Optimizing Embryo Collection for Application of CRISPR/Cas9 System and Generation of Fukutin Knockout Rat Using This Method.

Rat animal models are widely used owing to their relatively superior cognitive abilities and higher similarity compared with mouse models to human physiological characteristics. However, their use is limited because of difficulties in establishing embryonic stem cells and performing genetic modifications, and insufficient embryological research. In this study, we established optimal superovulation and fertilized-egg transfer conditions, including optimal hormone injection concentration (≥150 IU/kg of PMSG and hCG) and culture medium (mR1ECM), to obtain high-quality zygotes and establish in vitro fertilization conditions for rats. Next, sgRNA with optimal targeting activity was selected by performing PCR analysis and the T7E1 assay, and the CRISPR/Cas9 system was used to construct a rat model for muscular dystrophy by inducing a deficiency in the fukutin gene without any off-target effect detected. The production of fukutin knockout rats was phenotypically confirmed by observing a drop-in body weight to one-third of that of the control group. In summary, we succeeded in constructing the first muscular dystrophy disease rat model using the CRISPR/CAS9 system for increasing future prospects of producing various animal disease models and encouraging disease research using rats.

Conducting Bayesian-Classical Hybrid Power Analysis with R Package Hybridpower.

There are several approaches to incorporating uncertainty in power analysis. We review these approaches and highlight the Bayesian-classical hybrid approach that has been implemented in the R package hybridpower. Calculating Bayesian-classical hybrid power circumvents the problem of local optimality in which calculated power is valid if and only if the specified inputs are perfectly correct. hybridpower can compute classical and Bayesian-classical hybrid power for popular testing procedures including the t-test, correlation, simple linear regression, one-way ANOVA (with equal or unequal variances), and the sign test. Using several examples, we demonstrate features of hybridpower and illustrate how to elicit subjective priors, how to determine sample size from the Bayesian-classical approach, and how this approach is distinct from related methods. hybridpower can conduct power analysis for the classical approach, and more importantly, the novel Bayesian-classical hybrid approach that returns more realistic calculations by taking into account local optimality that the classical approach ignores. For users unfamiliar with R, we provide a limited number of RShiny applications based on hybridpower to promote the accessibility of this novel approach to power analysis. We end with a discussion on future developments in hybridpower.

Which is Better for Individual Participant Data Meta-Analysis of Zero-Inflated Count Outcomes, One-Step or Two-Step Analysis? A Simulation Study.

Meta-analysis using individual participant data (IPD) is an important methodology in intervention research because it (a) increases accuracy and precision of estimates, (b) allows researchers to investigate mediators and moderators of treatment effects, and (c) makes use of extant data. IPD meta-analysis can be conducted either via a one-step approach that uses data from all studies simultaneously, or a two-step approach, which aggregates data for each study and then combines them in a traditional meta-analysis model. Unfortunately, there are no evidence-based guidelines for how best to approach IPD meta-analysis for count outcomes with many zeroes, such as alcohol use. We used simulation to compare the performance of four hurdle models (3 one-step and 1 two-step models) for zero-inflated count IPD, under realistic data conditions. Overall, all models yielded adequate coverage and bias for the treatment effect in the count portion of the model, across all data conditions. However, in the zero portion, the treatment effect was underestimated in most models and data conditions, especially when there were fewer studies. The performance of both one- and two-step approaches depended on the formulation of the treatment effects, suggesting a need to carefully consider model assumptions and specifications when using IPD.

Prunetinoside Inhibits Lipopolysaccharide-Provoked Inflammatory Response via Suppressing NF-κB and Activating the JNK-Mediated Signaling Pathway in RAW264.7 Macrophage Cells.

Inflammation is a multifaceted response of the immune system at the site of injury or infection caused by pathogens or stress via immune cells. Due to the adverse effects of chemical drugs, plant-based compounds are gaining interest in current research. Prunetinoside or prunetin-5-O-glucoside (PUG) is a plant-based active compound, which possesses anti-inflammatory effects on immune cells. In this study, we investigate the effect of PUG on mouse macrophage RAW264.7 cells with or without stimulation of lipopolysaccharide (LPS). Cytotoxicity results showed that PUG is non-cytotoxic to the cells and it reversed the cytotoxicity in LPS-stimulated cells. The levels of nitric oxide (NO) and interleukin-6 (IL-6) were determined using a NO detection kit and IL-6 ELISA kit, respectively, and showed a significant decrease in NO and IL-6 in PUG-treated cells. Western blot and qRT-PCR were performed for the expression of two important pro-inflammatory cytokines, COX2 and iNOS, and found that their expression was downregulated in a dose-dependent manner. Other pro-inflammatory cytokines, such as IL-1ß, IL-6, and TNFα, had reduced mRNA expression after PUG treatment. Furthermore, a Western blot was performed to calculate the expression of NF-κB and MAPK pathway proteins. The results show that PUG administration dramatically reduced the phosphorylation of p-Iκbα, p-NF-κB 65, and p-JNK. Remarkably, after PUG treatment, p-P38 and p-ERK remain unchanged. Furthermore, docking studies revealed that PUG is covalently linked to NF-κB and suppresses inflammation. In conclusion, PUG exerted the anti-inflammatory mechanism by barring the NF-κB pathway and activating JNK. Thus, prunetinoside could be adopted as a therapeutic compound for inflammatory-related conditions.

Scutellarein Inhibits LPS-Induced Inflammation through NF-κB/MAPKs Signaling Pathway in RAW264.7 Cells.

Inflammation is a severe topic in the immune system and play a role as pro-inflammatory mediators. In response to such inflammatory substances, immune cells release cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß). Lipopolysaccharide (LPS) is known as an endotoxin in the outer membrane of Gram-negative bacteria, and it catalyzes inflammation by stimulating the secretion of inflammatory-mediated cytokines such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) by stimulated immune cells. Among the pathways involved in inflammation, nuclear factor kappa (NF-кB) and mitogen-activated protein kinases (MAPKs) are important. NF-kB is a diploid composed of p65 and IkBα and stimulates the pro- gene. MAPKs is a family consisting of the extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38, JNK and p38 play a role as proinflammatory mediators. Thus, we aim to determine the scutellarein (SCU) effect on LPS stimulated RAW264.7 cells. Furthermore, since scutellarein has been shown to inhibit the SARS coronavirus helicase and has been used in Chinese medicine to treat inflammatory disorders like COVID-19, it would be required to examine scutellarein's anti-inflammatory mechanism. We identified inflammation-inducing substances using western blot with RAW264.7 cells and SCU. And we discovered that was reduced by treatment with SCU in p-p65 and p-IκBα. Also, we found that p-JNK and p-ERK were also decreased but there was no effect in p-p38. In addition, we have confirmed that the iNOS was also decreased after treatment but there is no change in the expression of COX-2. Therefore, this study shows that SCU can be used as a compound to treat inflammation.

Modulation of thermal and thermoelectric transport in individual carbon nanotubes by fullerene encapsulation.

The potential impact of encapsulated molecules on the thermal properties of individual carbon nanotubes (CNTs) has been an important open question since the first reports of the strong modulation of electrical properties in 2002. However, thermal property modulation has not been demonstrated experimentally because of the difficulty of realizing CNT-encapsulated molecules as part of thermal transport microstructures. Here we develop a nanofabrication strategy that enables measurement of the impact of encapsulation on the thermal conductivity (κ) and thermopower (S) of single CNT bundles that encapsulate C 60, Gd@C 82 and Er 2@C 82. Encapsulation causes 35-55% suppression in κ and approximately 40% enhancement in S compared with the properties of hollow CNTs at room temperature. Measurements of temperature dependence from 40 to 320 K demonstrate a shift of the peak in the κ to lower temperature. The data are consistent with simulations accounting for the interaction between CNTs and encapsulated fullerenes.

Large-area formation of self-aligned crystalline domains of organic semiconductors on transistor channels using CONNECT.

The electronic properties of solution-processable small-molecule organic semiconductors (OSCs) have rapidly improved in recent years, rendering them highly promising for various low-cost large-area electronic applications. However, practical applications of organic electronics require patterned and precisely registered OSC films within the transistor channel region with uniform electrical properties over a large area, a task that remains a significant challenge. Here, we present a technique termed "controlled OSC nucleation and extension for circuits" (CONNECT), which uses differential surface energy and solution shearing to simultaneously generate patterned and precisely registered OSC thin films within the channel region and with aligned crystalline domains, resulting in low device-to-device variability. We have fabricated transistor density as high as 840 dpi, with a yield of 99%. We have successfully built various logic gates and a 2-bit half-adder circuit, demonstrating the practical applicability of our technique for large-scale circuit fabrication.

Ultrafast polarization response of an optically trapped single ferroelectric nanowire.

One-dimensional potassium niobate nanowires are of interest as building blocks in integrated piezoelectric devices, exhibiting large nonlinear optical and piezoelectric responses. Here we present femtosecond measurements of light-induced polarization dynamics within an optically trapped ferroelectric nanowire, using the second-order nonlinear susceptibility as a real-time structural probe. Large amplitude, reversible modulations of the nonlinear susceptibility are observed within single nanowires at megahertz repetition rates, developing on few-picosecond time-scales, associated with anomalous coupling of light into the nanowire.

Tuning interlayer coupling in large-area heterostructures with CVD-grown MoS2 and WS2 monolayers.

Band offsets between different monolayer transition metal dichalcogenides are expected to efficiently separate charge carriers or rectify charge flow, offering a mechanism for designing atomically thin devices and probing exotic two-dimensional physics. However, developing such large-area heterostructures has been hampered by challenges in synthesis of monolayers and effectively coupling neighboring layers. Here, we demonstrate large-area (>tens of micrometers) heterostructures of CVD-grown WS2 and MoS2 monolayers, where the interlayer interaction is externally tuned from noncoupling to strong coupling. Following this trend, the luminescence spectrum of the heterostructures evolves from an additive line profile where each layer contributes independently to a new profile that is dictated by charge transfer and band normalization between the WS2 and MoS2 layers. These results and findings open up venues to creating new material systems with rich functionalities and novel physical effects.

Doping against the native propensity of MoS2: degenerate hole doping by cation substitution.

Layered transition metal dichalcogenides (TMDs) draw much attention as the key semiconducting material for two-dimensional electrical, optoelectronic, and spintronic devices. For most of these applications, both n- and p-type materials are needed to form junctions and support bipolar carrier conduction. However, typically only one type of doping is stable for a particular TMD. For example, molybdenum disulfide (MoS2) is natively an n-type presumably due to omnipresent electron-donating sulfur vacancies, and stable/controllable p-type doping has not been achieved. The lack of p-type doping hampers the development of charge-splitting p-n junctions of MoS2, as well as limits carrier conduction to spin-degenerate conduction bands instead of the more interesting, spin-polarized valence bands. Traditionally, extrinsic p-type doping in TMDs has been approached with surface adsorption or intercalation of electron-accepting molecules. However, practically stable doping requires substitution of host atoms with dopants where the doping is secured by covalent bonding. In this work, we demonstrate stable p-type conduction in MoS2 by substitutional niobium (Nb) doping, leading to a degenerate hole density of ∼ 3 × 10(19) cm(-3). Structural and X-ray techniques reveal that the Nb atoms are indeed substitutionally incorporated into MoS2 by replacing the Mo cations in the host lattice. van der Waals p-n homojunctions based on vertically stacked MoS2 layers are fabricated, which enable gate-tunable current rectification. A wide range of microelectronic, optoelectronic, and spintronic devices can be envisioned from the demonstrated substitutional bipolar doping of MoS2. From the miscibility of dopants with the host, it is also expected that the synthesis technique demonstrated here can be generally extended to other TMDs for doping against their native unipolar propensity.

Three-dimensional nanostructured bilayer solid oxide fuel cell with 1.3 W/cm(2) at 450 °C.

Obtaining high power density at low operating temperatures has been an ongoing challenge in solid oxide fuel cells (SOFC), which are efficient engines to generate electrical energy from fuels. Here we report successful demonstration of a thin-film three-dimensional (3-D) SOFC architecture achieving a peak power density of 1.3 W/cm(2) obtained at 450 °C. This is made possible by nanostructuring of the ultrathin (60 nm) electrolyte interposed with a nanogranular catalytic interlayer at the cathode/electrolyte interface. We attribute the superior cell performance to significant reduction in both the ohmic and the polarization losses due to the combined effects of employing an ultrathin film electrolyte, enhancement of effective area by 3-D architecture, and superior catalytic activity by the ceria-based interlayer at the cathode. These insights will help design high-efficiency SOFCs that operate at low temperatures with power densities that are of practical significance.

Economic insecurities and patient-reported outcomes in patients with systemic lupus erythematosus in the USA: a cross-sectional analysis of data from the California Lupus Epidemiology Study.

BACKGROUND: Social determinants of health are consistently associated with systemic lupus erythematosus (SLE) outcomes. However, social determinants of health are typically measured with conventional socioeconomic status factors such as income or education. We assessed the association of economic insecurities (ie, food, housing, health care, and financial insecurity) with patient-reported outcomes in a cohort of patients with SLE. METHODS: In this cross-sectional analysis, data were derived from the California Lupus Epidemiology Study based in the San Francisco Bay Area, CA, USA. Participants were recruited between Feb 25, 2015, and Jan 10, 2018, from rheumatology clinics. Inclusion criteria were Bay Area residency; oral fluency in English, Spanish, Cantonese, or Mandarin; 18 years or older; ability to provide informed consent; and a physician confirmed SLE diagnosis. Food, housing, health care, and financial economic insecurities were assessed by validated screening tools. Patient-reported outcomes were obtained using PROMIS, Quality of Life in Neurological Disorders (known as Neuro-QoL) Cognitive Function short form, Patient Health Questionnaire (PHQ)-8, and General Anxiety Disorder (GAD)-7 instruments. Poverty was defined as household income of 125% or less of the federal poverty limit. Lower education was defined as less than college-graduate education. The association of economic insecurities with patient-reported outcomes was assessed by multivariable linear regression models adjusting for demographics, SLE disease characteristics, and comorbidities. We tested for interactions of insecurities with poverty and education. FINDINGS: The final cohort included 252 participants. Mean age was 49·7 (SD 13·4) years, 228 (90%) of 252 were women and 24 (10%) were men. 80 (32%) individuals self-identified as Asian, 26 (10%) as Black, 101 (40%) as White, eight (3%) as mixed race, and 37 (15%) as other race; 59 (23%) self-identified as Hispanic. 135 (54%) individuals had at least one insecurity. Insecurities were highly prevalent, and more common in those with poverty and lower education. Adjusted multivariate analyses revealed that participants with any insecurity had significantly worse scores across all measured patient-reported outcomes. For physical function, no insecurity had an adjusted mean score of 48·9 (95% CI 47·5-50·3) and any insecurity had 45·7 (44·3-47·0; p=0·0017). For pain interference, no insecurity was 52·0 (50·5-53·5) and any insecurity was 54·4 (53·0-55·8; p=0·031). For fatigue, no insecurity was 50·5 (48·8-52·3) and any insecurity was 54·9 (53·3-56·5; p=0·0005). For sleep disturbance, no insecurity was 49·9 (48·3-51·6) and any insecurity was 52·9 (51·4-54·5; p=0·012). For cognitive function, no insecurity was 49·3 (47·7-50·9) and any insecurity was 45·6 (44·1-47·0; p=0·0011). For PHQ-8, no insecurity was 4·4 (3·6-5·1) and any insecurity was 6·1 (5·4-6·8; p=0·0013). For GAD-7, no insecurity was 3·3 (2·6-4·1) and any insecurity was 5·2 (4·5-5·9; p=0·0008). Individuals with more insecurities had worse patient-reported outcomes. There were no statistically significant interactions between insecurities and poverty or education. INTERPRETATION: Having any economic insecurity was associated with worse outcomes for people with SLE regardless of poverty or education. The findings of this study provide insight into the relationship between economic insecurities and SLE outcomes and underscore the need to assess whether interventions that directly address these insecurities can reduce health disparities in SLE. FUNDING: US Centers for Disease Control, Rheumatology Research Foundation, and National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Regular medical checkup program (in K-MEDI hub) to enhance the welfare of laboratory dogs and pigs.

BACKGROUND: The importance of animal welfare is being recognized worldwide. Recently, the increasing demand for enhanced laboratory animal welfare has led to clinically featured transformations of animal research institutes. This study aims to describe the process and findings of veterinary medical check-ups and its influence on laboratory dogs and pigs welfare. Regular medical checkups were conducted by the attending veterinarian twice a year to ensure the health and welfare of dogs and pigs in our animal research institute. Based on the findings from the medical checkup, we assessed the current health of dogs and pigs,providing reasonable treatments to prevent the risk of complications. RESULTS: Blood tests and physical examinations revealed clinically relevant findings. Some of these findings were due to insufficient postoperative care after invasive surgical experiments and the remaining were predictable side effects after surgical experiments. However, one finding involved severe gum bleeding due to retained deciduous teeth. This animal was euthanized because it was judged to reach the humane endpoint. Majority of the dogs and pigs at our animal research institute were considered to be healthy, based on the comprehensive results of the medical checkups. CONCLUSIONS: Regular medical checkups by the attending veterinarian established enhanced animal welfare, ensuring the accuracy and reproducibility of animal studies. This pioneering veterinary animal care program can serve as a potential advanced guideline for animal research institutes to improve dogs and pigs welfare.

Effect of high-frequency chest wall oscillation on pulmonary function after pulmonary lobectomy for non-small cell lung cancer.

OBJECTIVE: We examined the feasibility of high-frequency chest wall oscillationtherapy in immediate postoperative lung recruitment after pulmonary lobectomy for non-small cell lung cancer compared to conventional chest physiotherapy. DESIGN: A prospective, single-blind, randomized trial was conducted at Samsung Medical Center between March 2010 and May 2010. SETTING: Patients were randomized to either the high-frequency chest wall oscillation group or the conventional percussive physiotherapy (control) group. PATIENTS: : Briefly, the eligibility criteria included 1) participants between the ages of 35 and 70 yrs, 2) candidates of lobectomy for non-small cell lung cancer, and 3) the first elective surgery of the day. Sixty-six patients were enrolled in the study. INTERVENTIONS: Patients in the control group had routine postoperative percussive chest physiotherapy four times a day. Participants in the high-frequency chest wall oscillation group received three sessions of high-frequency chest wall oscillation treatment every 8 hrs for 15 mins starting 4 hrs after surgery. All the treatments and measurements were performed by randomly assigned nursing staff who had received standardized education for respiratory care and who were not aware of the details of the study. MEASUREMENTS AND MAIN RESULTS: The primary outcome was postoperative change of forced expiratory volume for 1 sec, and secondary outcomes were changes in arterial oxygen partial pressure and saturation. Safety outcomes and pain scores were also investigated. Patients in the high-frequency chest wall oscillation group experienced significantly improved recovery of pulmonary function as assessed by forced expiratory volume for 1 sec on the third and fifth postoperative days (p = .03) and improved oxygenation on the first postoperative day (p < .01). There were no significant differences in pain score or analgesic requirements. There were no unexpected complications, such as hemodynamic deterioration, postoperative bleeding or chest tube, and wound problems associated with the high-frequency chest wall oscillation therapy. CONCLUSIONS: High-frequency chest wall oscillation therapy after pulmonary lobectomy resulted in significantly improved immediate postoperative pulmonary function recovery compared to conventional physiotherapy, without any significant adverse effects. These results suggest that high-frequency chest wall oscillation therapy may be a valuable tool in the postoperative care of non-small cell lung cancer patients with lobectomy.

A simplified ultrasound approach to diagnose testicular torsion and predict unsalvageable testis.

AIMS: To develop a decision tree model using US features to differentiate testicular torsion and other conditions of acute scrotum and to investigate predictive parameters of unsalvageable testis in testicular torsion. MATERIALS AND METHODS: Scrotal US was reviewed in patients aged <30 years who presented with acute scrotum from 2014 to 2020. US findings of whirlpool sign, testicular volume ratio, heterogeneous echotexture, testicular vascularity, epididymis enlargement and/or hyperemia, and avascular nodule were evaluated and compared. A decision tree model was created using the conditional inference tree analysis and the accuracy was calculated. Univariate logistic regression analysis was performed to find out the predictive US features of unsalvageable testes. RESULTS: Total of 381 patients (13.2±7.2 years old; range, 1 day-30 years) were included. Thirty-four patients were diagnosed with testicular torsion, and the others with orchitis or epididymo-orchitis (n=59), epididymitis (n=264), and appendage torsion (n=24). In the conditional inference tree analysis, whirlpool sign, avascular nodule, and increased testicular vascularity were the most significant discriminators (p<0.001), and the whirlpool sign was the first discriminator. The overall accuracy of the conditional inference tree was 91.1% (95% confidence interval [CI], 87.8-93.7%). Heterogeneous echotexture (odds ratio [OR], 74.99; 95% CI, 2.75-2046.26; p=0.01) and symptom-to-operation time >24 h (OR, 49.28; 95% CI, 1.92-1262.03; p=0.02) were significant predictors of unsalvageable testis. CONCLUSIONS: Conditional inference tree analysis showed that the whirlpool sign of the spermatic cord, avascular nodule, and altered testicular vascularity were significant discriminators. Heterogeneous echotexture and symptom-to-operation delay were important prognostic factors for unsalvageable testis.

Hyaluronidase 6 Does Not Affect Cumulus-Oocyte Complex Dispersal and Male Mice Fertility.

Glycosylphosphatidylinositol-anchored sperm hyaluronidases (HYAL) assist sperm penetration through the cumulus-oocyte complex (COC), but their role in mammalian fertilization remains unclear. Previously, we demonstrated that sperm from HYAL 5 and 7 double-knockout (dKO) mice produced significantly less offspring than sperm from wild-type mice due to defective COC dispersal. However, the HYAL6 gene remained active in the sperm from the dKO mice, indicating that they were not entirely infertile. This study explored the role of HYAL6 in fertilization by analyzing HYAL6-mutant mice. In this mouse model, HYAL5 and HYAL7 were present in the HYAL6-knockout sperm, and they could disperse hyaluronic acid. We found that HYAL6 was present on the surface of sperm. However, male mice lacking the HYAL6 gene had normal fertility, testicular integrity, and sperm characteristics. Furthermore, in vitro fertilization assays demonstrated that HYAL6-deficient epididymal sperm functioned normally. Therefore, HYAL6 is dispensable for fertilization.

Direct Quantification of Heat Generation Due to Inelastic Scattering of Electrons Using a Nanocalorimeter.

Transmission electron microscopy (TEM) is arguably the most important tool for atomic-scale material characterization. A significant portion of the energy of transmitted electrons is transferred to the material under study through inelastic scattering, causing inadvertent damage via ionization, radiolysis, and heating. In particular, heat generation complicates TEM observations as the local temperature can affect material properties. Here, the heat generation due to electron irradiation is quantified using both top-down and bottom-up approaches: direct temperature measurements using nanowatt calorimeters as well as the quantification of energy loss due to inelastic scattering events using electron energy loss spectroscopy. Combining both techniques, a microscopic model is developed for beam-induced heating and to identify the primary electron-to-heat conversion mechanism to be associated with valence electrons. Building on these results, the model provides guidelines to estimate temperature rise for general materials with reasonable accuracy. This study extends the ability to quantify thermal impact on materials down to the atomic scale.

Operando Study of Thermal Oxidation of Monolayer MoS2.

Monolayer MoS2 is a promising semiconductor to overcome the physical dimension limits of microelectronic devices. Understanding the thermochemical stability of MoS2 is essential since these devices generate heat and are susceptible to oxidative environments. Herein, the promoting effect of molybdenum oxides (MoO x ) particles on the thermal oxidation of MoS2 monolayers is shown by employing operando X-ray absorption spectroscopy, ex situ scanning electron microscopy and X-ray photoelectron spectroscopy. The study demonstrates that chemical vapor deposition-grown MoS2 monolayers contain intrinsic MoO x and are quickly oxidized at 100 °C (3 vol% O2/He), in contrast to previously reported oxidation thresholds (e.g., 250 °C, t ≤ 1 h in the air). Otherwise, removing MoO x increases the thermal oxidation onset temperature of monolayer MoS2 to 300 °C. These results indicate that MoO x promote oxidation. An oxide-free lattice is critical to the long-term stability of monolayer MoS2 in state-of-the-art 2D electronic, optical, and catalytic applications.

Bifidobacterium bifidum strains synergize with immune checkpoint inhibitors to reduce tumour burden in mice.

The gut microbiome can influence the development of tumours and the efficacy of cancer therapeutics1-5; however, the multi-omics characteristics of antitumour bacterial strains have not been fully elucidated. In this study, we integrated metagenomics, genomics and transcriptomics of bacteria, and analyses of mouse intestinal transcriptome and serum metabolome data to reveal an additional mechanism by which bacteria determine the efficacy of cancer therapeutics. In gut microbiome analyses of 96 samples from patients with non-small-cell lung cancer, Bifidobacterium bifidum was abundant in patients responsive to therapy. However, when we treated syngeneic mouse tumours with commercial strains of B. bifidum to establish relevance for potential therapeutic uses, only specific B. bifidum strains reduced tumour burden synergistically with PD-1 blockade or oxaliplatin treatment by eliciting an antitumour host immune response. In mice, these strains induced tuning of the immunological background by potentiating the production of interferon-γ, probably through the enhanced biosynthesis of immune-stimulating molecules and metabolites.