Tumour response following preoperative chemotherapy is affected by body mass index in patients with colorectal liver metastases.

BACKGROUND: Colorectal cancer is the third most prevalent malignancy globally and ranks second in cancer-related mortality, with the liver being the primary organ of metastasis. Preoperative chemotherapy is widely recommended for initially or potentially resectable colorectal liver metastases (CRLMs). Tumour pathological response serves as the most important and intuitive indicator for assessing the efficacy of chemotherapy. However, the postoperative pathological results reveal that a considerable number of patients exhibit a poor response to preoperative chemotherapy. Body mass index (BMI) is one of the factors affecting the tumorigenesis and progression of colorectal cancer as well as prognosis after various antitumour therapies. Several studies have indicated that overweight and obese patients with metastatic colorectal cancer experience worse prognoses than those with normal weight, particularly when receiving first-line chemotherapy regimens in combination with bevacizumab. AIM: To explore the predictive value of BMI regarding the pathologic response following preoperative chemotherapy for CRLMs. METHODS: A retrospective analysis was performed in 126 consecutive patients with CRLM who underwent hepatectomy following preoperative chemotherapy at four different hospitals from October 2019 to July 2023. Univariate and multivariate logistic regression models were applied to analyse potential predictors of tumour pathological response. The Kaplan-Meier method with log rank test was used to compare progression-free survival (PFS) between patients with high and low BMI. BMI < 24.0 kg/m2 was defined as low BMI, and tumour regression grade 1-2 was defined as complete tumour response. RESULTS: Low BMI was observed in 74 (58.7%) patients and complete tumour response was found in 27 (21.4%) patients. The rate of complete tumour response was significantly higher in patients with low BMI (29.7% vs 9.6%, P = 0.007). Multivariate analysis revealed that low BMI [odds ratio (OR) = 4.56, 95% confidence interval (CI): 1.42-14.63, P = 0.011], targeted therapy with bevacizumab (OR = 3.02, 95%CI: 1.10-8.33, P = 0.033), preoperative carcinoembryonic antigen level < 10 ng/mL (OR = 3.84, 95%CI: 1.19-12.44, P = 0.025) and severe sinusoidal dilatation (OR = 0.17, 95%CI: 0.03-0.90, P = 0.037) were independent predictive factors for complete tumour response. The low BMI group exhibited a significantly longer median PFS than the high BMI group (10.7 mo vs 4.7 mo, P = 0.011). CONCLUSION: In CRLM patients receiving preoperative chemotherapy, a low BMI may be associated with better tumour response and longer PFS.

Fermented calcium butyrate supplementation in post-peak laying hens improved ovarian function and tibia quality through the "gut-bone" axis.

The compromised egg quality and leg abnormality during the end of the laying cycle (after 40 weeks) have been leading to poor animal welfare and substantial economic losses. Therefore, the effects of fermented calcium (Ca) butyrate, produced by fermentation by Clostridium butyricum, on production, eggshell quality, and tibial property of hens were explored. A total of 192 Hy-line brown laying hens at 50-week-old were assigned to a basal diet or the basal diet with 300 mg/kg of the fermented Ca butyrate from 50 to 58 weeks of age. Each treatment had 6 replicates with 16 hens each. The diet supplemented with 300 mg/kg fermented Ca butyrate notably increased egg weight, ovarian follicle number, and eggshell strength (P = 0.072) as compared to the basal diet, which were associated with cytokine secretion, toll-like receptor signaling pathways, and intestinal immunity based on the RNA-seq data from the granulosa. Dietary Ca butyrate inclusion decreased the expression of ileal tumor necrosis factor-alpha and serum pro-inflammatory cytokine concentration, as well as increased the content of serum immunoglobulin A when compared to the basal diet (both P < 0.05). The birds that received fermented Ca butyrate diets exhibited higher villus height (P < 0.05) and upregulated expression of tight junction proteins, whereas it did not alter the composition of cecal microbiota (P > 0.05). In addition, the diet with fermented Ca butyrate reduced the number of osteoclasts in the proximal tibia and the level of C-terminal cross-linked telopeptide of type I collagen, a bone resorption marker (P < 0.05), whereas it tended to increase the concentration of the procollagen type I N-terminal propeptide that reflects bone formation marker in serum. Moreover, the layers fed fermented Ca butyrate diets possessed higher (P < 0.05) bone area and trabecular number of the proximal tibia, yield load, and ultimate load than those that consumed basal diets. Collectively, dietary fermented Ca butyrate supplementation in post-peak layer diets improved the ovarian function and tibia quality, which might be related to enhancing intestinal integrity and consequently decreasing inflammation mediated bone resorption.

Dietary supplementation with Clostridium butyricum and its ferment substance improves the egg quality and ovarian function in laying hens from 50 to 58 weeks of age.

The current study was conducted to explore the effects of dietary Clostridium butyricum (C. butyricum) and fermented calcium (Ca) butyrate produced by C. butyricum on the performance and egg quality of post-peak laying. A total of 384 50-week-old hens were fed a basal diet, the basal diet with 300 mg/kg of fermented Ca butyrate or 1 × 109 CFU/kg C. butyricum for 8 weeks. Hens received a C. butyricum exhibited higher yolk properties, albumen height, and Haugh unit. A diet with fermented Ca butyrate or C. butyricum increased the egg mass and the pre-grade yellow follicle number. RNA-sequencing (RNA-seq) data showed that these observations were associated with cytokine-cytokine receptor interaction and intestinal immune status. Accordingly, when compared with the basal diet group, Ca butyrate and C. butyricum addition decreased serum pro-inflammatory cytokine levels and increased the concentration of immunoglobulin A, along with improved intestinal barrier. In addition, dietary C. butyricum inclusion induced a higher abundance of Ruminococcaceae and Lachnospiraceae at the family level. In summary, dietary fermented Ca butyrate or C. butyricum supplementation improved egg quality and ovarian function, which might be related to the enhanced intestinal barrier and immunity in post-peak laying hens.

Dibenzothiophene Sulfone-Based Ambipolar-Transporting Blue-Emissive Organic Semiconductors Towards Simple-Structured Organic Light-Emitting Transistors.

The development of blue-emissive ambipolar organic semiconductor is an arduous target due to the large energy gap, but is an indispensable part for electroluminescent device, especially for the transformative display technology of simple-structured organic light-emitting transistor (SS-OLET). Herein, we designed and synthesized two new dibenzothiophene sulfone-based high mobility blue-emissive organic semiconductors (DNaDBSOs), which demonstrate superior optical property with solid-state photoluminescent quantum yield of 46-67 % and typical ambipolar-transporting properties in SS-OLETs with symmetric gold electrodes. Comprehensive experimental and theoretical characterizations reveal the natural of ambipolar property for such blue-emissive DNaDBSOs-based materials is ascribed to a synergistic effect on lowering LUMO level and reduced electron injection barrier induced by the interfacial dipoles effect on gold electrodes due to the incorporation of appropriate DBSO unit. Finally, efficient electroluminescence properties with high-quality blue emission (CIE (0.179, 0.119)) and a narrow full-width at half-maximum of 48 nm are achieved for DNaDBSO-based SS-OLET, showing good spatial control of the recombination zone in conducting channel. This work provides a new avenue for designing ambipolar emissive organic semiconductors by incorporating the synergistic effect of energy level regulation and molecular-metal interaction, which would advance the development of superior optoelectronic materials and their high-density integrated optoelectronic devices and circuits.

Recent advances in n-type and ambipolar organic semiconductors and their multi-functional applications.

Organic semiconductors have received broad attention and research interest due to their unique integration of semiconducting properties with structural tunability, intrinsic flexibiltiy and low cost. In order to meet the requirements of organic electronic devices and their integrated circuits, p-type, n-type and ambipolar organic semiconductors are all necessary. However, due to the limitation in both material synthesis and device fabrication, the development of n-type and ambipolar materials is quite behind that of p-type materials. Recent development in synthetic methods of organic semiconductors greatly enriches the range of n-type and ambipolar materials. Moreover, the newly developed materials with multiple functions also put forward multi-functional device applications, including some emerging research areas. In this review, we give a timely summary on these impressive advances in n-type and ambipolar organic semiconductors with a special focus on their synthesis methods and advanced materials with enhanced properties of charge carrier mobility, integration of high mobility and strong emission and thermoelectric properties. Finally, multi-functional device applications are further demonstrated as an example of these developed n-type and ambipolar materials.

Ultralow-Power Vertical Transistors for Multilevel Decoding Modes.

Organic field-effect transistors with parallel transmission and learning functions are of interest in the development of brain-inspired neuromorphic computing. However, the poor performance and high power consumption are the two main issues limiting their practical applications. Herein, an ultralow-power vertical transistor is demonstrated based on transition-metal carbides/nitrides (MXene) and organic single crystal. The transistor exhibits a high JON of 16.6 mA cm-2 and a high JON /JOFF ratio of 9.12 × 105 under an ultralow working voltage of -1 mV. Furthermore, it can successfully simulate the functions of biological synapse under electrical modulation along with consuming only 8.7 aJ of power per spike. It also permits multilevel information decoding modes with a significant gap between the readable time of professionals and nonprofessionals, producing a high signal-to-noise ratio up to 114.15 dB. This work encourages the use of vertical transistors and organic single crystal in decoding information and advances the development of low-power neuromorphic systems.

Combination of Cinnamaldehyde with Carvacrol or Thymol Improves the Mechanical Properties of Tibia in Post-Peak Laying Hens.

Roles of plant-derived cinnamaldehyde, carvacrol, and thymol in the gut and bone health of laying hens was evaluated in the present study. After acclimation for 2 weeks, a total 384 of 52-week-old laying hens were allocated into three groups for 6 weeks: (1) basal diet group (Ctrl), (2) combination of cinnamaldehyde with carvacrol group (CAR+CIN), and (3) blend of cinnamaldehyde with thymol (THY+CIN). The dietary essential oil level was 100 mg/kg. Each treatment group had eight replicate pens (16 birds/pen). The stiffness and ultimate load of the tibiae from both the CAR+CIN and THY+CIN groups were higher than that of the Ctrl group (p < 0.05), along with comparable tibia ash, calcium, and phosphorus content among groups. At the same time, the manipulation of essential oils upregulated the transcription abundances of intestinal barrier proteins to varying degrees, whereas the experimental treatment failed to affect the composition in phyla of cecal microbiota. When compared to the Ctrl group, birds fed the CAR+CIN and THY+CIN diet displayed decreased bone resorption markers, reduced interleukin-1 concentrations, and increased transforming growth factor beta levels in serum. These findings suggest that cinnamaldehyde with carvacrol or thymol in feed of hens could enhance intestinal barrier and improve the mechanical properties of tibiae through structural modelling but not increase the mineral density, which might be involved in suppressing inflammation-mediated bone resorption.

Dietary cinnamaldehyde with carvacrol or thymol improves the egg quality and intestinal health independent of gut microbiota in post-peak laying hens.

Essential oils have been proven to exert multiple effects on growth performance, production quality, and health status in poultry nutrition, which is dependent on the component and/or dose of essential oils. Diets with the optimal combination of essential oils might be able to improve the performance traits and welfare of laying hens. Therefore, this study was conducted to evaluate the effects of dietary essential oils, which are composed of cinnamaldehyde with carvacrol or thymol, on performance, egg quality, and intestinal health in post-peak laying hens. A total of 384, 50-week-old Hy-line brown laying hens were randomly divided into three groups with 8 replicates of 16 birds each: (1) a basal diet (Ctrl), (2) a basal diet with 100 mg/kg of essential oils consisting of 4.5% cinnamaldehyde with 13.5% carvacrol (CAR+CIN), and (3) a basal diet containing 100 mg/kg of essential oils composed of 4.5% cinnamaldehyde with 13.5% thymol (THY+CIN). The CAR+CIN diet increased the feed consumption from 52 to 55 weeks more than the Ctrl and the THY+CIN diet. Compared with the Ctrl group, the addition of essential oils decreased the dirty egg rate (P = 0.07) in the whole trial period. Regarding egg quality, the birds that received the CAR+CIN and THY+CIN diets increased the eggshell strength (P = 0.099) or Haugh unit (HU, p = 0.03) at 54 weeks, respectively. Supplementation of both CAR+CIN and THY+CIN diets significantly increased the ratio of villus height to crypt depth in the duodenum through increasing villus height and decreasing crypt depth as well as upregulated the mRNA abundances of duodenal occluding and cadherin (P < 0.05). However, the treatment with dietary essential oils did not notably change the proportion of cecal microbiota and bacterial diversity. This study suggested that dietary supplementation of cinnamaldehyde with carvacrol or thymol, the active components of essential oils, could promote egg quality in post-peak laying hens, which might be associated with improved intestinal development and barrier.

Clinical efficacy of avatrombopag and recombinant human thrombopoietin in the treatment of chronic liver disease-associated severe thrombocytopenia: A real-world study.

Purpose: To investigate the clinical efficacy of avatrombopag, an oral thrombopoietin receptor agonist, versus subcutaneous recombinant human thrombopoietin (rh-TPO) in the treatment of severe thrombocytopenia (TCP) associated with chronic liver disease (CLD). Methods: Clinical data of 250 patients with severe TCP associated with CLD were collected in a single hospital from January 2019 to January 2022. The main parameters measured were the therapeutic response rate, changes in platelets (PLTs), and adverse events. Propensity score matching (PSM) was used to avoid possible selection bias. Results: After PSM, a total of 154 patients were enrolled in the study: 77 in the avatrombopag group and 77 in the rh-TPO group. There was no statistically significant difference between the two groups in the effect of increasing the PLT count (Waldχ 2 = 1.659, p = 0.198; Waldχ 2 = 0.220, p = 0.639). In addition, no interaction between time and different medications was found (Waldχ 2 = 0.540, p = 0.910; Waldχ 2 = 1.273, p = 0.736). Interestingly, in the subgroup analysis, both before and after PSM, avatrombopag showed better clinical efficacy than rh-TPO in the treatment of TCP associated with CLD in Child‒Pugh Class A (88.89% vs. 63.41%, p =0.003; 81.33% vs. 61.76%, p = 0.043). Fewer patients reported dizziness in the avatrombopag group than in the rh-TPO group both before and after PSM (7.8% vs. 25.0%; 7.8% vs. 24.7%, p < 0.05). Conclusion: Both before and after PSM, avatrombopag showed better clinical efficacy than rh-TPO in the treatment of TCP associated with CLD in Child‒Pugh Class A and showed a lower incidence of dizziness in all patients.

Acidification of drinking water improved tibia mass of broilers through the alterations of intestinal barrier and microbiota.

OBJECTIVE: Diet acidification supplementation is known to influence intestinal morphology, gut microbiota, and on phosphorus (P) utilization of broilers. Alterations in intestinal barrier and microbiota have been associated with systemic inflammation and thus regulating bone turnover. Hence the effect of acidifier addition to drinking water on tibia mass and the linkages between intestinal integrity and bone were studied. METHODS: One-d-old male broilers were randomly assigned to normal water (control) or continuous supply of acidified water (2% the blend of 2-hydroxy-4-methylthiobutyric acid, lactic, and phosphoric acid) group with 5 replicates of 10 chicks per replicate for 42 d. RESULTS: Acidification of drinking water improved the ash percentage and calcium content of tibia at 42 d. Broilers receiving acidified water had increased serum P concentration compared to control birds. The acidified group showed improved intestinal barrier, evidenced by increased wall thickness, villus height, the villus height to crypt depth ratio, and upregulated mucin-2 expression in ileum. Broilers receiving drinking water containing mixed organic acids had a higher proportion of Firmicutes and the ratio of Firmicutes and Bacteroidetes, as well as a lower population of Proteobacteria. Meanwhile, the addition of acidifier to drinking water resulted in declined ileal and serum proinflammatory factors level and increased immunoglobulin concentrations in serum. Concerning bone remodeling, acidifier addition was linked to a decrease in serum C-terminal cross-linked telopeptide of type I collagen and tartrate-resistant acid phosphatase reflecting bone resorption, whereas it did not apparently change serum alkaline phosphatase activity that is a bone formation marker. CONCLUSION: Acidified drinking water increased tibia mineral deposition of broilers, which was probably linked with higher P utilization and decreased bone resorption through improved intestinal integrity and gut microbiota and through decreased systemic inflammation.

Intrinsic Linear Dichroism of Organic Single Crystals toward High-Performance Polarization-Sensitive Photodetectors.

The ability to detect light in photodetectors is central to practical optoelectronic applications, which has been demonstrated in inorganic semiconductor devices. However, so far, the study of polarization-sensitive organic photodetectors, which have unique applications in flexible and wearable electronics, has not received much attention. Herein, the construction of polarization-sensitive photodetectors based on the single crystals of a superior optoelectronic organic semiconductor, 2,6-diphenyl anthracene (DPA), is demonstrated. The systematic characterization of two-dimensionally grown DPA crystals with various techniques definitely show their strong anisotropy in molecular vibration, optical reflectance and optical absorption. In terms of polarization sensitivity, DPA-crystal based photodetectors exhibit a linear dichroic ratio up to ≈1.9. Theoretical calculations confirm that intrinsic linear dichroism, originated from the anisotropic in-plane crystal structure, is responsible for the polarization sensitivity of DPA crystals. This work opens up a new door for exploiting organic semiconductors for developing highly compact polarization photodetectors and providing new functionalities in novel flexible optical and optoelectronic applications.

1D Mixed-Stack Cocrystals Based on Perylene Diimide toward Ambipolar Charge Transport.

There is very limited repertoire of organic ambipolar semiconductors to date. Electron donor-acceptor alternative stacking is a unique and important binary motif for 1D mixed-stack cocrystals, opening up possibilities for the development of organic ambipolar semiconductors. Herein, four 1D mixed-stack cocrystals using N,N'-bis(perfluorobutyl)-1,7-dicyanoperylene-3,4:9,10-bis(dicarboximide) (PDICNF) as the acceptor and anthracene, pyrene, perylene, and meso-diphenyl tetrathia[22]annulene[2,1,2,1] (DPTTA) as the donors are achieved in a stoichiometric ratio (D:A = 1:1) through solution or vapor processed methods. Their packing structures, energy levels, charge transfer interactions, coassembling behaviors, and molecular orientations are systematically investigated by single-crystal X-ray analysis, absorption spectra, fluorescence quenching, Job's curve plot, and polarized photoluminescence measurements with the help of theoretical calculations. The donor-acceptor alternative stacking direction coincides with the long axis for all the four cocrystals. The field-effect transistors based on Pyrene-PDICNF show the electron mobility up to 0.19 cm2 V-1 s-1 , which is the highest value among perylene diimide-based cocrystals. Moreover, DPTTA-PDICNF cocrystals possess well-balanced electron and hole mobility with 1.7 × 10-2 and 2.0 × 10-2  cm2 V-1 s-1 respectively due to both hole and electron strong superexchange interactions, shedding light on the design of 1D mixed-stack cocrystals with excellent ambipolar transport behaviors.

Electrically Conductive Coordination Polymers for Electronic and Optoelectronic Device Applications.

Electrically conductive coordination polymers (generally known as metal-organic frameworks, MOFs) are a class of crystalline hybrid materials produced by the reasonable self-assembly of metal nodes and organic linkers. The unique and intriguing combination of inorganic and organic components endows coordination polymers with superior optical and electrical properties, which have recently aroused much attention in several electronic and optoelectronic technological applications. However, there are many challenging obstacles and issues that need to be addressed in this burgeoning field. In this Perspective, we first provide a fundamental understanding about the electronic design strategies that provide better guidance for realizing high conductivities and good mobilities in coordination polymers. We then examine the current established synthetic approaches to construct high-quality working samples of electrically conductive coordination polymers for device integration. This is followed by a discussion of the current state-of-the-art progress toward the preliminary achievements in (opto)electronic devices spanning chemiresistive sensors, field-effect transistors, organic photovoltaics, photodetectors, etc. Finally, we conclude this Perspective with the existing hurdles and limitations in this area, along with the critical directions and opportunities for future research.

Two-Dimensional Conjugated Polymer Synthesized by Interfacial Suzuki Reaction: Towards Electronic Device Applications.

Preparing two-dimensional conjugated polymers (2DCPs) with desirable structures and semiconducting properties is promising but remains a great challenge. Presented here is a new 2DCP, named 2D polytriethyltriindole (2DPTTI), which is efficiently synthesized by a modified interfacial Suzuki reaction from 2,7,12-tribromo-5,10,15-triethyltriindole (2-BrTTI) and 1,4-benzenediboronic acid dipinacol ester (BADE) precursors at room temperature. Wafer-scale free-standing 2DPTTI films with controllable thicknesses between 2.5 and 46.0 nm were obtained by adjusting the experimental conditions. The resulting 2DPTTI films, used as an active layer in organic field effect transistors (OFETs), exhibited typical p-type semiconducting properties and superior UV optoelectronic performance with a photosensitivity of 3.7×103 and responsivity of 1.4×103  A W-1 , as well as a light-blue fluorescence character. This report provides a general approach for constructing various semiconducting 2DCPs, by an interfacial Suzuki reaction, towards multifunctional organic electronics.

In Situ Strain and Damage Monitoring of GFRP Laminates Incorporating Carbon Nanofibers under Tension.

In this study, conductive carbon nanofibers (CNFs) were dispersed into epoxy resin and then infused into glass fiber fabric to fabricate CNF/glass fiber-reinforced polymer (GFRP) laminates. The electrical resistance and strain of CNF/GFRP laminates were measured simultaneously during tensile loadings to investigate the in situ strain and damage monitoring capability of CNF/GFRP laminates. The damage evolution and conduction mechanisms of the laminates were also presented. The results indicated that the percolation threshold of CNFs content for CNF/GFRP laminates was 0.86 wt % based on a typical power law. The resistance response during monotonic tensile loading could be classified into three stages corresponding to different damage mechanisms, which demonstrated a good ability of in situ damage monitoring of the CNF/GFRP laminates. In addition, the capacity of in situ strain monitoring of the laminates during small strain stages was also confirmed according to the synchronous and reversible resistance responses to strain under constant cyclic tensile loading. Moreover, the analysis of the resistance responses during incremental amplitude cyclic tensile loading with the maximum strain of 1.5% suggested that in situ strain and damage monitoring of the CNF/GFRP laminates were feasible and stable.

Paris Saponin II induced apoptosis via activation of autophagy in human lung cancer cells.

Paris Saponin II (PSII) has been shown anticancer activity against several cancer lines through the pro-apoptotic pathway. The aim of the study was to investigate the relationship between apoptosis and autophagy taking part in the anti-cancer mechanisms of PSII. In this study, PSII induced autophagy and apoptosis in dose- and time-dependent manners. Meanwhile, it induced autophagy as early as 2 h after exposure to 1 µM of PSII accompanying with apoptosis. Blockade of autophagy with chloroquine (CQ) attenuated apoptosis, while regulation of reactive oxygen species (ROS) by N-acetyl cysteine (NAC), gallic acid (GA) and H2O2 could not influence autophagy. In addition, PSII induced apoptosis via activation of autophagy, which might be associated with the activation of JNK and inhibition of PI3K/AKT/mTOR pathway. All in all, our research increased the understanding of the role of PSII regulating autophagy and apoptosis, which would hopefully provide prospective strategies for cancer therapy.