Development of an SNP marker set for marker-assisted backcrossing using genotyping-by-sequencing in tetraploid perilla.

High-quality molecular markers are essential for marker-assisted selection to accelerate breeding progress. Compared with diploid species, recently diverged polyploid crop species tend to have highly similar homeologous subgenomes, which is expected to limit the development of broadly applicable locus-specific single-nucleotide polymorphism (SNP) assays. Furthermore, it is particularly challenging to make genome-wide marker sets for species that lack a reference genome. Here, we report the development of a genome-wide set of kompetitive allele specific PCR (KASP) markers for marker-assisted recurrent selection (MARS) in the tetraploid minor crop perilla. To find locus-specific SNP markers across the perilla genome, we used genotyping-by-sequencing (GBS) to construct linkage maps of two F2 populations. The two resulting high-resolution linkage maps comprised 2326 and 2454 SNP markers that spanned a total genetic distance of 2133 cM across 16 linkage groups and 2169 cM across 21 linkage groups, respectively. We then obtained a final genetic map consisting of 22 linkage groups with 1123 common markers from the two genetic maps. We selected 96 genome-wide markers for MARS and confirmed the accuracy of markers in the two F2 populations using a high-throughput Fluidigm system. We confirmed that 91.8% of the SNP genotyping results from the Fluidigm assay were the same as the results obtained through GBS. These results provide a foundation for marker-assisted backcrossing and the development of new varieties of perilla.

Temperature and Host Plant Impacts on the Development of Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae): Linear and Nonlinear Modeling.

The tobacco cutworm, Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae), is one of the most serious pests in field crops, vegetables, and ornamentals. Temperatures (15, 20, 25, 27, 30, 35, and 40 °C), host plants (soybean (Glycine max (L.)), maize (Zea mays L.), groundnut (Arachis hypogaea L.) and azuki bean (Vigna angularis (Willd.) Ohwi & H. Ohashi,), and the artificial diet-dependent developmental parameters and survival of S. litura were examined in this study. Stage-specific parameters such as threshold development temperature (LDT) and thermal constant (K) (Degree day (DD)) were determined by linear and nonlinear models (Sharpe-Schoolfield-Ikemoto), respectively. The total developmental time (egg-adult) decreased with increasing temperature on host plants and with an artificial diet. The total immature developmental time varied from 106.29, 107.57, 130.40, 111.82, and 103.66 days at 15 °C to 22.47, 21.25, 25.31, 18.30, and 22.50 days at 35 °C on soybean, maize, groundnut, azuki bean, and artificial diet, respectively. The LDT for the total immature completion was 7.50, 9.48, 11.44, 12.32, and 7.95 °C on soybean, maize, groundnut, azuki bean, and artificial diet, respectively. The K for the total immature completion was 587.88, 536.84, 517.45, 419.44, and 586.95 DD on soybean, maize, groundnut, azuki bean, and artificial diet, respectively. Temperature and host plant interaction also influenced the longevity and survival of adults. The findings of this study can be used to predict the number of generations, spring emergence, and population dynamics of S. litura. The nutrient content analysis of the host plants is discussed in terms of the developmental patterns of S. litura.

Lignan-Rich Sesame (Sesamum indicum L.) Cultivar Exhibits In Vitro Anti-Cholinesterase Activity, Anti-Neurotoxicity in Amyloid-ß Induced SH-SY5Y Cells, and Produces an In Vivo Nootropic Effect in Scopolamine-Induced Memory Impaired Mice.

Alzheimer's disease, a major cause of dementia, is characterized by impaired cholinergic function, increased oxidative stress, and amyloid cascade induction. Sesame lignans have attracted considerable attention owing to their beneficial effects on brain health. This study investigated the neuroprotective potential of lignan-rich sesame cultivars. Among the 10 sesame varieties studied, Milyang 74 (M74) extracts exhibited the highest total lignan content (17.71 mg/g) and in vitro acetylcholinesterase (AChE) inhibitory activity (66.17%, 0.4 mg/mL). M74 extracts were the most effective in improving cell viability and inhibiting reactive oxygen species (ROS) and malondialdehyde (MDA) generation in amyloid-ß25-35 fragment-treated SH-SY5Y cells. Thus, M74 was used to evaluate the nootropic effects of sesame extracts and oil on scopolamine (2 mg/kg)-induced memory impairment in mice compared to the control cultivar (Goenback). Pretreatment with the M74 extract (250 and 500 mg/kg) and oil (1 and 2 mL/kg) effectively improved memory disorder in mice (demonstrated by the passive avoidance test), inhibited AChE, and enhanced acetylcholine (Ach) levels. Moreover, immunohistochemistry and Western blot results showed that the M74 extract and oil reversed the scopolamine-induced increase in APP, BACE-1, and presenilin expression levels in the amyloid cascade and decreased BDNF and NGF expression levels in neuronal regeneration.

Experience Using Adjuvant Bacteriophage Therapy for the Treatment of 10 Recalcitrant Periprosthetic Joint Infections: A Case Series.

Periprosthetic joint infections are a devastating complication of joint replacement surgery. One novel therapeutic that has potential to change the current treatment paradigm is bacteriophage therapy. Herein, we discuss our experiences with bacteriophage therapy for 10 recalcitrant periprosthetic joint infections and review the treatment protocols utilized to achieve successful outcomes.

Salphage: Salvage Bacteriophage Therapy for Recalcitrant MRSA Prosthetic Joint Infection.

Prosthetic joint infections are a devastating complication of joint replacement surgery. Consequently, novel therapeutics are needed to thwart the significant morbidity and enormous financial ramifications that are associated with conventional treatments. One such promising adjuvant therapeutic is bacteriophage therapy given its antibiofilm activity and its ability to self-replicate. Herein we discuss the case of a 70-year-old female who had a recalcitrant MRSA prosthetic knee and femoral lateral plate infection who was successfully treated with adjuvant bacteriophage therapy. Moreover, this case discusses the importance of propagating bacteriophage therapeutics on bacteria that are devoid of toxins and the need to ensure bacteriophage activity to all bacterial morphologies. Overall, this case reinforces the potential benefit of using personalized bacteriophage therapy for recalcitrant prosthetic joint infections, but more translational research is needed to thereby devise effective, reproducible clinical trials.

Effects of a single bolus of hydroxocobalamin on hemodynamics in vasodilatory shock.

PURPOSE: Hydroxocobalamin has been observed to cause transient hypertension in healthy subjects, but rigorous studies examining its efficacy are lacking. MATERIALS AND METHODS: Adults in shock who received hydroxocobalamin from 2017 to 2021 were analyzed retrospectively. Hourly hemodynamics from 24 h before and after treatment were collected, and the difference and hourly change of mean arterial pressure (MAP), systolic blood pressure (SBP), diastolic blood pressure (DBP), and norepinephrine-equivalent dose (NED) were examined in mixed-effects models. RESULTS: This study included 3992 hemodynamic data points from 35 patients and is the largest case series to date. In the mixed effects model, there was no difference in MAP 24-h after hydroxocobalamin administration (estimated fixed effect [EFE] -0.2 mmHg, p = 0.89). A two-piecewise mixed model found that the hourly change in MAP was not different from zero in either the pre-administration (EFE 0.0 mmHg/h, p = 0.80) or post-administration segments (EFE 0.0 mmHg/h, p = 0.55). Analysis of the SBP, DBP, and NED also found similar insignificant results. CONCLUSIONS: Although hydroxocobalamin has been observed to cause hypertension in healthy subjects, our results suggest that in patients with shock, hydroxocobalamin may not be effective in improving hemodynamics at 24 h after administration.

Alliance A011801 (compassHER2 RD): postneoadjuvant T-DM1 + tucatinib/placebo in patients with residual HER2-positive invasive breast cancer.

This report describes the rationale, purpose and design of A011801 (CompassHER2 RD), an ongoing prospective, multicenter, Phase III randomized trial. Eligible patients in the United States (US) and Canada with high-risk (defined as ER-negative and/or node-positive) HER2-positive (HER2+) residual disease (RD) after a predefined course of neoadjuvant chemotherapy and HER2-directed treatment are randomized 1:1 to adjuvant T-DM1 and placebo, versus T-DM1 and tucatinib. Patients have also received adjuvant radiotherapy and/or endocrine therapy, if indicated per standard of care guidelines. The primary objective of the trial is to determine if the invasive disease-free survival (iDFS) with T-DM1 plus tucatinib is superior to iDFS with T-DM1 plus placebo; other outcomes of interest include overall survival (OS), breast cancer-free survival (BCFS), distant recurrence-free survival (DRFS), brain metastases-free survival (BMFS) and disease-free survival (DFS). Correlative biomarker, quality of life (QoL) and pharmacokinetic (PK) end points are also evaluated.

Lay abstract In this research study (A011801; CompassHER2 RD), patients with early stage HER2-positive breast cancer who already received treatment with chemotherapy and anti-HER2 targeted therapies followed by surgery are mainly enrolled. If cancer is still present in the breast and/or lymph nodes at the time of surgery, there is a higher risk of a recurrence in the future, and enrollment on A011801 is an option. Usually, if there is tumor remaining after chemotherapy and anti-HER2 targeted therapies, the main treatment is the use of an FDA-approved intravenous drug called T-DM1. Additional treatment may also include radiotherapy and/or medications to block the activity of estrogen. The usual treatment approach reduces the likelihood of breast cancer recurring in the future. This study has been performed to answer the following question: Is the combination of T-DM1 and a newer drug tucatinib better than usual treatment with T-DM1 alone at preventing cancer from returning? Study participants will receive treatment with T-DM1 and placebo (a pill that looks like the study drug but contains no medication) or T-DM1 and tucatinib, for up to 14 cycles, unless their breast cancer returns or the side effects become too severe. Research bloods are taken on study along with standard blood work, and we also request a stored tumor sample from the original biopsy and from the breast cancer surgery for research purposes. Optional Quality of Life Questionnaires are also included in the trial. After the study, participants finish T-DM1 and placebo, or T-DM1 and tucatinib, and their doctor will continue to follow their condition with clinic visits every 6 months for 10 years and watch for side effects and for signs of breast cancer recurring. Clinical Trial Registration: NCT04457596 (ClinicalTrials.gov).

Identification of anthocyanin compositions in black seed coated Korean adzuki bean (Vigna angularis) by NMR and UPLC-Q-Orbitrap-MS/MS and screening for their antioxidant properties using different solvent systems.

The aim of the present research was to investigate the antioxidant properties and anthocyanin profiles in the black seed coated adzuki bean (Vigna angularis, Geomguseul cultivar). The acidic 60% methanol extract (40 µg/mL) contains the highest total phenolic and flavonoid contents (486 ± 3 mg GAE/100 g; 314 ± 10 mg CE/100 g) with potent antioxidant properties (trolox equivalent 1272 ± 26 and 662 ± 24 mg TE/100 g) against ABTS and DPPH radicals compared to other methanol-water ratios (20, 40, 80, and 100%). Ten anthocyanin components were identified in this extract including delphinidin-3,5-O-digalactoside (1), delphinidin-3,5-O-diglucoside (2), delphinidin-3-O-galactoside (3), delphinidin-3-O-glucoside (4), delphinidin-3-O-rutinoside (5), delphinidin-3-O-(p-coumaroyl)glucoside (6), cyanidin-3-O-glucoside (7), petunidin-3-O-galactoside (8), petunidin-3-O-glucoside (9) and petunidin-3-O-(p-coumaroyl)glucoside (10) via NMR spectroscopy and UPLC-Q-Orbitrap-MS/MS analysis. The key anthocyanins 3 and 4 of delphinidin type were isolated by reversed phase C-18 MPLC. Our results indicate that the anthocyanin profiles as well as the high phenolic and flavonoid contents are important factors determining the antioxidant effects of black adzuki bean.

Selection of Lactococcus lactis HY7803 for Glutamic Acid Production Based on Comparative Genomic Analysis.

Comparative genomic analysis was performed on eight species of lactic acid bacteria (LAB)-Lactococcus (L.) lactis, Lactobacillus (Lb.) plantarum, Lb. casei, Lb. brevis, Leuconostoc (Leu.) mesenteroides, Lb. fermentum, Lb. buchneri, and Lb. curvatus-to assess their glutamic acid production pathways. Glutamic acid is important for umami taste in foods. The only genes for glutamic acid production identified in the eight LAB were for conversion from glutamine in L. lactis and Leu. mesenteroides, and from glucose via citrate in L. lactis. Thus, L. lactis was considered to be potentially the best of the species for glutamic acid production. By biochemical analyses, L. lactis HY7803 was selected for glutamic acid production from among 17 L. lactis strains. Strain HY7803 produced 83.16 pmol/µl glutamic acid from glucose, and exogenous supplementation of citrate increased this to 108.42 pmol/µl. Including glutamic acid, strain HY7803 produced more of 10 free amino acids than L. lactis reference strains IL1403 and ATCC 7962 in the presence of exogenous citrate. The differences in the amino acid profiles of the strains were illuminated by principal component analysis. Our results indicate that L. lactis HY7803 may be a good starter strain for glutamic acid production.

Relieving acute pain (RAP) study: a proof-of-concept protocol for a randomised, double-blind, placebo-controlled trial.

INTRODUCTION: Physicians and other prescribing clinicians use opioids as the primary method of pain management after traumatic injury, despite growing recognition of the major risks associated with usage for chronic pain. Placebos given after repeated administration of active treatments can acquire medication-like effects based on learning mechanisms. This study hypothesises that dose-extending placebos can be an effective treatment in relieving clinical acute pain in trauma patients who take opioids. METHODS AND ANALYSIS: The relieving acute pain is a proof-of-concept randomised, placebo-controlled, double-blinded, single-site study enrolling 159 participants aged from 18 to 65 years with one or more traumatic injuries treated with opioids. Participants will be randomly assigned to three different arms. Arm 1 will receive the full dose of opioids with non-steroidal anti-inflammatory drugs (NSAIDs). Arm 2 will receive the 50% overall reduction in opioid dosage, dose-extending placebos and NSAIDs. Arm 3 (control) will receive NSAIDs and placebos. The trial length will be 3 days of hospitalisation (phase I) and 2-week, 1-month, 3-month and 6-month follow-ups (exploratory phase II). Primary and secondary outcomes include feasibility and acceptability of the study. Pain intensity, functional pain, emotional distress, rates of rescue therapy requests and patient-initiated medication denials will be collected. ETHICS AND DISSEMINATION: All activities associated with this protocol are conducted in full compliance with the Institutional Review Board policies and federal regulations. Publishing this study protocol will enable researchers and funding bodies to stay up to date in their fields by providing exposure to research activity that may not otherwise be widely publicised. DATE AND PROTOCOL VERSION IDENTIFIER: 3/6/2019 (HP-00078742). TRIAL REGISTRATION NUMBER: NCT03426137.

Identification of quantitative trait loci associated with flowering time in perilla using genotyping-by-sequencing.

Understanding the transition to the reproductive period is important for crop breeding. This information can facilitate the production of novel varieties that are better adapted to local environments or changing climatic conditions. Here, we report the development of a high-density linkage map based on genotyping-by-sequencing (GBS) for the genus perilla. Through GBS library construction and Illumina sequencing of an F2 population, a total of 9607 single-nucleotide polymorphism (SNP) markers were developed. The ten-group linkage map of 1309.39 cM contained 2518 markers, with an average marker density of 0.56 cM per linkage group (LG). Using this map, a total of six QTLs were identified. These quantitative trait loci (QTLs) are associated with three traits related to flowering time: days to visible flower bud, days to flowering, and days to maturity. Ortholog analysis conducted with known genes involved in the regulation of flowering time among different crop species identified GI, CO and ELF4 as putative perilla orthologs that are closely linked to the QTL regions associated with flowering time. These results provide a foundation that will be useful for future studies of flowering time in perilla using fine mapping, and marker-assisted selection for the development of new varieties of perilla.

Asparaginase Erwinia chrysanthemi effectively depletes plasma glutamine in adult patients with relapsed/refractory acute myeloid leukemia.

Depletion of glutamine (Gln) has emerged as a potential therapeutic approach in the treatment of acute myeloid leukemia (AML), as neoplastic cells require Gln for synthesis of cellular components essential for survival. Asparaginases deplete Gln, and asparaginase derived from Erwinia chrysanthemi (Erwinaze) appears to have the greatest glutaminase activity of the available asparaginases. In this Phase I study, we sought to determine the dose of Erwinaze that safely and effectively depletes plasma Gln levels to ≤ 120 µmol/L in patients with relapsed or refractory (R/R) AML. Five patients were enrolled before the study was halted due to issues with Erwinaze manufacturing supply. All patients received Erwinaze at a dose of 25,000 IU/m2 intravenously three times weekly for 2 weeks. Median trough plasma Gln level at 48 h after initial Erwinaze administration was 27.6 µmol/L, and 80% (lower limit of 1-sided 95% CI 34%) of patients achieved at least one undetectable plasma Gln value (< 12.5 µmol/L), with the fold reduction (FR) in Gln level at 3 days, relative to baseline, being 0.16 (p < 0.001 for rejecting FR = 1). No dose-limiting toxicities were identified. Two patients responded, one achieved partial remission and one achieved hematologic improvement after six doses of Erwinaze monotherapy. These data suggest asparaginase-induced Gln depletion may have an important role in the management of patients with AML, and support more pharmacologic and clinical studies on the mechanistically designed asparaginase combinations in AML.

Changes occurring in nutritional components (phytochemicals and free amino acid) of raw and sprouted seeds of white and black sesame (Sesamum indicum L.) and screening of their antioxidant activities.

The present study is the first to investigate the germination properties regarding phytochemicals, amino acids, total phenolics, and antioxidant capacities of white and black sesame seeds. Nutritional components and antioxidant effects showed considerable differences. Sesamine and sesamolin composition decreased (white: 4.21→1.72, 3.57→1.57 mg/g; black: 2.43→0.58, 1.36→0.45 mg/g) during germination. Moreover, catechin displayed the predominant composition in sprouted seeds with values of 13.50 mg/g (white) and 19.09 (black) mg/g followed by (-)-epicatechin and sinapic acid. Total phenolics increased by approximately 4 times upon germination, i.e., 503.1±27.1→ 2085.0±56.7 (white) and 645.8±31.5→2480.1±49.5 (black), mg GAE/g. Amino acids also remarkably increased in sprouted white (7.04→31.69mg/g) and black (6.55→26.97mg/g) seeds, with individual composition occurring in the following order: asparagine>arginine>tryptophan>leucine>alanine. In particular, arginine and tryptophan exhibited the greatest variations. The antioxidant effects against DPPH radical were stronger in sprouted seeds depending on the phytochemicals. Therefore, sprouted sesame can be utilized as an excellent source for functional foods.

Connecting charge transfer kinetics to device parameters of a narrow-bandgap polymer-based solar cell.

To achieve intrinsically light-weight flexible photovoltaic devices, a bulk-heterojunction-type active layer with a narrow-bandgap polymer is still considered as one of the most important candidates. Therefore, detailed information about the charge transfer efficiency from a photo-excited species on an electron-donating polymer to an electron acceptor is an important factor, given that it is among the most fundamental quantitative measures to understand the solar power conversion efficiency, in particular at the initial stage followed by primary exciton formation. To obtain accurate information in this regard, wide-range acceptor concentration-dependent transient absorption spectroscopy with femtosecond laser pulse excitation was performed using a representative narrow-bandgap polymer, commonly known as PTB7. The investigated acceptor concentration range covered was from 0.01 wt% up to 10 wt%, in addition to a 0 wt% pristine polymer sample and a sample with a conventional acceptor concentration of 60 wt%, which is important for high efficiency. From the kinetic data, an almost two orders of magnitude faster acceptor-induced charge transfer rate constant in addition to the native primary exciton lifetime of about 100 picoseconds could be extracted. These data were used to verify the suggested kinetic model and compare with device properties that show no meaningful loss during the extraction of photo-generated charge carriers.

Enhanced Absorption Study of Ginsenoside Compound K (20-O-ß-(D-Glucopyranosyl)-20(S)-protopanaxadiol) after Oral Administration of Fermented Red Ginseng Extract (HYFRG™) in Healthy Korean Volunteers and Rats.

To evaluate the pharmacokinetics of compound K after oral administration of HYFRG and RG in humans, an open-label, randomized, single-dose, fasting, and one-period pharmacokinetic study was conducted. After oral administration of a single 3 g dose of HYFRG and RG to 24 healthy Korean males, the mean (±SD) of AUC0-t and C max of compound K from HYFRG were 1466.83 ± 295.89 ng·h/mL and 254.45 ± 51.20 ng/mL, being 115.2- and 80-fold higher than those for RG (12.73 ± 7.83 ng·h/mL and 3.18 ± 1.70 ng/mL), respectively; in case of Sprague Dawley rats the mean (±SD) of AUC0-t and C max of compound K from HYFRG was 58.03 ± 32.53 ng·h/mL and 15.19 ± 10.69 ng/mL, being 6.3- and 6.0-fold higher than those from RG (9.21 ± 7.52 ng·h/mL and 2.55 ± 0.99 ng/mL), respectively. T max of compound K in humans and rats was 2.54 ± 0.92 and 3.33 ± 0.50 h for HYFRG and 9.11 ± 1.45 and 6.75 ± 3.97 hours for RG, respectively. In conclusion, the administration of HYFRG resulted in a higher and faster absorption of compound K in both humans and rats compared to RG.

The Neuro-Protective Effect of the Methanolic Extract of Perilla frutescens var. japonicaand Rosmarinic Acid against H2O2-Induced Oxidative Stress in C6 Glial Cells.

Neurodegenerative diseases are often associated with oxidative damage in neuronal cells. This study was conducted to investigate the neuro-protective effect of methanolic (MeOH) extract of Perilla frutescens var. japonica and its one of the major compounds, rosmarinic acid, under oxidative stress induced by hydrogen peroxide (H2O2) in C6 glial cells. Exposure of C6 glial cells to H2O2 enhanced oxidative damage as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and thiobarbituric acid-reactive substance assays. The MeOH extract and rosmarinic acid prevented oxidative stress by increasing cell viability and inhibiting cellular lipid peroxidation. In addition, the MeOH extract and rosmarinic acid reduced H2O2-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the transcriptional level. Moreover, iNOS and COX-2 protein expression was down-regulated in H2O2-indcued C6 glial cells treated with the MeOH extract and rosmarinic acid. These findings suggest that P. frutescens var. japonica and rosmarinic acid could prevent the progression of neurodegenerative diseases through attenuation of neuronal oxidative stress.

Analysis of yield of eleutherosides B and E in Acanthopanax divaricatus and A. koreanum grown with varying cultivation methods.

An analysis of the yield of eleutherosides B and E in Acanthopanax divaricatus and A. koreanum was performed using high performance liquid chromatography to evaluate production by different cultivation methods. In A. divaricatus and A. koreanum, the total content of eleutherosides B and E was 2.466-7.360 mg/g varying by plant section, 3.886-11.506 mg/g by pinching site, 3.655-10.083 mg/g by planting time, and 3.652-10.108 mg/g by fertilizer ratio. Thus the total content of eleutherosides B and E in A. divaricatus and A. koreanum differed depending on cultivation methods. These results present useful information for high eleutheroside content applications in A. divaricatus and A. koreanum. This information can affect selection of plant section and cultivation methods for nutraceutical, pharmaceutical, and cosmeceutical material development.

Comparison of shoulder and back muscle activation in caregivers according to various handle heights.

[Purpose] This study aims to improve the safety for caregivers and avoid musculoskeletal diseases by examining the shoulder and trunk muscle activity depending on wheelchair handle height as the caregiver provides propulsion to a wheelchair for wheelchair-bound patients. [Subjects] The participants were caregivers who met the criteria for this study (n=30). [Methods] To determine the activity of the shoulder and trunk muscles of caregivers depending on the handle height, the muscle activity was measured as a wheelchair was being pushed under three height conditions. [Results] According to the study results, the deltoid middle fiber, serratus anterior muscle, rhomboid muscle, and erector spinalis of lumbar part showed significantly low muscle activity at a height that produced an elbow joint flexion angle of 30°. Caregivers are highly likely to develop musculoskeletal disease if the handle height is excessively low. In addition, the burden on the shoulder and back muscles can be reduced at heights that lead to flexion of 30°. [Conclusions] As a caregiver pushes a wheelchair, the handle height has a close relationship with the burden on the shoulder and back muscles. If the handle height is excessively low, the caregiver is highly likely to develop musculoskeletal disease.

Photoinduced charge transfer in donor-acceptor (DA) copolymer: fullerene bis-adduct polymer solar cells.

Polymer solar cells (PSCs) consisting of fullerene bis-adduct and poly(3-hexylthiophene) (P3HT) blends have shown higher efficiencies than P3HT:phenyl C(61)-butyric acid methyl ester (PCBM) devices, because of the high-lying lowest unoccupied molecular orbital (LUMO) level of the fullerene bis-adducts. In contrast, the use of fullerene bis-adducts in donor-acceptor (DA) copolymer systems typically causes a decrease in the device's performance due to the decreased short-circuit current (J(SC)) and the fill factor (FF). However, the reason for such poor performance in DA copolymer:fullerene bis-adduct blends is not fully understood. In this work, bulk-heterojunction (BHJ)-type PSCs composed of three different electron donors with four different electron acceptors were chosen and compared. The three electron donors were (1) poly[(4,8-bis-(2-ethylhexyloxy)benzo[1,2-b:4,5-b']dithiophene)-2,6-diyl-alt-(5-octylthieno[3,4-c]pyrrole-4,6-dione)-1,3-diyl] (PBDTTPD), (2) poly[(4,8-bis-(2-ethylhexyloxy)benzo[1,2-b:4,5-b']dithiophene)-2,6-diyl-alt-(4-(2-ethylhexanoyl)-thieno[3,4-b]thiophene)-2,6-diyl] (PBDTTT-C), and (3) P3HT polymers. The four electron acceptors were (1) PCBM, (2) indene-C(60) monoadduct (ICMA), (3) indene-C(60) bis-adduct (ICBA), and (4) indene-C(60) tris-adduct (ICTA). To understand the difference in the performance of BHJ-type PSCs for the three different polymers in terms of the choice of fullerene acceptor, the structural, optical, and electrical properties of the blends were measured by the external quantum efficiency (EQE), photoluminescence, grazing incidence X-ray scattering, and transient absorption spectroscopy. We observed that while the molecular packing and optical properties cannot be the main reasons for the dramatic decrease in the PCE of the DA copolymers and ICBA, the value of the driving force for charge transfer (ΔG(CT)) is a key parameter for determining the change in J(SC) and device efficiency in the DA copolymer- and P3HT-based PSCs in terms of fullerene acceptor. The low EQE and J(SC) in PBDTTPD and PBDTTT-C blended with ICBA and ICTA were attributed to an insufficient ΔG(CT) due to the higher LUMO levels of the fullerene multiadducts. Quantitative information on the efficiency of the charge transfer was obtained by comparing the polaron yield, lifetime, and exciton dissociation probability in the DA copolymer:fullerene acceptor films.