Castration alters the ileum microbiota of Holstein bulls and promotes beef flavor compounds.

BACKGROUND: In the beef industry, bull calves are usually castrated to improve flavor and meat quality; however, this can reduce their growth and slaughter performance. The gut microbiota is known to exert a significant influence on growth and slaughter performance. However, there is a paucity of research investigating the impact of castration on gut microbiota composition and its subsequent effects on slaughter performance and meat flavor. RESULT: The objective of this study was to examine the processes via which castration hinders slaughter productivity and enhances meat quality. Bull and castrated calves were maintained under the same management conditions, and at slaughter, meat quality was assessed, and ileum and epithelial tissue samples were obtained. The research employed metagenomic sequencing and non-targeted metabolomics techniques to investigate the makeup of the microbiota and identify differential metabolites. The findings of this study revealed the Carcass weight and eye muscle area /carcass weight in the bull group were significantly higher than those in the steer group. There were no significant differences in the length, width, and crypt depth of the ileum villi between the two groups. A total of 53 flavor compounds were identified in the two groups of beef, of which 16 were significantly higher in the steer group than in the bull group, and 5 were significantly higher in the bull group than in the steer group. In addition, bacteria, Eukaryota, and virus species were significantly separated between the two groups. The lipid metabolism pathways of α-linolenic acid, linoleic acid, and unsaturated fatty acids were significantly enriched in the Steers group. Compared with the steer group, the organic system pathway is significantly enriched in the bull group. The study also found that five metabolites (LPC (0:0/20:3), LPC (20:3/0:0), LPE (0:0/22:5), LPE (22:5/0:0), D-Mannosamine), and three species (s_Cloning_vector_Hsp70_LexA-HP1, s_Bacteroides_Coprophilus_CAG: 333, and s_Clostridium_nexile-CAG: 348) interfere with each other and collectively have a positive impact on the flavor compounds of beef. CONCLUSIONS: These findings provide a basic understanding that under the same management conditions, castration does indeed reduce the slaughter performance of bulls and improve the flavor of beef. Microorganisms and metabolites contribute to these changes through interactions.

"Planeterranean" diet: the new proposal for the Mediterranean-based food pyramid for Asia.

BACKGROUND AND OBJECTIVES: The Mediterranean Diet (MD) has been recognized for its benefits for human health and sustainability for the planet, but it has considered not easy to reproduce in other populations. The United Nations Educational, Scientific and Cultural Organization (UNESCO) Chair on Health Education and Sustainable Development is fostering a research project (Planeterranea), aiming to identify a healthy dietary pattern based on local foods with the same MD features. The aim of our study is to develop a MD-based food pyramid for Asian populations. METHODS: Asia was stratified into six areas according to pedo-climatic conditions. For each region a comprehensive scoping review of local crops and typical foods was conducted on several databases such as the US Department of Agriculture (USDA)'s database, the Food and Agriculture Organization of the United Nations (FAO) website, and PubMed, focusing on both plant-based and animal-based foods. Narrative review was then conducted on the identified foods to determine their nutritional composition and planetary health impact. Finally, the collected information was used to build up the Asian food pyramid with details for each respective region. RESULTS: We proposed a food pyramid for Asian countries, guaranteeing the same nutritional intake and health benefits as MD, by considering dietary habits and typical foods of this population. From the bottom to the top, Asian fruits and vegetables present similar nutritional profile as those in MD. Whole grains (barley) may represent valid alternative to white rice. Sesame oil represents a source of unsaturated fats and an alternative to olive oil. Legumes (soybean), edible insects, mushrooms and algae, guarantee an adequate intake of plant-based proteins with a complete amino-acid profile and a low environmental impact with respect to animal-based ones. CONCLUSIONS: This work is a new insight of healthy and sustainable local food system based on MD principles for the Asian population.

Effects of Intrarenal Reflux on Renal Growth in Children With Grades III-V Primary Vesicoureteral Reflux.

The phenomenon of intrarenal reflux (IRR) has been considered a crucial link between vesicoureteral reflux (VUR) and segmental scarring. We conducted a study on renal length in 104 children diagnosed with Grades III-V VUR, with or without IRR, using contrast-enhanced voiding urosonography (ceVUS). The patients were divided into two treatment groups: the conservative antibiotic prophylaxis (CAP) group and the operation group, which were further categorized into two subgroups: the IRR group and the non-IRR group. Our findings revealed an incidence rate of 35.96% (41/114) for IRR occurrence, with 43.42% (33/76) occurring in upper renal segments, 32.89% (25/76) in lower segments, and 23.68% (18/76) in middle segments. In the CAP group where the effects of IRR persisted, the renal growth observed was as follows: IRR group-0.19 ± 0.13 cm; non-IRR group-0.39 ± 0.23 cm; contralateral negative group-0.66 ± 0.35 cm; control group-0.46 ± 0 .25 cm respectively (P < .05). In the operation group, where the effects of IRR were eliminated, the renal growth for the IRR group, non-IRR group, contralateral negative group, and control group was 0.46 ± 0.22 cm, 0.54 ± 0.31 cm, 0.67 ± 0 .42 cm, and 0.36 ± 0.17 cm respectively (P < .005). In conclusion, the presence of IRR can impact renal growth in children diagnosed with Grades III-V primary VUR. Following surgical intervention, the IRR kidney does not exhibit catch-up growth; however, it demonstrates parallel growth alongside the unaffected kidney. Conversely, the non-IRR kidney experiences catch-up growth. Therefore, for children presenting with Grades III-V primary VUR combined with IRR, a more aggressive treatment approach such as surgery is recommended.

Transcriptional regulation of NDUFA4L2 by NFIB induces sorafenib resistance by decreasing reactive oxygen species in hepatocellular carcinoma.

Sorafenib is one a first-line therapeutic drugs for advanced hepatocellular carcinoma (HCC). However, only 30% of patients benefit from sorafenib due to drug resistance. We and other groups have revealed that nuclear factor I B (NFIB) regulates liver regeneration and carcinogenesis, but its role in drug resistance is poorly known. We found that NFIB was more upregulated in sorafenib-resistant SMMC-7721 cells compared to parental cells. NFIB knockdown not only sensitized drug-resistant cells to sorafenib but also inhibited the proliferation and invasion of these cells. Meanwhile, NFIB promoted the proliferation and invasion of HCC cells in vitro and facilitated tumor growth and metastasis in vivo. Knocking down NFIB synergetically inhibited tumor growth with sorafenib. Mechanically, gene expression profiling and subsequent verification experiments proved that NFIB could bind with the promoter region of a complex I inhibitor NDUFA4L2 and promote its transcription. Transcriptional upregulation of NDUFA4L2 by NFIB could thus inhibit the sorafenib-induced reactive oxygen species accumulation. Finally, we found that NFIB was highly expressed in HCC tissues, and high NFIB expression level was associated with macrovascular invasion, advanced tumor stage, and poor prognosis of HCC patients (n = 156). In summary, we demonstrated that NFIB could transcriptionally upregulate NDUFA4L2 to enhance both intrinsic and acquired sorafenib resistance of HCC cells by reducing reactive oxygen species induction.

Real-world patient characteristics and treatment outcomes among nontransplanted multiple myeloma patients who received Bortezomib in combination with Lenalidomide and Dexamethasone as first line of therapy in the United States.

BACKGROUND: There is limited real-world evidence that describes patients with newly diagnosed multiple myeloma (NDMM) treated with the bortezomib, lenalidomide, and dexamethasone (VRd) triplet regimen. We evaluated patient characteristics and treatment outcomes among nontransplanted NDMM patients who received VRd as their first line of therapy (LOT) in US oncology practice settings. METHODS: This retrospective observational cohort study evaluated patients from the Flatiron MM Core Registry who received VRd as first LOT between November 1, 2015, and February 28, 2021. Progression-free survival (PFS) was analyzed using the Kaplan-Meier method. Associations between patient demographic and clinical characteristics and PFS were evaluated using a multivariable Cox proportional hazards model. RESULTS: A total of 2342 eligible patients with VRd as first LOT were identified (mean age, 67.0 years). Among all identified patients, 64.3% were ≥ 65 years of age, 25.5% were elderly (≥75 years), and 47.9% were frail. Among patients with available data, 21.2% had high-risk cytogenetics, and the majority had International Staging System (ISS) stage I/II disease (71.8%), and Eastern Cooperative Oncology Group performance status (ECOG PS) score 0/1 (81.2%). Median duration of therapy was 5.5 months. With median follow-up of 21.0 months, median PFS and time-to-next-treatment were 26.5 and 16.1 months, respectively. Higher risk of disease progression or death was seen in patients categorized as elderly (hazard ratio [HR] = 1.37; 95% confidence interval [CI]: 1.13-1.66 vs patients < 65 years), having high-risk cytogenetics (HR = 1.44; 95% CI: 1.19-1.75 vs standard risk), having ISS disease stages II and III (HR = 1.31; 95% CI: 1.06-1.63 and HR = 1.37; 95% CI: 1.10-1.70 versus stage I, respectively), and having worse ECOG PS score (≥2) (HR = 1.49; 95% CI: 1.22-1.81 versus functionally active patients). CONCLUSIONS: The majority of patients treated with VRd in this study were ≥ 65 years of age, were ISS stage I/II, had an ECOG PS score of 0/1, and had standard cytogenetic risk. Median PFS observed in real-world practice was notably shorter than that observed in the SWOG S0777 clinical trial. In nontransplanted patients treated with VRd as first LOT, a higher risk of disease progression or death was associated with older age, having high-risk cytogenetics, worse disease stage, and worse ECOG PS score.

Dietary amylose:amylopectin ratio influences the expression of amino acid transporters and enzyme activities for amino acid metabolism in the gastrointestinal tract of goats.

This study was designed to investigate the effects of dietary starch structure on muscle protein synthesis and gastrointestinal amino acid (AA) transport and metabolism of goats. Twenty-seven Xiangdong black female goats (average body weight = 9·00 ± 1·12 kg) were randomly assigned to three treatments, i.e., fed a T1 (normal maize 100 %, high amylose maize 0 %), T2 (normal maize 50 %, high amylose maize 50 %) and T3 (normal maize 0 %, high amylose maize 100 %) diet for 35 d. All AA in the ileal mucosa were decreased linearly as amylose:amylopectin increased in diets (P < 0·05). The plasma valine (linear, P = 0·03), leucine (linear, P = 0·04) and total AA content (linear, P = 0·03) increased linearly with the increase in the ratio of amylose in the diet. The relative mRNA levels of solute carrier family 38 member 1 (linear, P = 0·01), solute carrier family 3 member 2 (linear, P = 0·02) and solute carrier family 38 member 9 (linear, P = 0·02) in the ileum increased linearly with the increase in the ratio of amylose in the diet. With the increase in the ratio of amylose:amylopectin in the diet, the mRNA levels of acetyl-CoA dehydrogenase B (linear, P = 0·04), branched-chain amino acid transferase 1 (linear, P = 0·02) and branched-chain α-keto acid dehydrogenase complex B (linear, P = 0·01) in the ileum decreased linearly. Our results revealed that the protein abundances of phosphorylated mammalian target of rapamycin (p-mTOR) (P < 0·001), phosphorylated 4E-binding protein 1 (P < 0·001) and phosphorylated ribosomal protein S6 kinases 1 (P < 0·001) of T2 and T3 were significantly higher than that of T1. In general, a diet with a high amylose ratio could reduce the consumption of AA in the intestine, allowing more AA to enter the blood to maintain higher muscle protein synthesis through the mTOR pathway.

Patient characteristics associated with dose modifications for VRd among newly diagnosed multiple myeloma patients.

Aim: To evaluate among multiple myeloma (MM) patients, the proportions with first-line bortezomib/lenalidomide/dexamethasone (VRd) dose modifications and the associated baseline patient characteristics. Patients & methods: Adult MM patients treated with first-line VRd were selected from the Optum claims database. VRd dose modifications were defined based on lenalidomide dose. Results: Among 1497 MM patients, 33% received VRd lite and 22% VRd reduced. Compared with VRd regular, VRd lite usage was more likely to be associated with patients aged ≥75 years and female sex; VRd reduced usage was more likely to be associated with female sex and frailty. Conclusion: A large proportion of MM patients received VRd dose modifications in the real-world, which could potentially result in reduced effectiveness of VRd.

Evaluating key characteristics of ideal colorectal cancer screening modalities: the microsimulation approach.

BACKGROUND AND AIMS: Screening for colorectal cancer (CRC) can effectively reduce CRC incidence and mortality. Besides colonoscopy, tests for the detection of biomarkers in stool, blood, or serum, including the fecal immunochemical test (FIT), ColoGuard, Epi proColon, and PolypDx, have recently been advanced. We aimed to identify the characteristics of theoretic, highly efficient screening tests and calculated the effectiveness and cost effectiveness of available screening tests. METHODS: Using the microsimulation-based colon modeling open-source tool (CMOST), we simulated 142,501 theoretic screening tests with variable assumptions for adenoma and carcinoma sensitivity, specificity, test frequency, and adherence, and we identified highly efficient tests outperforming colonoscopy. For available screening tests, we simulated 10 replicates of a virtual population of 2 million individuals, using epidemiologic characteristics and costs assumptions of the United States. RESULTS: Highly efficient theoretic screening tests were characterized by high sensitivity for advanced adenoma and carcinoma and high patient adherence. All simulated available screening tests were effective at 100% adherence to screening and at expected real-world adherence rates. All tests were cost effective below the threshold of 100,000 U.S. dollars per life year gained. With perfect adherence, FIT was the most effective and cost-efficient intervention, whereas Epi proColon was the most effective at expected real-world adherence rates. In our sensitivity analysis, assumptions for patient adherence had the strongest impact on effectiveness of screening. CONCLUSIONS: Our microsimulation study identified characteristics of highly efficient theoretic screening tests and confirmed the effectiveness and cost-effectiveness of colonoscopy and available urine-, blood-, and stool-based tests. Better patient adherence results in superior effectiveness for CRC prevention in the whole population.

Cost of decentralized CAR T-cell production in an academic nonprofit setting.

Chimeric antigen receptor (CAR) T-cell therapy is a promising immunotherapy with high acquisition costs, and it has raised concerns about affordability and sustainability in many countries. Furthermore, the current centralized production paradigm for the T cells is less than satisfactory. Therefore, several countries are exploring alternative T-cell production modes. Our study is based on the T-cell production experience in a nonprofit setting in Germany. We first identified the work steps and main activities in the production process. Then we determined the fixed costs and variable costs. Main cost components included personnel and technician salaries, expenditure on equipment, a clean room, as well as production materials. All costs were calculated in 2018 euros and converted into U.S. dollars. For a clean room with one machine for closed and automated manufacturing installed, annual fixed costs summed up to approximately €438 098 ($584 131). The variable cost per production was roughly €34 798 ($46 397). At the maximum capacity of one machine, total cost per product would be close to €60 000 ($78 849). As shown in the scenario analysis, if three machines were to be installed in the clean room, per production cost could be as low as €45 000 (roughly $59905). If a cheaper alternative to lentivirus was used, per production total cost could be further reduced to approximately €33 000 (roughly $44309). Decentralized T-cell production might be a less costly and more efficient alternative to the current centralized production mode that requires a high acquisition cost.

Surface Hydrogen Atoms Promote Oxygen Activation for Solar Light-Driven NO Oxidization over Monolithic α-Ni(OH)2/Ni Foam.

Catalysis oxidization has been known to be an effective technique in environmental remediation. However, low efficiency for oxygen activation and difficult recovery of the catalysts in powdery form significantly limit the practical application. In this work, a new-type monolithic α-Ni(OH)2/Ni-foam was fabricated by the hydrothermal process. We found that H atoms of α-Ni(OH)2 can significantly promote oxygen activation, which endows it with favorable NO and NO2 oxidization confirmed by theoretical calculation and in situ DRIFTS. Furthermore, the introduction of Ni foam accelerated the pollutant gas transfer and charge carriers' separation because of its abundant porous structure and high conductivity and its monolithic property simplified the recycling operation. Consequently, the obtained α-Ni(OH)2/Ni-foam achieved an excellent NO oxidation (69.0%) and no toxic NO2 was detected under visible light illumination (λ > 420 nm), indicating its highly promising potential in environmental remediation. Our work provides a conceptually different fresh perception to promote oxygen activation for highly efficient gas purification.