Additive and Dominance Genome-Wide Association Studies Reveal the Genetic Basis of Heterosis Related to Growth Traits of Duhua Hybrid Pigs.

Heterosis has been extensively used for pig genetic breeding and production, but the genetic basis of heterosis remains largely elusive. Crossbreeding between commercial and native breeds provides a good model to parse the genetic basis of heterosis. This study uses Duhua hybrid pigs, a crossbreed of Duroc and Liangguang small spotted pigs, as materials to explore the genetic basis underlying heterosis related to growth traits at the genomic level. The mid-parent heterosis (MPH) analysis showed heterosis of this Duhua offspring on growth traits. In this study, we examined the impact of additive and dominance effects on 100 AGE (age adjusted to 100 kg) and 100 BF (backfat thickness adjusted to 100 kg) of Duhua hybrid pigs. Meanwhile, we successfully identified SNPs associated with growth traits through both additive and dominance GWASs (genome-wide association studies). These findings will facilitate the subsequent in-depth studies of heterosis in the growth traits of Duhua pigs.

Biodegradation of mixed litter-derived dissolved organic matter with varying evenness in a temperate freshwater wetland.

Litter-derived dissolved organic matter (DOM) plays an essential role in biogeochemical cycles. In wetlands, species relative abundance and its change have great influences on input features of litter-derived DOM, including chemical characteristics per se and functional diversity of chemical characteristics. Functional diversity is an important factor controlling organic matter biodegradation, but little is known in terms of the DOM. We mixed litter leachates of four macrophytes with a constant concentration (20 mg DOC L-1) but varying dominant species and volume ratios, i.e. 15:1:1:1 (low-evenness), 5:1:1:1 (mid-evenness), and 2:1:1:1 (high-evenness), generating a gradient of chemical characteristics and functional diversity (represented by functional dispersion index FDis). Based on a 42-d incubation, we measured degradation dynamics of these DOM mixtures, and analyzed potential determinants. After 42 days of incubation, the high-evenness treatments, along with mid-evenness treatments sometimes, had most degradation, while the low-evenness treatments always had least degradation. The degradation of mixtures related significantly to not only the volume-weighted mean chemical characteristics but also FDis. Furthermore, the FDis even explained more variation of degradation. The non-additive mixing effects, synergistic effects (faster degradation than predicted) in particular, on degradation of DOM mixtures were rather common, especially in the high- and mid-evenness treatments. Remarkably, the mixing effects increased linearly with the FDis values (r2adj. = 0.426). This study highlights the critical role of functional diversity in regulating degradation of mixed litter-derived DOM. Resulting changes in chemistry and composition of litter leachates due to plant community succession may exert substantial influences on biogeochemical cycling.

Synergistic and Additive Effects of Herbal Medicines in Combination with Chemotherapeutics: A Scoping Review.

BACKGROUND: Natural products are increasingly gaining interest as potential new drug candidates for cancer treatment. Herbal formula, which are combinations of several herbs, are primarily used in East Asia and have a long history of use that continues today. Recently, research exploring the combination of herbal formulas and chemotherapy for cancer treatment has been on the rise. METHODS: This study reviewed research on the co-administration of herbal formulas and chemotherapy for cancer treatment. The databases PubMed, Embase, and Cochrane Library were used for article searches. The following keywords were employed: "Antineoplastic agents," "Chemotherapy," "Phytotherapy," "Herbal medicine," "Drug synergism," and "Synergistic effect." The selection process focused on studies that investigated the synergistic interaction between herbal formulas and chemotherapeutic agents. RESULTS: Among the 30 studies included, 25 herbal formulas and 7 chemotherapies were used. The chemotherapy agents co-administered included cisplatin, 5-fluorouracil, docetaxel, doxorubicin, oxaliplatin, irinotecan, and gemcitabine. The types of cancer most frequently studied were lung, breast, and colon cancers. Most studies evaluating the anticancer efficacy of combined herbal formula and chemotherapy treatment were conducted in vitro or in vivo. DISCUSSION: Most studies reported synergistic effects on cytotoxicity, apoptosis, and tumor growth inhibition. These effects were found to be associated with cell cycle arrest, anti-angiogenesis, and gene expression regulation. Further studies leading to clinical trials are required. Clinical experiences in East Asian countries could provide insights for future research.

Genome-wide association study for milking speed in Fleckvieh cattle.

Milking speed is an important trait influencing udder health of dairy cows as well as labor efficiency. Yet, it has received little attention in genomic association studies. The main objective of this study was to determine regions and genes on the genome with a potential effect on milking speed in Fleckvieh (dual purpose Simmental) cattle. Genome-wide association studies were conducted using de-regressed breeding values of bulls as phenotypes. Six SNP on 4 autosomes were significantly associated with milking speed for additive effects. Significant regions on BTA4 and BTA19 correspond with findings for other dairy cattle breeds. Based on the observation of Fleckvieh breed managers, variation of milking speed in batches of daughters of some bulls is much higher than in daughter groups of other bulls. This difference in within family variation may be caused by transmission of alternative alleles of bulls being heterozygous for a gene affecting milking speed. To check on this, we considered standard deviation of yield deviations in milking speed of half-sib daughters as a new trait and performed GWAS for dominance effects. One signal on BTA5 passed the genome wide Bonferroni threshold that corresponded to the significant signal from standard GWAS on de-regressed breeding values. The key conclusion of this study is that several strong genomic signals were found for milking speed in Fleckvieh cattle and that the strongest of them are supported by similar findings in Brown Swiss and Holstein Friesian cattle. Milking speed is a complex trait whose sub-processes have not yet been elucidated in detail. Hence, it remains a challenge to link the associated regions on the genome with causal genes and their functions.

Large-Sample Genome-Wide Association Study of Resistance to Retained Placenta in U.S. Holstein Cows.

A genome-wide association study of resistance to retained placenta (RETP) using 632,212 Holstein cows and 74,747 SNPs identified 200 additive effects with p-values < 10-8 on thirteen chromosomes but no dominance effect was statistically significant. The regions of 87.61-88.74 Mb of Chr09 about 1.13 Mb in size had the most significant effect in LOC112448080 and other highly significant effects in CCDC170 and ESR1, and in or near RMND1 and AKAP12. Four non-ESR1 genes in this region were reported to be involved in ESR1 fusions in humans. Chr23 had the largest number of significant effects that peaked in SLC17A1, which was involved in urate metabolism and transport that could contribute to kidney disease. The PKHD1 gene contained seven significant effects and was downstream of another six significant effects. The ACOT13 gene also had a highly significant effect. Both PKHD1 and ACOT13 were associated with kidney disease. Another highly significant effect was upstream of BOLA-DQA2. The KITLG gene of Chr05 that acts in utero in germ cell and neural cell development, and hematopoiesis was upstream of a highly significant effect, contained a significant effect, and was between another two significant effects. The results of this study provided a new understanding of genetic factors underlying RETP in U.S. Holstein cows.

Nitrogen and Microelements Co-Drive the Decomposition of Typical Grass Litter in the Loess Plateau, China.

In grassland ecosystems, the decomposition of litter serves as a vital conduit for nutrient transfer between plants and soil. The aim of this study was to depict the dynamic process of grass litter decomposition and explore its major driver. Three typical grasses [Stipa bungeana Trin (St. B), Artemisia sacrorun Ledeb (Ar. S), and Thymus mongolicus Ronniger (Th. M)] were selected for long-term litter decomposition. Experiments were conducted using three single litters, namely, St. B, Ar. S, and Th. M, and four different compositions of mixed litter: ML1 (55% St. B and 45% Th. M), ML2 (55% St. B and 45% Ar. S), ML3 (75% St. B and 25% Th. M), and ML4 (75% St. B and 25% Ar. S). The dynamic patterns of mass and microelements (Ca, Mg, Fe, Mn, Cu, and Zn) within different litter groups were analyzed. Our findings indicated that, after 1035 days of decomposition, the proportion of residual mass for the single litters was as follows: Th. M (60.6%) > St. B (47.3%) > Ar. S (44.3%), and for the mixed groups it was ML1 (48.0%) > ML3 (41.6%) > ML2 (40.9) > ML4 (38.4%). Mixed cultivation of the different litter groups accelerated the decomposition process, indicating that the mixture of litters had a synergistic effect on litter decomposition. The microelements of the litter exhibited an initial short-term increase followed by long-term decay. After 1035 days of decomposition, the microelements released from the litter were, in descending order, Mg > Ca > Fe > Cu > Mn > Zn. Compared to the separately decomposed St. B litter, mixing led to an inhibition of the release of Ca (antagonistic effect), while it promoted the release of Mg, Cu, and Zn (synergistic effect). For the single litter, the stepwise regression analysis showed that Ca was the dominant factor determining early litter decomposition. Mg, Mn, and Cu were the dominant factors regulating later litter decomposition. For the mixed litter groups, Ca, Mn, and Mg were the dominant factors closely related to early decomposition, and TN emerged as a key factor regulating the mass loss of mixtures during later decomposition. In summary, nitrogen and microelements co-drive the decomposition of typical grass litter. Our study underscores that, in the succession process of grassland, the presence of multiple co-existing species led to a faster loss of plant-derived materials (litter mass and internal elements), which was primarily modulated by species identity and uniformity.

Impacts of litter microbial community on litter decomposition in the absence of soil microorganisms.

What is the effect of phyllosphere microorganisms on litter decomposition in the absence of colonization by soil microorganisms? Here, we simulated the litter standing decomposition stage in the field to study the differences in the composition and structure of the phyllosphere microbial community after the mixed decomposition of Populus × canadensis and Pinus sylvestris var. mongolica litter. After 15 months of mixed decomposition, we discovered that litters that were not in contact with soil had an antagonistic effect (the actual decomposition rate was 18.18%, which is lower than the expected decomposition rate) and the difference between the litters themselves resulted in a negative response to litter decomposition. In addition, there was no significant difference in bacterial and fungal community diversity after litter decomposition. The litter bacterial community was negatively responsive to litter properties and positively responsive to the fungal community. Importantly, we found that bacterial communities had a greater impact on litter decomposition than fungi. This study has enriched our understanding of the decomposition of litter itself and provided a theoretical basis for further exploring the "additive and non-additive effects" of litter decomposition and the mechanism of microbial drive. IMPORTANCE: The study of litter decomposition mechanism plays an important role in the material circulation of the global ecosystem. However, previous studies have often looked at contact with soil as the starting point for decomposition. But actually, standing litter is very common in forest ecosystems. Therefore, we used field simulation experiments to simulate the decomposition of litters without contact with soil for 15 months, to explore the combined and non-added benefits of the decomposition of mixed litters, and to study the influence of microbial community composition on the decomposition rate while comparing the differences of microbial communities.

Deciphering temporal growth patterns in maize: integrative modeling of phenotype dynamics and underlying genomic variations.

Quantifying the temporal or longitudinal growth dynamics of crops in diverse environmental conditions is crucial for understanding plant development, requiring further modeling techniques. In this study, we analyzed the growth patterns of two different maize (Zea mays L.) populations using high-throughput phenotyping with a maize population consisting of 515 recombinant inbred lines (RILs) grown in Texas and a hybrid population containing 1090 hybrids grown in Missouri. Two models, Gaussian peak and functional principal component analysis (FPCA), were employed to study the Normalized Green-Red Difference Index (NGRDI) scores. The Gaussian peak model showed strong correlations (c. 0.94 for RILs and c. 0.97 for hybrids) between modeled and non-modeled temporal trajectories. Functional principal component analysis differentiated NGRDI trajectories in RILs under different conditions, capturing substantial variability (75%, 20%, and 5% for RILs; 88% and 12% for hybrids). By comparing these models with conventional BLUP values, common quantitative trait loci (QTLs) were identified, containing candidate genes of brd1, pin11, zcn8 and rap2. The harmony between these loci's additive effects and growing degree days, as well as the differentiation of RIL haplotypes across growth stages, underscores the significant interplay of these loci in driving plant development. These findings contribute to advancing understanding of plant-environment interactions and have implications for crop improvement strategies.

Unraveling the effect of combined heat and high-pressure homogenization treatment on the improvement of chickpea protein solubility from the perspectives of colloidal state change and structural characteristic modification.

Chickpea protein (CP) is a promising plant protein ingredient, but the poor solubility has limited its broad application. In this study, heating followed by high-pressure homogenization (HPH) was used to improve the solubility of CP. The results showed that combined heat (80℃, 30 min) and HPH (80 MPa, 2 cycles) treatment exhibited an additive effect in improving the solubility of CP. This improvement could be attributed to the dissociation and the rearrangement of large insoluble protein aggregates into small-sized soluble protein aggregates, the increased exposure of hydrophobic residues and reactive sulfhydryl groups, the transformation of α-helices to ß-sheets and ß-turns. Moreover, the 11S subunits of CP could form reinforced disulfide covalent cross-links under heating + HPH, which may provide steric hindrance preventing the reassembly of large protein bodies. This work proposes an interesting approach to enhance the physicochemical properties of CP for tailoring techno-functional plant protein ingredients in food formulations.

Synergistic effects of arbuscular mycorrhizal fungi and biochar are highly beneficial to Ligustrum lucidum seedlings in Cd-contaminated soil.

Cadmium (Cd) contamination is a widespread environmental issue. There is a lack of knowledge about the impacts of applying arbuscular mycorrhizal fungi (AMF) and biochar, either alone or in their combination, on alleviating Cd phytotoxicity in Ligustrum lucidum. Therefore, a pot experiment was conducted in a greenhouse, where L. lucidum seedlings were randomly subjected to four regimes of AMF treatments (inoculation with sterilized AMF, with Rhizophagus irregularis, Diversispora versiformis, alone or a mixture of these two fungi), and two regimes of biochar treatments (with or without rice-husk biochar), as well as three regimes of Cd treatments (0, 15, and 150 mg kg-1), to examine the responses of growth, photosynthetic capabilities, soil enzymatic activities, nutritional concentrations, and Cd absorption of L. lucidum plants to the interactive effects of AMF, biochar, and Cd. The results demonstrated that under Cd contaminations, AMF alone significantly increased plant total dry weight, soil pH, and plant nitrogen (N) concentration by 84%, 3.2%, and 13.2%, respectively, and inhibited soil Cd transferring to plant shoot by 42.2%; biochar alone significantly enhanced net photosynthetic rate, soil pH, and soil catalase of non-mycorrhizal plants by 16.4%, 9%, and 11.9%, respectively, and reduced the soil Cd transferring to plant shoot by 44.7%; the additive effect between AMF and biochar greatly enhanced plant total dry weight by 101.9%, and reduced the soil Cd transferring to plant shoot by 51.6%. Furthermore, dual inoculation with D. versiformis and R. irregularis conferred more benefits on plants than the single fungal species did. Accordingly, amending Cd-contaminated soil with the combination of mixed-fungi inoculation and biochar application performed the best than either AMF or biochar alone. These responses may have been attributed to higher mycorrhizal colonization, soil pH, biomass accumulation, and biomass allocation to the roots, as well as photosynthetic capabilities. In conclusion, the combined use of mixed-fungi involving D. versiformis and R. irregularis and biochar addition had significant synergistic effects on enhancing plant performance and reducing Cd uptake of L. lucidum plants in Cd-contaminated soil.

Non-additive effects on biodegradation of moso bamboo litter- and broadleaf tree litter-leached dissolved organic matter mixtures in a subtropical forest of southern China.

Phyllostachys pubescens (moso bamboo) has extensively expanded to subtropical broadleaf forests. However, how moso bamboo expansion influences litter-leached dissolved organic matter (DOM) biodegradation is unclear. In this study, we collected fresh leaf litter of moso bamboo and 10 broadleaf tree species from a subtropical forest in southern China and extracted litter-leached dissolved organic carbon (DOC), dissolved total nitrogen (DTN), and dissolved total phosphorus (DTP). Then, using a 42-day incubation experiment, we measured litter-leached DOM biodegradation of the selected 11 species and assessed the relative mixing effects on biodegradation of bamboo litter- and broadleaf tree litter-leached DOM mixtures with volume mixing ratios of 1:3, 1:1, and 3:1. In the litter leachates, bamboo had lower DOC:DTN ratio, DOC:DTP ratio, and DOM aromaticity (i.e., lower SUVA254 and SUVA350 values) than most broadleaf tree species. Litter-leached DOM biodegradation did not differ among bamboo, Liquidambar formosana, Vernicia fordii, and Cyclobalanopsis glauca, but was greater for bamboo than for the other seven broadleaf tree species. Leaf litter-leached DOM biodegradation correlated negatively with DOC:DTN and DOC:DTP ratios, but exhibited no significant relationship with DOM aromaticity. Regardless of volume mixing ratios, antagonistic effects were observed when bamboo litter-leached DOM was mixed with broadleaf tree litter-leached DOM with comparable biodegradation, whereas synergistic effects occurred when bamboo litter-leached DOM was mixed with broadleaf tree litter-leached DOM with lower biodegradation. The relative mixing effects on DOM biodegradation increased linearly with elevated interspecific difference in litter-leached DOM biodegradation between bamboo and broadleaf tree species across the incubation periods. These findings indicate that moso bamboo expansion will substantially alter litter-leached DOM biodegradation by improving substrate quality and changing species interactions, and the magnitudes of such changing trends are dependent on the native tree litter-leached DOM biodegradation in subtropical broadleaf forests.

Physical activity diminished adverse associations of obesity with lipid metabolism in the population of rural regions of China.

The interactive effects of obesity and physical inactivity on lipid metabolism and prevalent dyslipidemia are scarcely reported in rural regions. 39029 subjects were obtained from the Henan Rural Cohort, and their metabolic equivalents (METs) of physical activity (PA) were computed. Independent associations of the obesity indices and PA with either lipid indices or prevalent dyslipidemia were analyzed by generalized linear models, and additive effects of obesity and PA on prevalent dyslipidemia were further quantified. Each obesity index was positively associated with total cholesterol, triglyceride, low-density lipoprotein or prevalent dyslipidemia but negatively associated with high-density lipoprotein, whereas the opposite association of PA with either each lipid index or prevalent dyslipidemia was observed. Joint association of PA and each obesity index with each lipid index and prevalent dyslipidemia was observed. Furthermore, the association of each obesity index in association with each lipid index was attenuated by increased PA levels.

Development of Single-Segment Substitution Lines and Fine-Mapping of qSPP4 for Spikelets Per Panicle and qGW9 for Grain Width Based on Rice Dual-Segment Substitution Line Z783.

Single segment substitution line (SSSL) libraries are an ideal platform for breeding by design. To develop SSSLs-Xihui18 covering the whole genome, a novel rice chromosome segment substitution line (CSSL), Z783, carrying two substitution segments (average length of 6.55 Mb) on Chr.4 and Chr.9 was identified, which was a gap in the library previously. Z783 was developed from the progeny of recipient "Xihui18" (an indica restorer line) and donor "Huhan3" (a japonica cultivar) by advanced backcross combined molecular marker-assisted selection (MAS). It displayed multiple panicles and less spikelets and wide grains. Then, a F2 population derived from Xihui18/Z783 was used to map quantitative trait loci (QTLs) for yield-related traits by the mixed linear model method. Nine QTLs were detected (p < 0.05). Furthermore, three SSSLs were constructed by MAS, and all 9 QTLs could be validated, and 15 novel QTLs could be detected by these SSSLs by a one-way ANOVA analysis. The genetic analysis showed that qSSP4 for less spikelets and qGW9 for wide grain all displayed dominant gene action in their SSSLs. Finally, qSSP4 and qGW9 were fine-mapped to intervals of 2.75 Mb and 1.84 Mb, on Chromosomes 4 and 9, respectively. The results lay a solid foundation for their map cloning and molecular breeding by design.

Mycobacteriophage D29 Lysin B exhibits promising anti-mycobacterial activity against drug-resistant Mycobacterium tuberculosis.

IMPORTANCE: To combat the rapidly emerging drug-resistant M. tuberculosis, it is now essential to look for alternative therapeutics. Mycobacteriophages can be considered as efficient therapeutics due to their natural ability to infect and kill mycobacteria including M. tuberculosis. Here, we have exploited the mycolyl-arabinogalactan esterase property of LysB encoded from mycobacteriophage D29. This study is novel in terms of targeting a multi-drug-resistant pathogenic strain of M. tuberculosis with LysB and also examining the combination of anti-TB drugs and LysB. All the experiments include external administration of LysB. Therefore, the remarkable lytic activity of LysB overcomes the difficulty to enter the complex cell envelope of mycobacteria. Targeting the intracellularly located M. tuberculosis by LysB and non-toxicity to macrophages take the process of the development of LysB as a drug one step ahead, and also, the interaction studies with rifampicin and isoniazid will help to form a new treatment regimen against tuberculosis.

Anti-leishmanial, immunomodulatory and additive potential effect of Piperine on Leishmania major: The in silico and in vitro study of Piperine and its combination.

BACKGROUND: Piperine (Pn), an indole alkaloid compound found in pepper, is an effective compound with anti-leishmanial medications that administered alone or in combination. This study aimed to use Pn for possible biochemical targets and to assess mechanisms of anti-leishmanial action and immunomodulatory roles. METHODS: The ability of Pn to bind to interleukin-12P40 (IL-12P40) and interferon-γ (IFN-γ) was investigated using molecular docking. The leishmanicidal effect of Pn, meglumine antimoniate (Glucantime®; MA), and Pn plus MA was assessed on Leishmania major promastigotes and amastigotes. A real-time PCR was applied to quantify cytokines gene expression in drug-treated murine macrophages. RESULTS: The molecular docking findings indicated that Pn could bind to IL-12P40/IFN-γ. In silico analyses showed an affinity of Pn to IL-12P40/IFN-γ, with the MolDock score of -236.91 and -64.87 kcal/mol, respectively. Pn plus MA reduced the proliferation rate of promastigote and amastigote forms of L. major compared to each drug alone (IC50 = 43.22 and 19.41 µg/mL, respectively). Moreover, the combination drug demonstrated no cytotoxicity as the selectivity index (SI) was 14.81. Also, Th1-related cytokines were upregulated, while Th2-related cytokines were downregulated in Pn combination-treated murine macrophages. CONCLUSIONS: The superior effectiveness of combination therapy on L. major warrants further investigations on the clinical potential of this combination in the treatment of leishmaniasis.

Genetic analysis of heat tolerance in hot pepper: insights from comprehensive phenotyping and QTL mapping.

High temperatures present a formidable challenge to the cultivation of hot pepper, profoundly impacting not only vegetative growth but also leading to flower and fruit abscission, thereby causing a significant reduction in yield. To unravel the intricate genetic mechanisms governing heat tolerance in hot pepper, an F2 population was developed through the crossing of two distinct genotypes exhibiting contrasting heat tolerance characteristics: DLS-161-1 (heat tolerant) and DChBL-240 (heat susceptible). The F2 population, along with the parental lines, was subjected to comprehensive phenotyping encompassing diverse morphological, physiological, and biochemical heat-related traits under high temperature conditions (with maximum temperature ranging from 31 to 46.5°C and minimum temperature from 15.4 to 30.5°C). Leveraging the Illumina Nova Seq-6000 platform, Double digest restriction-site associated DNA sequencing (ddRAD-seq) was employed to generate 67.215 Gb data, with subsequent alignment of 218.93 million processed reads against the reference genome of Capsicum annuum. Subsequent variant calling and ordering resulted in 5806 polymorphic SNP markers grouped into 12 LGs. Further QTL analysis identified 64 QTLs with LOD values ranging from 2.517 to 11.170 and explained phenotypic variance ranging from 4.05 to 19.39%. Among them, 21 QTLs, explaining more than 10% phenotypic variance, were identified as major QTLs controlling 9 morphological, 3 physiological, and 2 biochemical traits. Interestingly, several QTLs governing distinct parameters were found to be colocalized, suggesting either a profound correlation between the QTLs regulating these traits or their significant genomic proximity. In addition to the QTLs, we also identified 368380 SSR loci within the identified QTL regions, dinucleotides being the most abundant type (211,381). These findings provide valuable insights into the genetics of heat tolerance in hot peppers. The identified QTLs and SSR markers offer opportunities to develop heat-tolerant varieties, ensuring better crop performance under high-temperature conditions.

Effects of Mixed Baculovirus Infections in Biological Control: A Comprehensive Historical and Technical Analysis.

Baculoviruses are insect-specific DNA viruses that have been exploited as bioinsecticides for the control of agricultural and forest pests around the world. Mixed infections with two different baculoviruses have been found in nature, infecting the same host. They have been studied to understand the biology of virus interactions, their effects on susceptible insects, and their insecticidal implications. In this work, we summarize and analyze the in vivo baculovirus co-infections reported in the literature, mainly focusing on pest biocontrol applications. We discuss the most common terms used to describe the effects of mixed infections, such as synergism, neutralism, and antagonism, and how to determine them based on host mortality. Frequently, baculovirus co-infections found in nature are caused by a combination of a nucleopolyhedrovirus and a granulovirus. Studies performed with mixed infections indicated that viral dose, larval stage, or the presence of synergistic factors in baculovirus occlusion bodies are important for the type of virus interaction. We also enumerate and discuss technical aspects to take into account in studies on mixed infections, such as statistical procedures, quantification of viral inocula, the selection of instars, and molecular methodologies for an appropriate analysis of baculovirus interaction. Several experimental infections using two different baculoviruses demonstrated increased viral mortality or a synergistic effect on the target larvae compared to single infections. This can be exploited to improve the baculovirus-killing properties of commercial formulations. In this work, we offer a current overview of baculovirus interactions in vivo and discuss their potential applications in pest control strategies.

Anti-androgenic activity of novel flame retardants in mixtures: Newly identified contribution from tris(2,3-dibromopropyl) isocyanurate (TDBP-TAZTO).

In recent decades, male infertility has been on the rise, largely attributed to exposure to chemicals with endocrine-disrupting properties. The adverse effects of disrupting androgen actions on the development and reproductive health of children and adolescents have been extensively studied. Flame retardants (FRs), used in consumer products to delay flammability, have been identified as antagonists of the androgen receptor (AR), potentially leading to adverse outcomes in male reproductive health later in life. This study examined the interaction of eight novel FRs with the AR, employing an in vitro AR-dependent luciferase reporter gene assay utilizing MDA-kb2 cells. The investigation revealed the anti-androgenic activity of tris(2,3-dibromopropyl) isocyanurate (TDBP-TAZTO), a frequently detected FR in the environment. Furthermore, TDBP-TAZTO contributed to anti-androgenic activity when combined with six other anti-androgenic FRs. The mixture effects were predicted by three commonly employed models: concentration addition (CA), generalized CA, and independent action, with the CA model showcasing the highest accuracy. This suggests that all FRs act through a similar mechanism, as further confirmed by in silico molecular docking, indicating limited synergy or antagonism. Importantly, in the mixtures, each FR contributed to the induction of anti-androgenic effects at concentrations below their individual effective concentrations in single exposures. This raises concern for public health, especially considering the co-detection of these FRs and their potential co-occurrence with other anti-androgenic chemicals like bisphenols. Therefore, our findings, along with previous research, strongly support the incorporation of combined effects of mixtures in risk assessment to efficiently safeguard population health.

Positively Charged Semiconductor Conjugated Polymer Nanomaterials with Photothermal Activity for Antibacterial and Antibiofilm Activities In Vitro and In Vivo.

Biofilm infections are associated with most human bacterial infections and are prone to bacterial multidrug resistance. There is an urgent need to develop an alternative approach to antibacterial and antibiofilm agents. Herein, two positively charged semiconductor conjugated polymer nanoparticles (SPPD and SPND) were prepared for additive antibacterial and antibiofilm activities with the aid of positive charge and photothermal therapy (PTT). The positive charge of SPPD and SPND was helpful in adhering to the surface of bacteria. With an 808 nm laser irradiation, the photothermal activity of SPPD and SPND could be effectively transferred to bacteria and biofilms. Under the additive effect of positive charge and PTT, the inhibition rate of Staphylococcus aureus (S. aureus) treated with SPPD and SPND (40 µg/mL) could reach more than 99.2%, and the antibacterial activities of SPPD and SPND against S. aureus biofilms were 93.5 and 95.8%. SPPD presented better biocompatibility than SPND and exhibited good antibiofilm properties in biofilm-infected mice. Overall, this additive treatment strategy of positive charge and PTT provided an optional approach to combat biofilms.

Similar additive effects of doxorubicin in combination with photon or proton irradiation in soft tissue sarcoma models.

High-precision radiotherapy with proton beams is frequently used in the management of aggressive soft tissue sarcoma (STS) and is often combined with doxorubicin (Dox), the first-line chemotherapy for STS. However, current treatment approaches continue to result in high local recurrence rates often occurring within the treatment field. This strongly indicates the need of optimized treatment protocols taking the vast heterogeneity of STS into account, thereby fostering personalized treatment approaches. Here, we used preclinical STS models to investigate the radiation response following photon (X) or proton (H) irradiation alone and in combination with different treatment schedules of Dox. As preclinical models, fibrosarcoma (HT-1080), undifferentiated pleiomorphic sarcoma (GCT), and embryonal rhabdomyosarcoma (RD) cell lines were used; the latter two are mutated for TP53. The cellular response regarding clonogenic survival, apoptosis, cell-cycle distribution, proliferation, viability, morphology, and motility was investigated. The different STS cell types revealed a dose-dependent radiation response with reduced survival, proliferation, viability, and motility whereas G2/M phase arrest as well as apoptosis were induced. RD cells showed the most radiosensitive phenotype; the linear quadratic model fit could not be applied. In combined treatment schedules, Dox showed the highest efficiency when applied after or before and after radiation; Dox treatment only before radiation was less efficient. GCT cells were the most chemoresistant cell line in this study most probably due to their TP53 mutation status. Interestingly, similar additive effects could be observed for X or H irradiation in combination with Dox treatment. However, the additive effects were determined more frequently for X than for H irradiation. Thus, further investigations are needed to specify alternative drug therapies that display superior efficacy when combined with H therapy.