M1 macrophage-membrane-cloaked paclitaxel/ß-elemene nanoparticles targeting cervical cancer for enhanced therapy.

Cervical cancer is a leading cause of cancer-related mortality in females worldwide, necessitating urgent solutions for effective treatment. Paclitaxel (PTX), a natural diterpene alkaloid compound, has the ability to inhibit mitosis and induce programmed apoptosis in tumor cells. However, its toxicity and drug resistance limit its efficacy in certain cervical cancer patients. ß-elemene (ß-ELE) can reverse multidrug resistance by inhibiting ATP-binding cassette transporters, thereby enhancing chemotherapy drug retention. Therefore, we propose a combination therapy using PTX/ß-ELE to improve chemotherapy sensitivity. To enhance targeted drug delivery, we developed M1-macrophage-membrane-coated nanoparticles (M1@PLGA/PTX/ß-ELE) for co-delivery of PTX&ß-ELE. Through both in vitro and in vivo cervical cancer models, we demonstrated that M1@PLGA/PTX/ß-ELE effectively suppressed tumor progression and polarization of tumor-associated macrophages. Furthermore, H&E staining confirmed the high therapeutic biosafety of M1@PLGA/PTX/ß-ELE as there was no significant damage observed in major organs throughout the entire therapeutic process. Overall, this study presents a targeted biomimetic nanoplatform and combinatorial strategy that synergistically enhances chemosensitivity in malignant tumors.

SbPL1CE8 from Segatella bryantii combines with SbGH28GH105 in a multi-enzyme cascade for pectic biomass utilization.

Pectinases are useful biocatalysts for pectic biomass processing and are extensively used in the food/feed, textile and papermaking industries. Two pectinase genes, a pectate lyase (SbPL1CE8) and a polygalacturonase (SbGH28GH105) were isolated from Segatella bryantii and functionally characterized. Recombinant rSbPL1CE8 was most active against polygalacturonic acid (PGA) and pectin with a 60 % degree of esterification, with kcat/Km values of 721.18 ± 64.77 and 327.02 ± 22.44 mL/s/mg, respectively. Truncated rSbPL1 acted as a mesophilic alkaline pectate lyase, which was highly resistant to inactivation by methanol and ethanol. The rSbPL1CE8 exclusively digested PGA and pectin into unsaturated digalacturonate (uG2), which was further converted into galacturonic acid by rSbGH28GH105. The rSbPL1CE8 was highly effective for saccharification of waste materials from Zea mays, Oryza sativa and Arachis hypogaea processing, and for ramie fiber degumming. This novel pectate lyase has great potential for application in industrial pectic biomass processing.

AC099850.3 promotes HBV-HCC cell proliferation and invasion through regulating CD276: a novel strategy for sorafenib and immune checkpoint combination therapy.

BACKGROUND: This study investigates the molecular mechanisms of CC@AC&SF@PP NPs loaded with AC099850.3 siRNA and sorafenib (SF) for improving hepatitis B virus-related hepatocellular carcinoma (HBV-HCC). METHODS: A dataset of 44 HBV-HCC patients and their survival information was selected from the TCGA database. Immune genes related to survival status were identified using the ImmPort database and WGCNA analysis. A prognostic risk model was constructed and analyzed using Lasso regression. Differential analysis was performed to screen key genes, and their significance and predictive accuracy for HBV-HCC were validated using Kaplan-Meier survival curves, ROC analysis, CIBERSORT analysis, and correlation analysis. The correlation between AC099850.3 and the gene expression matrix was calculated, followed by GO and KEGG enrichment analysis using AC099850.3 and its co-expressed genes. HepG2.2.15 cells were selected for in vitro validation, and lentivirus interference, cell cycle determination, CCK-8 experiments, colony formation assays, Transwell experiments, scratch experiments, and flow cytometry were performed to investigate the effects of key genes on HepG2.2.15 cells. A subcutaneous transplanted tumor model in mice was constructed to verify the inhibitory effect of key genes on HBV-HCC tumors. Subsequently, pH-triggered drug release NPs (CC@AC&SF@PP) were prepared, and their therapeutic effects on HBV-HCC in situ tumor mice were studied. RESULTS: A prognostic risk model (AC012313.9, MIR210HG, AC099850.3, AL645933.2, C6orf223, GDF10) was constructed through bioinformatics analysis, showing good sensitivity and specificity in diagnostic prediction. AC099850.3 was identified as a key gene, and enrichment analysis revealed its impact on cell cycle pathways. In vitro cell experiments demonstrated that AC099850.3 promotes HepG2.2.15 cell proliferation and invasion by regulating immune checkpoint CD276 expression and cell cycle progression. In vivo, subcutaneously transplanted tumor experiments showed that AC099850.3 promotes the growth of HBV-HCC tumors in nude mice. Furthermore, pH-triggered drug release NPs (CC@AC&SF@PP) loaded with AC099850.3 siRNA and SF were successfully prepared and delivered to the in situ HBV-HCC, enhancing the effectiveness of combined therapy for HBV-HCC. CONCLUSIONS: AC099850.3 accelerates the cell cycle progression and promotes the occurrence and development of HBV-HCC by upregulating immune checkpoint CD276 expression. CC@AC&SF@PP NPs loaded with AC099850.3 siRNA and SF improve the effectiveness of combined therapy for HBV-HCC.

The impact of quercetin and paclitaxel combination on ovarian cancer cells.

Ovarian cancer is a highly lethal gynecological malignancy, emphasizing the need for effective treatment strategies. This study investigated the synergistic effects of quercetin and paclitaxel on ovarian cancer. Using SKOV3 and A2780 cell lines, we found that the combined treatment significantly enhanced cell apoptosis and inhibited invasion and migration compared to individual treatments. Then, we identified 32 common targets between quercetin/paclitaxel and ovarian cancer, with 29 genes showing differential expression between normal ovarian tissue and ovarian tumor tissue. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that quercetin and paclitaxel modulated cancer-related pathways in ovarian cancer treatment. Mechanistic analysis further discovered that the synergistic effect was mediated by downregulating ERBB2 and BIRC5 and upregulating CASP3 expression. This study provides strong evidence that quercetin enhances the effectiveness of paclitaxel in treating ovarian cancer.

Exploring the effects of Hippo signaling pathway on rumen epithelial proliferation.

BACKGROUND: The current understanding to the mechanism of rumen development is limited. We hypothesized that the Hippo signaling pathway controlled the proliferation of rumen epithelium (RE) during postnatal development. In the present study, we firstly tested the changes of the Hippo signaling pathway in the RE during an early growing period from d5 to d25, and then we expanded the time range to the whole preweaning period (d10-38) and one week post weaning (d45). An in vitro experiment was also carried out to verify the function of Hippo signaling pathway during RE cell proliferation. RESULTS: In the RE of lambs from d5 to d25, the expression of baculoviral IAP repeat containing (BIRC3/5) was increased, while the expressions of large tumor suppressor kinase 2 (LATS2), TEA domain transcription factor 3 (TEAD3), axin 1 (AXIN1), and MYC proto-oncogene (MYC) were decreased with rumen growth. From d10 to d38, the RE expressions of BIRC3/5 were increased, while the expressions of LATS2 and MYC were decreased, which were similar with the changes in RE from d5 to d25. From d38 to d45, different changes were observed, with the expressions of LATS1/2, MOB kinase activator 1B (MOB1B), and TEAD1 increased, while the expressions of MST1 and BIRC5 decreased. Correlation analysis showed that during the preweaning period, the RE expressions of BIRC3/5 were positively correlated with rumen development variables, while LAST2 was negatively correlated with rumen development variables. The in vitro experiment validated the changes of LATS2 and BIRC3/5 in the proliferating RE cells, which supported their roles in RE proliferation during preweaning period. CONCLUSIONS: Our results suggest that the LATS2-YAP1-BIRC3/5 axis participates in the RE cell proliferation and promotes rumen growth during the preweaning period.

Expression and characterization of a novel microbial GH9 glucanase, IDSGLUC9-4, isolated from sheep rumen.

OBJECTIVE: This study aimed to identify and characterize a novel endo-ß-glucanase, IDSGLUC9-4, from the rumen metatranscriptome of Hu sheep. METHODS: A novel endo-ß-glucanase, IDSGLUC9-4, was heterologously expressed in Escherichia coli and biochemically characterized. The optimal temperature and pH of recombinant IDSGLUC9-4 were determined. Subsequently, substrate specificity of the enzyme was assessed using mixed-linked glucans including barley ß-glucan and Icelandic moss lichenan. Thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), matrix assisted laser desorption ionization time of flight mass spectrometry analyses were conducted to determine the products released from polysaccharides and cello-oligosaccharides substrates. RESULTS: The recombinant IDSGLUC9-4 exhibited temperature and pH optima of 40°C and pH 6.0, respectively. It exclusively hydrolyzed mixed-linked glucans, with significant activity observed for barley ß-glucan (109.59±3.61 µmol/mg min) and Icelandic moss lichenan (35.35±1.55 µmol/mg min). TLC and HPLC analyses revealed that IDSGLUC9-4 primarily released cellobiose, cellotriose, and cellotetraose from polysaccharide substrates. Furthermore, after 48 h of reaction, IDSGLUC9-4 removed most of the glucose, indicating transglycosylation activity alongside its endo-glucanase activity. CONCLUSION: The recombinant IDSGLUC9-4 was a relatively acid-resistant, mesophilic endo-glucanase (EC 3.2.1.4) that hydrolyzed glucan-like substrates, generating predominantly G3 and G4 oligosaccharides, and which appeared to have glycosylation activity. These findings provided insights into the substrate specificity and product profiles of rumen-derived GH9 glucanases and contributed to the expanding knowledge of cellulolytic enzymes and novel herbivore rumen enzymes in general.

DOCK1 regulates the malignant biological behavior of endometrial cancer through c-Raf/ERK pathway.

BACKGROUND: The effect of DOCK1 gene on the biological behavior of endometrial carcinoma cells and its related pathway has not been reported. METHODS: The immunohistochemical method and western blot were utilized to analyze DOCK1 protein expression in endometrial tissues and cells, respectively. CCK-8, BrdU, transwell and flow cytometry were performed to analyze the effect of DOCK1 expression changes on the viability, proliferation, invasion, migration and apoptosis of endometrial cancer cells, respectively. The effects of DOCK1 gene on Bcl-2, MMP9, Ezrin, E-cadherin and c-RAF/ERK1/2 signaling pathway were evaluated by western blot. The xenograft models were constructed to analyze the effect of DOCK1 in vivo. RESULTS: DOCK1 expression was increased in endometrial cancer tissues and cells compared with those in normal adjacent tissues and cells. DOCK1 knockout could inhibit the malignant biological behavior of endometrial cancer cells, while DOCK1 overexpression played the opposite effect. The expression of E-cadherin was upregulated and those of MMP9, Ezrin, Bcl-2, p-c-RAF (S338) and p-ERK1/2 (T202/Y204) were downregulated after DOCK1 knockout, while DOCK1 overexpression played the opposite effect. Additionally, Raf inhibitor LY3009120 reversed the function of DOCK1 on malignant biological behavior. In vivo experiment results showed that the growth and weight of transplanted tumors in nude mice were inhibited after DOCK1 knockout. The changes of E-cadherin, MMP9, Ezrin and Bcl-2 expressions in the transplanted tumors were consistent with those in vitro. CONCLUSION: DOCK1 could enhance the malignant biological behavior of endometrial cancer cells, which might be through c-RAF/ERK1/2 signaling pathways in vitro and in vivo.

YAP1/TAZ Mediates Rumen Epithelial Cell Proliferation but Not Short-Chain Fatty Acid Metabolism In Vitro.

Promoting rumen development is closely related to the health and efficient growth of ruminants. The transcriptional co-activators Yes1-associated protein (YAP1) and WW domain-containing transcription regulator protein 1 (TAZ) are key regulators of the mammalian epithelium. In the present study, we assessed the impact of YAP1/TAZ on rumen epithelial (RE) cell proliferation using their activator GA-017 (GA) and inhibitor verteporfin (VP). We also investigated whether YAP1/TAZ-dependent alteration was involved in the RE developmental process induced by sodium butyrate (SB). The results indicated that GA promoted RE cell proliferation, while VP disrupted RE cell proliferation. The Hippo, Wnt, and calcium signaling pathways were altered following the regulation of YAP1/TAZ. Upon YAP1/TAZ activation, the expression of CCN1/2 increased. However, when YAP1/TAZ was inhibited, the expression of BIRC3 decreased. In the SB-treated cells, YAP1/TAZ-induced changes were not observed. SB increased the expressions of differentiated cell marker genes and genes involved in short-chain fatty acid (SCFA) metabolism, while YAP1/TAZ did not. Thus, YAP1/TAZ could be potential targets for regulating RE cell proliferation but not for SCFA metabolism. SB could not affect YAP1/TAZ. These findings broaden our understanding of the role of YAP1/TAZ and their regulators in RE development.

A rumen-derived bifunctional glucanase/mannanase uncanonically releases oligosaccharides with a high degree of polymerization preferentially from branched substrates.

Glycoside hydrolases (GHs) are known to depolymerize polysaccharides into oligo-/mono-saccharides, they are extensively used as additives for both animals feed and our food. Here we reported the characterization of IDSGH5-14(CD), a weakly-acidic mesophilic bifunctional mannanase/glucanase of GH5, originally isolated from sheep rumen microbes. Biochemical characterization studies revealed that IDSGH5-14(CD) exhibited preferential hydrolysis of mannan-like and glucan-like substrates. Interestingly, the enzyme exhibited significantly robust catalytic activity towards branched-substrates compared to linear polysaccharides (P < 0.05). Substrate hydrolysis pattern indicated that IDSGH5-14(CD) predominantly liberated oligosaccharides with a degree of polymerization (DP) of 3-7 as the end products, dramatically distinct from canonical endo-acting enzymes. Comparative modeling revealed that IDSGH5-14(CD) was mainly comprised of a (ß/α)8-barrel-like structure with a spacious catalytic cleft on surface, facilitating the enzyme to target high-DP or branched oligosaccharides. Molecular dynamics (MD) simulations further suggested that the branched-ligand, 64-α-D-galactosyl-mannohexose, was steadily accommodated within the catalytic pocket via a two-sided clamp formed by the aromatic residues. This study first reports a bifunctional GH5 enzyme that predominantly generates high-DP oligosaccharides, preferentially from branched-substrates. This provides novel insights into the catalytic mechanism and molecular underpinnings of polysaccharide depolymerization, with potential implications for feed additive development and high-DP oligosaccharides preparation.

Vibration modes of three-dimensional spiral cochlea covering the organ of Corti.

So far, explaining the mechanism on active phonosensitive amplification in the cochlea is a major and difficult medical question. Among them, one of the key problems is that the motion pattern of the organ of Corti (OC) is still unknown. To this end, a multi-scale cochlear model including a three-dimensional spiral OC was established based on CT data and light source imaging experimental data, which complete combined the macroscopic and microscopic structure. On the basis of verifying the reliability of the model, acoustic-solid coupling calculation and modal analysis were performed on the model, and the vibration modes of basilar membrane (BM) and structures of the OC at different characteristic frequencies were discussed. The results show that tectorial membrane (TM) exhibits completely different vibration modes from BM at low frequencies, while the two movements gradually synchronize as the frequency increases. The amplitude position of OC's motion moves laterally with increasing frequency from Deiters' cells to Hensen's cells and then back to Deiters' cells. The OC exhibits longitudinal vibrations following BM when BM's displacement is large, while it manifests more as lateral movement of Deiters' cells when BM's displacement is small. This model can well simulate the motion process of BM and OC in the lymphatic fluid, which provides theoretical support and a numerical simulation computational platform to explore the interaction between macroscopic and microscopic tissue structures of the overall cochlea.

Pathogenic mechanism analysis of cochlear key structural lesion and phonosensitive hearing loss.

Due to ethical issues and the very fine and complex structure of the cochlea, it is difficult to directly perform experimental measurement on the human cochlea. Therefore, the finite element method has become an effective and replaceable new research means. Accurate numerical analysis on human ear using finite element method can provide better understanding of sound transmission and can be used to assess the influence of diseases on hearing and to treat hearing loss. In this research, a three-dimensional (3D) finite element model (FEM) of the human ear of cochlea was presented to investigate the destruction of basilar membrane (BM), round window (RW) sclerosis and perilymph fistula, the key structures of the cochlea, and analyze the effects of these abnormal pathological states in the cochlea on cochlear hearing, resulting in the changes in cochlear sense structure biomechanical behavior and quantitative prediction of the degree and harm of the disorder to the decline of human hearing. Therefore, this paper can deepen reader's understanding of the cochlear biomechanical mechanism and provide a theoretical foundation for clinical otology.

Study on damage of the macrostructure of the cochlea under the impact load.

Due to the tiny and delicate structure of the cochlea, the auditory system is the most sensitive to explosion impact damage. After being damaged by the explosion impact wave, it usually causes long-term deafness, tinnitus, and other symptoms. To better understand the influence of impact load on the cochlea and basilar membrane (BM), a three-dimensional (3D) fluid-solid coupling finite element model was developed. This model accurately reflects the actual spatial spiral shape of the human cochlea, as well as the lymph environment and biological materials. Based on verifying the reliability of the model, the curve of impact load-amplitude response was obtained, and damage of impact load on the cochlea and the key macrostructure-BM was analyzed. The results indicate that impact wave at middle frequency has widest influence on the cochlea. Furthermore, impact loading causes tears in the BM and destroys the cochlear frequency selectivity.

3D sheep rumen epithelial structures driven from single cells in vitro.

Ruminants play a vital economic role as livestock, providing high-quality protein for humans. At present, 3D-cultured ruminant abomasum and intestinal organoids have been successfully established to study host and pathogen interaction. The rumen is a unique digestive organ of ruminants that occupies 70% of the volume of the digestive tract and its microbiota can decompose lignocellulose to support animal growth. Here we report a method for culturing rumen epithelial organoids. We found that single rumen epithelial cells form self-organized 3D structures representative of typical stratified squamous epithelium, which is similar to rumen epithelium. EGF, Noggin, Wnt3a, IGF-1, and FGF-10 significantly enhanced the seeding efficiency of organoids. Moreover, the inclusion of CHIR-99021, A83-01, SB202190, and Y-27632 is crucial for organoid formation and maintenance. Importantly, we demonstrate that rumen epithelial cells retain their ability to form organoids after passage, cryopreservation, and resuscitation. The rumen epithelial organoids express rumen cell type-specific genes, uptake fatty acids, and generate 2D cultures. In summary, our data demonstrate that it is feasible to establish organoids from single rumen epithelial cells, which is a novel in vitro system that may reduce the use of experimental animals.

Assessing the Effects of Dietary Cadmium Exposure on the Gastrointestinal Tract of Beef Cattle via Microbiota and Transcriptome Profile.

Cadmium (Cd) is an environmental pollutant, widely existing in soil, and can be absorbed and accumulated by plants. Hunan Province exhibits the worst cadmium contamination of farmland in China. Ruminants possess an abundant microbial population in the rumen, which enables them to tolerate various poisonous plants. To investigate whether the rumen microbiota could respond to Cd and mitigate the toxicity of Cd-accumulated maize to ruminants, 6-month-old cattle were fed with 85.82% (fresh basis) normal whole-plant maize silage diet (CON, n = 10) or Cd-accumulated whole-plant maize silage diet (CAM, n = 10) for 107 days. When compared to the CON cattle, CAM cattle showed significantly higher gain-to-feed ratio and an increased total bacterial population in the rumen, but a decreased total bacterial population in the colon. CAM cattle had higher relative abundance of Prevotella and Lachnospiraceae ND3007 group in the rumen, and Lachnospiraceae NK4A136 group and Clostridia vadinBB60 group in the colon. Notably, microbial correlations were enhanced in all segments of CAM cattle, especially Peptostreptococcaceae in the jejunum. Transcriptome analysis revealed down-regulation of several immune-related genes in the rumen of CAM cattle, and differentially expressed genes in the rumen were mostly involved in immune regulation. These findings indicated that feeding Cd-accumulated maize diet with a Cd concentration of 6.74 mg/kg dry matter (DM) could stimulate SCFA-related bacteria in the rumen, induce hormesis to promote weight gain, and improve energy utilization of cattle.

The early life immune dynamics and cellular drivers at single-cell resolution in lamb forestomachs and abomasum.

BACKGROUND: Four-chambered stomach including the forestomachs (rumen, reticulum, and omasum) and abomasum allows ruminants convert plant fiber into high-quality animal products. The early development of this four-chambered stomach is crucial for the health and well-being of young ruminants, especially the immune development. However, the dynamics of immune development are poorly understood. RESULTS: We investigated the early gene expression patterns across the four-chambered stomach in Hu sheep, at 5, 10, 15, and 25 days of age. We found that forestomachs share similar gene expression patterns, all four stomachs underwent widespread activation of both innate and adaptive immune responses from d 5 to 25, whereas the metabolic function were significantly downregulated with age. We constructed a cell landscape of the four-chambered stomach using single-cell sequencing. Integrating transcriptomic and single-cell transcriptomic analyses revealed that the immune-associated module hub genes were highly expressed in T cells, monocytes and macrophages, as well as the defense-associated module hub genes were highly expressed in endothelial cells in the four-stomach tissues. Moreover, the non-immune cells such as epithelial cells play key roles in immune maturation. Cell communication analysis predicted that in addition to immune cells, non-immune cells recruit immune cells through macrophage migration inhibitory factor signaling in the forestomachs. CONCLUSIONS: Our results demonstrate that the immune and defense responses of four stomachs are quickly developing with age in lamb's early life. We also identified the gene expression patterns and functional cells associated with immune development. Additionally, we identified some key receptors and signaling involved in immune regulation. These results help to understand the early life immune development at single-cell resolution, which has implications to develop nutritional manipulation and health management strategies based on specific targets including key receptors and signaling pathways.

Feasibility of feeding cadmium accumulator maize (Zea mays L.) to beef cattle: Discovering a strategy for eliminating phytoremediation residues.

Eco-friendly and efficient strategies for eliminating cadmium (Cd) phytoremediation plant residues are needed. The present study investigated the feasibility of feeding Cd accumulator maize to beef cattle. In total, 20 cattle at 6 months of age were selected and randomly allocated into two groups fed with 85.82% (fresh basis) Cd accumulator maize (CAM) or normal maize (control [Con]) silage diets for 107 d. Feeding CAM did not affect the body weight (P = 0.24), while it decreased feed intake and increased feed efficiency of beef cattle (P < 0.01). Feeding CAM increased serum concentrations of immunoglobulin A and G, complement 3 and 4, blood urea nitrogen, and low-density lipoprotein cholesterol, decreased serum concentrations of interleukin-6 and lipopolysaccharide (P < 0.05), and caused wider lumens in the renal tubules. The Cd residue in meat was 7 µg/kg beyond the restriction for human food. In the muscle, the unsaturated fatty acids (t11C18:1 and C20:4), Lys, Arg, Pro, and Cys were decreased, while the saturated fatty acids (C10:0, C12:0, and C17:0) and Leu were increased (P < 0.05). Therefore, at the current feeding level, phytoremediation maize increased the feed efficiency of beef cattle, but did present risks to cattle health and production safety, and decreased the meat nutrition and flavor. Further research must be performed to determine whether a lower proper dose of phytoremediation maize and an appropriate feeding period may be possible to ensure no risk to cattle health and the supply of safe meat for humans.

Minimally invasive enucleation versus open enucleation for benign or low-grade malignant pancreatic neoplasms: Effects on clinical outcomes and quality of life.

Introduction: The efficacy and safety of minimally invasive pancreatic enucleation (PE) have rarely been investigated. This study aimed to compare the perioperative and long-term outcomes of minimally invasive enucleation (MIEn) with those of open enucleation (OEn) for benign/low-grade malignant pancreatic neoplasms. Patients and Methods: Data collected from patients who underwent PE between January 2011 and June 2020 at our centre were analysed. Results: Forty-two patients who underwent MIEn (10 - robot-assisted and 32 - laparoscopic) and 47 who underwent OEn were included in this study. Compared with the OEn group, the MIEn group showed shorter operation time (147.6 ± 71.3 min vs. 183.1 ± 64.3 min), shorter post-operative hospital stay (11.5 ± 3.9 days vs. 13.4 ± 4.2 days), shorter off-bed activity time (2.9 ± 0.9 days vs. 3.7 ± 1.0 days) and lower estimated blood loss (EBL) (118.5 ± 59.2 mL vs. 153.1 ± 85.0 mL). Overall complication rate (47.6% vs. 55.3%), overall post-operative pancreatic fistula (POPF) rate (40.5% vs. 44.7%) and Grade B + C POPF rate (11.9% vs. 19.1%) were similar in both the groups. For neoplasms located in the proximal pancreas, MIEn showed more favourable perioperative outcomes than OEn. Unlike MIEn for superficial neoplasms, MIEn for neoplasms deeply embedded in the pancreas resulted in a longer operative time and tended to increase EBL and the incidence of complications and POPF. During the follow-up period, no significant differences were observed between these two groups in terms of pancreatic function or quality of life. Conclusions: Compared to OEn, MIEn is effective and safe for patients with benign or low-grade malignant pancreatic neoplasms. However, MIEn for embedded pancreatic neoplasms is recommended only in experienced centres because of the high rates of complications and POPF.

Epidemiology and outcome of individuals with intraductal papillary neoplasms of the bile duct.

BACKGROUND: Intraductal papillary neoplasm of the bile duct (IPNB) is a rare distinct subtype of precursor lesions of biliary carcinoma. IPNB is considered to originate from luminal biliary epithelial cells, typically displays mucin-hypersecretion or a papillary growth pattern, and results in cystic dilatation[1]. IPNB develops anywhere in the intrahepatic and extrahepatic biliary tracts, and can occur in various pathological stages from low-grade dysplasia to invasive carcinoma. IPNBs have similar phenotypic changes in the occurrence and development of all subtypes, and the prognosis is significantly better than that of traditional (non-papillary) cholangiocarcinoma. AIM: To evaluate the clinicopathological features of IPNB to provide evidence-based guidance for treatment. METHODS: Invasive IPNB, invasive intraductal papillary mucinous neoplasm of the pancreas (IPMN), and traditional cholangiocarcinoma data for affected individuals from 1975 to 2016 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Annual percentage changes (APCs) in the incidence and incidence-based (IB) mortality were calculated. We identified the independent predictors of overall survival (OS) and cancer-specific survival (CSS) in individuals with invasive IPNB. RESULTS: The incidence and IB mortality of invasive IPNB showed sustained decreases, with an APC of -4.5% (95%CI: -5.1% to -3.8%) and -3.3% (95%CI: -4.1% to -2.6%) (P < 0.001), respectively. Similar decreases in incidence and IB mortality were seen for invasive IPMN but not for traditional cholangiocarcinoma. Both OS and CSS for invasive IPNB were better than for invasive IPMN and traditional cholangiocarcinoma. A total of 1635 individuals with invasive IPNB were included in our prognosis analysis. The most common tumor sites were the pancreaticobiliary ampulla (47.9%) and perihilar tract (36.7%), but the mucin-related subtype of invasive IPNB was the main type, intrahepatically (approximately 90%). In the univariate and multivariate Cox regression analysis, age, tumor site, grade and stage, subtype, surgery, and chemotherapy were associated with OS and CSS (P < 0.05). CONCLUSION: Incidence and IB mortality of invasive IPNB trended steadily downward. The heterogeneity of IPNB comprises site and the tumor's mucin-producing status.

Alterations in nutrient digestion and utilization associated with different residual feed intake in Hu sheep.

Improving feed efficiency is crucial to the animal industry. Residual feed intake (RFI) is now regarded as an index of feed efficiency evaluation and is independent of growth characteristics. Our study aims to explore the alterations in growth performance and nutrient digestion in Hu sheep with different RFI phenotypes. Sixty-four male Hu sheep (body weight = 24.39 ± 1.12 kg; postnatal days = 90 ± 7.9) were selected for the study. After an evaluation period of 56 days and power analysis, samples were collected from 14 low RFI (L-RFI group, power = 0.95) and 14 high RFI sheep (H-RFI group, power = 0.95). The L-RFI sheep yielded a lower (P < 0.05) feed conversion ratio and dry matter intake; however, both groups exhibited similar average daily gain (P > 0.05). The acid detergent fiber, neutral detergent fiber, organic matter, and crude protein apparent digestibility were higher (P < 0.05) in L-RFI sheep. N intake and fecal N output (% of N intake) were lower (P < 0.05) and N retention (% of N intake) was higher (P < 0.05) in L-RFI sheep, whereas no difference (P > 0.05) was found in urine N output (% of N intake) between the 2 groups. Furthermore, L-RFI sheep gave lower (P < 0.05) serum glucose concentrations and higher (P < 0.05) non-esterified fatty acid concentrations. Meanwhile, a lower ruminal acetate molar proportion (P < 0.05) and higher propionate molar proportion (P < 0.05) were observed in L-RFI sheep. In summary, these results revealed that despite having lower dry matter intake, L-RFI sheep possess higher nutrient digestibility, N retention, ruminal propionate production and serum glucose utilization, in order to meet energy demands. Selection for low RFI sheep could reduce feed costs, which in turn provides economic benefits to the sheep industry.