; CCCP, 45.6%; CCP, 29.9%; INCP, 55.5%; P < 0.001), both for patients with very early tumors ≤2 cm (ARP, 74.7%; CCCP, 66.5%; CCP, 52.4%; INCP, 71.6%; P < 0.001) and for patients with liver metastases (ARP, 21.3%; CCCP, 10.6%; CCP, 5%; INCP, 16.8%; P < 0.001). Treatment at ARPs was associated with improved survival (median overall survival ARP, 91 mo; CCCP, 47 mo; CCP, 24.5 mo; INCP, 72 mo; P < 0.001).

Treatment of pNETs at academic/research programs is associated with more frequent resections and best survival outcomes. This survival benefit exists for early and late stages and after adjusting for known cofactors.
Treatment of pNETs at academic/research programs is associated with more frequent resections and best survival outcomes. This survival benefit exists for early and late stages and after adjusting for known cofactors.
Second-line (2L) chemotherapy is important for improved survival in patients with advanced pancreatic cancer (APC). However, approximately half of patients with APC do not receive 2L chemotherapy because of disease progression or adverse events. Baseline factors predictive of the receipt of 2L chemotherapy remain unknown. Therefore, we investigated predictive factors for the receipt of 2L chemotherapy in patients with APC.

Between January 2015 and March 2020, 53 patients with APC received nab-paclitaxel plus gemcitabine (AG) as first-line chemotherapy at our institute. Of these 53 patients, 29 patients received 2L chemotherapy, and 23 patients received best supportive care. Patients' characteristics were compared retrospectively, and predictive factors for the receipt of 2L chemotherapy were evaluated.

Sarcopenia and hypoalbuminemia at baseline were independent negative predictive factors for the receipt of 2L chemotherapy in multivariate analysis. Although the presence of sarcopenia did not affect the relative dose intensity through 8 weeks of AG therapy, patients with hypoalbuminemia had a significantly lower relative dose intensity.

Sarcopenia and hypoalbuminemia at baseline might be negative predictive factors for the receipt of 2L chemotherapy after AG treatment in patients with APC.
Sarcopenia and hypoalbuminemia at baseline might be negative predictive factors for the receipt of 2L chemotherapy after AG treatment in patients with APC.
Indications of preoperative treatment for resectable (R-) or borderline resectable (BR-) pancreatic ductal adenocarcinoma (PDAC) are unclear, and the protocol remains to be standardized.

Included 65 patients with R- and BR-PDAC with venous involvement (V-) received neoadjuvant chemoradiotherapy with S-1 and 50 Gy of radiation as the 5-week regimen. Lanifibranor The outcomes of this group were compared with those of 52 patients who underwent S-1 and 30 Gy of radiation as the 2-week regimen, previously collected as our prospective phase II study.

Compared with the 2-week regimen, there were no significant differences in the rate of protocol completion, adverse events, mortality and morbidity, or R0 resection in the 5-week regimen. In subgroup analyses of R-PDAC, there were no significant differences in overall survival and recurrence-free survival between the groups. In contrast, the 5-week regimen had significantly better overall survival and recurrence-free survival than the 2-week regimen for BRV-PDAC. Similar results were observed after propensity score matching analysis.

The 5-week regimen of neoadjuvant chemoradiotherapy has good clinical efficacy and safety for R- and BRV-PDAC. The 5-week regimen could achieve better outcomes than the 2-week regimen for BRV-PDAC. In contrast, both regimens achieved similar outcomes for R-PDAC.
The 5-week regimen of neoadjuvant chemoradiotherapy has good clinical efficacy and safety for R- and BRV-PDAC. The 5-week regimen could achieve better outcomes than the 2-week regimen for BRV-PDAC. In contrast, both regimens achieved similar outcomes for R-PDAC.
Cases of acute pancreatitis (AP) are increasing worldwide, and mortality remains high in severe cases. In 2015, the Japanese guidelines for the management of AP were revised. We aimed to clarify the clinical practice of AP in Japan and its trend during the revision of the guidelines using a Japanese nationwide administrative database.

We retrospectively analyzed 102,119 patients with AP who were hospitalized between April 2014 and March 2018. The study period was divided into the first period (the time before the revision fiscal years 2014 and 2015) and second period (after the revision 2016 and 2017).

Severe cases of AP accounted for 27.7% of total cases. The in-hospital mortality in severe cases was 5.7%. The mortality within 14 days of admission improved from 3.2% in the first period to 2.6% in the second period (P = 0.022). Referred patients had more severe diseases and a higher mortality. The mortality in patients who underwent endoscopic ultrasound-guided fistuloplasty for local complications (11.6%) was lower than that in patients who underwent percutaneous drainage (23.4%) or AP surgery (22.6%) (P < 0.001).

We clarified the clinical practice of AP including the improved mortality after the revision of the guidelines.
We clarified the clinical practice of AP including the improved mortality after the revision of the guidelines.
The aim of this article is to provide guidance to centers and organizations on the personnel (both physician and nonphysician) needed to create and sustain an optimal team, along with potential alternatives, to provide care to children with acute recurrent pancreatitis and chronic pancreatitis.

This document was developed in collaboration with the North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) Pancreas Committee and the National Pancreas Foundation (NPF) after several meetings.

This document highlights both physician and nonphysician personnel needed to provide multidisciplinary care to children with pancreatitis per the recommendation of the NASPGHAN Pancreas Committee members in year 2021 and added to the currently published NPF criteria. We summarize how the NPF criteria would fit with the recently published pediatric pancreatitis society articles from the NASPGHAN.

It is important to manage children with acute recurrent pancreatitis and chronic pancreatitis in a multidisciplinary setting.
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