Effect of Hydrogen Bonding and Chirality in Star-Shaped Molecules with Peripheral Triphenylamines: Liquid Crystal Semiconductors and Gels.

Organic semiconductors with well-defined architectures pose a suitable alternative to amorphous silicon-based inorganic semiconductors. Encouraged by the development of organic semiconductors based on columnar liquid crystals, herein, we report on a family of C3-symmetric star-shaped mesogens based on triphenylamine (TPA), a functional unit with strong electron donor character. Highly stable columnar phases with high hole mobility values were obtained out of this nonplanar functional unit, and this was achieved by using flexible amide spacers to join the TPA units to a tris(triazolyl)triazine (T) star-shaped core, allowing the formation of intermolecular hydrogen bonds. The presence of hydrogen bonds results in a stabilization of the columnar architectures either in bulk or in the presence of solvents by reinforcing π-stacking and van der Waals interactions, as deduced by Fourier-transform infrared (FTIR) and X-ray diffraction (XRD) studies. Furthermore, the introduction of a stereogenic center in the flexible spacer prompts the formation of chiral aggregates in the liquid crystal state and in the organogel formed in 1-octanol, as demonstrated by circular dichroism spectroscopy.

Capsaicin as a Dietary Additive for Dairy Cows: A Meta-Analysis on Performance, Milk Composition, Digestibility, Rumen Fermentation, and Serum Metabolites.

This study aimed to evaluate the effects of dietary supplementation with capsaicin (CAP) on productive performance, milk composition, nutrient digestibility, ruminal fermentation, and serum metabolites of dairy cows using a meta-analytical approach. The database included 13 studies, from which the response variables of interest were obtained. Data were analyzed using a random effects model, and results were expressed as weighted mean differences between treatments supplemented with and without CAP. Dietary supplementation with CAP increased (p < 0.05) dry matter intake, milk yield, feed efficiency, milk fat yield, and milk fat content. However, CAP supplementation did not affect (p > 0.05) milk protein and lactose yield, milk urea nitrogen, or milk somatic cell count. Greater (p < 0.05) apparent digestibility of dry matter and crude protein was observed in response to the dietary inclusion of CAP. Likewise, supplementation with CAP increased (p < 0.05) the rumen concentration of total volatile fatty acids. In contrast, CAP supplementation did not affect (p > 0.05) ruminal pH or the ruminal concentration of ammonia nitrogen, acetate, propionate, and butyrate. In blood serum, CAP supplementation increased (p < 0.05) the glucose concentration and decreased (p < 0.05) the concentration of non-esterified fatty acids. However, CAP supplementation did not affect (p > 0.05) the serum concentration of urea and beta-hydroxybutyrate. In conclusion, capsaicin can be used as a dietary additive to improve the productive performance, milk composition, and nutrient digestibility in dairy cows and, at the same time, improve the ruminal concentration of total volatile fatty acids and serum levels of glucose and non-esterified fatty acids.

Anthelmintic efficacy of an organic fraction from Guazuma ulmifolia leaves and evaluation of reactive oxidative stress on Haemonchus contortus.

This study describes the anthelmintic efficacy of an organic fraction (EtOAc-F) from Guazuma ulmifolia leaves and the evaluation of its reactive oxidative stress on Haemonchus contortus. The first step was to assess the anthelmintic effect of EtOAc-F at 0.0, 3.5, 7.0 and 14 mg kg of body weight (BW) in gerbil's (Meriones unguiculatus) artificially infected with H. contortus infective larvae (L3). The second step was to evaluate the preliminary toxicity after oral administration of the EtOAc-F in gerbils. Finally, the third step was to determine the relative expression of biomarkers such as glutathione (GPx), catalase (CAT), and superoxide dismutase (SOD) against H. contortus L3 post-exposition to EtOAc-F. Additionally, the less-polar compounds of EtOAc-F were identified by gas mass spectrophotometry (GC-MS). The highest anthelmintic efficacy (97.34%) of the organic fraction was found in the gerbils treated with the 14 mg/kg of BW. Histopathological analysis did not reveal changes in tissues. The relative expression reflects overexpression of GPx (p<0.05, fold change: 14.35) and over expression of SOD (p≤0.05, fold change: 0.18) in H. contortus L3 exposed to 97.44 mg/mL of EtOAc-F compared with negative control. The GC-MS analysis revealed the presence of 4-hydroxybenzaldehyde (1), leucoanthocyanidin derivative (2), coniferyl alcohol (3), ferulic acid methyl ester acetate (4), 2,3,4-trimethoxycinnamic acid (5) and epiyangambin (6) as major compounds. According to these results, the EtOAc-F from G. ulmifolia leaves exhibit anthelmintic effect and increased the stress biomarkers on H. contortus.

BID expression determines the apoptotic fate of cancer cells after abrogation of the spindle assembly checkpoint by AURKB or TTK inhibitors.

BACKGROUND: Drugs targeting the spindle assembly checkpoint (SAC), such as inhibitors of Aurora kinase B (AURKB) and dual specific protein kinase TTK, are in different stages of clinical development. However, cell response to SAC abrogation is poorly understood and there are no markers for patient selection. METHODS: A panel of 53 tumor cell lines of different origins was used. The effects of drugs were analyzed by MTT and flow cytometry. Copy number status was determined by FISH and Q-PCR; mRNA expression by nCounter and RT-Q-PCR and protein expression by Western blotting. CRISPR-Cas9 technology was used for gene knock-out (KO) and a doxycycline-inducible pTRIPZ vector for ectopic expression. Finally, in vivo experiments were performed by implanting cultured cells or fragments of tumors into immunodeficient mice. RESULTS: Tumor cells and patient-derived xenografts (PDXs) sensitive to AURKB and TTK inhibitors consistently showed high expression levels of BH3-interacting domain death agonist (BID), while cell lines and PDXs with low BID were uniformly resistant. Gene silencing rendered BID-overexpressing cells insensitive to SAC abrogation while ectopic BID expression in BID-low cells significantly increased sensitivity. SAC abrogation induced activation of CASP-2, leading to cleavage of CASP-3 and extensive cell death only in presence of high levels of BID. Finally, a prevalence study revealed high BID mRNA in 6% of human solid tumors. CONCLUSIONS: The fate of tumor cells after SAC abrogation is driven by an AURKB/ CASP-2 signaling mechanism, regulated by BID levels. Our results pave the way to clinically explore SAC-targeting drugs in tumors with high BID expression.

Triphenylamine-Containing Benzoic Acids: Synthesis, Liquid Crystalline and Redox Properties.

The synthesis, characterization and liquid crystalline and electrochemical properties of novel triarylamines, in which the triphenylamine platform is non-symmetrically modified with a 4-(6-oxyhexyloxy)benzoic acid group, are reported. Compounds show columnar liquid crystalline behavior, as confirmed through the use of polarized optical microscopy, differential scanning calorimetry and X-ray diffraction. Electrochemical properties were measured using cyclic voltammperometry, obtaining low oxidation potentials and HOMO values that were optimum for consideration as organic semiconductors in hole transport layers. In addition, the photoredox activity of one of these derivatives in dichloromethane was studied under light irradiation. A photooxidation/assembly process under white light irradiation occurs without the assistance of hydrogen bonding amide functional groups.

Meta-analysis of flavonoids use into beef and dairy cattle diet: Performance, antioxidant status, ruminal fermentation, meat quality, and milk composition.

The objective of this study was to evaluate the effects of dietary supplementation with flavonoids (FLAs) on animal performance, diet digestibility, antioxidant status in blood serum, rumen parameters, meat quality, and milk composition in beef and dairy cattle through a meta-analysis. Thirty-six peer-reviewed publications were included in the data set. The weighted mean differences (WMD) between the FLAs treatments and the control treatment were used to assess the effect size. Dietary supplementation with FLAs decreased feed conversion ratio (WMD = -0.340 kg/kg; p = 0.050) and increased (p < 0.05) dry matter intake (WMD = 0.191 kg/d), dry matter digestibility (WMD = 15.283 g/kg of DM), and daily weight gain (WMD = 0.061 kg/d). In blood serum, FLAs supplementation decreased the serum concentration of malondialdehyde (WMD = -0.779 nmol/mL; p < 0.001) and increased (p < 0.01) the serum concentration of superoxide dismutase (WMD = 8.516 U/mL), glutathione peroxidase (WMD = 12.400 U/mL) and total antioxidant capacity (WMD = 0.771 U/mL). A higher ruminal propionate concentration (WMD = 0.926 mol/100 mol; p = 008) was observed in response to FLAs supplementation. In meat, the dietary inclusion of FLAs decreased (p < 0.05) shear force (WMD = -1.018 kgf/cm2), malondialdehyde content (WMD = -0.080 mg/kg of meat), and yellowness (WMD = -0.460). Supplementation with FLAs decreased milk somatic cell count (WMD = -0.251 × 103 cells/mL; p < 0.001) and increased (p < 0.01) milk production (WMD = 1.348 kg/d), milk protein content (WMD = 0.080/100 g) and milk fat content (WMD = 0.142/100 g). In conclusion, dietary supplementation with FLAs improves animal performance and nutrient digestibility in cattle. In addition, FLAs improve the antioxidant status in blood serum and the quality of meat and milk.

Effects of Supplementation with Bee Pollen and Propolis on Growth Performance and Serum Metabolites of Rabbits: A Meta-Analysis.

The objective of this study was to evaluate the effects of bee pollen (BP) and propolis (PRO) supplementation on rabbits' productive performance and serum metabolites through a meta-analysis. Sixteen peer-reviewed publications were included in the data set. The rabbit strains used in the studies included in the data set were New Zealand White, V-line, Rex, and V-line crosses. Weighted mean differences (WMD) between treatments supplemented with BP or PRO and control treatments were used to assess the magnitude of the effect. BP supplementation decreased (p < 0.001) daily feed intake (DFI) and feed conversion ratio (FCR); however, increased (p < 0.001) average daily gain (ADG) and hot carcass yield (HCY). PRO supplementation reduced DFI (p = 0.041) and FCR (p < 0.001), and increased ADG (p < 0.001) and HCY (p = 0.005). In blood serum, BP supplementation increased total antioxidant capacity (TAC; p = 0.002) and decreased serum creatinine concentration (p = 0.049). Likewise, decreased serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) were detected in response to BP supplementation (p < 0.05). PRO supplementation increased the TAC in blood serum (p = 0.018); however, decreased serum concentrations of AST, ALT, and MDA were observed (p < 0.05). In conclusion, BP or PRO supplementation can be used as a natural growth promoter in rabbits, and both can also improve rabbits' antioxidant status. However, BP or PRO supplementation does not affect rabbits' renal or hepatic health status.

Real-world safety and effectiveness of maintenance niraparib for platinum-sensitive recurrent ovarian cancer: A GEICO retrospective observational study within the Spanish expanded-access programme.

AIM: To describe patient characteristics, effectiveness and safety in a real-world population treated with niraparib in the Spanish expanded-access programme. PATIENTS AND METHODS: This retrospective observational study included women with platinum-sensitive recurrent high-grade serous ovarian cancer who received maintenance niraparib within the Spanish niraparib expanded-access programme. Eligible patients had received ≥2 previous lines of platinum-containing therapy, remained platinum-sensitive after the penultimate line of platinum and had responded to the most recent platinum-containing therapy. Niraparib dosing was at the treating physician's discretion (300 mg/day fixed starting dose or individualised starting dose [ISD] according to baseline body weight and platelet count). Safety, impact of dose adjustments, patient characteristics and effectiveness were analysed using data extracted from medical records. RESULTS: Among 316 eligible patients, 80% had BRCA wild-type tumours and 66% received an ISD. Median niraparib duration was 7.8 months. The most common adverse events typically occurred within 3 months of starting niraparib. Median progression-free survival was 8.6 (95% confidence interval [CI] 7.6-10.0) months. One- and 2-year overall survival rates were 86% (95% CI 81-89%) and 65% (95% CI 59-70%), respectively. Dose interruptions, dose reductions, haematological toxicities and asthenia/fatigue were less common with ISD than fixed starting dose niraparib, but progression-free survival was similar irrespective of dosing strategy. Subsequent therapy included platinum in 71% of patients who received further treatment. CONCLUSION: Outcomes in this large real-world dataset of niraparib-treated patients are consistent with phase III trials, providing reassuring evidence of the tolerability and activity of niraparib maintenance therapy for platinum-sensitive recurrent ovarian cancer. GOV REGISTRATION: NCT04546373.

Trastuzumab deruxtecan in patients with central nervous system involvement from HER2-positive breast cancer: The DEBBRAH trial.

BACKGROUND: Trastuzumab deruxtecan (T-DXd) has shown durable antitumor activity in pretreated patients with HER2-positive advanced breast cancer (ABC), but its efficacy has not yet been evaluated in patients with active brain metastases (BMs). DEBBRAH aims to assess T-DXd in patients with HER2-positive or HER2-low ABC and central nervous system involvement. METHODS: This ongoing, five-cohort, phase II study (NCT04420598) enrolled patients with pretreated HER2-positive or HER2-low ABC with stable, untreated, or progressing BMs, and/or leptomeningeal carcinomatosis. Here, we report findings from HER2-positive ABC patients with non-progressing BMs after local therapy (n = 8; cohort 1), asymptomatic untreated BMs (n = 4; cohort 2), or progressing BMs after local therapy (n = 9; cohort 3). Patients received 5.4 mg/kg T-DXd intravenously once every 21 days. The primary endpoint was 16-week progression-free survival (PFS) for cohort 1 and intracranial objective response rate (ORR-IC) for cohorts 2 and 3. RESULTS: As of October 20, 2021, 21 patients received T-DXd. In cohort 1, 16-week PFS rate was 87.5% (95%CI, 47.3-99.7; P < .001). ORR-IC was 50.0% (95%CI, 6.7-93.2) in cohort 2 and 44.4% (95%CI, 13.7-78.8; P < .001) in cohort 3. Overall, the ORR-IC in patients with active BMs was 46.2% (95%CI, 19.2-74.9). Among patients with measurable intracranial or extracranial lesions at baseline, the ORR was 66.7% (12 out of 18 patients; 95%CI, 41.0-86.7), 80.0% (95%CI, 28.4-99.5) in cohort 1, 50.0% (95%CI, 6.7-93.2) in cohort 2, and 66.7% (95%CI, 29.9-92.5) in cohort 3. All responders had partial responses. The most common adverse events included fatigue (52.4%; 4.8% grade ≥3), nausea (42.9%; 0% grade ≥3), neutropenia (28.6%; 19% grade ≥3), and constipation (28.6%; 0% grade ≥3). Two (9.5%) patients suffered grade 1 interstitial lung disease/pneumonitis. CONCLUSIONS: T-DXd showed intracranial activity with manageable toxicity and maintained the quality of life in pretreated HER2-positive ABC patients with stable, untreated, or progressing BMs. Further studies are needed to validate these results in larger cohorts.

Challenging Endocrine Sensitivity of Hormone Receptor-Positive/HER2-Negative Advanced Breast Cancer with the Combination of Eribulin and Endocrine Therapy: The REVERT Study.

BACKGROUND: Luminal advanced breast cancer (ABC) patients eventually progress on endocrine therapy. REVERT aimed to explore whether eribulin could restore endocrine sensitivity in a randomized, non-comparative phase II trial. METHODS: Aromatase inhibitor (AI)-resistant patients with luminal ABC were randomized 1:1 to receive eribulin +/- AI. Patients were stratified by prior cyclin-dependent kinases 4/6 inhibitor (CDK4/6i) treatment. The primary endpoint was an investigator-assessed overall response rate (ORR) according to RECIST version 1.1 in the eribulin + AI arm. An interim analysis was planned with 11 evaluable patients according to a two-stage Simon design. RESULTS: Twenty-two patients were enrolled (15 eribulin + AI arm; 7 eribulin arm). The trial was terminated early in March 2021, with eight (36.4%) patients still on treatment. ORR was 26.7% in the eribulin + AI arm (95% CI, 7.8-55.1%; p = 0.0541). In the eribulin arm, two (28.6%) patients had an objective response (95% CI, 3.7-71.0%). The difference between the study arms was not significant (p = 0.918). The addition of AI to eribulin also failed to show improvement in other efficacy endpoints. A significant interaction between the treatment arm and previous CDK4/6i treatment was observed for ORR (p = 0.018) and progression-free survival (p = 0.084). Overall, the toxicity profile was consistent with the known safety profile of eribulin. No treatment-related deaths were reported. CONCLUSION: Eribulin + AI does not seem to improve outcomes compared with eribulin monotherapy in patients with AI-resistant luminal ABC. This chemo-endocrine approach deserves further investigation after progression to CDK4/6i-based therapy.

Supplying Bee Pollen and Propolis to Growing Rabbits: Effects on Growth Performance, Blood Metabolites, and Meat Quality.

The objective of this study was to evaluate the effect of supplementation with bee pollen (BP) and propolis (PRO) on productive performance, Eimeria oocyst counts in feces, blood metabolites, and the meat quality of growing rabbits. A total of 160 hybrid rabbits (California × New Zealand) of 30 days of age and 643 ± 8.0 g body weight (BW) were assigned to four treatments with 10 replicates each (four rabbits/replicate). The treatments were as follows: (1) CON: rabbits fed basal diet and not supplemented with BP or PRO; (2) BP500: CON + BP (500 mg/kg BW); (3) PRO50: CON + PRO (50 µL/kg BW); and (4) BP + PRO: CON + BP (500 mg/kg BW) + PRO (50 µL/kg BW). Higher daily weight gain (p = 0.04) and lower feed conversion rate (p = 0.03) were observed in rabbits supplemented with PRO50. In addition, supplementation with PRO50 and BP + PRO reduced the amount of Eimeria oocysts per gram of feces (p < 0.05). Most hematological and serum biochemical parameters were similar in rabbits of all treatments. Protein content, collagen, and meat color were similar between treatments. In conclusion, propolis supplementation (50 µL/kg BW) can prevent coccidiosis and act as a natural growth promoter in rabbits without affecting animal health and meat quality.

In Vitro Anthelmintic Activity of a Hydroalcoholic Extract from Guazuma ulmifolia Leaves against Haemonchus contortus.

The purpose of the present study was to assess the ovicidal and larvicidal activity of a hydroalcoholic extract (HAE) and their fractions (aqueous, Aq-F and organic, EtOAc-F) from Guazuma ulmifolia leaves using Haemonchus contortus as a biological model. The egg hatching inhibition (EHI) and larval mortality against infective larvae (L3) tests were used to determine the anthelmintic effect of the treatments. The extract and fractions were tested at different concentrations against eggs and L3. Additionally, distilled water and methanol were used as negative controls and ivermectin as a positive control. The extract and fractions were subjected to HPLC analysis to identify the major compounds. The HAE displayed the highest ovicidal activity (100% EHI at 10 mg/mL). Fractionation of the HA extract allowed increasing the nematicidal effect in the EtOAc-F (100% EHI at 0.62 mg/mL and 85.35% mortality at 25 mg/mL). The phytochemical analysis of the extract and fractions revealed the presence of kaempferol, ethyl ferulate, ethyl coumarate, flavonol, luteolin, ferulic acid, luteolin rhamnoside, apigenin rutinoside, coumaric acid derivative, luteolin glucoside, and quercetin glucoside. These results suggest that G. ulmifolia leaves could be potential candidates for the control of H. contortus or other gastrointestinal parasitic nematodes.

Essential Oils as a Dietary Additive for Small Ruminants: A Meta-Analysis on Performance, Rumen Parameters, Serum Metabolites, and Product Quality.

There is an increasing pressure to identify natural feed additives that improve the productivity and health of livestock, without affecting the quality of derived products. The objective of this study was to evaluate the effects of dietary supplementation with essential oils (EOs) on productive performance, rumen parameters, serum metabolites, and quality of products (meat and milk) derived from small ruminants by means of a meta-analysis. Seventy-four peer-reviewed publications were included in the data set. Weighted mean differences (WMD) between the EOs treatments and the control treatment were used to assess the magnitude of effect. Dietary inclusion of EOs increased (p < 0.05) dry matter intake (WMD = 0.021 kg/d), dry matter digestibility (WMD = 14.11 g/kg of DM), daily weight gain (WMD = 0.008 kg/d), and feed conversion ratio (WMD = −0.111). The inclusion of EOs in small ruminants' diets decreased (p < 0.05) ruminal ammonia nitrogen concentration (WMD = −0.310 mg/dL), total protozoa (WMD = −1.426 × 105/mL), methanogens (WMD = −0.60 × 107/mL), and enteric methane emissions (WMD = −3.93 L/d) and increased ruminal propionate concentration (WMD = 0.726 mol/100 mol, p < 0.001). The serum urea concentration was lower (WMD = −0.688 mg/dL; p = 0.009), but serum catalase (WMD = 0.204 ng/mL), superoxide dismutase (WMD = 0.037 ng/mL), and total antioxidant capacity (WMD = 0.749 U/mL) were higher (p < 0.05) in response to EOs supplementation. In meat, EOs supplementation decreased (p < 0.05) the cooking loss (WMD = −0.617 g/100 g), malondialdehyde content (WMD = −0.029 mg/kg of meat), yellowness (WMD = −0.316), and total viable bacterial count (WMD = −0.780 CFU/g of meat). There was higher (p < 0.05) milk production (WMD = 0.113 kg/d), feed efficiency (WMD = 0.039 kg/kg), protein (WMD = 0.059 g/100 g), and lactose content in the milk (WMD = 0.100 g/100 g), as well as lower somatic cell counts in milk (WMD = −0.910 × 103 cells/mL) in response to EOs supplementation. In conclusion, dietary supplementation with EOs improves productive performance as well as meat and milk quality of small ruminants. In addition, EOs improve antioxidant status in blood serum and rumen fermentation and decrease environmental impact.

Performance of Holstein-Friesian calves drinking desalinated water in the preweaning period

Background: High salinity of drinking water can adversely affect health and productive performance of calves during artificial rearing. Objective: To evaluate the effect of drinking water total dissolved salts (TDS) content on productive performance of Holstein-Friesian calves during artificial rearing. Methods: Twenty-nine newborn Holstein-Friesian calves weighing 39±0.94 kg at birth were randomly assigned to two treatment groups for 56 d. Treatment 1 (n=14) consisted of drinking water with 1,469±75 mg L-1 TDS, while treatment 2 (n=15) used drinking water from the same source but filtered by reverse osmosis to contain 107±31 mg L-1 TDS. Results: Water intake was numerically affected by TDS concentration, increasing 13% (p>0.08) when drinking low-TDS water (3,554 versus 3,088 ml d-1). Feed intake (dry basis) decreased 26% (500 versus 676 g d-1; p0.05) by TDS content in the drinking water. Conclusion: Desalinated water improves productive performance of Holstein-Friesian calves during artificial rearing.

Antecedentes: Una alta salinidad del agua de bebida puede afectar negativamente la salud y el comportamiento productivo de los terneros durante la crianza. Objetivo: Evaluar el efecto del contenido de sales disueltas totales (SDT) en el agua de bebida sobre el comportamiento productivo de los terneros durante la crianza artificial. Métodos: Veintinueve terneros Holstein- Friesian recién nacidos, con 39±0,94 kg de peso vivo fueron asignados aleatoriamente a dos tratamientos. El tratamiento 1 consistió de 14 terneros que bebieron agua con 1.469±75 mg L-1 de SDT; mientras que al tratamiento 2 se asignaron 15 terneros que recibieron agua de la misma fuente, pero filtrada mediante el procedimiento de ósmosis inversa y conteniendo 107±31 mg L-1 de SDT. Resultados: La concentración de SDT afectó numéricamente el consumo de agua durante los 56 días de lactancia (p>0,08), incrementándose 13% cuando los terneros bebieron agua con bajo contenido de sales (3.554 vs 3.088 ml d-1). El consumo de alimento (base seca) disminuyó 26% (500 vs 676 g d-1; p0,05). Conclusión: El agua de bebida desalinizada mejora el comportamiento productivo de terneros Holstein durante la crianza artificial.

Antecedentes: Alta salinidade da água potável pode afetar adversamente a saúde e o desempenho produtivo de bezerros durante o acasalamento. Objetivo: Avaliar o efeito do total de sais dissolvidos (TSD) na água potável sobre o comportamento dos bezerros durante a lactação. Métodos: Vinte e nove terneiros Holstein-Friesian recém-nascidos, com 39±0,94 kg de peso vivo, foram designados aleatoriamente a dois tratamentos. O tratamento 1 considerou 14 terneiros os quais beberam água com 1.469±75 mg L-1 do total de sais dissolvidos (TSD); enquanto ao tratamento 2 se designaram 15 terneiros bebendo água da mesma fonte filtrada através do procedimento de osmose inversa e contendo 107±31 mg L-1 de TSD. Resultados: O consumo de água de bezerros durante os 56 dias de lactação artificial foi ligeiramente afetado pela concentração de TDS na água potável (p>0,08) e aumentou em 13% quando os bezerros beberam água com baixo teor de sal (3.554 vs 3.088 ml d-1); o consumo de alimento sólido (base seca) diminuiu em 26% (500 vs 676 g d-1; p0,05) pelo conteúdo de TSD na água de beber. Conclusão: A dessalinização da água de beber melhora o comportamento produtivo de terneiros Holstein durante o período de lactação artificial..

Effects of a Polyherbal Dietary Additive on Performance, Dietary Energetics, Carcass Traits, and Blood Metabolites of Finishing Lambs.

The objective of this study was to evaluate the effects of dietary supplementation of a polyherbal additive (PA) containing hydrolyzable tannins, flavonoids, and essential oils on productive performance, dietary energetics, carcass and meat characteristics, and blood metabolites of lambs in their finishing phase. Twenty-eight Pelibuey × Katahdin lambs (20.52 ± 0.88 kg body weight (BW)) were housed in individual pens and assigned to four treatments (n = 7) with different doses of PA: 0 (CON), 1 (PA1), 2 (PA2), and 3 (PA3) g of PA kg−1 of DM for 56 days. Compared to the CON, lambs in PA1 treatment had higher average daily gain (p = 0.03), higher dietary energy utilization (p = 0.01), greater backfat thickness (p = 0.02), greater Longissimus dorsi muscle area (p = 0.01), and better feed conversion ratio (p = 0.02). PA supplementation did not affect (p > 0.05) dry matter intake, carcass yield, biometric measures, and meat chemical composition. All hematological and most of the blood biochemical parameters were similar in lambs of all treatments (p > 0.05). However, compared to the CON, lambs assigned to the PA3 treatment had lower serum urea concentration (p = 0.05) and higher serum albumin concentration (p = 0.03). In conclusion, low doses of PA could be used as a growth promoter in finishing lambs without affecting dry matter intake, carcass yield, meat chemical composition, and health status of the lambs. However, more in vivo research is needed to better understand the impact of bioactive compounds from PA used on productivity, metabolism, and health status of finishing lambs.

Growth Performance, Meat Quality and Antioxidant Status of Sheep Supplemented with Tannins: A Meta-Analysis.

The objective of this study was to evaluate the effects of dietary supplementation with tannins (TANs) on productive performance, carcass characteristics, meat quality, oxidative stability, and blood serum antioxidant capacity of sheep through a meta-analysis. Using Scopus, Web of Science, ScienceDirect, and PubMed databases, a systematic search was performed for studies published in scientific journals that investigated the effects of TANs supplementation on the variables of interest. Only studies with weaned or older sheep were included. The data analyzed were extracted from 53 peer-reviewed publications. The sheep included in the present study were between 2 and 6 months old, and between 12 and 31 kg of body weight. The effects of TANs were analyzed using random-effects statistical models to examine the standardized mean difference (SMD) between treatments with TANs and control (no TANs). Heterogeneity was explored by meta-regression and a subgroup analysis was performed for covariates that were significant. Supplementation with TANs did not affect dry matter intake, pH, color (L* and b*), Warner-Bratzler shear force, cooking loss and meat chemical composition (p > 0.05). Supplementation with TANs increased daily weight gain (SMD = 0.274, p < 0.05), total antioxidant capacity (SMD = 1.120, p < 0.001), glutathione peroxidase enzyme activity (SMD = 0.801, p < 0.001) and catalase (SMD = 0.848, p < 0.001), and decreased malondialdehyde (MDA) concentration in blood serum (SMD = -0.535, p < 0.05). Supplementation with TANs decreased feed conversion rate (SMD = -0.246, p < 0.05), and the concentration of MDA (SMD = -2.020, p < 0.001) and metmyoglobin (SMD = -0.482, p < 0.05) in meat. However, meat redness (SMD = 0.365), hot carcass yield (SMD = 0.234), cold carcass yield (SMD = 0.510), backfat thickness (SMD = 0.565) and the Longissimus dorsi muscle area (SMD = 0.413) increased in response to TANs supplementation (p < 0.05). In conclusion, the addition of tannins in sheep diets improves productive performance, antioxidant status in blood serum, oxidative stability of meat and some other characteristics related to meat and carcass quality.

Potential Effects of Delphinidin-3-O-Sambubioside and Cyanidin-3-O-Sambubioside of Hibiscus sabdariffa L. on Ruminant Meat and Milk Quality.

The objective was to review the potential effects of adding anthocyanin delphinidin-3-O-sambubioside (DOS) and cyanidin-3-O-sambubioside (COS) of HS in animal diets. One hundred and four scientific articles published before 2021 in clinics, pharmacology, nutrition, and animal production were included. The grains/concentrate, metabolic exigency, and caloric stress contribute to increasing the reactive oxygen species (ROS). COS and DOS have antioxidant, antibacterial, antiviral, and anthelmintic activities. In the rumen, anthocyanin might obtain interactions and/or synergisms with substrates, microorganisms, and enzymes which could affect the fiber degradability and decrease potential methane (CH4) emissions; since anthocyanin interferes with ruminal fatty acids biohydrogenation (BH), they can increase the n-3 and n-6 polyunsaturated fatty acids (PUFA), linoleic acid (LA), and conjugated linoleic acid (CLA) in milk and meat, as well as improving their quality. Anthocyanins reduce plasma oxidation and can be deposited in milk and meat, increasing antioxidant activities. Therefore, the reduction of the oxidation of fats and proteins improves shelf-life. Although studies in ruminants are required, COS and DOS act as inhibitors of the angiotensin-converting enzyme (ACEi) and rennin expression, regulating the homeostatic control and possibly the milk yield and body weight. By-products of HS contain polyphenols as calyces with positive effects on the average daily gain and fat meat quality.

Growth Performance, Carcass Characteristics, and Blood Metabolites of Lambs Supplemented with a Polyherbal Mixture.

The objective of this study was to determine the effects of the supplementation of a polyherbal mixture (HM) on the productive performance, carcass characteristics, meat quality, and the profile of blood metabolites of lambs fed a high-concentrate diet. Thirty-six male Pelibuey lambs (25.21 ± 0.96 kg BW) were housed in individual pens during a 56-day feeding period and were randomly assigned to four treatments: (1) Control (CON): Basal diet without HM; (2) HM1: CON + 1 g of HM kg-1 dry matter (DM); (3) HM2: CON + 2 g of HM kg-1 DM; and (4) HM3: CON + 3 g of HM kg-1 DM. Data were analyzed using the GLM (General Linear Model) procedure of statistical analysis system (SAS), and linear and quadratic effects were tested to evaluate the effects of the HM level. A quadratic increase was observed in the dry matter intake and in daily weight gain (p < 0.05) of lambs fed with HM2 and HM1, respectively. However, final body weight, body condition, carcass characteristics, and meat quality were similar among treatments (p > 0.05). It was observed a linear increase (p < 0.05) in the mean corpuscular hemoglobin concentration. Lymphocytes in blood from lambs supplemented with the HM1 diet increased and segmented neutrophils decreased compared to lambs receiving the CON treatment (p < 0.05). The concentration of uric acid in the blood had a linear increase (p < 0.05) and the serum creatinine level decreased (p < 0.05) as the HM dietary dose increased. In conclusion, dietary inclusion of 2 and 1 g of HM kg-1 of DM improves feed consumption and daily weight gain, respectively, without affecting carcass characteristics, meat quality, and health status on finishing lambs.

Supramolecular Functionalizable Linear-Dendritic Block Copolymers for the Preparation of Nanocarriers by Microfluidics.

Hybrid linear-dendritic block copolymers (LDBCs) having dendrons with a precise number of peripheral groups that are able to supramolecular bind functional moieties are challenging materials as versatile polymeric platforms for the preparation of functional polymeric nanocarriers. PEG2k-b-dxDAP LDBCs that are based on polyethylene glycol (PEG) as hydrophilic blocks and dendrons derived from bis-MPA having 2,6-diacylaminopyridine (DAP) units have been efficiently synthesized by the click coupling of preformed blocks, as was demonstrated by spectroscopic techniques and mass spectrometry. Self-assembly ability was first checked by nanoprecipitation. A reproducible and fast synthesis of aggregates was accomplished by microfluidics optimizing the total flow rate and phase ratio to achieve spherical micelles and/or vesicles depending on dendron generation and experimental parameters. The morphology and size of the self-assemblies were studied by TEM, Cryogenic Transmission Electron Microscopy (cryo-TEM), and Dynamic Light Scattering (DLS). The cytotoxicity of aggregates synthesized by microfluidics and the influence on apoptosis and cell cycle evaluation was studied on four cell lines. The self-assemblies are not cytotoxic at doses below 0.4 mg mL-1. Supramolecular functionalization using thymine derivatives was explored for reversibly cross-linking the hydrophobic blocks. The results open new possibilities for their use as drug nanocarriers with a dynamic cross-linking to improve nanocarrier stability but without hindering disassembly to release molecular cargoes.

Multiplex Detection of Clinically Relevant Mutations in Liquid Biopsies of Cancer Patients Using a Hybridization-Based Platform.

BACKGROUND: With the advent of precision oncology, liquid biopsies are quickly gaining acceptance in the clinical setting. However, in some cases, the amount of DNA isolated is insufficient for Next-Generation Sequencing (NGS) analysis. The nCounter platform could be an alternative, but it has never been explored for detection of clinically relevant alterations in fluids. METHODS: Circulating-free DNA (cfDNA) was purified from blood, cerebrospinal fluid, and ascites of patients with cancer and analyzed with the nCounter 3 D Single Nucleotide Variant (SNV) Solid Tumor Panel, which allows for detection of 97 driver mutations in 24 genes. RESULTS: Validation experiments revealed that the nCounter SNV panel could detect mutations at allelic fractions of 0.02-2% in samples with ≥5 pg mutant DNA/µL. In a retrospective analysis of 70 cfDNAs from patients with cancer, the panel successfully detected EGFR, KRAS, BRAF, PIK3CA, and NRAS mutations when compared with previous genotyping in the same liquid biopsies and paired tumor tissues [Cohen kappa of 0.96 (CI = 0.92-1.00) and 0.90 (CI = 0.74-1.00), respectively]. In a prospective study including 91 liquid biopsies from patients with different malignancies, 90 yielded valid results with the SNV panel and mutations in EGFR, KRAS, BRAF, PIK3CA, TP53, NFE2L2, CTNNB1, ALK, FBXW7, and PTEN were found. Finally, serial liquid biopsies from a patient with NSCLC revealed that the semiquantitative results of the mutation analysis by the SNV panel correlated with the evolution of the disease. CONCLUSIONS: The nCounter platform requires less DNA than NGS and can be employed for routine mutation testing in liquid biopsies of patients with cancer.