Memristive switching in the surface of a charge-density-wave topological semimetal.

Owing to the outstanding properties provided by nontrivial band topology, topological phases of matter are considered as a promising platform towards low-dissipation electronics, efficient spin-charge conversion, and topological quantum computation. Achieving ferroelectricity in topological materials enables the non-volatile control of the quantum states, which could greatly facilitate topological electronic research. However, ferroelectricity is generally incompatible with systems featuring metallicity due to the screening effect of free carriers. In this study, we report the observation of memristive switching based on the ferroelectric surface state of a topological semimetal (TaSe4)2I. We find that the surface state of (TaSe4)2I presents out-of-plane ferroelectric polarization due to surface reconstruction. With the combination of ferroelectric surface and charge-density-wave-gapped bulk states, an electric-switchable barrier height can be achieved in (TaSe4)2I-metal contact. By employing a multi-terminal-grounding design, we manage to construct a prototype ferroelectric memristor based on (TaSe4)2I with on/off ratio up to 103, endurance over 103 cycles, and good retention characteristics. The origin of the ferroelectric surface state is further investigated by first-principles calculations, which reveals an interplay between ferroelectricity and band topology. The emergence of ferroelectricity in (TaSe4)2I not only demonstrates it as a rare but essential case of ferroelectric topological materials, but also opens new routes towards the implementation of topological materials in functional electronic devices.

Vascular reconstruction provides short-term and long-term survival benefits for patients with hilar cholangiocarcinoma: A retrospective, multicenter study.

BACKGROUND: In patients with hilar cholangiocarcinoma (HCCA), radical resection can be achieved by resection and reconstruction of the vasculature. However, whether vascular reconstruction (VR) improves long-term and short-term prognosis has not been demonstrated comprehensively. METHODS: This was a retrospective multicenter study of patients who received surgery for HCCA with or without VR. Variables associated with overall survival (OS) and recurrence-free survival (RFS) were identified based on Cox regression. Kaplan-Meier curves were used to explore the impact of VR. Restricted mean survival time (RMST) was used for comparisons of short-term survival between the groups. Patients' intraoperative and postoperative characteristics were compared. RESULTS: Totally 447 patients were enrolled. We divided these patients into 3 groups: VR with radical resections (n = 84); non-VR radical resections (n = 309) and non-radical resection (we pooled VR-nonradical and non-VR nonradical together, n = 54). Cox regression revealed that carbohydrate antigen 242 (CA242), vascular invasion, lymph node metastasis and poor differentiation were independent risk factors for OS and RFS. There was no significant difference of RMST between the VR and non-VR radical groups within 12 months after surgery (10.18 vs. 10.76 mon, P = 0.179), although the 5-year OS (P < 0.001) and RFS (P < 0.001) were worse in the VR radical group. The incidences of most complications were not significantly different, but those of bile leakage (P < 0.001) and postoperative infection (P = 0.009) were higher in the VR radical group than in the non-VR radical group. Additionally, the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) up to 7 days after surgery tended to decrease in all groups. There was no significant difference in the incidence of postoperative liver failure between the VR and non-VR radical groups. CONCLUSIONS: Radical resection can be achieved with VR to improve the survival rate without worsening short-term survival compared with resection with non-VR. After adequate assessment of the patient's general condition, VR can be considered in the resection.

Association of the electrical parameters and photosynthetic characteristics of the tea tree manifests its response to simulated karst drought.

Tea plantations in Karst regions suffer from the serious effects of frequent temporary karst droughts, leading to a decline in tea production and quality in the region. The close relationship between growth and electrical parameters of plants, including physiological capacitance, resistance and impedance, can be used to accurately monitor their plant water status online, quickly, accurately, timely and nondestructively. In this study, three tea tree cultivars of Zhonghuang No.2 (ZH), Wuniuzao (WNZ), and Longjing 43 (LJ) with different levels of drought resistance were selected as experimental materials, and experiments were carried out under controlled conditions according to control (soil water content of 40-45%, D0), (keeping D0 no watering to 5 days, D5), (keeping D0 no watering to 10 days, D10), (the first day after D10 is rehydrated to D0 is regarded as R1) and (the fifth day after D10 rehydration to D0 is regarded as R5), to determine intracellular water metabolism and nutrient translocation characteristics based on intrinsic electrical parameters. The photosynthetic characteristics and chlorophyll fluorescence parameters were also determined to investigate the response of water metabolism to simulated karst drought in the three tea tree cultivars. The results indicated that the water metabolism patterns responded to environmental water changes with a medium water-holding capacity, medium water transport rate, and low water-use efficiency, and the nutrient patterns in those tea tree varieties demonstrated with a high nutrient flux per unit area, low nutrient transfer rate, and high nutrient transport capacity. After rehydration, only the electrical characteristics of WNZ returned to the D0 levels, but the net photosynthetic rate of all varieties returned to or even exceeded the D0 levels. The chlorophyll fluorescence parameters could not be used to characterize the recoverability of metabolism in tea trees. The electrical characteristics quickly reflected the response of the water metabolism in plants to environmental changes, and the fusion of electrical characteristics and photosynthetic characteristics was able to more quickly, accurately, and comprehensively reflect the response of water metabolism to temporary karst drought.

Preparation of Pueraria lobata Root-Derived Exosome-Like Nanovesicles and Evaluation of Their Effects on Mitigating Alcoholic Intoxication and Promoting Alcohol Metabolism in Mice.

Purpose: Pueraria lobata (P. lobata), a dual-purpose food and medicine, displays limited efficacy in alcohol detoxification and liver protection, with previous research primarily focused on puerarin in its dried roots. In this study, we investigated the potential effects and mechanisms of fresh P. lobata root-derived exosome-like nanovesicles (P-ELNs) for mitigating alcoholic intoxication, promoting alcohol metabolism effects and protecting the liver in C57BL/6J mice. Methods: We isolated P-ELNs from fresh P. lobata root using differential centrifugation and characterized them via transmission electron microscopy, nanoscale particle sizing, ζ potential analysis, and biochemical assays. In Acute Alcoholism (AAI) mice pre-treated with P-ELNs, we evaluated their effects on the timing and duration of the loss of the righting reflex (LORR), liver alcohol metabolism enzymes activity, liver and serum alcohol content, and ferroptosis-related markers. Results: P-ELNs, enriched in proteins, lipids, and small RNAs, exhibited an ideal size (150.7 ± 82.8 nm) and negative surface charge (-31 mV). Pre-treatment with 10 mg/(kg.bw) P-ELNs in both male and female mice significantly prolonged ebriety time, shortened sobriety time, enhanced acetaldehyde dehydrogenase (ALDH) activity while concurrently inhibited alcohol dehydrogenase (ADH) activity, and reduced alcohol content in the liver and serum. Notably, P-ELNs demonstrated more efficacy compared to P-ELNs supernatant fluid (abundant puerarin content), suggesting alternative active components beyond puerarin. Additionally, P-ELNs prevented ferroptosis by inhibiting the reduction of glutathione peroxidase 4 (GPX4) and reduced glutathione (GSH), and suppressing acyl-CoA synthetase long-chain family member 4 (ACSL4) elevation, thereby mitigating pathological liver lipid accumulation. Conclusion: P-ELNs exhibit distinct exosomal characteristics and effectively alleviate alcoholic intoxication, improve alcohol metabolism, suppress ferroptosis, and protect the liver from alcoholic injury. Consequently, P-ELNs hold promise as a therapeutic agent for detoxification, sobriety promotion, and prevention of alcoholic liver injury.

Discovery of a Promising CBP/p300 Degrader XYD129 for the Treatment of Acute Myeloid Leukemia.

The epigenetic target CREB (cyclic-AMP responsive element binding protein) binding protein (CBP) and its homologue p300 were promising therapeutic targets for the treatment of acute myeloid leukemia (AML). Herein, we report the design, synthesis, and evaluation of a class of CBP/p300 PROTAC degraders based on our previously reported highly potent and selective CBP/p300 inhibitor 5. Among the compounds synthesized, 11c (XYD129) demonstrated high potency and formed a ternary complex between CBP/p300 and CRBN (AlphaScreen). The compound effectively degraded CBP/p300 proteins and exhibited greater inhibition of growth in acute leukemia cell lines compared to its parent compound 5. Furthermore, 11c demonstrated significant inhibition of tumor growth in a MOLM-16 xenograft model (TGI = 60%) at tolerated dose schedules. Our findings suggest that 11c is a promising lead compound for the treatment of AML.

Efficient catalytic oxidation of formaldehyde by defective g-C3N4-anchored single-atom Pt: A DFT study.

Indoor volatile formaldehyde is a serious health hazard. The development of low-temperature and efficient nonhomogeneous oxidation catalysts is crucial for protecting human health and the environment but is also quite challenging. Single-atom catalysts (SACs) with active centers and coordination environments that are precisely tunable at the atomic level exhibit excellent catalytic activity in many catalytic fields. Among two-dimensional materials, the nonmagnetic monolayer material g-C3N4 may be a good platform for loading single atoms. In this study, the effect of nitrogen defect formation on the charge distribution of g-C3N4 is discussed in detail using density functional theory (DFT) calculations. The effect of nitrogen defects on the activated molecular oxygen of Pt/C3N4 was systematically revealed by DFT calculations in combination with molecular orbital theory. Two typical reaction mechanisms for the catalytic oxidation of formaldehyde were proposed based on the Eley-Rideal (E-R) mechanism. Pt/C3N4-V3N was more advantageous for path 1, as determined by the activation energy barrier of the rate-determining step and product desorption. Finally, the active centers and chemical structures of Pt/C3N4 and Pt/C3N4-V3N were verified to have good stability at 375 K by determination of the migration energy barriers and ab initio molecular dynamics simulations. Therefore, the formation of N defects can effectively anchor single-atom Pt and provide additional active sites, which in turn activate molecular oxygen to efficiently catalyze the oxidation of formaldehyde. This study provides a better understanding of the mechanism of formaldehyde oxidation by single-atom Pt catalysts and a new idea for the development of Pt as well as other metal-based single-atom oxidation catalysts.

Multicenter propensity score-matched analysis to compare perioperative morbidity after laparoscopic or robotic complex hepatectomy for solitary hepatocellular carcinoma.

BACKGROUND: Postoperative complications are vital factors affecting the prognosis of patients with hepatocellular carcinoma (HCC), especially for complex hepatectomy. The present study aimed to compare perioperative complications between laparoscopic and robotic complex hepatectomy (LCH vs. RCH). METHODS: Patients with solitary HCC after complex hepatectomy were collected from a multicenter database. Propensity score-matched (PSM) analysis was adopted to control confounding bias. Multivariable analysis was performed to determine the prognostic factors. RESULTS: 436 patients were included. After PSM, 43 patients were included in both the LCH and RCH groups. The results showed that compared to LCH, RCH had lower rates of blood loss and transfusion, and lower postoperative 30-day and major morbidity, and post-hepatectomy liver failure (PHLF) (all P < 0.05). Additionally, the length of hospital stay was shorter in the RCH group (P = 0.026). Multivariable analysis showed RCH is an independent protective factor for reducing the 30-day morbidity, major morbidity and PHLF. CONCLUSION: RCH has advantages over LCH in the minimally invasive treatment of complex HCC, as it can reduce the incidence of postoperative morbidity. Therefore, RCH should be considered for patients with HCC who require complex hepatectomy.

Experience and training needs of nurses in military hospital on emergency rescue at high altitude: a qualitative meta-synthesis.

BACKGROUND: Nurses play an important role in the treatment of war wounds on the plateau, and they face multiple challenges and a variety of needs in their caregiving process. This study aimed to systematically integrate and evaluate qualitative research data to understand the altitude emergency rescue experience and training needs of nurses in military hospitals and provide them with targeted assistance. METHODS: We critically assessed the study using the Joanna Briggs Institute Critical Assessment Checklist for Qualitative Research. Extraction, summarization and meta-synthesis of qualitative data. Cochrane Library, PubMed, Embase, FMRS, CINAHL, PsycINFO, Chinese National Knowledge Infrastructure (CNKI), Wanfang Database (CECDB), VIP Database, and China Biomedical Database (CBM) were searched for relevant studies published from the establishment of the database to May 2023. Additionally, we conducted a manual search of the references of the identified studies. Registered on the PROSPERO database (CRD42024537104). RESULTS: A total of 17 studies, including 428 participants, were included, and 139 research results were extracted, summarized into 10 new categories, and formed 3 meta-themes. Meta-theme 1: mental state of military nurses during deployment. Meta-theme 2: the experience of military nurses during deployment. Meta-theme 3: training needs for emergency care. CONCLUSIONS: Emergency rescue of high-altitude war injuries is a challenging process. Leaders should pay full attention to the feelings and needs of military nurses during the first aid process and provide them with appropriate support.

Aerobic glycolysis of vascular endothelial cells: a novel perspective in cancer therapy.

Vascular endothelial cells (ECs) are monolayers of cells arranged in the inner walls of blood vessels. Under normal physiological conditions, ECs play an essential role in angiogenesis, homeostasis and immune response. Emerging evidence suggests that abnormalities in EC metabolism, especially aerobic glycolysis, are associated with the initiation and progression of various diseases, including multiple cancers. In this review, we discuss the differences in aerobic glycolysis of vascular ECs under normal and pathological conditions, focusing on the recent research progress of aerobic glycolysis in tumor vascular ECs and potential strategies for cancer therapy.

Discovery and pharmacological characterization of 1,2,3,4-tetrahydroquinoline derivatives as RORγ inverse agonists against prostate cancer.

The retinoic acid receptor-related orphan receptor γ (RORγ) is regarded as an attractive therapeutic target for the treatment of prostate cancer. Herein, we report the identification, optimization, and evaluation of 1,2,3,4-tetrahydroquinoline derivatives as novel RORγ inverse agonists, starting from high throughput screening using a thermal stability shift assay (TSA). The representative compounds 13e (designated as XY039) and 14a (designated as XY077) effectively inhibited the RORγ transcriptional activity and exhibited excellent selectivity against other nuclear receptor subtypes. The structural basis for their inhibitory potency was elucidated through the crystallographic study of RORγ LBD complex with 13e. Both 13e and 14a demonstrated reasonable antiproliferative activity, potently inhibited colony formation and the expression of AR, AR regulated genes, and other oncogene in AR positive prostate cancer cell lines. Moreover, 13e and 14a effectively suppressed tumor growth in a 22Rv1 xenograft tumor model in mice. This work provides new and valuable lead compounds for further development of drugs against prostate cancer.

A Prognostic Model Based on the Log Odds Ratio of Positive Lymph Nodes Predicts Prognosis of Patients with Rectal Cancer.

OBJECTIVE: This study aimed to compare the prognostic value of rectal cancer by comparing different lymph node staging systems, and a nomogram was constructed based on superior lymph node staging. METHODS: Overall, 8700 patients with rectal cancer was obtained from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. The area under the curve (AUC), the C index, and the Akaike informativeness criteria (AIC) were used to examine the predict ability of various lymph node staging methods. Prognostic indicators were assessed using univariate and multivariate COX regression, and further correlation nomograms were created after the data were randomly split into training and validation cohorts. To evaluate the effectiveness of the model, the C index, calibration curves, decision curves (DCA), and receiver operating characteristic curve (ROC) were used. We ran Kaplan-Meier survival analyses to look for variations in risk classification. RESULTS: While compared to the N-stage positive lymph node ratio (LNR), the log odds ratio of positive lymph nodes (LODDS) had the highest predictive effectiveness. Multifactorial COX regression analyses were used to create nomograms for overall survival (OS) and cancer-specific survival (CSS). The C indices of OS and CSS for this model were considerably higher than those for TNM staging in the training cohort. The created nomograms demonstrated good efficacy based on ROC, rectification, and decision curves. Kaplan-Meier survival analysis revealed notable variations in patient survival across various patient strata. CONCLUSIONS: Compared to AJCC staging, the LODDS-based nomograms have a more accurate predictive effectiveness in predicting OS and CSS in patients with rectal cancer.

Survival benefit from adjuvant TACE combined with Lenvatinib for patients with hepatocellular carcinoma and microvascular invasion after curative hepatectomy.

BACKGROUND AND AIMS: The prognosis of patients with hepatocellular carcinoma (HCC) undergoing hepatectomy is unsatisfactory, especially for those with microvascular invasion (MVI). This study aimed to determine the impact of adjuvant transcatheter arterial chemoembolization (TACE) and Lenvatinib on the prognosis of patients with HCC and MVI after hepatectomy. METHODS: Patients diagnosed with HCC and MVI were reviewed, and stratified into four groups according to adjuvant TACE and/or Lenvatinib. Multivariate Cox regression analyses are used to determine independent risk factors. RESULTS: 346 patients were included, and divided into four groups (Group I, TACE+ Lenvatinib; Group II, Lenvatinib; Group III, TACE; Group IV, without adjuvant therapy). Multivariable analysis showed that compared to Group IV, Group I had the best effect on improving the overall survival (OS, HR 0.321, 95%CI 0.099-0.406, P = 0.001) and recurrence-free survival (RFS, HR 0.319, 95%CI 0.129-0.372, P = 0.001). Additionally, compared with Group II or Group III, Group I also can significantly improve the OS and RFS. There is no significant difference between Group II and Group III in OS and RFS. CONCLUSION: The combination of TACE and Lenvatinib should be considered for anti-recurrence therapy for patients with HCC and MVI after hepatectomy.

Comparing planned versus ad hoc coronary microvascular assessment: Early findings from the Coronary Microvascular Disease Registry.

BACKGROUND: Coronary microvascular dysfunction (CMD) is an etiology for angina with non-obstructive coronary disease. However, the initial adoption of CMD assessment, whether planned or conducted ad hoc, is limited. We characterize planned and ad hoc CMD assessments and highlight evolving trends of a CMD referral center. METHODS: We analyzed outpatient data from the Coronary Microvascular Disease Registry from 2021 to 2023. Patients were categorized into planned or ad hoc CMD assessment groups, and baseline characteristics, hospital stay, medications, and physiological measurements were compared. Secondary analysis evaluated a CMD referral center's evolution. RESULTS: Of 101 included outpatients, 67.3 % underwent ad hoc procedures and 32.7 % planned procedures. Average age was 63.1 ± 10.1 years. The planned procedure group was 87.9 % female, and the ad hoc procedure group was 51.5 % female. There were no significant differences in index of microvascular resistance or coronary flow reserve between groups. Hospital stay duration was <1 day for both groups, and neither reported complications. Ad hoc patients were more frequently prescribed aspirin before (64.7 % vs. 36.4 %, p = 0.007) and after the procedure (66.2 % vs. 39.4 %, p = 0.01). CMD rates were higher for planned procedures (30.3 % vs. 10.3 %, p = 0.01). We observed that CMD referral centers have more planned procedures and a higher rate of positive results over time. CONCLUSION: CMD referral centers' planned procedures, and subsequent positive cases, increased over time. This emphasizes the importance of planned procedures, appropriate patient selection, and increased awareness of CMD among healthcare providers. CLINICAL TRIAL REGISTRATION: Coronary Microvascular Disease (CMD) Registry, NCT05960474, https://clinicaltrials.gov/study/NCT05960474.

Bioinspired Robust Gas-Permeable On-Skin Electronics: Armor-Designed Nanoporous Flash Graphene Assembly Enhancing Mechanical Resilience.

Soft on-skin electrodes play an important role in wearable technologies, requiring attributes such as wearing comfort, high conductivity, and gas permeability. However, conventional fabrication methods often compromise simplicity, cost-effectiveness, or mechanical resilience. In this study, a mechanically robust and gas-permeable on-skin electrode is presented that incorporates Flash Graphene (FG) integrated with a bioinspired armor design. FG, synthesized through Flash Joule Heating process, offers a small-sized and turbostratic arrangement that is ideal for the assembly of a conductive network with nanopore structures. Screen-printing is used to embed the FG assembly into the framework of polypropylene melt-blown nonwoven fabrics (PPMF), forming a soft on-skin electrode with low sheet resistance (125.2 ± 4.7 Ω/□) and high gas permeability (≈10.08 mg cm⁻2 h⁻¹). The "armor" framework ensures enduring mechanical stability through adhesion, washability, and 10,000 cycles of mechanical contact friction tests. Demonstrating capabilities in electrocardiogram (ECG) and electromyogram (EMG) monitoring, along with serving as a self-powered triboelectric sensor, the FG/PPMF electrode holds promise for scalable, high-performance flexible sensing applications, thereby enriching the landscape of integrated wearable technologies.

Enantioselective synthesis of chiral α,α-dialkyl indoles and related azoles by cobalt-catalyzed hydroalkylation and regioselectivity switch.

General, catalytic and enantioselective construction of chiral α,α-dialkyl indoles represents an important yet challenging objective to be developed. Herein we describe a cobalt catalyzed enantioselective anti-Markovnikov alkene hydroalkylation via the remote stereocontrol for the synthesis of α,α-dialkyl indoles and other N-heterocycles. This asymmetric C(sp3)-C(sp3) coupling features high flexibility in introducing a diverse set of alkyl groups at the α-position of chiral N-heterocycles. The utility of this methodology has been demonstrated by late-stage functionalization of drug molecules, asymmetric synthesis of bioactive molecules, natural products and functional materials, and identification of a class of molecules exhibiting anti-apoptosis activities in UVB-irradiated HaCaT cells. Ligands play a vital role in controlling the reaction regioselectivity. Changing the ligand from bi-dentate L6 to tridentate L12 enables CoH-catalyzed Markovnikov hydroalkylation. Mechanistic studies disclose that the anti-Markovnikov hydroalkylation involves a migratory insertion process while the Markovnikov hydroalkylation involves a MHAT process.

Full color control and patterned display device from cyan/magenta/yellow water-dispersed electrochromic polymer nanoparticles systems.

Electrochromic polymers (ECPs) have great application potential in flexible displays, and there is an increasing expectation of using green methods to form ECP films. Herein, we propose a modified microemulsion method to prepare Cyan/Magenta/Yellow (C/M/Y) water-dispersed electrochromic polymer nanoparticles systems. Three polymer films (WDECP-C/M/Y) maintain similar electrochemical properties compared to their corresponding organic solvent-based polymer films. It is intriguing that WDECP-C/M/Y exhibit better electrochromic properties in terms of higher cycling stability (97.24%, 95.05%, and 52.84%, respectively) and faster switching time (0.94 s, 1.09 s, and 1.34 s for coloring time, respectively) due to the introduction of nanoparticles. In addition, it can achieve various desired colors by blending the C/M/Y water-dispersed electrochromic polymer nanoparticles systems in different ratios. The calculated chromaticity coordinates of the blending polymer films show close values to the experimental observation, and the calculated ΔE*ab values range from 2.6 to 10.3, which may provide theoretical guidance for precisely color control. Finally, large-scale and patterned devices were assembled, which can achieve colored-to-colorless reversible electrochromism at a low driving voltage of 0 to 1.5 V. This work puts forward a universal and environmentally sustainable strategy to prepare water-dispersed electrochromic polymer nanoparticles systems, demonstrating their wide range of applications in display devices and electronic tags.

Mechanical properties, collagen and glycosaminoglycan content of equine superficial digital flexor tendons are not affected by training.

Physical activity can activate extracellular matrix (ECM) protein synthesis and influence the size and mechanical properties of tendon. In this study, we aimed to investigate whether different training histories of horses would influence the synthesis of collagen and other matrix proteins and alter the mechanical properties of tendon. Samples from superficial digital flexor tendon (SDFT) from horses that were either (a) currently race trained (n = 5), (b) previously race trained (n = 5) or (c) untrained (n = 4) were analysed for matrix protein abundance (mass spectrometry), collagen and glycosaminoglycan (GAG) content, ECM gene expression and mechanical properties. It was found that ECM synthesis by tendon fibroblasts in vitro varied depending upon the previous training history. In contrast, fascicle morphology, collagen and GAG content, mechanical properties and ECM gene expression of the tendon did not reveal any significant differences between groups. In conclusion, although we could not identify any direct impact of the physical training history on the mechanical properties or major ECM components of the tendon, it is evident that horse tendon cells are responsive to loading in vivo, and the training background may lead to a modification in the composition of newly synthesised matrix.

Precise planning based on 3D-printed dry-laboratory models can reduce perioperative complications of laparoscopic surgery for complex hepatobiliary diseases: a preoperative cohort study.

BACKGROUND & AIMS: Complications after laparoscopic liver resection (LLR) are important factors affecting the prognosis of patients, especially for complex hepatobiliary diseases. The present study aimed to evaluate the value of a three-dimensional (3D) printed dry-laboratory model in the precise planning of LLR for complex hepatobiliary diseases. METHODS: Patients with complex hepatobiliary diseases who underwent LLR were preoperatively enrolled, and divided into two groups according to whether using a 3D-printed dry-laboratory model (3D vs. control group). Clinical variables were assessed and complications were graded by the Clavien-Dindo classification. The Comprehensive Complication Index (CCI) scores were calculated and compared for each patient. Multivariable analysis was performed to determine the risk factors of postoperative complications. RESULTS: Sixty-two patients with complex hepatobiliary diseases underwent the precise planning of LLR. Among them, thirty-one patients acquired the guidance of a 3D-printed dry-laboratory model, and others were only guided by traditional enhanced CT or MRI. The results showed no significant differences between the two groups in baseline characters. However, compared to the control group, the 3D group had a lower incidence of intraoperative blood loss, as well as postoperative 30-day and major complications, especially bile leakage (all P < 0.05). The median score on the CCI was 20.9 (range 8.7-51.8) in the control group and 8.7 (range 8.7-43.4) in the 3D group (mean difference, -12.2, P = 0.004). Multivariable analysis showed the 3D model was an independent protective factor in decreasing postoperative complications. Subgroup analysis also showed that a 3D model could decrease postoperative complications, especially for bile leakage in patients with intrahepatic cholelithiasis. CONCLUSION: The 3D-printed models can help reduce postoperative complications. The 3D-printed models should be recommended for patients with complex hepatobiliary diseases undergoing precise planning LLR.

Development of natural perfume as potential fungicide candidates: construction and biological evaluation of vanillin analogs bearing the 1,3,4-oxadiazole/1,3-thiazolidin-4-one fragments.

Two series of vanillin derivatives containing 1,3,4-oxadiazole and 1,3-thiazolidin-4-one scaffolds were prepared and evaluated for their antifungal activity. The results revealed that compounds 6j (29.73 µg/ml) and 7a (38.15 µg/ml) displayed excellent inhibitory activity against the spore of Fusarium solani. The inhibitory activity of compound 7d (10.53 µg/ml) against the spore of Alternaria solani was more than 42-fold that of vanillin. Compound 7a (37.54 µg/ml) showed better antifungal activity against the spore of B. cinerea than positive controls. The cytotoxicity assay confirmed that compounds 6k, 7a, and 7d showed good selectivity and less toxicity to normal mammalian cells.

The NTE domain of PTENα/ß promotes cancer progression by interacting with WDR5 via its SSSRRSS motif.

PTENα/ß, two variants of PTEN, play a key role in promoting tumor growth by interacting with WDR5 through their N-terminal extensions (NTEs). This interaction facilitates the recruitment of the SET1/MLL methyltransferase complex, resulting in histone H3K4 trimethylation and upregulation of oncogenes such as NOTCH3, which in turn promotes tumor growth. However, the molecular mechanism underlying this interaction has remained elusive. In this study, we determined the first crystal structure of PTENα-NTE in complex with WDR5, which reveals that PTENα utilizes a unique binding motif of a sequence SSSRRSS found in the NTE domain of PTENα/ß to specifically bind to the WIN site of WDR5. Disruption of this interaction significantly impedes cell proliferation and tumor growth, highlighting the potential of the WIN site inhibitors of WDR5 as a way of therapeutic intervention of the PTENα/ß associated cancers. These findings not only shed light on the important role of the PTENα/ß-WDR5 interaction in carcinogenesis, but also present a promising avenue for developing cancer treatments that target this pathway.