Microbial signatures predictive of short-term prognosis in severe pneumonia.

Objective: This retrospective cohort study aimed to investigate the composition and diversity of lung microbiota in patients with severe pneumonia and explore its association with short-term prognosis. Methods: A total of 301 patients diagnosed with severe pneumonia underwent bronchoalveolar lavage fluid metagenomic next-generation sequencing (mNGS) testing from February 2022 to January 2024. After applying exclusion criteria, 236 patients were included in the study. Baseline demographic and clinical characteristics were compared between survival and non-survival groups. Microbial composition and diversity were analyzed using alpha and beta diversity metrics. Additionally, LEfSe analysis and machine learning methods were employed to identify key pathogenic microorganism associated with short-term mortality. Microbial interaction modes were assessed through network co-occurrence analysis. Results: The overall 28-day mortality rate was 37.7% in severe pneumonia. Non-survival patients had a higher prevalence of hypertension and exhibited higher APACHE II and SOFA scores, higher procalcitonin (PCT), and shorter hospitalization duration. Microbial α and ß diversity analysis showed no significant differences between the two groups. However, distinct species diversity patterns were observed, with the non-survival group showing a higher abundance of Acinetobacter baumannii, Klebsiella pneumoniae, and Enterococcus faecium, while the survival group had a higher prevalence of Corynebacterium striatum and Enterobacter. LEfSe analysis identified 29 distinct terms, with 10 potential markers in the non-survival group, including Pseudomonas sp. and Enterococcus durans. Machine learning models selected 16 key pathogenic bacteria, such as Klebsiella pneumoniae, significantly contributing to predicting short-term mortality. Network co-occurrence analysis revealed greater complexity in the non-survival group compared to the survival group, with differences in central genera. Conclusion: Our study highlights the potential significance of lung microbiota composition in predicting short-term prognosis in severe pneumonia patients. Differences in microbial diversity and composition, along with distinct microbial interaction modes, may contribute to variations in short-term outcomes. Further research is warranted to elucidate the clinical implications and underlying mechanisms of these findings.

MicroRNAs as Bile-based biomarkers in pancreaticobiliary cancers (MIRABILE): a cohort study.

BACKGROUND: Biliary obstruction can be due to both malignant and benign pancreaticobiliary disease. Currently, there are no biomarkers that can accurately help make this distinction. MicroRNAs (miRNAs) are stable molecules in tissue and biofluids that are commonly deregulated in cancer. The MIRABILE study aimed to identify miRNAs in bile that can differentiate malignant from benign pancreaticobiliary disease. MATERIALS AND METHODS: There were 111 patients recruited prospectively at endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC) for obstructive jaundice, and bile was aspirated for cell-free RNA (cfRNA) extraction and analysis. In a discovery cohort of 78 patients (27 with pancreatic ductal adenocarcinoma (PDAC), 14 cholangiocarcinoma (CCA), 37 benign disease), cfRNA was subjected to small-RNA sequencing. LASSO regression was used to define bile miRNA signatures, and NormFinder to identify endogenous controls. In a second cohort of 87 patients (34 PDAC, 14 CCA, 39 benign disease), RT-qPCR was used for validation. RESULTS: LASSO regression identified 14 differentially-expressed bile miRNAs of which 6 were selected for validation. When comparing malignant and benign pancreaticobiliary disease, bile miR-340 and miR-182 were validated and significantly differentially expressed (P<0.05 and P<0.001, respectively). This generated an AUC of 0.79 (95%CI 0.70-0.88, sensitivity 65%; specificity 82%) in predicting malignant disease. CONCLUSION: Bile collected during biliary drainage contains miRNAs able to differentiate benign from malignant pancreaticobiliary diseases in patients with obstructive jaundice. These bile miRNAs have the potential to increase diagnostic accuracy.

Novel Halogenated Curcumin-Mediated Photodynamic Inactivation for the Preservation of Small Yellow Croaker (Larimichthys polyactis).

A novel class of halogenated curcumin, X-Cur (X = F, Cl, or Br), was synthesized, and its photosensitivity was evaluated. The results showed that Br-Cur with the highest singlet oxygen (1O2) generation capacity exhibited a better photodynamic inactivation (PDI) effect on the small yellow croaker (Larimichthys polyactis) than curcumin. This was attributed to the heavy atom effect of Br, which resulted in Br-Cur having the smallest singlet-triplet energy difference ΔEst(S1-T3) (0.140 eV) and the largest spin-orbit coupling value (0.642262 cm-1). When L. polyactis was treated with 0.025 wt % Br-Cur and exposed to blue LED irradiation (450 nm, 20 mW/cm2) for 20 min, the increase in the total volatile basic nitrogen content (28.23 ± 2.38 mg/100 g on day 6), pH, and total viable count (6.13 ± 0.06 log CFU/g on day 6) could be effectively controlled. Accordingly, Br-Cur is a promising photosensitizer for PDI preservation.

Dimensionless analysis-based permeability model of reinforced concrete under tension.

Water permeability of reinforced concrete is essential for transportation of ingress ions inside concrete structures. The coupling effect of permeability and loading presents a challenge for the experimental simulation of water-permeate reinforced concrete subjected to tension. This renders the development of the model based on dimensionless analysis, using a series of experimental tests from an innovative experimental system that allows simultaneous measurement of permeability and crack width. The experiments focused on both ordinary concrete and high strength concrete under tension. The relationship between permeability and variables such as deformation, diameter of rebars, tensile load, and crack width under tension was formulated through multiple regression analysis using the testing data. The load to deformation characteristics determines the permeability of the concrete under tension. The proposed model accounts for the influence of continuous loading on permeability, as demonstrated by the robust analysis and proposed yield effective point. The robust analysis demonstrates that the diameter of the rebar, load, and crack width exert minimal influence on the permeability of concrete at lower significance levels. However, permeability variations become pronounced from 0.5 threshold, with significant changes observed between 0.5 and 0.9 thresholds. The findings indicate a differential impact of the variables on the permeability of concrete under tension. The yield-effective points delineate the relationship between the rebar diameter, load, and crack-width on the permeability of concrete with a threshold of 0.5, 0.5, and 0.58, respectively. At a threshold of 0.78, higher permeability will occur in the concrete, attributed to the prevalence of deformation. This deformation highlights the parameters with the most significant influence on the permeability of concrete under tension. The robust analysis and yield effective point derivative are useful parameters to measure concrete permeability and evaluate the behavior of the permeability model under tension.

Unlocking the diagnostic power of plasma extracellular vesicle miR-200 family in pancreatic ductal adenocarcinoma.

BACKGROUND: Distinguishing benign from malignant pancreaticobiliary disease is challenging because of the absence of reliable biomarkers. Circulating extracellular vesicles (EVs) have emerged as functional mediators between cells. Their cargos, including microRNAs (miRNAs), are increasingly acknowledged as an important source of potential biomarkers. This multicentric, prospective study aimed to establish a diagnostic plasma EV-derived miRNA signature to discriminate pancreatic ductal adenocarcinoma (PDAC) from benign pancreaticobiliary disease. METHODS: Plasma EVs were isolated using size exclusion chromatography (SEC) and characterised using nanoparticle tracking analysis, electron microscopy and Western blotting. EV-RNAs underwent small RNA sequencing to discover differentially expressed markers for PDAC (n = 10 benign vs. 10 PDAC). Candidate EV-miRNAs were then validated in a cohort of 61 patients (n = 31 benign vs. 30 PDAC) by RT-qPCR. Logistic regression and optimal thresholds (Youden Index) were used to develop an EV-miR-200 family model to detect cancer. This model was tested in an independent cohort of 95 patients (n = 30 benign, 33 PDAC, and 32 cholangiocarcinoma). RESULTS: Small RNA sequencing and RT-qPCR showed that EV-miR-200 family members were significantly overexpressed in PDAC vs. benign disease. Combined expression of the EV-miR-200 family showed an AUC of 0.823. In an independent validation cohort, application of this model showed a sensitivity, specificity and AUC of 100%, 88%, and 0.97, respectively, for diagnosing PDAC. CONCLUSIONS: This is the first study to validate plasma EV-miR-200 members as a clinically-useful diagnostic biomarker for PDAC. Further validation in larger cohorts and clinical trials is essential. These findings also suggest the potential utility in monitoring response and/or recurrence.

Introduction of day-case robotic liver surgery: a case series from a tertiary hepatobiliary and pancreatic centre.

BACKGROUND: Liver surgery is associated with a significant hospital stay regardless the type of liver resection. A large incision is essential for open liver surgery which is a major factor in the course of the patient's recovery. For patients with small parenchyma liver lesions requiring surgical resection, robotic surgery potentially offers the opportunity to transform the patient's post-operative course. A day-case robotic liver resection pathway was formulated and implemented at our institution when patients were planned for discharge within 24 h of admission for liver surgery. METHODS: Single surgeon case series of cases performed at a tertiary hepatobiliary and pancreatic centre between September 2022 and November 2023. The inclusion criteria were non-anatomical wedge resections, < 2 anatomical segmental resections, left lateral hepatectomy and minimally invasive surgery. RESULTS: This is the first series of robotic day-case minor liver resection in the United Kingdom. 20 patients were included in this case series. The mean operative time was 86.6 ± 30.9 min and mean console time was 58.6 ± 24.5 min. Thirteen patients (65%) were discharged within 24 h of surgery. The main cause of hospitalisation beyond 24 h was inadequate pain relief. There were no Clavien-Dindo grade III or above complications, no 30-day readmission and 90-day mortalities. CONCLUSION: This case series demonstrates that robotic day-case liver resection is safe and feasible. Robust follow-up pathways must be in place to allow for the safe implementation of this approach, to monitor for any complications and to allow intervention as required in a timely manner.

Effect analysis of repeated transcranial magnetic stimulation combined with fluoxetine in the treatment of first-episode adolescent depression.

Objectives: This study aims to evaluate the efficacy of repeated transcranial magnetic stimulation (rTMS) combined with fluoxetine in enhancing the early antidepressant response in first-episode adolescent depression cases, providing insights for patient diagnosis and treatment. Methods: One hundred and thirty-five adolescents experiencing their first depressive episode were randomly assigned to either a sham group treated with fluoxetine or to low or high repetitive transcranial magnetic stimulation (rTMS) groups receiving both rTMS and fluoxetine. Therapeutic effects were assessed by comparing changes in Hamilton Depression Scale (HAMD-17) scores, cognitive function scores from the Wisconsin Card Sorting Test (WCST), and Clinical Global Impression-improvement (CGI-I) scores, along with recording adverse reactions. Results: The total effectiveness rate in the rTMS groups (Low, 95.56%; High, 97.78%) was significantly higher than in the Sham rTMS group (80%) (F = 11.15, P<0.0001). Post-treatment, not only the Low but also the High rTMS group exhibited more significant reductions in HAMD-17 (Low, 21.05; High, 21.45) and CGI-I scores (Low, 3.44; High, 3.60) compared to the Sham rTMS group (HAMD-17, 16.05; CGI-I, 2.57) (two weeks: F = 7.889, P = 0.0006; four weeks: F = 15.900, P<0.0001). Additionally, the two rTMS groups exhibited fewer erroneous responses and persistent errors in the WCST and completed more WCST categorizations than the Sham rTMS group. There was no significant difference in adverse reaction rates between the groups (F=4.421, P=0.0794). Conclusions: The combination of fluoxetine with rTMS demonstrates enhanced therapeutic effectiveness in treating adolescent depression, effectively controlling disease progression, reducing depressive symptoms, and improving cognitive function, making it a valuable clinical approach.

Curcumin-loaded food-grade nano-silica hybrid material exhibiting improved photodynamic effect and its application for the preservation of small yellow croaker (Larimichthys polyactis).

Two types of curcumin-loaded food-grade nano-silica (F-SiO2) hybrid materials were successfully synthesized using the rotary evaporation method (F-SiO2@Cur) and the adsorption method (Cur@F-SiO2). The microstructure and spectral analyses confirmed that the curcumin in F-SiO2@Cur was loaded within the nanopores in a non-aggregate form rather than being adsorbed onto the surface (Cur@F-SiO2). Additionally, F-SiO2@Cur exhibited remarkable water solubility (1510 ± 50.33 µg/mL) and photostability (a photodegradation ratio of only 59.22 %). Importantly, F-SiO2@Cur obtained a higher capacity for the generation of singlet oxygen (1O2) compared to control groups. Consequently, F-SiO2@Cur-mediated photodynamic inactivation (PDI) group attained the highest score in sensory evaluation and the best color protection effect in PDI experiment of small yellow croaker (Larimichthys polyactis) at 4 °C. Moreover, F-SiO2@Cur could effectively controlled total volatile basic nitrogen (TVB-N) content, pH, and total viable count (TVC), thereby prolonging the shelf life. Therefore, F-SiO2@Cur-mediated PDI is an effective fresh-keeping technology for aquatic products.

Generation and persistency of combustion-derived environmentally persistent free radicals from phenolic compounds over a Fe2O3/SiO2 surface.

Combustion of organic solid wastes releases phenolic compounds which can act as precursors in the formation of environmentally persistent free radicals (EPFRs) in the post-flame, cooling zone of waste combustion. The study investigated the generation mechanism of EPFRs from phenolic compounds catalyzed by transition metals in air atmosphere under simulated combustion conditions. Representative combustion-derived phenolic compounds were used, and SiO2 particulates containing different mass ratio of Fe2O3 were synthesized as carriers. EPFRs formed had g-factors between 1.9998 and 2.0066, indicating phenoxyl-, cyclopentadienyl-, and semiquinone-type radicals, along with paramagnetic F-centers. The promotion effect of phenolic compounds on EPFR formation during heating decreased as catechol > hydroquinone > phenol > p-cresol. This trend is related to hydroxyl groups and activation energy. In particular, catechol chemically adsorbed on Fe2O3 at 600 K led to the formation of EPFRs with relatively high spin concentrations (up to 1.28 × 1017 spin/g). Higher Fe2O3 concentrations promoted the transformation of phenoxyl-type radicals into cyclopentadienyl-type and paramagnetic F-centers. However, as the Fe2O3 loading increased from 1.25% to 5%, the density of EPFRs decreased. The findings related to the influence of various precursors and Fe2O3 concentration on EPFR formation provide valuable insights for estimating EPFR generation and associated risk during combustion processes.

[Hologram quantitative structure-activity relationship on the gas chromatographic retention index of plant essential oil constituents].

The gas chromatography retention index (RI) is an important parameter for the identification of different types of compounds in the field of chromatographic analysis; however, the experimental collection of RI values is a extremely cumbersome process. Thus, there is an urgent need for the establishment of a simple, efficient, and accurate model for the prediction of the RI values of compounds. In this study, first, the experimental RI values for 60 plant essential oil constituents were obtained. Next, a model describing the hologram quantitative structure-activity relationship (HQSAR) between the structural properties of the essential oil constituents and their RI values was investigated and constructed. The optimal HQSAR model was established by setting the model parameters "fragment size", "fragment distinction", "hologram length" and "principal components" to "1-4", "C, Ch", "199", and "4", respectively. Finally, the predictive ability of the model was verified using external test set validation and leave-one-out cross-validation (LOO-CV). The experimental results were as follows, the root mean square error of prediction (RMSEP), predictive determination coefficient ([Formula: see text]), concordance correlation coefficient (CCC), and mean relative error (MRE) for external test set validation were 40.45, 0.984, 0.968, and 2.20%, respectively. Meanwhile, the root mean square error of cross validation (RMSECV) and MRE for LOO-CV were 72.56 and 4.17%, respectively. These findings demonstrate that the established HQSAR model has a good predictive ability and can accurately predict the RI values of plant essential oil constituents. In addition, the molecular contribution maps of the HQSAR model revealed that the RI values of aromatic compounds increase when hydroxyl groups are connected to their alkyl chains. Aliphatic compounds feature long chain alkyl groups, which can lead to an increase in RI values. The above phenomena highlight the promising application prospects of HQSAR for studying the RI values of plant essential oil constituents. Therefore, this study provides a reliable theoretical basis for predicting the RI values of other essential oil constituents.

Efficient fabrication of bioinspired soft, ridged-slippery surfaces with large-range anisotropic wettability for droplet manipulation.

The droplet lossless directional motion control on slippery surfaces holds immense promise for applications in microfluidic chips, hazardous substance detection, chemical dispensing, etc. However, a significant challenge in this domain lies in efficiently developing soft, slippery surfaces with large-range anisotropic wettability and compatibility for curved scenarios. This study addressed this challenge through a quick 3D printing-assisted method to produce soft, ridged-slippery surfaces (SRSSs) as the droplet manipulation platform. The SRSSs demonstrated substantial anisotropic rolling resistances, measuring 116.9 µN in the perpendicular direction and 7.7 µN in the parallel direction, exhibiting a ratio of 15.2. Combining several extents of anisotropic wettability on a soft substrate could realize diverse reagent manipulation functions. Furthermore, these SRSSs showcased high compatibility with various droplet constituents, impressive liquid impact resistance, self-repair capability, and mechanical durability and thermal durability, ensuring exceptional applicability. As proofs of concept, the SRSSs were successfully applied in droplet control and classification for heavy metal ion detection, mechanical arm-based droplet grab and release, and cross-species transport, showcasing their remarkable versatility, compatibility, and practicality in advanced droplet microfluidic chips and water harvesting applications.

A multicenter clinical AI system study for detection and diagnosis of focal liver lesions.

Early and accurate diagnosis of focal liver lesions is crucial for effective treatment and prognosis. We developed and validated a fully automated diagnostic system named Liver Artificial Intelligence Diagnosis System (LiAIDS) based on a diverse sample of 12,610 patients from 18 hospitals, both retrospectively and prospectively. In this study, LiAIDS achieved an F1-score of 0.940 for benign and 0.692 for malignant lesions, outperforming junior radiologists (benign: 0.830-0.890, malignant: 0.230-0.360) and being on par with senior radiologists (benign: 0.920-0.950, malignant: 0.550-0.650). Furthermore, with the assistance of LiAIDS, the diagnostic accuracy of all radiologists improved. For benign and malignant lesions, junior radiologists' F1-scores improved to 0.936-0.946 and 0.667-0.680 respectively, while seniors improved to 0.950-0.961 and 0.679-0.753. Additionally, in a triage study of 13,192 consecutive patients, LiAIDS automatically classified 76.46% of patients as low risk with a high NPV of 99.0%. The evidence suggests that LiAIDS can serve as a routine diagnostic tool and enhance the diagnostic capabilities of radiologists for liver lesions.

Functional enrichment analysis reveals the involvement of DARS2 in multiple biological pathways and its potential as a therapeutic target in esophageal carcinoma.

OBJECTIVE: The enzyme Aspartyl tRNA synthetase 2 (DARS2) is a crucial enzyme in the mitochondrial tRNA synthesis pathway, playing a critical role in maintaining normal mitochondrial function and protein synthesis. However, the role of DARS2 in ESCA is unclear. MATERIALS AND METHODS: Transcriptional data of pan-cancer and ESCA were downloaded from UCSC XENA, TCGA, and GEO databases to analyze the differential expression of DARS2 between tumor samples and normal samples, and its correlation with clinicopathological features of ESCA patients. R was used for GO, KEGG, and GSEA functional enrichment analysis of DARS2 co-expression and to analyze the connection of DARS2 with glycolysis and m6A-related genes. In vitro experiments were performed to assess the effects of interfering with DARS2 expression on ESCA cells. TarBase v.8, mirDIP, miRTarBase, ENCORI, and miRNet databases were used to analyze and construct a ceRNA network containing DARS2. RESULTS: DARS2 was overexpressed in various types of tumors. In vitro experiments confirmed that interfering with DARS2 expression significantly affected the proliferation, migration, apoptosis, cell cycle, and glycolysis of ESCA cells. DARS2 may be involved in multiple biological pathways related to tumor development. Furthermore, correlation and differential analysis revealed that DARS2 may regulate ESCA m6A modification through its interaction with METTL3 and YTHDF1. A ceRNA network containing DARS2, DLEU2/has-miR-30a-5p/DARS2, was successfully predicted and constructed. CONCLUSIONS: Our findings reveal the upregulation of DARS2 in ESCA and its association with clinical features, glycolysis pathway, m6A modification, and ceRNA network. These discoveries provide valuable insights into the molecular mechanisms underlying ESCA.

A comprehensive metabolomics analysis of volatile and non-volatile compounds in matcha processed from different tea varieties.

Tea varieties play a crucial role on the quality formation of matcha. This research aimed to examine the impact of four specific tea plant varieties (Okumidori, Longjing 43, Zhongcha108, and E'Cha 1) on various aspects of matcha, including sensory evaluation, major components, color quality, volatile and non-volatile metabolomic profiles. The findings revealed that the levels of tea polyphenols, ester catechins, nonester catechins, and amino acids varied among these four varieties. Notably, 177 significant different metabolites, such as phenolic acids, flavonoids, tannins, alkaloids were identified among 1383 non-volatile compounds. In addition, 97 key aroma-active compounds were identified based on their odor activity value exceeding 1. Aldehydes, heterocyclic compounds, and ketones were closely associated with the formation of volatile metabolites. Overall, this study enhances our understanding of how different tea plant varieties impact the quality of matcha, and can provide valuable guidance for improving matcha varieties in a favorable direction.

Food-grade silica-loaded gallic acid nanocomposites: Synthesis and mechanism for enhancing water-based biological activity.

As the low water solubility of gallic acid (GA), its biological activities such as water-based antioxidant effect may be greatly reduced. Therefore, GA-loaded nanocomposites (F-SiO2@GA) with high water solubility were synthesized via solvent evaporation using food-grade silica (F-SiO2) as carriers in this work. The assessment of antioxidant capacity revealed that F-SiO2@GA exhibited considerably greater free-radical scavenging ability than free GA and the physical mixture of F-SiO2 and GA. In the photooxidation experiment of food-grade gardenia yellow pigment (GYP), F-SiO2@GA showed a notable antioxidant effect on GYP solution. Additionally, in the storage experiment on chilled whiteleg shrimp (Litopenaeus vannamei) treated with F-SiO2@GA, pH, total volatile basic nitrogen (TVBN), and thiobarbituric acid reactive substance (TBARS) values were effectively inhibited. In conclusion, the internal encapsulation of GA effectively prevented the self-aggregation phenomenon, thereby facilitating the exposure of its active phenolic hydroxyl group and significantly enhancing its water-based biological activity.

Bioavailability transition path of phosphorus species during the sewage sludge incineration process.

Sewage sludge incineration ash (SSIA) is rich in phosphorus (P), thus being considered as a reliable source of phosphorus recovery. Different P species behaved significant bioavailability. Based on this, a comprehensive investigation into the bioavailability transition path of P species during sewage sludge (SS) incineration was conducted. P predominantly existed in the form of inorganic phosphorus (IP) in SS with a higher concentration of non-apatite inorganic phosphorus (NAIP) and less concentration of apatite inorganic phosphorus (AP). During the SS incineration process, OP existed in the flocs and cell structures of SS underwent destruction, the released P then combined with metal elements such as Ca, Mg, Fe, and Al to form AP species (Ca/Mg-P) and NAIP species (Fe/Al/Mn-P), and the NAIP decomposition to release into gas phase. This was the initial step for enhancing the bioavailability of P species. As temperature increased and the incineration process progressed, the low-temperature-resistant NAIP dissociated, and the metal-binding sites of Al, Fe and Mn in NAIP species were gradually replaced by the Ca and Mg thus forming thermal stability AP species (Ca/Mg-P, such as CaHPO4, Ca2PO4Cl, and Mg3(PO4)2 et al.). This step was crucial for the bioavailability improvement of P species during the incineration process. Therefore, the IP proportions in TP were extremely high (＞98%), and this value gradually increased as incineration temperature raised. The higher incineration temperature, the lower NAIP concentration and higher AP concentration. Besides, additives such as coal/rice husk/eggshell played a significant affect. Additives wither higher Ca content were inclined to react with P to form Ca/Mg-P (AP), while the presence of SO2 would react with Ca metals to form CaSO4 thus inhibiting the formation of AP species (such as CaHPO4 and CaPO4Cl). This results could provide theoretical support for the efficient and directional migration of P during sewage sludge incineration.

Microwave-Assisted Rapid Synthesis of MOF-Based Single-Atom Ni Catalyst for CO2 Electroreduction at Ampere-Level Current.

Carbon-based single-atom catalysts (SACs) have attracted tremendous interest in heterogeneous catalysis. However, the common electric heating techniques to produce carbon-based SACs usually suffer from prolonged heating time and tedious operations. Herein, a general and facile microwave-assisted rapid pyrolysis method is developed to afford carbon-based SACs within 3 min without inert gas protection. The obtained carbon-based SACs present high porosity and comparable carbonization degree to those obtained by electric heating techniques. Specifically, the single-atom Ni implanted N-doped carbon (Ni1 -N-C) derived from a Ni-doped metal-organic framework (Ni-ZIF-8) exhibits remarkable CO Faradaic efficiency (96 %) with a substantial CO partial current density (jCO ) up to 1.06 A/cm2 in CO2 electroreduction, far superior to the counterpart obtained by traditional pyrolysis with electric heating. Mechanism investigations reveal that the resulting Ni1 -N-C presents abundant defective sites and mesoporous structure, greatly facilitating CO2 adsorption and mass transfer. This work establishes a versatile approach to rapid and large-scale synthesis of SACs as well as other carbon-based materials for efficient catalysis.

Complete Primary Pathological Response Following Neoadjuvant Treatment and Radical Resection for Pancreatic Ductal Adenocarcinoma.

INTRODUCTION: Neoadjuvant treatment (NAT) for borderline (BD) or locally advanced (LA) primary pancreatic cancer (PDAC) is now a widely adopted approach. We present a case series of patients who have achieved a complete pathological response of the primary tumour on final histology following neoadjuvant chemotherapy +/- chemoradiation and radical surgery. METHODS: Patients who underwent radical pancreatic resection following neoadjuvant treatment between March 2006 and March 2023 at a single institution were identified by retrospective case note review of a prospectively maintained database. RESULTS: Ten patients were identified to have a complete primary pathological response (ypT0) on postoperative histology. Before treatment, five patients were considered BD and five were LA according to National Comprehensive Cancer Network guidelines. All patients underwent staging Computed Tomography (CT) and nine underwent 18Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET/CT) imaging, with a mean maximum standardized uptake value (SUVmax) of the primary lesion at 6.14 ± 1.98 units. All patients received neoadjuvant chemotherapy, and eight received further chemoradiotherapy prior to resection. Mean pre- and post-neoadjuvant treatment serum Ca19-9 was 148.0 ± 146.3 IU/L and 18.0 ± 18.7 IU/L, respectively (p = 0.01). The mean duration of NAT was 5.6 ± 1.7 months. The mean time from completion of NAT to surgery was 13.1 ± 8.3 weeks. The mean lymph node yield was 21.1 ± 10.4 nodes, with one patient found to have 1 lymph node involved. All resections were reported to be R0. The mean length of stay was 11.8 ± 6.2 days. At the time of analysis, one death was reported at 35 months postoperatively. Two cases of recurrence were reported at 16 months (surgical bed) and 33 months (pulmonary). All other patients remain alive and under active surveillance. The current overall survival is 26.6 ± 20.7 months and counting. CONCLUSIONS: Complete primary pathological response is uncommon but possible following neoadjuvant treatment in patients with PDAC. Further work to identify the common denominator within this unique cohort may lead to advances in the therapeutic approach and offer hope for patients diagnosed with borderline or locally advanced pancreatic ductal adenocarcinoma.

A bile-based microRNA signature for differentiating malignant from benign pancreaticobiliary disease.

Differentiating between pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CCA) is crucial for the appropriate course of treatment, especially with advancements in the role of neoadjuvant chemotherapies for PDAC, compared to CCA. Furthermore, benign pancreaticobiliary diseases can mimic malignant disease, and indeterminate lesions may require repeated investigations to achieve a diagnosis. As bile flows in close proximity to these lesions, we aimed to establish a bile-based microRNA (miRNA) signature to discriminate between malignant and benign pancreaticobiliary diseases. We performed miRNA discovery by global profiling of 800 miRNAs using the NanoString nCounter platform in prospectively collected bile samples from malignant (n = 43) and benign (n = 14) pancreaticobiliary disease. Differentially expressed miRNAs were validated by RT-qPCR and further assessed in an independent validation cohort of bile from malignant (n = 37) and benign (n = 38) pancreaticobiliary disease. MiR-148a-3p was identified as a discriminatory marker that effectively distinguished malignant from benign pancreaticobiliary disease in the discovery cohort (AUC = 0.797 [95% CI 0.68-0.92]), the validation cohort (AUC = 0.772 [95% CI 0.66-0.88]), and in the combined cohorts (AUC = 0.752 [95% CI 0.67-0.84]). We also established a two-miRNA signature (miR-125b-5p and miR-194-5p) that distinguished PDAC from CCA (validation: AUC = 0.815 [95% CI 0.67-0.96]; and combined cohorts: AUC = 0.814 [95% CI 0.70-0.93]). Our research stands as the largest, multicentric, global profiling study of miRNAs in the bile from patients with pancreaticobiliary disease. We demonstrated their potential as clinically useful diagnostic tools for the detection and differentiation of malignant pancreaticobiliary disease. These bile miRNA biomarkers could be developed to complement current approaches for diagnosing pancreaticobiliary cancers.

Robotic Distal Pancreatectomy Yields Superior Outcomes Compared to Laparoscopic Technique: A Single Surgeon Experience of 123 Consecutive Cases.

Technical limitations of laparoscopic distal pancreatectomy (LDP), in comparison to robotic distal pancreatectomy (RDP), may translate to high conversion rates and morbidity. LDP and RDP procedures performed between December 2008 and January 2023 in our tertiary referral hepatobiliary and pancreatic centres were analysed and compared with regard to short-term outcomes. A total of 62 consecutive LDP cases and 61 RDP cases were performed. There was more conversion to open surgeries in the laparoscopic group compared with the robotic group (21.0% vs. 1.6%, p = 0.001). The LDP group also had a higher rate of postoperative complications (43.5% vs. 23.0%, p = 0.005). However, there was no significant difference between the two groups in terms of major complication or pancreatic fistular after operations (p = 0.20 and p = 0.71, respectively). For planned spleen-preserving operations, the RDP group had a shorter mean operative time (147 min vs. 194 min, p = 0.015) and a reduced total length of hospital stay compared with the LDP group (4 days vs. 7 days, p = 0.0002). The failure rate for spleen preservation was 0% in RDP and 20% (n = 5/25) in the LDP group (p = 0.009). RDP offered a better method for splenic preservation with Kimura's technique compared with LDP to avoid the risk of splenic infarction and gastric varices related to ligation and division of splenic pedicles. RDP should be the standard operation for the resection of pancreatic tumours at the body and tail of the pancreas without involving the celiac axis or common hepatic artery.