Search

Sulfur-driven autotrophic denitrification (SAD) process is a cost-effective and sustainable method for nitrogen removal from wastewater. However, a higher concentration of zinc ions (Zn(II)) flowing into wastewater treatment plants poses a potential threat to the SAD process. This study examined that a half maximal inhibitory concentration (IC 50 ) of Zn(II) was 7 mg·L -1 in the SAD process. Additionally, the addition of 20 mg·L -1 Zn(II) resulted in a severe accumulation of nitrite to 150.20 ± 6.00 mg·L -1 when the initial concentration of nitrate was 500 mg·L -1 . Moreover, the activities of nitrate reductase, nitrite reductase, dehydrogenase and electron transport system were significantly inhibited under Zn(II) stress. The addition of Zn(II) inhibited EPS secretion and worsened electrochemical properties. The result was attributed to the spontaneous binding between EPS and Zn(II), with a ΔG of -17.50 KJ·mol -1 and a binding constant of 1.77 × 10 4  M -1 , respectively. Meanwhile, the protein, fulvic acid, and humic-like substances occurred static quenching after Zn(II) addition, with -OH and -C=O groups providing binding sites. The binding sequence was fulvic acid→protein→humic acid and -OH → -C=O. Zn(II) also reduced the content of α-helix, which was unfavorable for electron transfer. Additionally, the Zn(II) loosened protein structure, resulting in a 50 % decrease in α-helix/(β-sheet+random coil). This study reveals the effect of Zn(II) on the SAD process and enhances our understanding of EPS behavior under metal ions stress., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aim: To determine whether social support and psychological resiliency are significant mediators of the associations between risk perception and quality of working life in Chinese nurses working with infectious diseases., Design: A cross-sectional study., Methods: A cross-sectional survey of 879 nurses in infectious diseases department of specialty or general hospitals in China completed online questionnaires on the nurses' risk perception questionnaire, quality of working life, psychological resilience and the social support rating scale., Results: Our study observed that risk perception directly negatively influences the quality of working life of infectious disease nurses, while psychological resilience and social support positively chain mediate this relationship., Conclusion: Critical elements impacting the quality of working life of infectious disease nurses are risk perception, psychological resilience and social support. Managers may think about decreasing the level of risk perception and enhancing the quality of working life of infectious disease nurses by enhancing their psychological resilience and providing support., Public Contribution: The quality of working life of infectious disease nurses should be a priority for nursing management; it is critical to maintain their health and well-being, raise the quality of care and lower turnover. Managers should create resilience-building programmes and support tools to assist nurses properly perceive risks and adopt protective strategies to deal with them to improve the quality of working life for nurses., (© 2024 The Author(s). Nursing Open published by John Wiley & Sons Ltd.)

Live virus vaccine (LVV) purification, employing chromatography, can be challenged by low binding capacities and elution yields. Alternatively, processes relying solely on enzymatic digestion steps and size-based membrane separations can be limited by suboptimal reduction of process related impurities and poorly scalable unit operations. Here, we demonstrate that the combination of flowthrough mode chromatography and an ultrafiltration/diafiltration (UF/DF) unit operation delivers a purification process for two different LVV candidates, V590 and Measles, expressed in adherent Vero cells. For V590, chromatography with mixed mode cation exchange resins returned final product yields of ∼50% and logarithmic reduction values (LRVs) of 1.7->3.4 and 2.5-3.0 for host cell DNA (hcDNA) and host cell proteins (HCPs), respectively. For Measles, chromatography with mixed mode anion exchange resins returned final product yields of ∼50% and LRVs of 1.6 and 2.2 for hcDNA and HCPs, respectively. For both V590 and Measles processing, the employed resins cleared a key HCP, fibronectin, which could foul the UF/DF unit operation, and thusly enabling it to further reduce HCPs and to formulate the final LVV products. This integrated purification process utilizes the complementary action of the two unit operations and its applicability across LVVs supports its consideration for their processing., (© 2023 Merck Sharp & Dohme LLC. Biotechnology and Bioengineering published by Wiley Periodicals LLC.)

The structures of three 1:1 cocrystal forms of etoricoxib {ETR; systematic name: 5-chloro-2-(6-methylpyridin-3-yl)-3-[4-(methylsulfonyl)phenyl]pyridine, C 18 H 15 ClN 2 O 2 S} have been synthesized and characterized by single-crystal X-ray diffraction; these are etoricoxib-benzoic acid (1/1), C 18 H 15 ClN 2 O 2 S·C 7 H 6 O 2 (ETR-Bz), etoricoxib-4-fluorobenzoic acid (1/1), C 18 H 15 ClN 2 O 2 S·C 7 H 5 FO 2 (ETR-PFB), and etoricoxib-4-nitrobenzoic acid (1/1), C 18 H 15 ClN 2 O 2 S·C 7 H 5 NO 4 (ETR-PNB). Powder X-ray diffraction and thermal differential scanning calorimetry-thermogravimetry (DSC-TG) techniques were also used to characterize these multicomponent systems. Due to the influence of the corresponding acids, ETR shows different conformations. Furthermore, the energetic contributions of the supramolecular motifs have been established by energy framework studies of the stabilizing interaction forces and are consistent with the thermal stability of the cocrystals.

The platelet to lymphocyte ratio (PLR) is the marker of host inflammation and it is a potential significant prognostic indicator in various different tumors. The serum carbohydrate antigen 19-9 (CA19-9) is a tumor-associated antigen and it is associated with poor prognosis of gallbladder cancer (GBC). We aimed to analyze the prognostic value of the combination of preoperative PLR and CA19-9 in patients with GBC. A total of 287 GBC patients who underwent curative surgery in our institution was included. To analyze the relationship between PLR and CA19-9 and clinicopathological features. A receiver operating characteristic (ROC) curve was used to identify the optimal cutoff value for PLR and CA19-9. The Kaplan-Meier method was used to estimate the overall survival (OS). Meanwhile, the univariate and multivariate Cox regression models were used to assess the risk factors for OS. The cutoff values of 146.82 and 36.32U/ml defined as high PLR and high CA19-9, respectively. Furthermore, survival analysis showed that patients with PLR > 146.82 and CA19-9 > 36.32 U/ml had a worse prognosis than patients with PLR ≤ 146.82 and CA19-9 ≤ 36.32 U/ml, respectively. The multivariate analysis demonstrated that PLR (hazard ratio (HR) = 1.863, 95% CI: 1.366-2.542, P < 0.001) and CA19-9 (HR = 1.412, 95% CI: 1.021-1.952, P = 0.037) were independent prognostic factors in the GBC patients. When we combined these two parameters, the area under the ROC curve increased from 0.624 (PLR) and 0.661 (CA19-9) to 0.711. In addition, the 1-, 3-, and 5-year OS of group A (patients with PLR ≤ 146.82 and CA19-9 ≤ 36.32 U/ml), group B (patients with either of PLR > 146.82 or CA19-9 > 36.32 U/ml) and group C (patients with PLR > 146.82 and CA19-9 > 36.32 U/ml) were 83.6%, 58.6%, 22.5%, 52.4%, 19.5%, 11.5%, and 42.3%, 11.9%, 0%, respectively. The preoperative PLR and serum CA19-9 are associated with prognosis of patients with GBC. The combination of PLR and CA19-9 may serve as a significant prognostic biomarker for GBC patients superior to either PLR or CA19-9 alone., (© 2024. Italian Society of Surgery (SIC).)

Objective: To analyze the differences of clinical features of acute gout flare and postoperative infection under arthroscopy of knee gouty arthritis patients to offer guiding opinions of clinical diagnosis and treatment., Methods: Between January 2017 and December 2022, 235 patients with gouty knee osteoarthritis were admitted, and underwent arthroscopic debridement combined with synovectomy. Among them, 35 cases had fever with a temperature higher than 38 °C postoperatively while acute inflammatory appears under redness, swelling, heat and pain of the operated joints. There were 29 males and 6 females, with an average age of (41.48±13.90) years old. Among them 23 patients were diagnosed with acute gout attack, and recovered well after being given colchicine and prednisolone;12 patients were diagnosed with postoperative joint infection, and were cured after being given anti-infective treatments and cleaning and rinsing of the joint cavity. The two groups of patients were compared and analyzed in terms of preoperative general data, surgical conditions, hematology, joint fluid, limb function and other clinical characteristics., Results: There were no significant difference in the preoperative general data between two groups. The onset of fever in the postoperative acute gout flare group occurred mostly within 48 hours, significantly earlier than that in the postoperative infection group( P =0.037). The visual analogue scale score was significantly higher in the acute gout flare group (5.32±1.38) score than in the postoperative infection group (2.45±0.68) score ( P =0.000), while 14 patients with acute gout flare were accompanied by severe pain in other joints. Hematologically, indicators such as white blood cell counts and ratios were significantly higher in both groups. In terms of inflammatory indicators, IL-6, erythrocyte sedimentation rate, procalcitonin and other inflammatory indicators were significantly elevated in both groups, but there was no statistical difference between two groups. The C-reactive protein level in the postoperative infection group (220.97±116.30) mg·L -1 was higher than that in the postoperative acute gout attack group(120.67±82.45) mg·L -1 ( P =0.006). Blood uric acid (316.55±112.84) μmol·L -1 was higher in the acute postoperative gout flare group than in the postoperative infection group (159.14±126.92) μmol·L -1 ( P =0.001). In the joint fluid examination of the postoperative infection group, the glucose metabolism indicator was significantly lower than that of the acute gout flare group, and five of them had positive bacterial cultures., Conclusion: The symptoms of acute gout flare could be mistaken as postoperative infection due to their similarity, therefore requires careful differentiation. Differential diagnosis should be based on a combination of clinical signs, hematology and joint fluid findings, and targeted treatment should be given to avoid serious complications.

Background: Gallbladder mixed neuroendocrine-non-neuroendocrine neoplasm generally consists of a gallbladder neuroendocrine tumor and a non-neuroendocrine component. The World Health Organization (WHO) in 2019 established a guideline requiring each component, both neuroendocrine and non-neuroendocrine, to account for a minimum of 30% of the tumor mass., Methods: Patients after surgery resection and diagnosed at microscopy evaluation with pure gallbladder neuroendocrine carcinoma (GBNEC), gallbladder mixed adeno-neuroendocrine carcinoma (GBMANEC, GBNEC≥30%), and gallbladder carcinoma mixed with a small fraction of GBNEC (GBNEC <30%) between 2010 and 2022 at West China Hospital of Sichuan University were collated for the analyses. Demographic features, surgical variables, and tumor characteristics were evaluated for association with patients' overall and recurrence-free survival (OS and RFS)., Results: The study included 26 GBNEC, 11 GBMANEC, 4 gallbladder squamous-cell carcinoma (GBSCC), and 7 gallbladder adenocarcinoma (GBADC) mixed with a small fraction of GBNEC. All patients had stage III or higher tumors (AJCC 8th edition). The majority of included patients (79.17%) underwent curative surgical resection (R0), with only ten patients having tumoral resection margins. In the analysis comparing patients with GBNEC percentage (GBNEC≥30% vs. GBNEC<30%), the basic demographics and tumor characteristics of most patients were comparable. The prognosis of these patients was also comparable, with a median OS of 23.65 months versus 20.40 months (P=0.13) and a median RFS of 17.1 months versus 12.3 months (P=0.24). However, patients with GBADC or GBSCC mixed with GBNEC <30% had a statistically significant decreased OS and RFS (both P<0.0001)) compared with GBNEC and GBMANEC. Patients with GBNEC who exhibited advanced tumor stages and lymphovascular invasion had a higher risk of experiencing worse overall survival (OS) and recurrence-free survival (RFS). However, a 30% GBNEC component was not identified as an independent risk factor., Conclusion: Patients with GBNEC were frequently diagnosed at advanced stages and their prognosis is poor. The 30% percentage of the GBNEC component is not related to the patient's survival., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hu, Wang, Ma, Hu, Gu, Liu, Lv, Yang, Dai, Zou, Jin and Li.)

Objective: Our study aims to evaluate the predictive accuracy of functional liver remnant volume (FLRV) in post-hepatectomy liver failure (PHLF) among surgically-treated jaundiced patients with hilar cholangiocarcinoma (HCCA)., Methods: We retrospectively reviewed surgically-treated jaundiced patients with HCCA between June, 2000 and June, 2018. The correlation between FRLV and PHLF were analyzed. The optimal cut off value of FLRV in jaundiced HCCA patients was also identified and its impact was furtherly evaluated., Results: A total of 224 jaundiced HCCA patients who received a standard curative resection (43 patients developed PHLF) were identified. Patients with PHLF shared more aggressive clinic-pathological features and were generally in a more advanced stage than those without PHLF. An obvious inconsistent distribution of FLRV in patients with PHLF and those without PHLF were detected. FLRV (continuous data) had a high predictive accuracy in PHLF. The newly-acquired cut off value (FLRV = 53.5%, sensitivity = 81.22%, specificity = 81.4%) showed a significantly higher predictive accuracy than conventional FLRV cut off value (AUC: 0.81 vs. 0.60, p < 0.05). Moreover, patients with FLRV lower than 53.5% also shared a significantly higher major morbidity rate as well as a worse prognosis, which were not detected for FLRV of 40%., Conclusion: For jaundiced patients with HCCA, a modified FLRV of 53.5% is recommended due to its great impact on PHLF, as well as its correlation with postoperative major morbidities as well as overall prognosis, which might help clinicians to stratify patients with different therapeutic regimes and outcomes. Future multi-center studies for training and validation are required for further validation., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

We use efficient coding principles borrowed from sensory neuroscience to derive the optimal neural population to encode a reward distribution. We show that the responses of dopaminergic reward prediction error neurons in mouse and macaque are similar to those of the efficient code in the following ways: the neurons have a broad distribution of midpoints covering the reward distribution; neurons with higher thresholds have higher gains, more convex tuning functions and lower slopes; and their slope is higher when the reward distribution is narrower. Furthermore, we derive learning rules that converge to the efficient code. The learning rule for the position of the neuron on the reward axis closely resembles distributional reinforcement learning. Thus, reward prediction error neuron responses may be optimized to broadcast an efficient reward signal, forming a connection between efficient coding and reinforcement learning, two of the most successful theories in computational neuroscience., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

People procrastinate, but why? One long-standing hypothesis is that temporal discounting drives procrastination: in a task with a distant future reward, the discounted future reward fails to provide sufficient motivation to initiate work early. However, empirical evidence for this hypothesis has been lacking. Here, we used a long-term real-world task and a novel measure of procrastination to examine the association between temporal discounting and real-world procrastination. To measure procrastination, we critically measured the entire time course of the work progress instead of a single endpoint, such as task completion day. This approach allowed us to compute a fine-grained metric of procrastination. We found a positive correlation between individuals' degree of future reward discounting and their level of procrastination, suggesting that temporal discounting is a cognitive mechanism underlying procrastination. We found no evidence of a correlation when we, instead, measured procrastination by task completion day or by survey. This association between temporal discounting and procrastination offers empirical support for targeted interventions that could mitigate procrastination, such as modifying incentive systems to reduce the delay to a reward and lowering discount rates., (© 2024. The Author(s).)

Board, card or video games have been played by virtually every individual in the world. Games are popular because they are intuitive and fun. These distinctive qualities of games also make them ideal for studying the mind. By being intuitive, games provide a unique vantage point for understanding the inductive biases that support behaviour in more complex, ecological settings than traditional laboratory experiments. By being fun, games allow researchers to study new questions in cognition such as the meaning of 'play' and intrinsic motivation, while also supporting more extensive and diverse data collection by attracting many more participants. We describe the advantages and drawbacks of using games relative to standard laboratory-based experiments and lay out a set of recommendations on how to gain the most from using games to study cognition. We hope this Perspective will lead to a wider use of games as experimental paradigms, elevating the ecological validity, scale and robustness of research on the mind., (© 2024. Springer Nature Limited.)

Artemyriantholides A-K (1-11) as well as 14 known compounds (12-25) were isolated from Artemisia myriantha var. pleiocephala (Asteraceae). The structures and absolute configuration of compounds 2 and 8-9 were confirmed by the single crystal X-ray diffraction analyses, and the others were elucidated by MS, NMR spectral data and electronic circular dichroism calculations. All compounds were chemically characterized as guaiane-type sesquiterpenoid dimers (GSDs). Compound 1 was the first example of the GSD fused via C-3/C-11' and C-5/C-13' linkages, and compounds 2 and 5 were rare GSDs containing chlorine atoms. Eleven compounds showed obvious inhibitory activity in HepG2, Huh7 and SK-Hep-1 cell lines by antihepatoma assay to provide the IC 50 values ranging from 7.9 to 67.1 μM. Importantly, compounds 5 and 8 exhibited the best inhibitory activity with IC 50 values of 14.2 and 18.8 (HepG2), 9.0 and 11.5 (Huh7), and 8.8 and 11.3 μM (SK-Hep-1), respectively. The target of compound 5 was predicted to be MAP2K2 by a computational prediction model. The interaction between compound 5 and MAP2K2 was conducted to give docking score of -9.0 kcal/mol by molecular docking and provide K D value of 43.7 μM by Surface Plasmon Resonance assay., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Metabolite profiling has the potential to comprehensively bridge phenotypes and complex heterogeneous physiological and pathological states. We performed a metabolomics study using parallel liquid chromatography-mass spectrometry (LC-MS) combined with multivariate data analysis to screen for biomarkers of primary aldosteronism (PA) from a cohort of 111 PA patients and 218 primary hypertension (PH) patients. Hydrophilic interaction chromatography and reversed-phase liquid chromatography separations were employed to obtain a global plasma metabolome of endogenous metabolites. The satisfactory classification between PA and PH patients was obtained using the MVDA model. A total of 35 differential metabolites were screened out and identified. A diagnostic biomarker panel was established using the least absolute shrinkage and selection operator (LASSO) binary logistic regression model and receiver operating characteristic analysis. Joint analysis with clinical indicators, including plasma supine aldosterone level, plasma orthostatic aldosterone level, body mass index, and blood potassium, revealed that the combination of metabolite biomarker panel and plasma supine aldosterone has the best clinical diagnostic efficacy., (© 2024 John Wiley & Sons Ltd.)

The ability to sustain internal representations of the sensory environment beyond immediate perception is a fundamental requirement of cognitive processing. In recent years, debates regarding the capacity and fidelity of the working memory (WM) system have advanced our understanding of the nature of these representations. In particular, there is growing recognition that WM representations are not merely imperfect copies of a perceived object or event. New experimental tools have revealed that observers possess richer information about the uncertainty in their memories and take advantage of environmental regularities to use limited memory resources optimally. Meanwhile, computational models of visuospatial WM formulated at different levels of implementation have converged on common principles relating capacity to variability and uncertainty. Here we review recent research on human WM from a computational perspective, including the neural mechanisms that support it., (© 2024. Springer Nature Limited.)

Guaianolide dimers represent a unique class of natural products with anticancer activities, but their low content in plants has limited in-depth pharmacological studies. Lavandiolide I is a guaianolide dimer isolated from Artemisia species, and had been synthesized on a ten-gram scale in four steps with 60 % overall yield, which showed potent antihepatoma activity on the HepG2, Huh7, and SK-Hep-1 cell lines with IC 50 values of 12.1, 18.4, and 17.6 µM, respectively. To explore more active dimers, 33 lavandiolide I derivatives were designed, synthesized, and evaluated for their inhibitory activity on human hepatoma cell lines. Among them, 10 derivatives were more active than lavandiolide I and sorafenib on the three cell lines. The primary structure-activity relationship concluded that the introduction of aldehyde, ester, azide, amide, carbamate and urea functional groups at C-14' of the guaianolide dimer significantly enhanced the antihepatoma activity. Among these compounds, derivatives 25, 27, and 33 enhanced antihepatoma activity more than 1.2-5.8 folds than that of lavandiolide I, and demonstrated low toxicity to the human liver cell lines (THLE-2) and good safety profiles with selective index ranging from 1.3 to 3.4, while lavandiolide I was more toxic to THLE-2 cells. This work provides new insights into enhancing the antihepatoma efficacy and reducing the toxicity of sesquiterpenoid dimers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Intrahepatic cholangiocarcinoma (ICC) is a highly malignant neoplasm and characterized by desmoplastic matrix. The heterogeneity and crosstalk of tumor microenvironment remain incompletely understood., Methods: To address this gap, we performed Weighted Gene Co-expression Network Analysis (WGCNA) to identify and construct a cancer associated fibroblasts (CAFs) infiltration biomarker. We also depicted the intercellular communication network and important receptor-ligand complexes using the single-cell transcriptomics analysis of tumor and Adjacent normal tissue., Results: Through the intersection of TCGA DEGs and WGCNA module genes, 784 differential genes related to CAFs infiltration were obtained. After a series of regression analyses, the CAFs score was generated by integrating the expressions of EVA1A, APBA2, LRRTM4, GOLGA8M, BPIFB2, and their corresponding coefficients. In the TCGA-CHOL, GSE89748, and 107,943 cohorts, the high CAFs score group showed unfavorable survival prognosis (p < 0.001, p = 0.0074, p = 0.028, respectively). Additionally, a series of drugs have been predicted to be more sensitive to the high-risk group (p < 0.05). Subsequent to dimension reduction and clustering, thirteen clusters were identified to construct the single-cell atlas. Cell-cell interaction analysis unveiled significant enhancement of signal transduction in tumor tissues, particularly from fibroblasts to malignant cells via diverse pathways. Moreover, SCENIC analysis indicated that HOXA5, WT1, and LHX2 are fibroblast specific motifs., Conclusions: This study reveals the key role of fibroblasts - oncocytes interaction in the remodeling of the immunosuppressive microenvironment in intrahepatic cholangiocarcinoma. Subsequently, it may trigger cascade activation of downstream signaling pathways such as PI3K-AKT and Notch in tumor, thus initiating tumorigenesis. Targeted drugs aimed at disrupting fibroblasts-tumor cell interaction, along with associated enrichment pathways, show potential in mitigating the immunosuppressive microenvironment that facilitates tumor progression., (© 2024. The Author(s).)

Background: The application of three-dimensional (3D) reconstruction has been extensively adopted in hepatectomy navigation, 1 yet its utilization in laparoscopic radical resection of perihilar cholangiocarcinoma (pHCCA) remains underexplored., Video: A 54-year-old male patient, classified as Child-Pugh B, presented a small neoplasm situated at the left hepatic duct proximate to the right hepatic and common hepatic ducts. An enhanced abdominal computed tomographic scan identified a solitary lesion measuring 2.8 × 2.4 cm. 3D reconstruction exposed tumor invasion into the left hepatic artery and left portal vein. Given the lesion's unique location, a pure laparoscopic left hepatectomy and caudate lobectomy were executed using a no-touch en block technique post patient consent. Concurrently, extrahepatic bile duct resection, radical lymphadenectomy with skeletonization, and biliary reconstruction were performed., Results: The 3D reconstruction-guided laparoscopic left hepatectomy and caudate lobectomy were successfully completed in 425 min with minimal blood loss (50 mL). The histological grading was T2bN0M0 (stage II). The patient was discharged on the sixth postoperative day without complications, and postoperative treatment included mono-drug chemotherapy with capecitabine. No recurrence was observed at the 6-month follow-up., Conclusion: Our experience suggests that 3D reconstruction-guided laparoscopic radical resection may offer increased precision and efficiency in selected pHCCA patients. This approach can potentially yield outcomes comparable with or superior to open surgery, given standardized lymph node dissection by skeletonization, use of the no-touch en block technique, appropriate digestive tract reconstruction, and reduced bleeding and liver damage., (© 2024. Society of Surgical Oncology.)

Sulfur-driven autotrophic denitrification (SAD) exhibits significant benefits in treating low carbon/nitrogen wastewater. This study presents an eco-friendly, cost-effective, and highly efficient method for enhancing nitrogen removal performance. The addition of biochar prepared at 300 °C (BC300) notably increased nitrogen removal efficiency by 31.60 %. BC300 concurrently enhanced electron production, the activities of the electron transfer system, and electron acceptors. With BC300, the ratio of NADH/NAD + rose 2.00±0.11 times compared to without biochar, and the expression of NAD(P)H dehydrogenase genes was markedly up-regulated. In the electron transfer system, BC300 improved the electroactivity of extracellular polymeric substances and the activities of NADH dehydrogenase and complex III in intracellular electron transfer. Subsequently, electrons were directed into denitrification enzymes, where the nar, nir, nor, and nos related genes were highly expressed with BC300 addition. Significantly, BC300 activated the Clp and quorum sensing systems, positively influencing numerous gene expressions and microbial communication. Furthermore, the O%, H%, molar O/C, and aromaticity index in biochar were identified as crucial bioavailable parameters for enhancing nitrogen removal in the SAD process. This study not only confirms the application potential of biochar in SAD, but also advances our comprehension of its underlying mechanisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Sulfur-driven autotrophic denitrification (SAD) granular process has significant advantages in treating low-carbon/nitrogen wastewater; however, the slow growth rate of sulfur-oxidizing bacteria (SOB) results in a prolonged start-up duration. In this study, the thiosulfate-driven autotrophic denitrification (TAD) was successfully initiated by inoculating anaerobic granular sludge on Day 7. Additionally, the electron donor was successfully transferred to the cheaper elemental sulfur from Day 32 to Day 54 at the nitrogen loading rate of 176.2 g N m -3 d -1 . During long term experiment, the granules maintained compact structures with the α-helix/(β-sheet + random coil) of 29.5-40.1 %. Extracellular electron transfer (EET) pathway shifted from indirect to direct when electron donors were switched thiosulfate to elemental sulfur. Microbial analysis suggested that thiosulfate improved EET involving enzymes activity. Thiobacillus and Sulfurimonas were dominant in TAD, whereas Longilinea was enriched in elemental sulfur-driven autotrophic denitrification. Overall, this strategy achieved in-situ enrichment of SOB in granules, thereby shortening start-up process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To comprehensively understand the disease burden of liver cirrhosis and other chronic liver diseases caused by alcohol use in China from 1990 to 2019, as well as to predict the trends in disease burden from 2020 to 2030. Methods: The analysis utilized data from the Global Burden of Disease study in 2019 (GBD2019). Key indicators such as incidence rate, mortality rate, disability-adjusted life years (DALY), years of life lost due to premature mortality, and years lived with disability were selected to describe the disease burden of alcohol-related liver cirrhosis and other chronic liver diseases in China from 1990 to 2019. The estimated annual percentage change (EAPC) was used to depict the temporal trends in disease burden. Furthermore, a Bayesian age-period-cohort (BAPC) model was constructed using R software to predict the age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) of alcohol-related liver cirrhosis and other chronic liver diseases in China from 2020 to 2030. Results: From 1990 to 2019, the incidence of alcohol-related liver cirrhosis and other chronic liver diseases in China showed an upward trend, with an EAPC of 0.31% (95% CI : 0.10%-0.52%). However, the DALY declined, with an EAPC of -2.81% (95% CI : -2.92% - -2.70%). The ASMR showed a downward trend, with an EAPC of -2.55% (95% CI : -2.66% - -2.45%). The highest incidence of cirrhosis of liver caused by alcohol and other chronic liver diseases was reported in the age group of 35-49 years, while the ASMR increased gradually with age, with a significant rise after the age of 30. The age-standardized DALY rate peaked between the ages of 55 and 64. The disease burden indicators for males were consistently higher than those for females during the same period. According to the predictions of the BAPC model, from 2020 to 2030, the ASIR for cirrhosis of liver caused by alcohol and other chronic liver diseases in the entire population of China was projected to increase from 3.45/100 000 in 2020 to 3.78/100 000 in 2030, a growth of 9.57%. Conversely, the ASMR was expected to decrease from 1.45/100 000 in 2020 to 1.24/100 000 in 2030, a reduction of 14.48%. Conclusions: The disease burden of cirrhosis of liver caused by alcohol and other chronic liver diseases remained serious in China, especially in men and the middle-aged to elderly population. There is a pressing need to prioritize attention and resources towards these groups. Despite the projected decrease in ASMR, the ASIR continued to rise and is expected to persist in its upward trend until 2030.

Background: The neutrophil-lymphocyte ratio (NLR) and platelet distribution width (PDW) are associated with poor prognosis in various cancers. We aimed to analyze the prognostic value of the combination of preoperative NLR and PDW in patients with gallbladder carcinoma (GBC)., Methods: A total of 287 GBC patients who underwent curative-intent surgery in our institution was included. The relationship between NLR and PDW and clinicopathological features were analyzed. The receiver operating characteristic (ROC) curves were used to determine the optimal cutoff value for NLR and PDW. Overall survival (OS) was estimated using the Kaplan-Meier method. Meanwhile, the univariate and multivariate Cox regression models were used to assess the risk factors for OS., Results: The optimal cutoff value of NLR and PDW was 3.00 and 14.76, respectively. In addition, survival analysis demonstrated that patients with NLR > 3.00 and PDW > 14.76 had a worse prognosis than patients with NLR ≤ 3.00 and PDW ≤ 14.76, respectively. The multivariate analysis showed that NLR and PDW were independent prognostic factors in the patients with GBC. When we combined NLR and PDW, the area under the ROC curve increased from 0.665 (NLR) and 0.632 (PDW) to 0.676. Moreover, the 1-, 3-, and 5-year OS of group A (patients with NLR ≤ 3.00 and PDW ≤ 14.76), group B (patients with either of NLR > 3.00 or PDW > 14.76) and group C (patients with NLR > 3.00 and PDW > 14.76) were 88.7%, 62.6%, 28.1%, 65.1%, 26.9%, 13.1%, and 34.8%, 8.3%, 0%, respectively., Conclusion: The combination of NLR and PDW may serve as a significant prognostic biomarker for GBC patients superior to either NLR or PDW alone., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Accurate evaluation of the axillary lymph node (ALN) status is needed for determining the treatment protocol for breast cancer (BC). The value of magnetic resonance imaging (MRI)-based tumor heterogeneity in assessing ALN metastasis in BC is unclear., Purpose: To assess the value of deep learning (DL)-derived kinetic heterogeneity parameters based on BC dynamic contrast-enhanced (DCE)-MRI to infer the ALN status., Study Type: Retrospective., Subjects: 1256/539/153/115 patients in the training cohort, internal validation cohort, and external validation cohorts I and II, respectively., Field Strength/sequence: 1.5 T/3.0 T, non-contrast T1-weighted spin-echo sequence imaging (T1WI), DCE-T1WI, and diffusion-weighted imaging., Assessment: Clinical pathological and MRI semantic features were obtained by reviewing histopathology and MRI reports. The segmentation of the tumor lesion on the first phase of T1WI DCE-MRI images was applied to other phases after registration. A DL architecture termed convolutional recurrent neural network (ConvRNN) was developed to generate the KH image (kinetic heterogeneity of DCE-MRI image) score that indicated the ALN status in patients with BC. The model was trained and optimized on training and internal validation cohorts, tested on two external validation cohorts. We compared ConvRNN model with other 10 models and the subgroup analyses of tumor size, magnetic field strength, and molecular subtype were also evaluated., Statistical Tests: Chi-squared, Fisher's exact, Student's t, Mann-Whitney U tests, and receiver operating characteristics (ROC) analysis were performed. P < 0.05 was considered significant., Results: The ConvRNN model achieved area under the curve (AUC) of 0.802 in the internal validation cohort and 0.785-0.806 in the external validation cohorts. The ConvRNN model could well evaluate the ALN status of the four molecular subtypes (AUC = 0.685-0.868). The patients with larger tumor sizes (>5 cm) were more susceptible to ALN metastasis with KH image scores of 0.527-0.827., Data Conclusion: A ConvRNN model outperformed traditional models for determining the ALN status in patients with BC., Level of Evidence: 3 TECHNICAL EFFICACY: Stage 2., (© 2024 International Society for Magnetic Resonance in Medicine.)

Background: The significance of peri-neural invasion (PNI) in resected patients with hilar cholangiocarcinoma (HCCA) has been rarely explored. Our study was performed to evaluate the significance of PNI in resected HCCA patients in terms of tumor biological features and long-term survival., Methods: We retrospectively reviewed surgically-treated HCCA patients between June, 2000 and June 2018. SPSS 25.0 software was used for statistical analysis., Results: A total of 239 resected HCCA patients were included (No. PNI: 138). PNI indicated more aggressive tumor biological features. Major vascular reconstruction was more frequently performed in patients with PNI (34.8% vs 24.8%, P = 0.064). Patients with PNI shared a significantly higher percentage of surgical margin width <5 mm (29.0% vs 16.8%, P = 0.02). The proportion of patients with T1-2 disease (31.2% vs 40.6%, P = 0.085) or I-II disease (21% vs 34.7%, P = 0.014) was significantly lower in patients with PNI. The overall morbidity rate was significantly higher in patients with PNI (P = 0.042). A much worse overall survival (OS) (P = 0.0003) or disease-free survival (DFS) (P = 0.0011) in patients with PNI. Even after matching vital prognostic factors, a significantly worse OS (P = 0.0003) or DFS (P = 0.0002) was still observed in patients with PNI. PNI was an independent prognostic factor in both OS (P = 0.011) and DFS (P = 0.024)., Conclusion: PNI indicated more aggressive tumor biological features and more advanced tumor stage in patients with resected HCCA. PNI can be an independent prognostic factor in both OS and DFS. Future multi-center studies covering various races or populations are required for further validation., Competing Interests: Declaration of competing interest All authors declare have no conflict of interest to disclose., (Copyright © 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Background: Combined hepatocellular carcinoma and cholangiocarcinoma (CHCC-CC) is a rare subtype of primary liver malignancy and has been treated equally as intra-hepatic cholangiocarcinoma (IHCC) according to the 8th AJCC staging system. Owing to its rarity, its prognostic factors have been rarely explored and defined., Methods: PubMed, EMBASE, the Cochrane Library and Web of Science were searched up till January 1st, 2023 and eligible studies were restricted to studies reported prognostic factors of resected CHCC-CC. Standard Parmar modifications were used to determine pooled univariable hazard ratios (HRs)., Results: A total of eleven studies with 1286 patients with resected classical CHCC-CC were finally included. Pooled results indicated that serum tumor biomarkers, including AFP, CA199, and CEA, were prognostic factors for postoperative overall survival (OS) and disease-free survival (DFS). Moreover, liver cirrhosis (P = 0.010), HBV infection (P = 0.030), and HCV infection (P < 0.001) were prognostic factors for OS. Age (HR = 1.03, P = 0.005) was a prognostic factor for DFS. Tumor size (OS: HR = 2, P < 0.001, DFS: HR = 2.15, P < 0.001), tumor number (OS: HR = 2.05, P < 0.001; DFS: HR = 1.96, P = 0.006), surgical margin (OS: HR = 2.33, <0.001001; DFS: HR = 2.35, P < 0.001), node metastasis (OS: HR = 2.96, P < 0.001; DFS: HR = 2.1, P < 0.001), vascular invasion (OS: HR = 2.17, P < 0.001; DFS: HR = 2.64, P < 0.001), and postoperative prophylactic trans-arterial chemotherapy embolization (PPTACE) (OS: HR = 1.67, P = 0.04; DFS: HR = 2.31, P < 0.001) were common prognostic factors for OS and DFS., Conclusion: Various risk factors unmentioned in the 8th AJCC staging system were identified. These promising findings would facilitate a more personalized predictive model and help clinicians to stratify patients with different survival outcomes., Competing Interests: Declaration of competing interest All authors declare have no conflicts of interest to disclose., (© 2023 Published by Elsevier Ltd.)

Nucleolus was an important cellular organelle. The abnormal morphology and number of the nucleolus have been considered as diagnostic biomarkers for some human diseases. However, the imaging agent based on nucleolus was limited. In this manuscript, a series of nucleolar fluorescent probes based on naphthalimide derivatives (NI-1 ∼ NI-5) had been designed and synthesized. NI-1 ∼ NI-5 could penetrate cell membranes and nuclear membranes, achieve clear nucleolar staining in living cells. These results suggested that the presence of amino groups on the side chains of naphthalimide backbone could enhance the targeting to the cell nucleolus. In addition, the molecular docking results showed that NI-1 ∼ NI-5 formed hydrogen bonds and hydrophobic interactions with RNA, and exhibited enhanced fluorescence upon binding with RNA. These results will provide favorable support for the diagnosis and treatment of nucleolus-related diseases in the future., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Tumor necrosis has been indicated to correlate with dismal survival outcomes of a variety of solid tumors. However, the significance and prognostic value of tumor necrosis remain unclear in gallbladder carcinoma. The aim of this research is to explore the relationships between necrosis with long-term survival and tumor-related biological characteristics of patients with gallbladder carcinoma., Patients and Methods: Patients with gallbladder carcinoma who accepted curative-intent resection in West China Hospital of Sichuan University (China) between January 2010 and December 2021 were retrospectively analyzed. Tumor necrosis was determined by staining the patient's original tissue sections with hematoxylin and eosin. Based on the presence of tumor necrosis, the pathologic features and survival outcomes were compared., Results: This study enrolled 213 patients with gallbladder carcinoma who underwent curative-intent surgery, of whom 89 had tumor necrosis. Comparative analyses indicated that patients with tumor necrosis had more aggressive clinicopathological features, such as larger tumor size (p = 0.002), poorer tumor differentiation (p = 0.029), more frequent vascular invasion (p < 0.001), presence of lymph node metastasis (p = 0.014), and higher tumor status (p = 0.01), and experienced poorer survival. Univariate and multivariate analyses revealed that tumor necrosis was an independent prognostic factor for overall survival (multivariate: HR 1.651, p = 0.026) and disease-free survival (multivariate: HR 1.589, p = 0.040)., Conclusions: Tumor necrosis can be considered as an independent predictive factor for overall survival and disease-free survival among individuals with gallbladder carcinoma, which was a valuable pathologic parameter., (© 2023. Society of Surgical Oncology.)

Girls and women are underrepresented in chess. Here, we explored the role of gender bias in this phenomenon. Specifically, we investigated whether parents and mentors (e.g., coaches) show bias against the female youth players in their lives. Parents and mentors ( N = 286; 90.6% men) recruited through the U.S. Chess Federation reported their evaluations of and investment in youth players ( N = 654). We found evidence of bias on some, but not all, measures. Most strikingly, parents and mentors thought that female youth players' highest potential chess ratings were on average lower than male players', a bias that was exacerbated among parents and mentors who believed that success in chess requires brilliance. In addition, mentors who endorsed (vs. rejected) this belief also reported that female mentees were more likely to drop out of chess due to low ability. These findings provide the first large-scale evidence of bias against youth female players and hold implications for the role of parents and mentors in other domains that, like chess, are culturally associated with intellectual ability and exhibit substantial gender imbalances (e.g., science and technology). (PsycInfo Database Record (c) 2024 APA, all rights reserved).

An influential account of neuronal responses in primary visual cortex is the normalized energy model. This model is often implemented as a multi-stage computation. The first stage is linear filtering. The second stage is the extraction of contrast energy, whereby a complex cell computes the squared and summed outputs of a pair of the linear filters in quadrature phase. The third stage is normalization, in which a local population of complex cells mutually inhibit one another. Because the population includes cells tuned to a range of orientations and spatial frequencies, the result is that the responses are effectively normalized by the local stimulus contrast. Here, using evidence from human functional MRI, we show that the classical model fails to account for the relative responses to two classes of stimuli: straight, parallel, band-passed contours (gratings), and curved, band-passed contours (snakes). The snakes elicit fMRI responses that are about twice as large as the gratings, yet a traditional divisive normalization model predicts responses that are about the same. Motivated by these observations and others from the literature, we implement a divisive normalization model in which cells matched in orientation tuning ("tuned normalization") preferentially inhibit each other. We first show that this model accounts for differential responses to these two classes of stimuli. We then show that the model successfully generalizes to other band-pass textures, both in V1 and in extrastriate cortex (V2 and V3). We conclude that even in primary visual cortex, complex features of images such as the degree of heterogeneity, can have large effects on neural responses., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Fang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Outcomes of laparoscopic liver resection (LLR) versus open LR (OLR) for intrahepatic cholangiocarcinoma (ICCA) are heterogeneous. We aimed to compare LLR and OLR for ICCA based on propensity-score-matched (PSM) studies. Two reviewers independently searched the online databases (PubMed, Embase, and Cochrane Library) for PSM studies that compared LLR and OLR for ICCA. The Ottawa-Newcastle Quality Assessment Scale with a cutoff of ≥ 7 was used to define higher-quality literature. Only 'high-quality' PSM analyses of the English language that met all our inclusion criteria were considered. A total of ten PSM trials were included in the analyses. Compared with OLR, although the lymph node dissection (LND) (RR = 0.67) and major hepatectomy rates were lower in the LLR group (RR = 0.87), higher R0 resections (RR = 1.05) and lower major complications (Clavien-Dindo grade ≥ III) (RR = 0.72) were also observed in the LLR group. In addition, patients in the LLR group showed less estimated blood loss (MD = - 185.52 ml) and shorter hospital stays as well (MD = - 2.75 days). Further analysis found the overall survival (OS) (HR = 0.91), disease-free survival (DFS) (HR = 0.95), and recurrence-free survival (HR = 0.80) for patients with ICCA after LLR were all comparable to those of OLR. LLR for selected ICCA patients may be technically safe and feasible, providing short-term benefits and achieving oncological efficacy without compromising the long-term survival of the patients., (© 2023. The Author(s).)

Objective: Our meta-analysis was performed to explore the prognostic factors for overall survival among post-hepatectomy patients with spontaneous ruptured hepatocellular carcinoma (SRHCC)., Methods: PubMed, EMBASE, the Cochrane Library, and Web of Science were all searched up for relevant studies regarding prognostic factors with SRHCC. RevMan5.3 software and Stata 14.0 software were used for statistical analysis., Results: A total of nineteen studies with 1876 resected SRHCC patients were finally identified. Pooled results indicated that preoperative AFP (high vs low) (P = 0.003), concurrent liver cirrhosis (yes vs no) (P = 0.02), preoperative liver function (child A vs non-child A) (P = 0.0007), tumor size (large vs small) (P < 0.00001), tumor number (solitary vs multiple) (P = 0.002), satellite foci (yes vs no) (P = 0.0006), micro-vascular invasion (yes vs no) (P < 0.00001), type of hepatectomy (major or minor) (P = 0.04), surgical margin (R + vs R -) (P < 0.00001), and type of hepatectomy (emergency hepatectomy vs staged hepatectomy) (P = 0.005) were prognostic factors for overall survival among post-hepatectomy SRHCC patients., Conclusion: Apart from some conventional prognostic factors identified in resected patients with SRHCC, numerous prognostic factors have also been unmasked, which might provide clinical reference to stratify patients with different therapeutic regimes., (© 2023. The Society for Surgery of the Alimentary Tract.)

Salicylic acid (SA) is one of the chemical molecules, involved in plant growth and immunity, thereby contributing to the control of pests and pathogens, and even applied in fruit and vegetable preservation. However, only a few tools have ever been designed or executed to understand the physiological processes induced by SA or its function in plant immunity and residue detection in food. Hence, three Rh6G-based fluorogenic chemosensors were synthesized to detect phytohormone SA based on the "OFF-ON" mechanism. The probes showed high selectivity, ultrafast response time (<60 s), and nanomolar detection limit for SA. Moreover, the probe possessed outstanding profiling that can be successfully used for SA imaging of callus and plants. Furthermore, the fluorescence pattern indicated that SA could occur in the distal transport in plants. These remarkable results contribute to improving our understanding of the multiple physiological and pathological processes involved in SA for plant disease diagnosis and for the development of immune activators. In addition, SA detection in some agricultural products used probes to extend the practical application because its use is prohibited in some countries and is harmful to SA-sensitized persons. Interestingly, the as-obtained test paper displayed that SA could be imaged by ultraviolet (UV) and was directly visible to the naked eye. Given the above outcomes, these probes could be used to monitor SA in vitro and in vivo, including, but not limited to, plant biology, food residue detection, and sewage detection.

When developing models in cognitive science, researchers typically start with their own intuitions about human behavior in a given task and then build in mechanisms that explain additional aspects of the data. This refinement step is often hindered by how difficult it is to distinguish the unpredictable randomness of people's decisions from meaningful deviations between those decisions and the model. One solution for this problem is to compare the model against deep neural networks trained on behavioral data, which can detect almost any pattern given sufficient data. Here, we apply this method to the domain of planning with a heuristic search model for human play in 4-in-a-row, a combinatorial game where participants think multiple steps into the future. Using a data set consisting of 10,874,547 games, we train deep neural networks to predict human moves and find that they accurately do so while capturing meaningful patterns in the data. Thus, deviations between the model and the best network allow us to identify opportunities for model improvement despite starting with a model that has undergone substantial testing in previous work. Based on this analysis, we add three extensions to the model that range from a simple opening bias to specific adjustments regarding endgame planning. Overall, our work demonstrates the advantages of model comparison with a high-performance deep neural network as well as the feasibility of scaling cognitive models to massive data sets for systematically investigating the processes underlying human sequential decision-making., (© 2023. The Author(s).)

Gallbladder neuroendocrine carcinoma (GBNEC) is rare and characterized by a low degree of tumor differentiation. The clinical features of GBNEC versus gallbladder adenocarcinoma (GBADC) remain a subject of debate. A total of 201 GBADC and 36 GBNEC cases that underwent surgery resection between January 2010 and 2022 at the Department of Biliary Surgery, West China Hospital, Sichuan University were included. A 1:1 propensity score matching (PSM) was performed based on seven predefined variables: age, sex, the American Joint Committee on Cancer (AJCC) stage, resection status, perineural invasion (PNI), lymphovascular invasion (LVI), and degree of tumor differentiation. Compared with GBADC, GBNEC patients were younger (median age 56.0 vs 64.0 years; P = 0.001), and more patients presented with advanced stages of tumor (P = 0.003). Patients with GBNEC also had a higher rate of PNI (55.6% vs 22.4%; P < 0.001), and LVI (63.9% vs 45.80%; P = 0.658). Before PSM, GBNEC patients had inferior prognoses compared with GBADC patients with a shorter median overall survival (mOS) (15.02 vs 20.11 months; P = 0.0028) and a shorter median recurrence-free survival (mRFS) (10.30 vs 15.17 months; P = 0.0028). However, after PSM analyses, there were no differences in OS (mOS 18.6 vs 18.0 months; P=0.24) or RFS (mRFS 10.98 vs 12.02 months; P = 0.39) between the GBNEC and GBADC cases. After multivariate analysis, tumor diagnosis (GBNEC vs GBADC) was not identified as an independent risk factor for shorter RFS (P = 0.506) or OS (P = 0.731). Unfavorable pathological features, including advanced AJCC tumor stages, poor differentiation, presence of LVI, and positive resection margins (all P < 0.05), were independent risk factors for inferior OS and RFS. GBNEC is difficult to diagnose early and has a prognosis comparable to stage-matched poorly differentiated GBADC. Tumor diagnosis (either GBADC or GBNEC) was not an independent risk factor for the patient's OS. Unfavorable pathological features of the neoplasm are the main determinants.

The study of the brain's representations of uncertainty is a central topic in neuroscience. Unlike most quantities of which the neural representation is studied, uncertainty is a property of an observer's beliefs about the world, which poses specific methodological challenges. We analyze how the literature on the neural representations of uncertainty addresses those challenges and distinguish between 'code-driven' and 'correlational' approaches. Code-driven approaches make assumptions about the neural code for representing world states and the associated uncertainty. By contrast, correlational approaches search for relationships between uncertainty and neural activity without constraints on the neural representation of the world state that this uncertainty accompanies. To compare these two approaches, we apply several criteria for neural representations: sensitivity, specificity, invariance and functionality. Our analysis reveals that the two approaches lead to different but complementary findings, shaping new research questions and guiding future experiments., (© 2023. Springer Nature America, Inc.)

Background: The nuclear grading of ductal carcinoma in situ (DCIS) affects its clinical risk. The aim of this study was to investigate the possibility of predicting the nuclear grading of DCIS, by magnetic resonance imaging (MRI)-based radiomics features. And to develop a nomogram combining radiomics features and MRI semantic features to explore the potential role of MRI radiomic features in the assessment of DCIS nuclear grading., Methods: A total of 156 patients (159 lesions) with DCIS and DCIS with microinvasive (DCIS-MI) were enrolled in this retrospective study, with 112 lesions included in the training cohort and 47 lesions included in the validation cohort. Radiomics features were extracted from Dynamic contrast-enhanced MRI (DCE-MRI) phases 1 st and 5 th . After feature selection, radiomics signature was constructed and radiomics score (Rad-score) was calculated. Multivariate analysis was used to identify MRI semantic features that were significantly associated with DCIS nuclear grading and combined with Rad-score to construct a Nomogram. Receiver operating characteristic curves were used to evaluate the predictive performance of Rad-score and Nomogram, and decision curve analysis (DCA) was used to evaluate the clinical utility., Results: In multivariate analyses of MRI semantic features, larger tumor size and heterogeneous enhancement pattern were significantly associated with high-nuclear grade DCIS (HNG DCIS). In the training cohort, Nomogram had an area under curve (AUC) of 0.879 and Rad-score had an AUC of 0.828. Similarly, in the independent validation cohort, Nomogram had an AUC value of 0.828 and Rad-score had an AUC of 0.772. In both the training and validation cohorts, Nomogram had a significantly higher AUC value than Rad-score (P<0.05). DCA confirmed that Nomogram had a higher net clinical benefit., Conclusions: MRI-based radiomic features can be used as potential biomarkers for assessing nuclear grading of DCIS. The nomogram constructed by radiomic features combined with semantic features is feasible in discriminating non-HNG and HNG DCIS., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-23-132/coif). The authors have no conflicts of interest to declare., (2023 Gland Surgery. All rights reserved.)

This study is designed to compare drug encapsulation by cucurbit[7]uril and β-cyclodextrin, using fluorofenidone as a model drug. Single-crystal X-ray diffraction analysis was employed to successfully determine the crystal structures of fluorofenidone·H + @cucurbit[7]uril Form, fluorofenidone@cucurbit[7]uril Form, and fluorofenidone@β-cyclodextrin Form. Keto-enol tautomerization of fluorofenidone mediated by cucurbit[7]uril in acid solution is confirmed by crystal structures, pH titration, and nuclear magnetic resonance experiments. However, β-cyclodextrin cannot cause the keto-enol tautomerization of fluorofenidone under similar conditions. The phase solubility study demonstrates that cucurbit[7]uril has a much higher solubilization capacity for fluorofenidone than β-cyclodextrin in 0.1 M HCl since the K c values of fluorofenidone with cucurbit[7]uril and β-cyclodextrin were 1223.97 ± 452.68 and 78.49 ± 10.56 M -1 , respectively. Excellent solubility can be attributed to the keto-enol tautomerization of fluorofenidone under the conditions of cucurbit[7]uril in acid solution. The enol form of fluorofenidone is encapsulated by cucurbit[7]uril by hydrogen bonding interaction and hydrophobic interaction to increase binding affinity. Rat pharmacokinetic studies demonstrate that the area under the plasma concentration-time curve from time 0 to 7 h value of fluorofenidone@cucurbit[7]uril complex is 1.70-fold greater than that of free fluorofenidone, and the mean residence time from time 0 to 7 h is slightly prolonged from 1.29 to 1.76 h ( P < 0.01) after oral administration. However, no significant difference is found between fluorofenidone and fluorofenidone@β-cyclodextrin complex. This work indicates that the induction of keto-enol tautomerization of drugs using macrocyclic molecules has the potential to be an effective method to improve their solubility and bioavailability, providing valuable insights for the application of macrocyclic molecules in the biomedical field.

We introduce a LabVIEW-based control program that significantly improves the efficiency and flexibility in positioning and shooting solid targets in laser-plasma experiments. The hardware driven by this program incorporates a target positioning subsystem and an imaging subsystem, which enables us to install up to 400 targets for one experimental campaign and precisely adjust them in six freedom degrees. The overall architecture and the working modes of the control program are demonstrated in detail. In addition, we characterized the distributions of target positions of every target holder and simultaneously saved the target images, resulting in a large dataset that can be used to train machine learning models and develop image recognition algorithms. This versatile control system has become an indispensable platform when preparing and conducting laser-plasma experiments., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Objective: This study aims to compare the efficacy and safety of denosumab, teriparatide, zoledronic acid, and ibandronic acid for the treatment of women with postmenopausal osteoporosis., Materials and Methods: Randomized controlled trials (RCTs) were searched in Medline, Embase, and Cochrane up to April 2022. Statistical analysis was performed using R 4.1.3 software, and quality evaluation was conducted using Review Manager 5.3., Results: 51 RCTs containing 39,095 patients met our selection criteria. The efficacy results indicated that teriparatide was more effective than ibandronic acid in reducing vertebral fractures [relative risk (RR) = 0.536; 95% confidence interval (CI) (0.266, 0.998)]. Denosumab [mean difference (MD) = -4.19; 95% CI (-8.03, -0.355)] and teriparatide [MD = 4.64; 95% CI (1.60, 7.72)] showed better efficacy than ibandronic acid in improving spine bone mineral density (BMD). Denosumab showed better efficacy than teriparatide in improving radius BMD [MD = -4.14; 95% CI (-6.72, -1.54)], hip bone mineral density (BMD) [MD = -2.01; 95% CI (-3.80, -0.162)], and one-third radius BMD [MD = -3.63; 95% CI (-7.04, -0.151)]. Denosumab was associated with the greatest benefit in increasing radius BMD [the surface under the cumulative ranking curve area (SUCRA) = 0.999], hip BMD [surface under the cumulative ranking curve area (SUCRA) = 0.979], femoral neck BMD (SUCRA = 0.971), one-third radius BMD (SUCRA = 0.994) and preventing vertebral fractures (SUCRA = 0.806). Teriparatide was associated with the greatest benefit in preventing non-vertebral fractures (SUCRA = 0.927) and improving spine BMD (SUCRA = 0.899). The safety results indicated that teriparatide was safer than zoledronic acid regarding the risk of adverse events [RR = 0.958; 95% CI (0.919, 0.988)]. Teriparatide was associated with the greatest benefit in preventing adverse events (SUCRA = 0.908) and serious adverse events (SUCRA = 0.813)., Conclusions: Our current results suggested that when considering both safety and efficacy, denosumab or teriparatide might be a better choice for women with postmenopausal osteoporosis.

Objective: Our study was performed to evaluate the significance of countable and treatable metastatic liver disease (CTMLD) in patients with gallbladder carcinoma (GBC) after curative-intent surgery., Methods: Resected GBC patients between September 2010 and January 2021 were reviewed. Comparative analyses between patients with CTMLD and those without it were performed. A propensity score matching analysis was conducted for further validation., Results: A total of 326 resected GBC patients were identified (33 with CTMLD). A significantly higher preoperative CA199 level was detected in those with CTMLD (p = 0.0160). Significantly higher incidences of major hepatectomy (p = 0.0010), lymph node metastasis (p < 0.0001), direct liver invasion (p < 0.0001), moderate to poor differentiation status (p < 0.0001), and T3-4 disease (p < 0.0001) were detected in patients with CTMLD. Even sharing comparable surgical margin status, patients with CTMLD still shared a significantly higher recurrence rate (93.9% vs. 57.3%, p < 0.0001) as well as a significantly higher recurrence rate within 6 months after surgery (63.6% vs. 14.7%, p < 0.0001). A significantly worse overall survival (median survival time: 12 vs. 33 months, p < 0.0001) or disease-free survival (median recurrence-free time: 6 vs. 30 months, p < 0.0001) was acquired in patients with CTMLD. After matching, a significantly higher early recurrence rate was still detected. Adjuvant chemotherapy seemed to have survival benefit for patients with CTMLD., Conclusion: CTMLD was an indicator of advanced disease and served as an independent predictor of early recurrence among resected GBC patients. Whether curative-intent surgery is superior to nonsurgical treatment among GBC patients with CTMLD remains to be explored in future prospective studies., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Most patients with resected bile tract cancers (BTCs) survive for less than 5 years; however, some achieve better prognosis. The tumor microbiome can improve survival by regulating the tumor immune microenvironment. However, whether the tumor microbiome promotes immune cell infiltration in BTCs is unknown. This study aimed to determine the association between CD8 + T lymphocyte infiltration and the tumor microbiome in patients with resected BTCs., Methods: Archived formalin-fixed paraffin-embedded tumor specimens were collected from patients with resected BTCs and analyzed using 16S rRNA gene sequencing to identify that prognosis-related and significantly differentially enriched taxa. Gene ontology (GO) analysis of the differentially enriched taxa was used to assess how CD8 + T lymphocyte infiltration is affected by the tumor microbiome of BTCs., Results: We enrolled 32 patients with resected BTCs. The high CD8 + lymphocyte-infiltration (CD8 hi ) group had four significantly enriched taxa, and in the low CD8 + lymphocyte-infiltration (CD8 low ) group comprised one significantly enriched taxon. Patients with higher Clostridia abundance (enriched in the CD8 hi group) experienced longer overall survival than those with lower abundance. The enrichment of Clostridia in the CD8 hi group corresponded with lower CCL2 expression and downregulation of phosphatidylinositol 3-kinase activity, which might decrease myeloid-derived suppressor cell recruitment to the tumor milieu, thus increasing CD8 + lymphocyte infiltration in BTCs., Conclusions: The tumor microbiome is related to CD8 + T lymphocyte infiltration in patients with resected BTCs. The relationship between tumor Clostridia and high infiltration of CD8 + T lymphocytes might reflect decreased recruitment of myeloid-derived suppressor cells via the PI3K-CCL2-CCR2 axis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Bidirectional communication between the developing conceptus and endometrium is essential for pregnancy recognition and establishment in ruminants. We dissect the transcriptomic dynamics of sheep conceptus and corresponding endometrium at pre- and peri-implantation stages using single-cell RNA sequencing. Spherical blastocysts contain five cell types, with 68.62% trophectoderm cells. Strikingly, elongated conceptuses differentiate into 17 cell types, indicating dramatic cell fate specifications. Cell-type-specific gene expression delineates the features of distinctive trophectoderm lineages and indicates that the transition from polar trophectoderm to trophoblast increases interferon-tau expression and likely drives elongation initiation. We identify 13 endometrium-derived cell types and elucidate their molecular responses to conceptus development. Integrated analyses uncover multiple paired transcripts mediating the dialogues between extraembryonic membrane and endometrium, including IGF2-IGF1R, FGF19-FGFR1, NPY-NPY1R, PROS1-AXL, and ADGRE5-CD55. These data provide insight into the molecular regulation of conceptus elongation and represent a valuable resource for functional investigations of pre- and peri-implantation ruminant development., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Salicylic acid (SA) is a key hormone that regulates plant growth and immunity, and understanding the physiologic processes induced by SA enables the development of highly pathogen-resistant crops. Here, we report the synthesis of three new SA-sensors (R1-R3) from hydroxyphenol derivatives of a rhodamine-acylhydrazone scaffold and their characterization by NMR and HRMS. Spectroscopic analyses revealed that structural variations in R1-R3 resulted in sensors with different sensitivities for SA. Sensor R2 (with the 3-hydroxyphenyl modification) outperformed R1 (2-hydroxyphenyl) and R3 (4-hydroxyphenyl). The SA-detection limit of R2 is 0.9 μM with an ultra-fast response time (<60 s). In addition, their plant imaging indicated that designed sensor R2 is useful for the further study of SA biology and the discovery and development of new inducers of plant immunity.

The significance of peri-neural invasion (PNI) in patients with gallbladder carcinoma (GBC) after curative surgery remains unknown. Current study was performed to evaluate the significance of PNI in resected GBC patients in terms of tumor-related biological features and long-term survival. Patients with GBC between September 2010 and September 2020 were reviewed and analyzed. SPSS 25.0 software were used for statistical analysis. A total of 324 resected GBC patients were identified (No. PNI: 64). An elevated preoperative Ca19.9 level (P = 0.001), obstructive jaundice (P = 0.001), liver invasion (P < 0.0001), lymph-vascular invasion (P < 0.0001), lymph-node metastasis (P < 0.0001), and poor or moderate differentiation status (P = 0.036) were more frequently detected in patients with PNI. Major hepatectomy (P = 0.019), bile duct resection (P < 0.0001), combined multi-visceral resections (P = 0.001), and combined major vascular resections and reconstructions (P = 0.002) were also more frequently detected. However, a significantly lower R0 rate (P < 0.0001) was acquired in patients with PNI. Patients with PNI were generally more advanced disease and shared a much worse prognosis even after matching. PNI was an independent prognostic factor of disease-free survival as well as an independent predictor of early recurrence. Postoperative adjuvant chemotherapy has brought an obvious survival benefit in resected GBC patients with PNI. PNI could be regarded as an indicator of worse prognosis and could serve as an independent predictor of early recurrence. Postoperative adjuvant chemotherapy was correlated with an improved survival for resected GBC patients with PNI. Upcoming multicenter studies covering various races are warranted for further validation., (© 2023. Italian Society of Surgery (SIC).)

Artemyrianolide H (AH) is a germacrene-type sesquiterpenolid isolated from Artemisia myriantha, and showed potent cytotoxicity against three human hepatocellular carcinoma cell lines HepG2, Huh7, and SK-Hep-1 with IC 50 values of 10.9, 7.2, and 11.9 µM, respectively. To reveal structure-activity relationship, 51 artemyrianolide H derivatives including 19 dimeric analogs were designed, synthesized, and assayed for their cytotoxicity against three human hepatoma cell lines. Among them, 34 compounds were more active than artemyrianolide H and sorafenib on the three cell lines. Especially, compound 25 exhibited the most promising activity with IC 50 values of 0.7 (HepG2), 0.6 (Huh7), and 1.3 µM (SK-Hep-1), which were 15.5, 12.0, and 9.2-fold higher than that of AH and 16.4, 16.3 and 17.5-fold higher than that of sorafenib. Cytotoxicity evaluation on normal human liver cell lines (THLE-2) demonstrated good safety profile of compound 25 with SI of 1.9 (HepG2), 2.2 (Huh 7) and 1.0 (SK-Hep1). Further studies revealed that compound 25 dose-dependently arrested cells at G2/M phase which was correlated with the up-regulation of both cyclin B1 and p-CDK1, and induced apoptosis through the activation of mitochondrial pathways in HepG2 cells. In addition, the migratory and invasive abilities in HepG2 cells after treatment with 1.5 μM of compound 25 were decreased by 89% and 86% with the increase of E-cadherin expression accompanied by the decrease of N-cadherin, vimentin expression. Bioinformatics analysis based on machine learning predicted that PDGFRA and MAP2K2 might be acting targets of compound 25, and SPR assays demonstrated compound 25 were bound with PDGFRA and MAP2K2 with K D value of 0.168 nM, and 8.49 µM, respectively. This investigation proposed that compound 25 might be considered as a promising lead compound for the development of antihepatoma candidate., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)