Effects of betaine supplementation on dry matter intake, milk characteristics, plasma non-esterified fatty acids, and ß-hydroxybutyric acid in dairy cattle: a meta-analysis.

Betaine supplementation in dairy cattle has gained attention due to its potential benefits to production and health as a methyl donor, which can play a crucial role in the metabolism of dairy cows. The objective of the current meta-analysis was to quantify the effects of betaine supplementation on milk production, composition, ß-hydroxybutyric acid (BHBA), and non-esterified fatty acids (NEFA). A systematic literature search was carried out, all relevant studies were retrieved, and the meta-analysis was carried out. The mean difference (MD) for dry matter intake (DMI) using the random-effects model was 0.499 kg/d (P < 0.0001). The subgroup analysis indicated that supplementing betaine in heat-stressed cows increased DMI by 0.584 kg/d (P < 0.001), while in cows not exposed to heat stress, DMI was increased by 0.381 kg/d (P = 0.007). The energy-corrected milk (ECM) increased by 1.36 kg/d (P < 0.0001). The milk fat yield was significantly increased in betaine-supplemented cows (MD = 0.040 kg/d, 95% CI = 0.015 to 0.065). The milk protein yield (kg/d) (MD = 0.014, P = 0.138) was increased (MD = 0.035, P = 0.0005) by betaine supplementation. The lactose yield (kg/d) was also significantly higher (MD = 0.055, P = 0.020) in betaine-supplemented cows. The standardized mean difference (SMD) for NEFA (SMD = - 0.447, 95% CI = - 1.029 to 0.135, P = 0.114) and BHBA (SMD = - 0.130, 95% CI = - 0.491 to 0.234). In conclusion, the findings from this meta-analysis suggest that betaine supplementation positively influences DMI, ECM, milk fat yield, milk lactose yield, and milk protein yield. Subgroup analysis further indicated that the positive effects on DMI are greater in heat-stressed cows compared to those not exposed to heat stress. The analysis did not find significant effects on the levels of NEFA or BHBA, suggesting that betaine supplementation may not directly influence these metabolic parameters.

The aim of this meta-analysis was to examine the effects of dietary betaine supplementation on dairy cows' dry matter intake, milk production, milk composition, non-esterified fatty acids, and ß-hydroxybutyric acid. The results indicated that the supplementation of betaine increased dry matter intake (+0.584 kg/d/cow), energy-corrected milk (+1.36 kg/d), milk fat yield (+ 0.040 kg/d), milk protein yield (+ 0.014 kg/d), and lactose yield (+ 0.055 kg/d). ß-Hydroxybutyric acid and plasma non-esterified fatty acids were not influenced by betaine supplementation in dairy cattle.

Investigating the relationship between heat load and shade seeking behaviour in dairy buffaloes.

The study presented in this Research Communication aimed to investigate the relationship between physiological responses, body surface temperature and shade-seeking behaviour in Nili Ravi dairy buffaloes during summer months. We enrolled 60 buffaloes, and each animal was observed for three consecutive days starting before sunrise until they moved towards the shade structures. A repeated measures ANOVA was employed to assess the changes in physiological parameters and body surface temperature between the early morning and the occurrence of shade-seeking behaviour. The average temperature humidity index and heat load index during the behavioural monitoring period (0400 to 1200 h) were 81.3 ± 6.5 and 92.9 ± 17, respectively (mean ± sd). There was no significant difference in core body temperature between sunrise and the time of shade-seeking event. However, the buffaloes had a slightly higher respiration rate at the time of shade-seeking (19.2 vs. 22.4 breaths/min). In addition, body surface temperature, measured at the flank region, shoulder, base of the ear and forehead was significantly higher at the occurrence of shade-seeking behaviour compared to the early morning. On average, the buffaloes sought shade when the surface temperature was 2°C higher than the temperature recorded before sunrise. Overall, the current findings suggest that body surface temperature, rather than core body temperature was strongly associated with shade-seeking behaviour in dairy buffaloes. These findings could be useful in developing strategies to mitigate the effects of heat stress in dairy buffalo herds and thereby improve animal welfare.

Effects of dietary chromium supplementation on blood biochemical parameters in dairy cows: A multilevel meta-analytical approach.

Chromium (Cr) has been reported to modulate blood biochemistry in dairy cows. However, there is a discrepancy in the literature regarding the effects of dietary Cr supplementation on various blood parameters. This meta-analysis aimed to evaluate the effects of Cr supplementation in dairy cows on blood glucose, insulin, glucagon, nonesterified fatty acid (NEFA), cortisol, and serum total protein (STP) concentrations. Following relevant literature data extraction, a 3-level meta-analytical random effect model was fitted to the data expressed as standardized mean difference (SMD) of outcome measures of control versus Cr-supplemented cows (i.e., difference in mean between control and treatment group or pooled standard deviation). The SMD can be categorized as having a small effect (0.20), a moderate effect (0.50), and a large effect (0.80). The meta-regression identified the potential sources of heterogeneity, including the body weight of cows, experimental duration/duration of Cr supplementation, blood sampling time (3 wk before parturition until 4 wk after parturition categorized as the transition period, else as the nontransition period), and form of Cr complexes. Blood glucose did not differ significantly between control and Cr-supplemented cows with an estimated SMD of µ = 0.0071 (95% confidence interval [CI]: -0.212 to 0.226). The effect of Cr supplementation on blood insulin was also nonsignificant with an SMD of µ = 0.0007 (95% CI: -0.191 to 0.193). Cows receiving Cr supplements had significantly higher levels of glucagon than controls (95% CI: 0.116 to 0.489), with an estimated SMD = 0.303. Combined transition and nontransition data suggest Cr supplementation did not affect the concentration of NEFA. However, in transition cows, Cr supplementation significantly decreased blood NEFA levels as compared with controls (95% CI: -0.522 to -0.0039), with estimated SMD = -0.263. The estimated SMD was µ = -0.1983 (95% CI: -0.734 to 0.337) for cortisol and -0.0923 (95% CI: -0.316 to 0.131) for total protein. In summary, Cr supplementation in the transition cows decreased NEFA concentration. Blood glucose, insulin, cortisol, and STP concentrations were unaffected. However, Cr supplementation increased glucagon concentration.

Effects of Iron Oxide Nanoparticle Supplementation on the Growth Performance, Serum Metabolites, Meat Quality, and Jejunal Basal Morphology in Broilers.

The current research aimed to evaluate the supplemental effects of iron oxide nanoparticles (IONPs) on production performance, viscera development, blood metabolites, redox status, meat quality, and jejunal histology in broilers. A total of 300 day-old broilers were randomly divided into six groups with five replicates per group. Birds were fed on a corn soybean-based diet supplemented with 0, 20, 40, 60, or 80 mg/kg IONPs or 80 mg/kg of FeSO4 for 35 days. The feed conversion ratio (FCR) was improved in birds supplemented with 60 mg/kg IONPs. The pH24h was lower in birds supplemented with 40 mg/kg IONPs compared to that of the bulk group. Pectoral muscle fascicle diameter and fiber density were significantly increased in 20 mg/kg IONP-supplemented birds compared to those of the bulk group, respectively. The muscle fiber diameter was higher in 40 mg/kg IONP-supplemented birds compared with the bulk group. The jejunal villus height, crypt depth, and villus surface area were significantly increased with 60 mg/kg IONP supplementation, whereas villus width was decreased in birds supplemented with 40 mg/kg IONPs. The villus-height-to-crypt-depth ratio was lower in IONP-supplemented birds compared to the bulk group. IONP supplementation improved the FCR, jejunal, and pectoral muscle morphology without affecting the carcass characteristics and redox status of broilers.

Validation of a body condition scoring system in Nili Ravi dairy buffaloes (Bubalus bubalis): inter- and intra-assessor variability.

The aim of the research reported in this Research Communication was to apply the 5-point body condition scoring (BCS) system to dairy buffaloes and subjectively validate it by assessing the intra- and inter-assessor agreement. For this purpose, the BCS system developed for dairy cows was applied to buffaloes. A total of 230 Nili Ravi buffaloes of varying parity, lactation stages and pregnancy status were enrolled from the Buffalo Research Institute, Pattoki, Pakistan. Four observers independently assigned BCS values to each enrolled buffalo in two phases, as follows: (1) during phase I, the assessors were trained for BCS assessment using a BCS chart developed by Elanco Animal Health Ltd.; and (2) during phase II, the assessors were trained using live buffaloes for BCS assessment. Kappa statistics (kw) were used to determine the intra- and inter-assessor agreement. The results revealed that the exact overall inter- and intra-assessor agreement was moderate (kw = 0.48-0.55) and increased to substantial levels after training on live animals (kw = 0.63-0.87). Furthermore, the intra- and inter-assessor exact agreement was higher (kw = 0.57-0.58) for buffaloes tied to the mangers compared to the buffaloes standing in the loafing area (kw = 0.50). The inter-assessor agreements within 0.25 and 0.5 points were almost perfect (kw = 0.97-1.0). The current results suggested that the 5-point BCS system (using a scale from 1 to 5 with 0.25 increments) had substantial agreement for assessment and repeatability when applied to buffaloes.

Heat treatment of colostrum at 60°C decreases colostrum immunoglobulins but increases serum immunoglobulins and serum total protein: A meta-analysis.

Calves are born hypogammaglobulinemic; thus, the newborn calf's immune defense relies on the ingestion and absorption of colostrum, which provides energy, immunoglobulins, immune cells, and cytokines to the newborn calf. A heat treatment applied to colostrum for 60 min at 60°C has been found to be effective at reducing the total bacterial count while preserving the colostrum IgG levels. The objective of this work was to perform a meta-analysis on the association between the characteristics of heat-treated colostrum and the concentration of colostrum IgG, serum IgG concentration, and serum total protein (STP). A meta-analysis was carried out based on existing peer-reviewed literature. Publications comparing colostrum IgG, serum IgG, and STP for heat-treated or raw frozen colostrum were included. The different heating temperatures applied to the colostrum were divided into 2 subgroups: high temperature (HT; >60°C) and low temperature (LT; ≤60°C). Twelve studies, including 21 trials, met the inclusion criteria for colostrum IgG concentration. The results indicated decreases in colostrum IgG by 20.6 g/L [95% confidence interval (CI) = 11.8-29.4] for HT and 5.38 g/L (95% CI = 2.9-7.8) for LT when colostrum was heat-treated compared with raw or frozen colostrum. Heterogeneity was high to moderate (I2 = 82% for HT and 65% for LT). The heat treatment of colostrum was also associated with a nonsignificant decrease in serum IgG by 3.40 g/L for HT (95% CI = 7.54-0.74) but a significant increase in serum IgG by 2.65 g/L for LT (95% CI = 1.51-3.79). The regression model indicated that heterogeneity was not explained by any moderators. The heat treatment of colostrum was also associated with a significant increase in STP by 0.21 g/dL for LT (95% CI = 0.07-0.35). In conclusion, the present work demonstrated that the heat treatment of colostrum ≤60°C decreased colostrum IgG by 5.38 g/L for LT and increased serum IgG by 2.65 g/L and STP by 0.21 g/dL. When compared with the range of values observed in the field for serum IgG, the present results are of high interest for the cattle industry. Because immune colostrum benefits also include cytokines and immune cells, further work is required to evaluate the effect of colostrum heat treatment on these 2 immune components of colostrum.

Effect of body condition score at calving on transition success in Nili Ravi buffaloes.

Body condition score (BCS) at calving is a vital indicator of the effectiveness of the beginning of lactation in dairy animals. The purpose of this study was to examine the effect of BCS at calving on milk production and transition success in dairy buffaloes. Thirty-six (36) Nili Ravi buffaloes were enrolled at 40 days of expected calving and followed through 90 days of lactation. The buffaloes were categorized into three groups according to their BCS (on a scale of 1-5 with 0.25 increments) as follows: 1) low, buffaloes with BCS ≤ 3.0; 2) medium, buffaloes with BCS 3.25-3.5; and 3) high, buffaloes with BCS ≥ 3.75. All buffaloes were fed a similar diet ad libitum. The lactation diet had increased concentrate allowance according to milk yield. The results revealed that the BCS at calving did not affect milk yield; however, fat percentage (fat%) was lower in the low-BCS group. Dry matter intake (DMI) was similar among the treatment groups, although post-calving BCS loss was greater in the high-BCS group compared to the medium- and the low-BCS groups. Similarly, the buffaloes in the high-BCS group had higher non-esterified fatty acids (NEFA) concentration compared to the low- and medium-BCS groups. No cases of metabolic disorders were observed during the study. The present results suggest that the buffaloes in the medium-BCS group appeared to perform better compared to the low- and the high-BCS groups with respect to milk fat% and blood NEFA concentration.

Effect of Physical Form and Level of Wheat Straw Inclusion on Growth Performance and Blood Metabolites of Fattening Goat.

The inclusion of straw in high concentrate total mixed rations (TMRs) of male fattening goats can provide the necessary fiber to prevent ruminal acidosis and maintain growth. The objective of this study was to evaluate the effects of the physical form (PF) of the diet (pelleted vs. conventional) and the straw level (SL) of wheat straw (WS) (15% versus 25%) in total mixed rations on feed intake, growth, total tract digestibility, and blood metabolites of fattening goats. Thirty-two male Beetal goats (27.4 ± 0.28 kg body weight (BW)) were divided randomly into the following four dietary treatments with a 2 × 2 factorial arrangement (n = 8/treatment): (1) CTMR15 (conventional TMR containing 15% WS), (2) CTMR25 (conventional TMR containing 25% WS), (3) PTMR15 (pelleted TMR containing 15% WS), and (4) PTMR25 (pelleted TMR containing 25% WS). Both conventional and pelleted 15% WS TMR had 33.7% neutral detergent fiber (NDF) and 19.3% acid detergent fiber (ADF), whereas in 25% WS TMR the NDF and ADF contents were 38.7% and 22.9%, respectively. The experimental diets were formulated to be iso-nitrogenous (crude protein (CP) = 15%). The dry matter intake (DMI) (1.265 vs. 1.044 kg/day) and average daily gain (ADG) (0.176 vs. 0.143 kg/day) were higher (p < 0.05) in pelleted vs. conventional TMR-fed goats. Irrespective of the PF of the TMR, the 15% WS-fed animals had greater (p < 0.05) DMI (1.206 vs. 1.102 kg/day) and ADG (0.172 vs. 0.144 kg) when compared to those fed on 25% WS diets. Furthermore, feed-to-gain ratio (F:G) was higher (p < 0.05) in the 25% WS-fed goats when compared with the 15% WS-fed animals. Digestibility coefficients, nitrogen balancing, hepatic enzymes, blood metabolites, and hematological parameters were similar (p > 0.05) across all treatments. In conclusion, feeding pelleted TMR with WS improved DMI and growth performance as compared to those fed conventional TMR, and 15% WS performed better than 25% WS without exerting any adverse effects on blood metabolites, liver enzymes, or hematological parameters.

Effects of Physical Forms of Total Mixed Rations on Intake, Weaning Age, Growth Performance, and Blood Metabolites of Crossbred Dairy Calves.

This study evaluated the effects of hay-based total mix ration (TMR) in pelleted or unpelleted form on intake, weaning age, performance parameters, blood metabolites, and cost-effectiveness in crossbred dairy calves during the preweaning period under hot climatic conditions. Thirty calves (4 ± 1 days (d) old), were assigned to one of the three dietary treatments in a randomized complete block design. Treatments assigned were: (1) conventional calf starter (CCS); without hay (2) TMR containing 85% calf starter and 15% chopped oat hay (OH) and (3) pelleted TMR (PTMR) containing 85% calf starter and 15% OH. Colostrum-fed calves were offered four liters (L) of whole milk each, during the first week, followed by six L daily. Calves were weaned off milk gradually on the basis of targeted starter intake of 200, 600, and 800 grams, after which they were considered weaned. Environmental temperature, feed intake, and health scores were recorded daily. The calves experienced heat stress with an average temperature-humidity index (THI) of 80.06 ± 3.42. Results revealed that average daily dry matter intake (DMI), average daily gain (ADG), and feed efficiency (FE) were not different (P > 0.05) among the treatments. Changes in body measurements, rumen development parameters, and blood metabolites were also not affected by the treatments (P > 0.05). Average weaning age in PTMR was 5.4 d earlier as compared to CCS. Feed cost per unit gain tended to be lower for PTMR compared with CCS-fed (86%) calves. Feeding pelleted TMR containing 15% OH tended to reduce the weaning age and feed cost per unit gain without affecting growth performance, intake, FE, and health parameters in crossbred calves under heat stress conditions.

1,4-Diazepines: A Review on Synthesis, Reactions and Biological Significance.

BACKGROUND: 1,4-Diazepines are two nitrogen containing seven membered heterocyclic compounds and associated with a wide range of biological activities. Due to its medicinal importance, scientists are actively involved in the synthesis, reactions and biological evaluation of 1,4-diazepines since number of decades. OBJECTIVE: The primary purpose of this review is to discuss the synthetic schemes and reactivity of 1,4- diazepines. This article also describes biological aspects of 1,4-diazepine derivatives, that can be usefully exploited for the pharmaceutical sector. CONCLUSION: This review summarizes the abundant literature on synthetic routes, chemical reactions and biological attributes of 1,4-diazepine derivatives. We concluded that 1,4-diazepines have significant importance due to their biological activities like antipsychotic, anxiolytic, anthelmintic, anticonvulsant, antibacterial, antifungal and anticancer. 1,4-diazepine derivatives with significant biological activities could be explored for potential use in the pharmaceutical industries.

Genetic Basis Underlying Correlations Among Growth Duration and Yield Traits Revealed by GWAS in Rice (Oryza sativa L.).

Avoidance of disadvantageous genetic correlations among growth duration and yield traits is critical in developing crop varieties that efficiently use light and energy resources and produce high yields. To understand the genetic basis underlying the correlations among heading date and three major yield traits in rice, we investigated the four traits in a diverse and representative core collection of 266 cultivated rice accessions in both long-day and short-day environments, and conducted the genome-wide association study using 4.6 million single nucleotide polymorphisms (SNPs). There were clear positive correlation between heading date and grain number per panicle, and negative correlation between grain number per panicle and panicle number, as well as different degrees of correlations among other traits in different subspecies and environments. We detected 47 pleiotropic genes in 15 pleiotropic quantitative trait loci (pQTLs), 18 pleiotropic genes containing 37 pleiotropic SNPs in 8 pQTLs, 27 pQTLs with r2 of linkage disequilibrium higher than 0.2, and 39 pairs of interactive genes from 8 metabolic pathways that may contribute to the above phenotypic correlations, but these genetic bases were different for correlations among different traits. Distributions of haplotypes revealed that selection for pleiotropic genes or interactive genes controlling different traits focused on genotypes with weak effect or on those balancing two traits that maximized production but sometimes their utilization strategies depend on the traits and environment. Detection of pQTLs and interactive genes and associated molecular markers will provide an ability to overcome disadvantageous correlations and to utilize the advantageous correlations among traits through marker-assisted selection in breeding.

Genetic Architecture and Candidate Genes for Deep-Sowing Tolerance in Rice Revealed by Non-syn GWAS.

Dry direct-seeding of rice is rapidly increasing in China, but variable planting depth associated with machine sowing can lead to low seedling emergence rates. Phenotype analysis of 621 rice accessions showed that mesocotyl length (ML) was induced by deep soil covering and was important in deep-sowing tolerance in the field. Here, we performed and compared GWAS using three types of SNPs (non-synonymous SNP, non-synonymous SNPs and SNPs within promoters and 3 million randomly selected SNPs from the entire set of SNPs) and found that Non-Syn GWAS (GWAS using non-synonyomous SNP) decreased computation time and eliminated confounding by other loci relative to GWAS using randomly selected SNPs. Thirteen QTLs were finally detected, and two new major-effect genes, named OsML1 and OsML2, were identified by an integrated analysis. There were 2 and 7 non-synonymous SNPs in OsML1 and OsML2, respectively, from which 3 and 4 haplotypes were detected in cultivated rice. Combinations of superior haplotypes of OsML1 and OsML2 increased ML by up to 4 cm, representing high emergence rate (85%) in the field with 10 cm of soil cover. The studies provide key loci and naturally occurring alleles of ML that can be used in improving tolerance to dry direct-seeding.

Synthesis of Functionalized 1H-Indenes and Benzofulvenes through Iodocyclization of o-(Alkynyl)styrenes.

A convenient method for the preparation of synthetically useful 3-iodoindene derivatives has been developed. This protocol, based on the 5-endo iodocyclization reaction of o-(alkynyl)styrenes, represents one of the scarce examples of halocyclizations using olefins as nucleophilic counterparts and allows the synthesis of both 3-iodo-1H-indenes (from ß-alkyl-ß-alkyl/aryl-o-(alkynyl)styrenes) and 3-iodobenzofulvenes (from ß,ß-diaryl-o-(alkynyl)styrenes) in good yields under mild reaction conditions. In addition, related alkoxyiodocyclization processes are described, which are particularly interesting in their intramolecular version because they allow the synthesis of heteropolycyclic structures containing the indene core. Finally, the usefulness of the prepared 3-iodoindenes has been demonstrated by the synthesis of several polysubstituted indene derivatives through conventional palladium-catalyzed cross-coupling reactions and iodine-lithium exchange processes.

Pupal diapause termination in Bactrocera minax: an insight on 20-hydroxyecdysone induced phenotypic and genotypic expressions.

The Chinese citrus fruit fly, Bactrocera minax, is an economically important pest of citrus. It exhibits pupal diapause from November to May to combat harsh environmental conditions. Such a long pupal diapause is a barrier for laboratory rearing and development of control strategies against this pest. In the present study, 20-hydroxyecdysone (20E) was used to break pupal diapause of B. minax by topical application. After diapause termination by 20E treated, the pupal ontogenetic processes were observed along the temporal trajectory. The pupal response time to 20E was estimated by detecting the relative expression of 20E responsive genes at different times after 20E-treatment. Results revealed that 20E could effectively terminate the pupal diapause in a dose-dependent manner and significantly shorten the time for 50% adult emergence (Et50). 20E response genes, including ecr, broad and foxo, were up-regulated within 72h, indicating these genes are involved in pupal metamorphosis and diapause termination processes. Morphological changes showed the pupal metamorphosis began ~7 days after 20E-treatment at 22 °C. This study does not only pave the way for artificial rearing in the laboratory through manipulating of pupal diapause termination, but also deepens our understanding of the underlying pupal diapause termination mechanism of B. minax.

Gold(I)-catalyzed cycloisomerizations and alkoxycyclizations of ortho-(alkynyl)styrenes.

Indenes and related polycyclic structures have been efficiently synthesized by gold(I)-catalyzed cycloisomerizations of appropriate ortho-(alkynyl)styrenes. Disubstitution at the terminal position of the olefin was demonstrated to be essential to obtain products originating from a formal 5-endo-dig cyclization. Interestingly, a complete switch in the selectivity of the cyclization of o-(alkynyl)-α-methylstyrenes from 6-endo to 5-endo was observed by adding an alcohol to the reaction media. This allowed the synthesis of interesting indenes bearing an all-carbon quaternary center at C1. Moreover, dihydrobenzo[a]fluorenes can be obtained from substrates bearing a secondary alkyl group at the ß-position of the styrene moiety by a tandem cycloisomerization/1,2-hydride migration process. In addition, diverse polycyclic compounds were obtained by an intramolecular gold-catalyzed alkoxycyclization of o-(alkynyl)styrenes bearing a nucleophile in their structure. Finally, the use of a chiral gold complex allowed access to elusive chiral 1H-indenes in good enantioselectivities.

Straightforward synthesis of dihydrobenzo[a]fluorenes through Au(I)-catalyzed formal [3 + 3] cycloadditions.

Dihydrobenzo[a]fluorene derivatives have been prepared by a formal intramolecular [3 + 3] cycloaddition of o-alkynylstyrenes bearing a secondary alkyl group at the ß-position of the styrene moiety. The process, catalyzed by a cationic gold(I) complex, involves a 1,2-hydride migration as the key step. 6,11-Dihydro-5H-benzo[a]fluorenes could be obtained from the initially generated 6,6a-dihydro-5H-benzo[a]fluorenes by subsequent heating of the reaction mixture under gold(I) or Brønsted acid catalysis or directly by conducting the reactions at high temperature.

Halocyclization of o-(alkynyl)styrenes. Synthesis of 3-halo-1H-indenes.

o-(Alkynyl)styrenes undergo halocarbocyclization processes via a 5-endo-dig ring closure. By this strategy an efficient synthesis of 3-halo-1H-indene derivatives has been developed.

Efficient synthesis of salicylates by catalytic [3 + 3] cyclizations of 1,3-bis(silyl enol ethers) with 1,1,3,3-tetramethoxypropane.

Salicylic acid derivatives were prepared by Me3SiOTf-catalyzed [3 + 3] cyclization of 1,3-bis(silyl enol ethers) with 1,1,3,3-tetramethoxypropane.