Sorting nexin 5 mediates virus-induced autophagy and immunity.

Autophagy, a process of degradation that occurs via the lysosomal pathway, has an essential role in multiple aspects of immunity, including immune system development, regulation of innate and adaptive immune and inflammatory responses, selective degradation of intracellular microorganisms, and host protection against infectious diseases1,2. Autophagy is known to be induced by stimuli such as nutrient deprivation and suppression of mTOR, but little is known about how autophagosomal biogenesis is initiated in mammalian cells in response to viral infection. Here, using genome-wide short interfering RNA screens, we find that the endosomal protein sorting nexin 5 (SNX5)3,4 is essential for virus-induced, but not for basal, stress- or endosome-induced, autophagy. We show that SNX5 deletion increases cellular susceptibility to viral infection in vitro, and that Snx5 knockout in mice enhances lethality after infection with several human viruses. Mechanistically, SNX5 interacts with beclin 1 and ATG14-containing class III phosphatidylinositol-3-kinase (PI3KC3) complex 1 (PI3KC3-C1), increases the lipid kinase activity of purified PI3KC3-C1, and is required for endosomal generation of phosphatidylinositol-3-phosphate (PtdIns(3)P) and recruitment of the PtdIns(3)P-binding protein WIPI2 to virion-containing endosomes. These findings identify a context- and organelle-specific mechanism-SNX5-dependent PI3KC3-C1 activation at endosomes-for initiation of autophagy during viral infection.

Nanosized Porphyrin-Containing Covalent Organic Polymer to Enhance Ferroptosis in Photodynamic Treatment of Tumor Cells via Glutathione Depletion.

A porphyrin-containing nanoscale covalent organic polymer (COP) was fabricated from 5,10,15,20-tetra(4-carboxyphenyl)porphyrin (TCPP) and cystamine via an acylation reaction. On the one hand, TCPP can induce tumor cell death by laser irradiation. Due to the presence of disulfide bonds of cystamine which can react with glutathione, it exhibits depletion of glutathione and accumulation of peroxides in tumor cells. Ultimately by the hyaluronic acid to encapsulate the COP to get S-COP@HA, the nanoparticle with a size of 168.6 nm also exhibits good tumor accumulation and biosafety. Significant inhibition of tumor cell growth was observed after two consecutive doses of S-COP@HA at relatively low laser densities. This combination therapy was proved to reduce the level of reduced glutathione in tumor cells, where ferroptosis occurs after photodynamic treatment. Overall, this study presents a potent, good therapeutic option for the effective enhancement of photodynamic therapy by glutathione depletion.

Association of baseline sleep duration and sleep quality with seizure recurrence in newly treated patients with epilepsy.

OBJECTIVE: Although sleep duration and sleep quality are considered to be significant factors associated with epilepsy and seizure risk, findings are inconsistent, and their joint association remains uncertain. This study aimed to determine independent and joint associations of these two modifiable sleep features with seizure recurrence risk in newly treated patients with epilepsy (PWE). METHODS: This is a prospective cohort study of newly treated PWE at a comprehensive epilepsy center in northeast China between June 2020 and December 2023. Self-reported sleep duration and sleep quality were collected at baseline. All patients were followed for 12 months for recurrent seizures. Cox proportional hazard regression models were used to estimate the hazard ratios (HRs) of seizure recurrence. Models fitted with restricted cubic spline were conducted to test for linear and nonlinear shapes of each association. RESULTS: A total of 209 patients were included, and 103 experienced seizure recurrence during follow-up. Baseline short sleep was significantly associated with greater risk of seizure recurrence (adjusted HR = 2.282, 95% confidence interval [CI] = 1.436-3.628, p < .001). Sleep duration (h/day) and recurrent seizure risk showed a significant nonlinear U-shaped association, with a nadir at 8 h/day. Baseline poor sleep quality was significantly associated with greater risk of seizure recurrence (adjusted HR = 1.985, 95% CI = 1.321-2.984, p < .001). Pittsburgh Sleep Quality Index score and seizure recurrence risk exhibited a positive linear association. Participants with a combination of poor quality-short sleep showed the highest risk of seizure recurrence (adjusted HR = 3.13, 95% CI = 1.779-5.507, p < .001) compared to the referent good quality-intermediate sleep group. SIGNIFICANCE: Baseline sleep duration and sleep quality were independently and jointly associated with risk of seizure recurrence in newly treated PWE. Our results point to an important potential role of baseline sleep duration and sleep quality in shaping seizure risk.

Recyclable N-Heterocyclic Carbene Porous Coordination Polymers with Two Distinct Metal Sites for Transformation of CO2 to Cyclic Carbonates.

Single-component catalysts with integrated multiple reactive centers could work in concert to achieve enhanced activity tailored for specific catalytic reactions, but they remain underdeveloped. Herein, we report the construction of heterogeneous bimetallic porous coordination polymers (PCPs) containing both porphyrin and N-heterocyclic carbene (NHC) metal sites via the coordinative assembly of the NHC functionalities. Three heterobimetallic PCPs (TIPP-Zn-Pd, TIPP-Cu-Pd and TIPP-Ni-Pd) have been prepared to verify this facile synthetic strategy for the first time. In order to establish a cooperative action toward the catalytic CO2 cycloaddition with epoxides, an additional tetraalkylammonium bromide functionality has also been incorporated into these polymeric structures through the N-substituent of the NHC moieties. The resulting heterogeneous bimetallic catalyst TIPP-Zn-Pd exhibits the best catalytic performance in CO2 cycloaddition with styrene oxide (SO) under solvent-free conditions at atmospheric pressure and is applicable to a wide range of epoxides. More importantly, TIPP-Zn-Pd works smoothly and is recyclable in the absence of a cocatalyst under 1.0 MPa of CO2 at 60 °C. This indicates that TIPP-Zn-Pd is quite competitive with the reported heterogeneous catalysts, which typically require a high reaction temperature above 100 °C under cocatalyst-free conditions. Thus, this work provides a new approach to design heterogeneous bimetallic PCP catalysts for high-performance CO2 fixation under mild reaction conditions.

Effects of elevated remnant cholesterol on outcomes of acute ischemic stroke patients receiving mechanical thrombectomy.

OBJECTIVE: Large cohort studies provided evidence that elevated remnant cholesterol (RC) was an important risk factor for ischemic stroke. However, the association between high RC and clinical outcomes in acute ischemic stroke (AIS) individuals was still undetermined. METHODS: This retrospective study enrolled 165 AIS patients undergoing mechanical thrombectomy in one tertiary stroke center. We divided patients into two groups based on the median of their RC levels (0.49 mmol/L). The modified Rankin Scale (mRS) was used to evaluate the primary outcome 90 days after the onset of symptoms. The mRS scores ≤ 2 and ≤ 1 at 90 days were deemed as favorable and excellent outcomes, respectively. RESULTS: In the overall AIS patients undergoing mechanical thrombectomy, there was no obvious distinction between the high and low RC group at 90-day favorable outcome (41.0% vs. 47.1%, P = 0.431) or excellent outcome (23.1% vs. 31.0%, P = 0.252). In the subgroup analysis stratified by stroke etiology, non-large artery atherosclerosis (non-LAA) stroke patients yielded with less favorable or excellent prognosis in the high RC group (26.8% vs. 46.8%, adjusted OR = 0.31, 95%CI: 0.11-0.85, P = 0.023; or 12.2% vs. 29.0%, adjusted OR = 0.18, 95%CI: 0.04-0.80, P = 0.024, respectively.). Post hoc power analyses indicated that the power was sufficient for favorable outcome (80.38%) and excellent outcome (88.72%) in non-LAA stroke patients. Additionally, RC can enhance the risk prediction value of a poor outcome (mRS scores 3-6) based on traditional risk indicators (including age, initial NIHSS score, operative duration, and neutrophil-to-lymphocyte ratio) for non-LAA stroke patients (AUC = 0.86, 95%CI: 0.79-0.94, P < 0.001). CONCLUSION: In AIS patients undergoing mechanical thrombectomy, elevated RC was independently related to poor outcome for non-LAA stroke patients, but not to short-term prognosis of LAA stroke patients.

Effect of remimazolam on intra-operative hypotension: Systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Hypotension is common during anaesthesia. Increasing number of studies have reported that remimazolam may be associated with lower incidence of intra-operative hypotension compared with other anaesthetics. However, the results remain controversial. OBJECTIVE: This study aimed to evaluate the influence of remimazolam on intra-operative hypotension and its related outcomes (hypoxaemia, bradycardia and time to awake). DESIGN: A systematic review of randomised controlled trials (RCTs) with meta-analyses. DATA SOURCES: PubMed, Cocharane and Embase databases were searched to identify eligible RCTs published up to June 2024. ELIGIBILITY CRITERIA: RCTs published in English were eligible for inclusion. The study patients were 18 years or older who were administered with remimazolam and other positive control agents in either the pre-operative or intra-operative period. The incidence of intra-operative hypotension was identified in these studies. RESULTS: This study evaluated 34 trials including 4847 individuals. Basing on moderate-certainty evidence, we found that remimazolam administration reduced the incidence of intra-operative hypotension [risk ratio (RR) = 0.48, 95% confidence interval (95% CI): 0.41 to 0.57] and bradycardia (16 studies, n = 2869, RR = 0.40, 95% CI: 0.29 to 0.54). No difference was observed in the incidence of hypoxaemia (RR = 0.70, 95% CI: 0.48 to 1.01) and time to awake (MD = -0.91, 95% CI: -2.42 to 0.60). The remarkable association between remimazolam and hypotension remained robust and significant, regardless of general anaesthesia or procedural sedation (P < 0.01, I2 = 82%). No significant difference was found between different control drugs (P = 0.97, I2 = 82%). CONCLUSION: Moderate-quality evidence shows that remimazolam administration to patients undergoing general anaesthesia or procedural sedation decreases the incidence of intra-operative hypotension and bradycardia.

Clinical insights into tuberculosis otitis media: diagnosis, treatment, and management outcomes.

OBJECTIVES: The diagnosis of tuberculosis otitis media (TBOM) remains a great challenge. This study aims to suggest potential diagnostic clues and proper management of TBOM. METHODS: The study is a retrospective review of TBOM cases that were treated at our department, between January 2015 and June 2023. Summarizing their clinical characteristics, diagnosis, and treatment. Additionally, a literature review is conducted. RESULTS: Eight cases of TBOM, 6 female and 2 male patients, median age was 32 years old, were included in the study. TBOM mainly presents with symptoms of otorrhea, hearing loss, and occasional early-onset facial palsy. One case had a positive Purified Protein Derivative (PPD) before the operation. Middle ear tissue was pathologically biopsied in 7 cases, with 3 cases testing positive for Acid Fast Bacillus and 6 cases testing positive for Mycobacterium tuberculosis PCR. Middle ear surgery and Anti-tubercular treatment (ATT) were completed in all cases. The median follow-up was 11 months. No cases of TB relapse were observed. CONCLUSIONS: Proper suspicion and confirmation of TBOM is the primary clinical orientation. Middle ear surgery combination with ATT results in satisfactory outcomes. Hearing reconstruction should be performed after ATT is completed.

Loss of TREM2 diminishes CAA despite an overall increase of amyloid load in Tg-SwDI mice.

INTRODUCTION: The microglial receptor triggering receptor expressed on myeloid cells 2 (TREM2) is a major risk factor for Alzheimer's disease (AD). Experimentally, Trem2 deficiency affects parenchymal amyloid beta (Aß) deposition. However, the role of TREM2 in cerebrovascular amyloidosis, especially cerebral amyloid angiopathy (CAA), remains unexplored. METHODS: Tg-SwDI (SwDI) mice, a CAA-prone model of AD, and Trem2 knockout mice were crossed to generate SwDI/TWT, SwDI/THet, and SwDI/TKO mice, followed by pathological and biochemical analyses at 16 months of age. RESULTS: Loss of Trem2 led to a dramatic decrease in CAA and microglial association, despite a marked increase in overall brain Aß load. Single nucleus RNA sequencing analysis revealed that in the absence of Trem2, microglia were activated but trapped in transition to the fully reactive state, with distinct responses of vascular cells. DISCUSSION: Our study provides the first evidence that TREM2 differentially modulates parenchymal and vascular Aß pathologies, offering significant implications for both TREM2- and Aß-targeting therapies for AD. HIGHLIGHTS: Triggering receptor expressed on myeloid cells 2 (TREM2) differentially modulates brain parenchymal and vascular amyloidosis. Loss of Trem2 markedly reduces cerebral amyloid angiopathy despite an overall increase of amyloid beta load in Tg-SwDI mice. Microglia are trapped in transition to the fully reactive state without Trem2. Perivascular macrophages and other vascular cells have distinct responses to Trem2 deficiency. Balanced TREM2-targeting therapies may be required for optimal outcomes.

Cyclic Multi-Site Chelation for Efficient and Stable Inverted Perovskite Solar Cells.

Trap-assisted non-radiative recombination losses and moisture-induced degradation significantly impede the development of highly efficient and stable inverted (p-i-n) perovskite solar cells (PSCs), which require high-quality perovskite bulk. In this research, we mitigate these challenges by integrating thermally stable perovskite layers with Lewis base covalent organic frameworks (COFs). The ordered pore structure and surface binding groups of COFs facilitate cyclic, multi-site chelation with undercoordinated lead ions, enhancing the perovskite quality across both its bulk and grain boundaries. This process not only reduces defects but also promotes improved energy alignment through n-type doping at the surface. The inclusion of COF dopants in p-i-n devices achieves power conversion efficiencies (PCEs) of 25.64% (certified 24.94%) for a 0.0748-cm2 device and 23.49% for a 1-cm2 device. Remarkably, these devices retain 81% of their initial PCE after 978 hours of accelerated aging at 85˚C, demonstrating remarkable durability. Additionally, COF-doped devices demonstrate excellent stability under illumination and in moist conditions, even without encapsulation.

Tyrosine phosphorylation of band 3 impairs the storage quality of suspended red blood cells in the Tibetan high-altitude polycythemia population.

Due to environmental hypoxia on the Tibetan Plateau, local residents often exhibit a compensative increase in hemoglobin concentration to maintain the body's oxygen supply. However, increases in hemoglobin and hematocrit (Hct) pose a serious challenge to the quality of stored suspended red blood cells (SRBCs) prepared from the blood of high-hemoglobin populations, especially populations at high altitude with polycythemia in Tibet. To explore the difference in storage quality of SRBCs prepared from plateau residents with a high hemoglobin concentration, blood donors were recruited from Tibet (> 3600 m) and Chengdu (≈ 500 m) and divided into a high-altitude control (HAC) group, high-altitude polycythemia (HAPC) group and lowland control (LLC) group according to their hemoglobin concentration and altitude of residence. The extracellular acidification rate (ECAR), pyruvate kinase (PK) activity and band 3 tyrosine phosphorylation were analyzed on the day of blood collection. Then, whole-blood samples were processed into SRBCs, and storage quality parameters were analyzed aseptically on days 1, 14, 21 and 35 of storage. Overall, we found that tyrosine 21 phosphorylation activated glycolysis by releasing glycolytic enzymes from the cytosolic domain of band 3, thus increasing glucose consumption and lactate accumulation during storage, in the HAPC group. In addition, band 3 tyrosine phosphorylation impaired erythrocyte deformability, accompanied by the highest hemolysis rate in the HAPC group, during storage. We believe that these results will stimulate new ideas to further optimize current additive solutions for the high-hemoglobin population in Tibet and reveal new therapeutic targets for the treatment of HAPC populations.

Mutanofactin promotes adhesion and biofilm formation of cariogenic Streptococcus mutans.

Cariogenic Streptococcus mutans is known as a predominant etiological agent of dental caries due to its exceptional capacity to form biofilms. From strains of S. mutans isolated from dental plaque, we discovered, in the present study, a polyketide/nonribosomal peptide biosynthetic gene cluster, muf, which directly correlates with a strong biofilm-forming capability. We then identified the muf-associated bioactive product, mutanofactin-697, which contains a new molecular scaffold, along with its biosynthetic logic. Further mode-of-action studies revealed that mutanofactin-697 binds to S. mutans cells and also extracellular DNA, increases bacterial hydrophobicity, and promotes bacterial adhesion and subsequent biofilm formation. Our findings provided an example of a microbial secondary metabolite promoting biofilm formation via a physicochemical approach, highlighting the importance of secondary metabolism in mediating critical processes related to the development of dental caries.

Chemical Synthesis of a Keto Sugar Nucleotide.

Keto sugar nucleotides (KSNs) are common and versatile precursors to various deoxy sugar nucleotides, which are substrates for the corresponding glycosyltransferases involved in the biosynthesis of glycoproteins, glycolipids, and natural products. However, there has been no KSN synthesized chemically due to the inherent instability. Herein, the first chemical synthesis of the archetypal KSN TDP-4-keto-6-deoxy-d-glucose (1) is achieved by an efficient and optimized route, providing feasible access to other KSNs and analogues, thereby opening a new avenue for new applications.

Serum liver fibrosis markers predict hepatic decompensation in compensated cirrhosis.

BACKGROUND AND AIM: The literature is sparse on the association between serum liver fibrosis markers and the development of hepatic decompensation in patients with compensated cirrhosis. We aimed to assessed whether the serum liver fibrosis markers are predictive of the occurrence of hepatic decompensation. METHODS: We ascertained 688 cirrhotic patients with varying etiologies, between December 2015 to December 2019. Serum hyaluronic acid (HA), laminin (LN), collagen IV (CIV), and N-terminal propeptide of type III collagen (PIIINP) levels were measured at enrollment. All subjects were followed for at least 6 months for occurrence of hepatic decompensation. Cox proportional hazard regression models were used to estimate the hazard ratios (HRs) of hepatic decompensation during follow-up. RESULTS: During a median follow-up of 22.0 (13.0-32.0) months, decompensation occurred in 69 (10.0%) patients. Multivariate analysis indicated that higher LN (HR: 1.008, 95% confidence interval [CI]: 1.002-1.014, P = 0.011) and CIV (HR: 1.004, 95% CI: 1.001-1.007, P = 0.003) levels were independently associated with hepatic decompensation. Furthermore, patients in the tertile 2 and tertile 3 groups for CIV levels had HRs of 4.787 (1.419, 16.152) (P = 0.012) and 5.153 (1.508, 17.604) (P = 0.009), respectively, for occurrence of decompensation event compared with those in the tertile 1 group. CONCLUSION: Serum liver fibrosis markers, particularly in CIV, appeared to be reliable biomarkers of disease progression and liver decompensation in patients with compensated cirrhosis with varying etiologies.

The Albumin-Bilirubin Score as a Predictor of Liver-Related Mortality in Primary Biliary Cholangitis with Compensated Cirrhosis.

BACKGROUND: Although several prognostic scores have been reported to correlate with the prognosis of primary biliary cholangitis (PBC) patients, there are limited tools to predict the prognosis of PBC with compensated cirrhosis. This study aimed to evaluate the prognostic performance of the albumin-bilirubin (ALBI) score in PBC patients with compensated cirrhosis. METHODS: We conducted a retrospective longitudinal study of 219 patients with compensated PBC cirrhosis to evaluate the prognostic performance of the ALBI using Cox regression model, receiver operating characteristic (ROC) curve, and Kaplan-Meier method. RESULTS: During follow-up, a total of 19 subjects (8.7%) met the primary endpoint of liver-related death or liver transplantation (LT). Patients who died/underwent LT have higher ALBI score (-1.06 vs. -2.06, p < 0.001) at baseline than those who survived. ALBI score (hazard ratio: 15.011, 95% confidence interval [CI]: 5.045-44.665, p < 0.001) was associated with an increase in liver-related mortality or LT. ALBI score had the best discriminative capacity to predict the 5-year liver-related mortality (area under the ROC curve: 0.871, 95% CI [0.820, 0.913]) compared with other prognostic scores. The ROC curve showed that the best cut-off value of ALBI score was -1.47, with 90.0% sensitivity and 76.6% specificity. Also, the probability of transplant-free survival decreased with increasing ALBI grade (log-rank p = 0.003). The 5-year transplant-free survival rates of patients in grade 1, grade 2, and grade 3 were 100.0%, 96.4%, and 89.4%, respectively. CONCLUSION: ALBI score is a simple and effective predictive factor estimating the clinical outcome of patients with compensated PBC cirrhosis and provides better prognostic performance compared with other prognostic scores.

Factors related to the severity of obsessive-compulsive symptoms and their impact on suicide risk in epileptic patients.

OBJECTIVE: To explore relevant factors for the severity of obsessive-compulsive symptoms (OCSs) in adult epileptic patients and investigate whether the severity of OCSs is a mediator in the relationship between depressive/anxiety symptoms and suicide risk in epileptic patients. METHODS: This was a cross-sectional study from a hospital in Northeast China. Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Neurological Disorders Depression Inventory for Epilepsy (NDDIE), Generalized Anxiety Disorder (GAD-7), and Nurses' Global Assessment of Suicide Risk (NGASR) were used to assess the severity of OCSs, depressive symptoms, anxiety symptoms, and suicide risk in epileptic patients, respectively. The independent factors of the severity of OCSs and their mediating effects in the relationship between depressive/anxiety symptoms and suicide risk were evaluated by regression analyses and mediator models, respectively. RESULTS: NDDIE scores (ß = 0.404, p < 0.001), GAD-7 scores (ß = 0.247, p = 0.009), and polytherapy (ß = 0.119, p = 0.032) were the independent factors of Y-BOCS scores. The Y-BOCS scores partially mediated the relationship between GAD-7 scores and NGASR scores (standardized coefficients of indirect effect = 0.109, Bootstrap 95% CI = 0.024 to 0.214). Still, they did not mediate the relationship between NDDIE scores and NGASR scores (standardized coefficients of indirect effect = 0.062, Bootstrap 95% CI = -0.024 to 0.169). CONCLUSIONS: Depressive symptoms, anxiety symptoms, and polytherapy are independently associated with the severity of OCSs in epileptic patients. Depressive and anxiety symptoms mediate the effect of the severity of OCSs on suicide risk in epileptic patients completely.

Alexithymia and related factors among patients with epilepsy.

OBJECTIVE: Alexithymia is a psychiatric symptom characterized by difficulties in emotion recognition, expression, and regulation. The purpose of our study was to investigate the prevalence of alexithymia among patients with epilepsy (PWE) and related factors. METHODS: By the means of a cross-sectional study, we consecutively recruited PWE who visited the First Hospital of Jilin University. The demographical information and clinical data were collected. Toronto Alexithymia Scale-20 (TAS-20), Emotion Regulation Questionnaire (ERQ), Kilifi Stigma Scale for Epilepsy (KSSE), Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), Generalized Anxiety Disorder-7 (GAD-7), and Nurses' Global Assessment of Suicide Risk scale (NGASR) scales were applied to assess alexithymia, emotion regulation strategies, and the presence of comorbid psychiatric symptoms. RESULTS: A total of 203 PWE were included. The differences in education, monthly per capita income of the family, and the number of antiepileptic drugs were statistically significant among these three groups with alexithymia, possible alexithymia, and non-alexithymia (p < 0.05). Toronto Alexithymia Scale-20 scores were significantly and positively correlated with BMI (rho = 0.143, p = 0.042). Expression suppression, stigma, and generalized anxiety were independent risk factors for alexithymia (R2 = 0.471, F = 19.075, p < 0.001). CONCLUSIONS: A high prevalence of alexithymia (18.7%) was found in PWE. Alexithymia is primarily influenced by the emotional regulation strategies, anxiety, and stigma among PWE. It tends to be a mood symptom or personality trait rather than a direct result of epilepsy.

Mitochondrial dysfunction in the pathogenesis of acute pancreatitis.

The mechanism of cell damage during acute pancreatitis (AP) has not been fully elucidated, and there is still a lack of specific or effective treatments. Increasing evidence has implicated mitochondrial dysfunction as a key event in the pathophysiology of AP. Mitochondrial dysfunction is closely related to calcium (Ca2+) overload, intracellular adenosine triphosphate depletion, mitochondrial permeability transition pore openings, loss of mitochondrial membrane potential, mitophagy damage and inflammatory responses. Mitochondrial dysfunction is an early triggering event in the initiation and development of AP, and this organelle damage may precede the release of inflammatory cytokines, intracellular trypsin activation and vacuole formation of pancreatic acinar cells. This review provides further insight into the role of mitochondria in both physiological and pathophysiological aspects of AP, aiming to improve our understanding of the underlying mechanism which may lead to the development of therapeutic and preventive strategies for AP.

Biosynthesis and bioactivities of microbial genotoxin colibactins.

Covering: up to 2021Colibactin(s), a group of secondary metabolites produced by the pks island (clb cluster) of Escherichia coli, shows genotoxicity relevant to colorectal cancer and thus significantly affects human health. Over the last 15 years, substantial efforts have been exerted to reveal the molecular structure of colibactin, but progress is slow owing to its instability, low titer, and elusive and complex biosynthesis logic. Fortunately, benefiting from the discovery of the prodrug mechanism, over 40 precursors of colibactin have been reported. Some key biosynthesis genes located on the pks island have also been characterised. Using an integrated bioinformatics, metabolomics, and chemical synthesis approach, researchers have recently characterised the structure and possible biosynthesis processes of colibactin, thereby providing new insights into the unique biosynthesis logic and the underlying mechanism of the biological activity of colibactin. Early developments in the study of colibactin have been summarised in several previous reviews covering various study periods, whereas the two most recent reviews have focused primarily on the chemical synthesis of colibactin. The present review aims to provide an update on the biosynthesis and bioactivities of colibactin.

Boron-, Sulfur- and Nitrogen-Doped Polycyclic Aromatic Hydrocarbon Multiple Resonance Emitters for Narrow-Band Blue Emission.

Two boron-, sulfur- and nitrogen-doped polycyclic aromatic hydrocarbon multiple resonance thermally activated delayed fluorescence emitters with high photoluminescent quantum efficiency (88 %) and rapid reverse intersystem crossing (kRISC = 1.0×105  s-1 ) are designed and synthesized, enabling efficient narrow-band blue electroluminescence at 473 nm with full width at half maximum of 29 nm and maximum external quantum efficiency of 22.0 %, which provides an avenue to expand the structure library for multiple resonance emitters and an approach to regulate their emission properties.

Twenty-year span of global acute pancreatitis trends: A bibliometric analysis.

OBJECTIVE: This study aims to investigate the global research routine and trends of acute pancreatitis over the last twenty years based on the production, hotspots, and frontiers of published articles as well as to provide the global health system with a bibliometric reference. METHODS: The Web of Science core collection database was retrieved for acute pancreatitis original articles and review articles published from January 1, 1999 to May 17, 2020. Duplicates and discrete papers were excluded. Articles were evaluated for several characteristics including number of citations, publication time, country of origin, institution, journal and authorship. RESULTS: A total of 7001 articles originated from 94 countries and were published in 1263 journals. The China contributed most articles (1752) followed by USA (1214). The research was major published in specialized journals including the Pancreas (511) and pancreatology (351). Universities were the main institutions of science progress. High-impact articles focused on the fields of clinical medicine. A steady growth was observed in the last 20 years from 1999 to 2020. CONCLUSION: This comprehensive bibliometric study indicates that severe acute pancreatitis and necrotizing pancreatitis are significant topic in the acute pancreatitis research. The structured information may be helpful in understanding research trends, and locating research hot spots and gaps in this domain.