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Mantle cell lymphoma (MCL) is a rare and aggressive form of non‐Hodgkin lymphoma. Challenges in its treatment include relapse, drug resistance, and a short survival period. The Hedgehog/GLI1 (Hh/GLI1) and Wnt/β‐catenin pathways are crucial in cancer cell proliferation, survival, and drug resistance, making them significant targets for anticancer research. This study aimed to assess the effectiveness of combining inhibitors for both pathways against MCL and investigate the underlying molecular mechanisms. The co‐expression of key proteins from the Hh/GLI1 and Wnt/β‐catenin pathways was observed in MCL. Targeting the Hh/GLI1 pathway with the GLI1 inhibitor GANT61 and the Wnt/β‐catenin pathway with the CBP/β‐catenin transcription inhibitor ICG‐001, dual‐target therapy was demonstrated to synergistically suppressed the activity of MCL cells. This approach promoted MCL cell apoptosis, induced G0/G1 phase blockade, decreased the percentage of S‐phase cells, and enhanced the sensitivity of MCL cells to the drugs adriamycin and ibrutinib. Both GANT61 and ICG‐001 downregulated GLI1 and β‐catenin while upregulating GSK‐3β expression. The interaction between Hh/GLI1 and Wnt/β‐catenin pathways was mediated by GANT61‐dependent Hh/GLI1 inhibition. Moreover, GLI1 knockdown combined with ICG‐001 synergistically induced apoptosis and increased drug sensitivity of MCL cells to doxorubicin and ibrutinib. GANT61 attenuated the overexpression of β‐catenin and decreased the inhibition of GSK‐3β in MCL cells. Overall, the combined targeting of both the Hh/GLI1 and Wnt/β‐catenin pathways was more effective in suppressing proliferation, inducing G0/G1 cycle retardation, promoting apoptosis, and increasing drug sensitivity of MCL cells than mono treatments. These findings emphasize the potential of combinatorial therapy for treating MCL patients. [ABSTRACT FROM AUTHOR]

Nitrogen‐containing corrosion inhibitors have a wide range of promising applications, and current conventional corrosion design and evaluation methods are largely based on empirical speculation and extensive exploratory experiments. Unfortunately, these efforts are often associated with high costs, long lead times, and a lot of "blind work." In this work, we have computationally screened the quantum chemical parameters of five nitrogen‐containing corrosion inhibitor molecules and their corrosion inhibition properties by a molecular simulation method based on density functional theory calculations. The ultimate relationship between the corrosion inhibition efficiency (IE) of an adsorbent and its quantum chemical parameters was analyzed using linear regression by comparing the various quantum mechanical parameters of each inhibitor molecule, as well as the fraction of electrons (ΔN) that are transferred to the metal surface from the chemisorbed inhibitor molecule. Five different nitrogen‐containing corrosion inhibitor molecules were screened based on structural similarity. Meanwhile, their corrosion inhibition performance was evaluated using the most relevant structure–activity equations. The results showed that the synergistic effect between the corrosion inhibition performance and the orbital energies of highest occupied molecular orbital and lowest unoccupied molecular orbital was optimal under the HF/6‐31G(d) method, and the corresponding structure–activity relationship was established. Based on these results, a specific inhibitor molecule was found to have excellent corrosion inhibition performance with a predicted corrosion IE of up to 94.12 %. [ABSTRACT FROM AUTHOR]

BACKGROUND: Astragali Radix (also known as Astragulus) is a traditional medicinal and edible homologous plant for tonifying Qi. Honey‐processed Astragalus is a dosage form of Astragali Radix processed with honey, which exhibited better efficacy of tonifying Qi than the raw product. Polysaccharides are their main active components. RESULTS: APS2a and HAPS2a were initially isolated from Astragulus and honey‐processed Astragulus. Both of them are highly branched acidic heteropolysaccharides containing ɑ‐configuration and β‐configuration glycosidic bonds. The molecular weight and the molecular dimension of HAPS2a decreased and the GalA contained in APS2a was converted to Gal in HAPS2a. The α‐configuration galactose residue 1,3,4‐α‐Galp in the backbone of APS2a was converted to the corresponding β‐configuration galactose residue 1,3,4‐β‐Galp in the backbone of HAPS2a and the uronic acid residue T‐α‐GalpA in the sidechain of APS2a was converted to the corresponding neutral residue T‐α‐Galp in the side chain of HAPS2a. Bioactivity results showed that HAPS2a had better probiotic effects on Bacteroides ovatus, Bacteroides thetaiotaomicron, Bifidobacterium longum and Lactobacillus rhamnosus strains than APS2a. After degradation, the molecular weights of HAPS2a and APS2a decreased with the changes in their monosaccharide composition. The contents of total short‐chain fatty acids (SCFAs) and other organic acids in HAPS2a group were higher than APS2a group. CONCLUSIONS: Two novel high‐molecular‐weight polysaccharides named APS2a and HAPS2a had different probiotic activities in vitro, which might be due to their structural differences before and after honey processing. Both of them might be possibly used as an immunopotentiator in healthy foods or dietary supplement. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Manipulating Majorana zero modes (MZMs) holds significant promise in propelling the field of topological quantum computation. While scanning tunneling microscopy (STM) exhibits remarkable capabilities in characterizing MZMs, additional geometrical constraints are imperative for achieving precise and controllable manipulation of these zero modes. To this end, it is of great help to integrate a micro mask within a molecular beam epitaxy (MBE) system to grow specific patterns containing MZMs. Here, a scenario for manipulating the MZMs in the vortex cores based on a triangular grid architecture is proposed. Additionally, a stencil lithography setup that is compatible with a combined MBE and STM system is introduced and experimentally demonstrated. A fine‐tuning of the Pb patterns, between a hexagonal antidot lattice to a triangular grid array, is achieved by adjusting the spatial gap between the stencil mask and the underlying substrate. This study provides new possibilities for the fabrication and investigation of Majorana devices. [ABSTRACT FROM AUTHOR]

The damp‐heat (DH) degradation of silicon heterojunction (SHJ) solar modules leads to severe power loss, necessitating superior‐quality encapsulation materials. Herein, it is aimed to investigate the mechanical, thermal, and optical properties of ethylene vinyl acetate (EVA), polyolefin elastomer (POE), and thermoplastic polyolefin (TPO). TPO demonstrates the lowest water vapor transmission rate (WVTR) of only 3.14 g (m2·day)−1, which is approximately seven times lower than that of EVA. The Fourier transform infrared spectroscopy of EVA demonstrates a loss of the carbonyl group, revealing the formation of acetic acid under DH stress, which is not observed in POE and TPO. Both glass/back sheet and glass/glass (G/G) modules show a significant influence of encapsulant material on DH degradation. The maximum output power (Pmax) of the G/TPO/G single‐cell module maintains 96.6% of its initial value after 1000 h DH stress. After sealing the edge, the G/G commercial‐size modules encapsulated with lower WVTR encapsulants display excellent DH reliability, and Pmax degrades <4.8% after 3000 h of DH stress. The predicted levelized cost of energy (LCOE) decreases ≈0.11 US cents/(KW h), which boosts additional power generation and illustrates the remarkable potential for the SHJ solar modules meeting the requirements of reliable, sustainable, and low‐LCOE systems. [ABSTRACT FROM AUTHOR]

Transparent conductive oxide (TCO) film acts as the window layer and carrier transport layer of silicon heterojunction (SHJ) solar cells. The optoelectrical and contact properties of TCO films, as well as the sputtering damage, limit the further efficiency improvement. Herein, the microstructure, morphology, and optoelectrical properties of sputtering‐prepared zinc‐doped indium oxide (IZO) are analyzed. The substrate temperature has a significant impact on the film growth and the cell performance. The IZO film is amorphous when substrate temperature is below 200 °C, while it seems the emergence of nanocrystals with the increased temperature, resulting in the highest conductivity (3070 S cm−1) and carrier mobility (47.9 cm2 V−1 s−1). In addition, the low carrier concentration and surface potential of IZO promote less optical parasitic absorption and higher work function. The IZO films are applied as the contact layer of SHJ solar cells. An impressive efficiency of 24.02% on an M2‐sized wafer is achieved, indicating great potential for the mass production application after careful optimization. [ABSTRACT FROM AUTHOR]

Background: Since 1910, omentectomy has been an essential component of radical gastrectomy for advanced gastric cancer. However, researchers have recently questioned the benefit of omentectomy in radical gastrectomy. The aim of this meta-analysis was to compare omentectomy and omentum preservation in gastrectomy for advanced gastric cancer in terms of survival outcomes and short-term outcomes. Methods: The PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched. Studies that compared omentum preservation with omentectomy were included. Overall survival (OS) and relapse-free survival (RFS) were analyzed as primary outcomes. Results: Of 3509 records screened, one randomized clinical trial and five propensity-score matched retrospective studies with 1661 patients were selected. Omentum preservation was associated with improved OS (hazard ratio [HR] = 0.757, 95% confidence interval [CI] = 0.603–0.950, P = 0.016, I2 = 0%), but not with improved RFS (HR = 0.821, 95% CI = 0.668–1.009, P = 0.060, I2 = 9%) compared with omentectomy for advanced gastric cancer. Furthermore, less blood loss and shorter operation time were found in the omentum preservation group than in the omentectomy group. Additionally, the rate of peritoneal recurrence, the number of harvested lymph nodes, and the incidences of postoperative complications and ileus were comparable in the two groups. Conclusions: Basing on the current literature, gastrectomy with omentum preservation was associated with improved OS and short-term outcomes compared with omentectomy for advanced gastric cancer. Further randomized trials are required to confirm the survival benefit of omentum-preserving gastrectomy. [ABSTRACT FROM AUTHOR]

Introduction: Polygoni Multiflori Caulis (PMC) has been used as a traditional Chinese medicine for a long time in China. However, hepatotoxic events of PMC have been reported in recent years, but the potential toxic compounds have remained unclear. Dianthrones as the secondary plant metabolites were revealed to potential hepatotoxicity in a previous study. However, no reports focused on dianthrones in PMC. Objective: In the quest for exploring potential hepatotoxic compounds in PMC, the aim of this work was to undertake a comprehensive characterisation of dianthrones in PMC. Methods: A simple and effective macroporous absorbent resin column chromatography method was established in this study to enrich the minor dianthrones from PMC extracts. Exploration and characterisation of dianthrones in PMC was conducted by an ultra‐high‐performance liquid chromatography‐quadrupole time‐of‐flight tandem mass spectrometry (UPLC‐QTOF‐MS/MS) method and information dependent acquisition (IDA) mode. The aglycones of dianthrone glycosides were further verified by acid hydrolysis method. Results: Seventy‐two dianthrone glycosides and their five aglycones were discovered and tentatively characterised in PMC for the first time, of which 29 dianthrones were identified as potential new compounds. Dianthrone glycosides could be classified into three types according to their aglycone structures, and their fragmentation pathway rules and diagnosed ions were also summarised comprehensively. Conclusion: This was the first comprehensive investigation on dianthrones in PMC. The result would help to fully understand the phytochemical constituents and toxic components in PMC, and highlight the need for further toxicological investigations of the dianthrones in PMC due to their potential hepatotoxicity correlation. A macroporous absorbent resin enrichment method coupled with UPLC/Q‐TOF‐MS/MS was utilized to identify the minor dianthrones in Polygoni Multiflori Caulis. Seventy‐seven dianthrones were tentatively identified inPolygoni Multiflori Caulis for the first time, including 30 potential new compounds. The acid hydrolysis method was established for structural verification. [ABSTRACT FROM AUTHOR]

The hot deformation characteristics of Nickel‐based corrosion resistant alloy was studied in the temperature range of 1050°C to 1200°C and the strain rate range of 0.001 to 0.1 second−1 by employing hot compression tests. The results show that the peak stress increases with decreasing temperature and increasing strain rate, and the apparent activation energy is about 409 kJ/mol. Based on the Avrami equation through using the critical strain (εc) and the strain for 50% DRX (ε0.5), a kinetic model for dynamic recrystallization (DRX) was established, where the model parameters could be obtained using the modified Zener‐Hollomon parameter (Z*). Applying the model, the predicted value of the steady‐state strain (εss) and the strain for maximum softening rate (εm) agree well with the experimental results. Accordingly, the relationship between εm and ε0.5 is established, which is mainly dependent on the Avrami exponent (n). When n < 3.25, εm becomes less than ε0.5 and the difference in between decreases with increasing the strain rate or decreasing the deformation temperature. Finally, through observing DRX microstructure under different deformation conditions, a power law relation between DRX grain size (Ddrx) and Z*, with an exponent of −0.36, was found. [ABSTRACT FROM AUTHOR]

Aim: Surgeons have concerns whether high ligation (HL) of the inferior mesenteric artery (IMA) increases the incidence of anastomotic leakage (AL). This meta‐analysis aimed to evaluate the influence of HL of the IMA on AL compared with low ligation (LL). Methods: PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov databases were searched. Randomized controlled trial studies that compared HL with LL of the IMA in anterior resection for rectal cancer and reported AL outcomes were eligible for inclusion. The odds ratios and mean differences were analysed by a random‐effects model. Trial sequential analysis was performed to minimize the risk of random errors. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to evaluate the quality of evidence for outcomes. Results: Of the 531 records screened, five randomized controlled trials with 779 patients were selected for analysis. The pooled incidence of AL was 12.1% (95% Cl 7.77–18.26) in the HL group and 9.7% (95% Cl 5.79–15.82) in the LL group (OR 1.20, 95% CI 0.77–1.87, P = 0.42). In trial sequential analysis, the cumulative Z‐score curve exceeded the futility boundary, although the required information size of 1060 had not been reached. The quality of evidence was judged to be high according to the GRADE approach. Conclusions: This meta‐analysis shows that HL of the IMA does not increase the incidence of AL in anterior resection for rectal cancer. [ABSTRACT FROM AUTHOR]

Honey‐processed Astragalus is a widely used traditional Chinese medicine that has a better effect on reinforcing "Qi" (vital energy) than the raw one. A comparative study of metabolites analysis between them in rat serum for finding the bioactive ingredients was carried out using serum pharmacochemistry and multivariate statistical analysis. The blood collection methods and time were optimized first. Then the prototypes and metabolites in serum samples after oral administration were investigated by ultra‐high‐performance liquid chromatography coupled with electrospray ionization quadrupole time‐of‐flight mass spectrometry integrated with principal component analysis and orthogonal partial least squares discriminant analysis. The contents of metabolites were also analyzed to evaluate the metabolic profile differences. As a result, nine prototypes and 36 metabolites were identified. Only two prototypes and 15 metabolites were different between raw and honey‐processed Astragalus. Their biotransformation reactions contained the process of oxidation, demethylation, and hydrolysis in phase I and glucuronide conjugation or sulfate conjugation in phase II. Most of the detected metabolites were transformed from isoflavones and isoflavanes. Our results expand the knowledge about the influence of honey‐processing on Astragalus and suggest the different curative effects between raw and honey‐processed Astragalus might due to their therapeutic material discrepancy. [ABSTRACT FROM AUTHOR]

Comparative study of laparoscopic versus open technique for simultaneous resection of colorectal cancer and liver metastases with propensity score analysis. Single-incision laparoscopic surgery for simultaneous resection of rectal cancer and liver metastases - a video vignette Therefore, SILS may be feasible in simultaneous resection of primary rectal cancer and liver metastases. [Extracted from the article]

Abstract: Honey‐processed Astragalus, a widely used Qi‐tonifying and immunomodulating herb in traditional Chinese medicine, has strengthened the tonic effects and achieved fewer side effects compared with astragali radix in clinical application. Here, we focus on Qi‐tonifying biomarkers and pathways of honey‐processed Astragalus using urine metabolomics that provide the basis for building the linkage between metabolites in rat urine and its symptoms. The spleen Qi deficiency model group, normal group, astragali radix group, and honey‐processed Astragalus group were implemented to evaluate Qi‐tonifying effects. Twelve potential biomarkers were screened by multivariate statistical analysis by using ultra high performance liquid chromatography with quadrupole time‐of‐flight mass spectrometry. Furthermore, pathways activity profiling showed unique pathways that are primarily involved in tryptophan metabolism, tricarboxylic acids cycle, and methionine metabolism. The results demonstrated that metabolomics coupled with pathway activity profiling were promising tools. It might serve as a novel methodological clue to systematically dissect the underlying Qi‐tonifying mechanism of honey‐processed Astragalus. [ABSTRACT FROM AUTHOR]

Although doxorubicin (Dox) is widely used in clinical treatment for solid tumors, it causes many side-effects such as heart and kidney damage, bone marrow suppression, and drug resistance. Legumain is a lysosomal protease that is elevated and associated with an invasive and metastatic phenotype in a number of solid tumors. In this study, we designed and synthesized a Dox prodrug, N-benzyloxycarbonyl-Ala-Ala-Asn-Doxorubicin ( CBZ- AAN-Dox), with 94% purity. Single substrate kinetic assays demonstrated hLegumain-specific enzymatic cleavage and activation of the prodrug in vitro, and this enzymatic cleavage of the prodrug substrate was more sensitive in acidic conditions, releasing more than 70% of Dox after 24 h. Treatment of tumor cells with our prodrug demonstrated a much higher IC50 value, significantly enhanced uptake of the prodrug, and considerably less cellular toxicity compared to Dox treatment alone. Our study presents a novel prodrug, CBZ- AAN-Dox, to potentially increase both the safety and efficacy of clinical treatment of tumors by exploiting the tumor's innate expression of legumain. [ABSTRACT FROM AUTHOR]

Four novel oxidovanadium( IV) complexes, [ VO(hntdtsc)( PHIP)] ( 1) (hntdtsc = 2-hydroxy-1-naphthaldehyde thiosemicarbazone, PHIP= 2-phenyl-imidazo[4,5-f]1,10-phenanthroline), [ VO(hntdtsc)( DPPZ)]( 2)( DPPZ= dipyrido[3,2-a:2',3'-c]phenazine), [ VO(satsc)( PHIP)]( 3) (satsc=salicylaldehyde thiosemicarbazone), and [ VO(satsc)( DPPZ)]( 4), have been prepared and characterized. The chemical nuclease activities and photocleavage reactions of the complexes were tested. All four complexes can efficiently cleave pBR322 DNA, and complex 1 has the best cleaving ability. The antitumor properties of these complexes were examined with three different tumor cell lines using MTT assay. Their antitumor mechanism has been analyzed using cell cycle analysis, fluorescence microscopy of apoptosis, and Annexin V- FITC/ PI assay. The results showed that the growth of human neuroblastoma ( SH- SY5Y, SK-N- SH) and human breast adenocarcinoma ( MCF-7) cells were inhibited significantly with very low IC50 values. Complex 1 was found to be the most potent antitumor agent among the four complexes. It can cause G0/G1 phase arrest of the cell cycle and exhibited significant induced apoptosis in SK-N- SH cells and displayed typical morphological apoptotic characteristics. In addition, they all displayed reasonable abilities to scavenge hydroxyl radical, and complex 1 was the best inhibitor. [ABSTRACT FROM AUTHOR]

CC chemokine receptor 4 (CCR4) has attracted much attention as a promising therapeutic drug target for CCR4 + tumor cells and Tregs. CCR4 is expressed on some tumor cells such as T-cell acute lymphoblastic leukemia (ALL), adult T-cell leukemia/lymphoma (ATLL), adult peripheral T cell lymphoma (PTCL) and cutaneous T cell lymphoma (CTCL). CCR4 is also expressed on majority of Tregs, mainly effector Tregs. In this study we have successfully developed three versions of diphtheria-toxin based anti-human CCR4 immunotoxins (monovalent, bivalent and single-chain fold-back diabody). Binding analysis by flow cytometry showed that all three versions of the anti-human CCR4 immunotoxins bound to the human CCR4 + tumor cell line as well as CCR4 + human PBMC. The bivalent isoform bound stronger than its monovalent counterpart and the single-chain foldback diabody isoform was the strongest among the three versions. In vitro efficacy analysis demonstrated that the bivalent isoform was 20 fold more potent in inhibiting cellular proliferation and protein synthesis in human CCR4 + tumor cells compared to the monovalent anti-human CCR4 immunotoxin. The single-chain fold-back diabody isoform was 10 fold more potent than its bivalent counterpart and 200 fold more potent than its monovalent counterpart. The in vivo efficacy was assessed using a human CCR4 + tumor-bearing mouse model. The immunotoxin significantly prolonged the survival of tumor-bearing NOD/SCID IL-2 receptor γ −/− ( NSG ) mice injected with human CCR4 + acute lymphoblastic leukemia cells compared with the control group. This novel anti-human CCR4 immunotoxin is a promising drug candidate for targeting human CCR4 + tumor cells and Tregs in vivo . [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Radix Astragali, commonly known as Astragalus, is a traditional medicinal and edible plant valued for its Qi‐tonifying properties. The dosage form of Radix Astragali processed with honey, known as honey‐processed Astragalus (HPA), shows improved Qi‐tonifying efficacy as compared to the raw product. Polysaccharides are the main bioactive ingredients in its aqueous extract. This study used a multiomics approach integrating microbiomics and metabolomics to elucidate the Qi‐tonifying mechanisms of honey‐processed Astragalus polysaccharides (HAPS).HAPS‐treated mice showed improved symptom scores, spleen and thymus indices, serum cytokines (tumor necrosis factor α, interleukin 1β) and intestinal mucosa secretory immunoglobulin A (SIgA) compared to the mice with spleen Qi deficiency. The analysis of gut microbiota indicated that HAPS regulated the relative abundance of Bacteroidetes, Bacteroides, Proteobacteria and Helicobacter, thereby improving intestinal flora dysbiosis in mice with spleen Qi deficiency. Eleven biomarkers in fecal metabolomics analysis were screened and identified, primarily associated with linoleic acid metabolism, sphingolipid metabolism, glycerophospholipid metabolism and biosynthesis of unsaturated fatty acids. Furthermore, comprehensive analyses demonstrated that HAPS regulates palmitic acid and sphingolipid metabolism by modulating the abundance of Bacteroidetes, which in turn increased the levels of intestinal mucosal SIgA and restored intestinal mucosal immune function in mice with spleen Qi deficiency.Our findings revealed that HAPS is an essential active ingredient of HPA, and its Qi‐tonifying mechanism is closely related to the improvement of intestinal immune function. These findings lay the foundation for the application of HAPS as an immunomodulatory agent in health and dietary foods. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

I Dear Editor i , Anastomotic leakage (AL) is a severe complication of anterior resection for rectal cancer, with an incidence varying from 3.5% to 17.4% [1-3]. Some studies [4,5] consider high ligation (HL) of the inferior mesenteric artery (IMA) as a risk factor for AL. Recently, we published a high-quality meta-analysis [6] which only included randomized controlled trials and concluded that HL of the IMA did not increase the incidence of AL in anterior resection. [Extracted from the article]