A retrotransposon insertion in the Mao1 promoter results in erect pubescence and higher yield in soybean.

Adaptive changes in crops contribute to the diversity of agronomic traits, which directly or indirectly affect yield. The change of pubescence form from appressed to erect is a notable feature during soybean domestication. However, the biological significance and regulatory mechanism underlying this transformation remain largely unknown. Here, we identified a major-effect locus, PUBESCENCE FORM 1 (PF1), the upstream region of Mao1, that regulates pubescence form in soybean. The insertion of a Ty3/Gypsy retrotransposon in PF1 can recruit the transcription factor GAGA-binding protein to a GA-rich region, which up-regulates Mao1 expression, underpinning soybean pubescence evolution. Interestingly, the proportion of improved cultivars with erect pubescence increases gradually with increasing latitude, and erect-pubescence cultivars have a higher yield possibly through a higher photosynthetic rate and photosynthetic stability. These findings open an avenue for molecular breeding through either natural introgression or genome editing toward yield improvement and productivity.

Transcriptome profiling reveals the impact of various levels of biochar application on the growth of flue-cured tobacco plants.

BACKGROUND: Biochar, a carbon-rich source and natural growth stimulant, is usually produced by the pyrolysis of agricultural biomass. It is widely used to enhance plant growth, enzyme activity, and crop productivity. However, there are no conclusive studies on how different levels of biochar application influence these systems. METHODS AND RESULTS: The present study elucidated the dose-dependent effects of biochar application on the physiological performance, enzyme activity, and dry matter accumulation of tobacco plants via field experiments. In addition, transcriptome analysis was performed on 60-day-old (early growth stage) and 100-day-old (late growth stage) tobacco leaves to determine the changes in transcript levels at the molecular level under various biochar application levels (0, 600, and 1800 kg/ha). The results demonstrated that optimum biochar application enhances plant growth, regulates enzymatic activity, and promotes biomass accumulation in tobacco plants, while higher biochar doses had adverse effects. Furthermore, transcriptome analysis revealed a total of 6561 differentially expressed genes (DEGs) that were up- or down-regulated in the groupwise comparison under different treatments. KEGG pathways analysis demonstrated that carbon fixation in photosynthetic organisms (ko00710), photosynthesis (ko00195), and starch and sucrose metabolism (ko00500) pathways were significantly up-regulated under the optimal biochar dosage (600 kg/ha) and down-regulated under the higher biochar dosage (1800 kg/ha). CONCLUSION: Collectively, these results indicate that biochar application at an optimal rate (600 kg/ha) could positively affect photosynthesis and carbon fixation, which in turn increased the synthesis and accumulation of sucrose and starch, thus promoting the growth and dry matter accumulation of tobacco plants. However, a higher biochar dosage (1800 kg/ha) disturbs the crucial source-sink balance of organic compounds and inhibits the growth of tobacco plants.

Soybean hypocotyl elongation is regulated by a MYB33-SWEET11/21-GA2ox8c module involving long-distance sucrose transport.

The length of hypocotyl affects the height of soybean and lodging resistance, thus determining the final grain yield. However, research on soybean hypocotyl length is scarce, and the regulatory mechanisms are not fully understood. Here, we identified a module controlling the transport of sucrose, where sucrose acts as a messenger moved from cotyledon to hypocotyl, regulating hypocotyl elongation. This module comprises four key genes, namely MYB33, SWEET11, SWEET21 and GA2ox8c in soybean. In cotyledon, MYB33 is responsive to sucrose and promotes the expression of SWEET11 and SWEET21, thereby facilitating sucrose transport from the cotyledon to the hypocotyl. Subsequently, sucrose transported from the cotyledon up-regulates the expression of GA2ox8c in the hypocotyl, which ultimately affects the length of the hypocotyl. During the domestication and improvement of soybean, an allele of MYB33 with enhanced abilities to promote SWEET11 and SWEET21 has gradually become enriched in landraces and cultivated varieties, SWEET11 and SWEET21 exhibit high conservation and have undergone a strong purified selection and GA2ox8c is under a strong artificial selection. Our findings identify a new molecular pathway in controlling soybean hypocotyl elongation and provide new insights into the molecular mechanism of sugar transport in soybean.

A Flexible Wearable Sensor Based on Laser-Induced Graphene for High-Precision Fine Motion Capture for Pilots.

There has been a significant shift in research focus in recent years toward laser-induced graphene (LIG), which is a high-performance material with immense potential for use in energy storage, ultrahydrophobic water applications, and electronic devices. In particular, LIG has demonstrated considerable potential in the field of high-precision human motion posture capture using flexible sensing materials. In this study, we investigated the surface morphology evolution and performance of LIG formed by varying the laser energy accumulation times. Further, to capture human motion posture, we evaluated the performance of highly accurate flexible wearable sensors based on LIG. The experimental results showed that the sensors prepared using LIG exhibited exceptional flexibility and mechanical performance when the laser energy accumulation was optimized three times. They exhibited remarkable attributes, such as high sensitivity (~41.4), a low detection limit (0.05%), a rapid time response (response time of ~150 ms; relaxation time of ~100 ms), and excellent response stability even after 2000 s at a strain of 1.0% or 8.0%. These findings unequivocally show that flexible wearable sensors based on LIG have significant potential for capturing human motion posture, wrist pulse rates, and eye blinking patterns. Moreover, the sensors can capture various physiological signals for pilots to provide real-time capturing.

Diverse flowering responses subjecting to ambient high temperature in soybean under short-day conditions.

Flowering time is one of important agronomic traits determining the crop yield and affected by high temperature. When facing high ambient temperature, plants often initiate early flowering as an adaptive strategy to escape the stress and ensure successful reproduction. However, here we find opposing ways in the short-day crop soybean to respond to different levels of high temperatures, in which flowering accelerates when temperature changes from 25 to 30 °C, but delays when temperature reaches 35 °C under short day. phyA-E1, possibly photoperiodic pathway, is crucial for 35 °C-mediated late flowering, however, does not contribute to promoting flowering at 30 °C. 30 °C-induced up-regulation of FT2a and FT5a leads to early flowering, independent of E1. Therefore, distinct responsive mechanisms are adopted by soybean when facing different levels of high temperatures for successful flowering and reproduction.

A Direct Method for Synthesis of Quinoxalines and Quinazolinones Using Epoxides as Alkyl Precursor.

An iodine-mediated one-pot synthesis of pyrrolo/indolo [1,2-a]quinoxalines and quinazolin-4-one via utilizing epoxides as alkyl precursors under metal-free conditions has been described. Both 1-(2-aminophenyl)-pyrrole and 2-aminobenzamide could be applied to this protocol. A total of 33 desired products were obtained with moderate to good yields. This methodology was suitable for wide-scale preparation and the obtained products could be further modified into promising pharmaceutically active reagents.

Aerobic exercise improves intestinal mucosal barrier dysfunction through TLR4/MyD88/NF-κB signaling pathway in diabetic rats.

This study examined the effects of aerobic exercise on the intestinal mucosal barrier dysfunction in diabetic rats. We established a diabetic rats model consisting of three groups: normal control (NC), diabetes control (DC), and diabetes eight-week aerobic exercise (DE). We measured serum fasting blood glucose (FBG), insulin (INS), diamine oxidase (DAO), D(-)-lactate (D-Lac), lipopolysaccharide (LPS), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and insulin resistance index (HOMA-IR). Intestinal sections of tissue were stained with H&E and examined using transmission electron microscopy. Expressions of occludin, claudin-1, toll-like receptor-4 (TLR4), myeloid differentiation primary response protein 88 (MyD88), and nuclear factor-κB (NF-κB) in small intestinal mucosa were determined by Western Blot. In comparison to NC, FBG, HOMA-IR, DAO, D-Lac, TNF-α, IL-6, and LPS were increased (P < 0.05) in DC, whereas INS, villus height, crypt depth, and mucosal thickness were decreased (P < 0.05). In comparison to DC, FBG, DAO, D-Lac, TNF-α, and LPS were decreased (P < 0.05) in DE, whereas INS, villus height, crypt depth, and mucosal thickness were increased (P < 0.05). In comparison to NC, occludin and claudin-1 were decreased (P < 0.05) in DC, whereas TLR4, MyD88, and NF-κB were increased (P < 0.05). In comparison to DC, occludin and claudin-1 were increased (P < 0.05) in DE, whereas TLR4, MyD88, and NF-κB were decreased (P < 0.05). In conclusion, eight-week aerobic exercise improved intestinal mucosal barrier dysfunction in diabetic rats, by inhibiting LPS release, TLR4/MyD88/NF-κB signaling pathway, and pro-inflammatory cytokines expression.

Role of heat treatment in improving replication quality of PDMS double-casting.

An efficient and eco-friendly method utilizing the heat treatment of the PDMS master is proposed for improving the replication quality of PDMS double-casting. The effects of heat treatment on interfacial adhesion are investigated in terms of uncured low molecular weight chains, surface energy, and surface roughness. The PDMS master treated at 150 °C for 72 h shows the highest replication quality of micropatterns with a diameter and height of 30 µm.

N,N-Dimethylformamide as Carbon Synthons for the Synthesis of N-Heterocycles: Pyrrolo/Indolo[1,2-a]quinoxalines and Quinazolin-4-ones.

N,N-dimethylformamide (DMF) as synthetic precursors contributing especially the methyl, acyl, and amino groups has played a significant role in heterocycle syntheses and functionalization. In this protocol, a wide range of pyrrolo/indolo[1,2-a]quinoxalines and quinazolin-4-ones were obtained in moderate to good yields by using elemental iodine without any metal or peroxides. We considered that N-methyl and N-acyl of DMF participate and complete the reaction separately through different mechanisms, which displayed potential still to be explored of DMF.

Rapid excavating a FLOWERING LOCUS T-regulator NF-YA using genotyping-by-sequencing.

Soybean (Glycine max (L.) Merrill) is one of the most important crop plants in the world as an important source of protein for both human consumption and livestock fodder. As flowering time contributes to yield, finding new QTLs and further identifying candidate genes associated with various flowering time are fundamental to enhancing soybean yield. In this study, a set of 120 recombinant inbred lines (RILs) which was developed from a cross of two soybean cultivars, Suinong4 (SN4) and ZK168, were genotyped by genotyping-by-sequencing (GBS) approach and phenotyped to expand the cognitive of flowering time by quantitative trait loci (QTL) analysis. Eventually, three stable QTLs related to flowering time which were detected separately located on chromosome 14, 18, and 19 under long-day (LD) conditions. We predicted candidate genes for each QTL and carried out association analyses between the putative causal alleles and flowering time. Moreover, a transient transfection assay was performed and showed that NUCLEAR FACTOR YA 1b (GmNF-YA1b) as a strong candidate for the QTL on chromosome 19 might affect flowering time by suppressing the expression of FLOWERING LOCUS T (GmFT) genes in soybean. QTLs detected in this study would provide fundamental resources for finding candidate genes and clarify the mechanisms of flowering which would be helpful for breeding novel high-yielding soybean cultivars. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-021-01237-w.

A flowering time locus dependent on E2 in soybean.

Soybean [Glycine max (L.) Merrill] is very sensitive to changes in photoperiod as a typical short-day plant. Photoperiodic flowering influences soybean latitudinal adaptability and yield to a considerable degree. Identifying new quantitative trait loci (QTLs) controlling flowering time is a powerful initial approach for elucidating the mechanisms underlying flowering time and adaptation to different latitudes in soybean. In this study, we developed a Recombinant Inbred Lines (RILs) population and recorded flowering time under natural long-day conditions. We also constructed a high-density genetic map by genotyping-by-sequencing and used it for QTL mapping. In total, we detected twelve QTLs, four of which are stable and named by qR1-2, qR1-4, qR1-6.1, and qR1-10, respectively. Among these four QTLs, qR1-4 and qR1-6.1 are novel. QTL mapping in two sub-populations classified by the genotype of the maturity locus E2, genetic interaction evaluation between E2 and qR1-2, and qRT-PCR indicated that E2 has an epistatic effect on qR1-2, and that causal gene of qR1-2 acts upstream of E2. We presumed the most likely candidate genes according to the resequencing data and briefly analyzed the geographic distributions of these genes. These findings will be beneficial for our understanding of the mechanisms underlying photoperiodic flowering in soybean, contribute to further investigate of E2, and provide genetic resources for molecular breeding of soybean. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-021-01224-1.

Natural variation of the Dt2 promoter controls plant height and node number in semi-determinant soybean.

Soybean (Glycine max (L.) Merrill) is an important legume crop worldwide. Plant height (PH) is a quantitative trait that is closely related to node number (NN) and internode length (IL) on the main stem, which together affect soybean yield. To identify candidate genes controlling these three traits in soybean, we examined a recombinant inbred line (RIL) population derived from a cross between two soybean varieties with semi-determinate stems (Dt1Dt1Dt2Dt2), JKK378 and HXW. A quantitative trait locus (QTL) named qPH18 was identified that simultaneously controls PH, NN, and IL; this region harbors the semi-determinant gene Dt2. Sequencing of the Dt2 promoter from JKK378 identified three polymorphisms relative to HXW, including two single nucleotide polymorphism (SNPs) and an 18-bp insertion/deletion polymorphism (Indel). Dt2 expression was lower in the qPH18JKK378 group than in the qPH18HXW group, whereas the expression level of the downstream gene Dt1 showed the opposite tendency. A transient transfection assay confirmed that Dt2 promoter activity is lower in JKK378 compared to HXW. We propose that the polymorphisms in the dominant Dt2 promoter underlie the differences in Dt2 expression and its downstream gene Dt1 in the two parents, thereby affecting PH, NN, IL, and grain weight per plant without altering stem growth habit. Compared to the PH18HXW allele, the qPH18JKK378 allele suppresses Dt2 expression, which releases the inhibition of Dt1 expression, thus enhancing NN and grain yield. Our findings shed light on the mechanism underlying NN and PH in soybean and provide a molecular marker to facilitate breeding. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-021-01235-y.

A recent retrotransposon insertion of J caused E6 locus facilitating soybean adaptation into low latitude.

Soybean (Glycine max) is an important legume crop that was domesticated in temperate regions. Soybean varieties from these regions generally mature early and exhibit extremely low yield when grown under inductive short-day (SD) conditions at low latitudes. The long-juvenile (LJ) trait, which is characterized by delayed flowering and maturity, and improved yield under SD conditions, allowed the cultivation of soybean to expand to lower latitudes. Two major loci control the LJ trait: J and E6. In the current study, positional cloning, sequence analysis, and transgenic complementation confirmed that E6 is a novel allele of J, the ortholog of Arabidopsis thaliana EARLY FLOWERING 3 (ELF3). The mutant allele e6PG , which carries a Ty1/Copia-like retrotransposon insertion, does not suppress the legume-specific flowering repressor E1, allowing E1 to inhibit Flowering Locus T (FT) expression and thus delaying flowering and increasing yields under SD conditions. The e6PG allele is a rare allele that has not been incorporated into modern breeding programs. The dysfunction of J might have greatly facilitated the adaptation of soybean to low latitudes. Our findings increase our understanding of the molecular mechanisms underlying the LJ trait and provide valuable resources for soybean breeding.

Effects of Diabetic Ketoacidosis on Executive Function in Children With Type 1 Diabetes: Evidence From Wisconsin Card Sorting Test Performance.

OBJECTIVE: Diabetic ketoacidosis (DKA) in patients with type 1 diabetes mellitus (T1DM) is known to affect memory function, but little is known about its impact on executive function. This study aimed to determine whether a history of DKA was associated with changes in executive function in children with T1DM. METHODS: The sample consisted of 99 patients with T1DM with histories of DKA, 82 patients with T1DM without DKA, and 100 healthy controls aged 7 to 18 years. Neuropsychological function and emotion assessments were performed in all participants. The Wisconsin Card Sorting Test (WCST) was used to assess executive function. RESULTS: Compared with healthy controls, the DKA group (but not the non-DKA group) had a significantly lower mean intelligence quotient (IQ; p = .006, Cohen d = 0.528) and a significantly higher rate of WCST perseverative errors (p = .006, Cohen d = 0.475). In the DKA group, the age at DKA onset was significantly associated with the IQ (p = .001) and the number of completed WCST categories (p = .046). Higher hemoglobin A1c levels were associated significantly with lower IQ (p < .001), increased rate of WCST perseverative errors (p = .015), and completion of fewer WCST categories (p = .027). CONCLUSIONS: DKA has implications for executive function in children with T1DM. These findings emphasize the importance of DKA prevention in patients with known T1DM, especially younger children with newly diagnosed T1DM.

Optimism outweighs neuroticism and anxiety sensitivity to predict insomnia symptoms in women after surgery for breast cancer.

PURPOSE: Insomnia symptoms are common among women who have undergone surgery for breast cancer. Personality traits are also believed to have an impact on sleep. However, there are no reports to address the effects of personality traits on sleep in women with breast cancer. This study examined the separate and competing roles of neuroticism, anxiety sensitivity, and optimism in predicting post-surgery insomnia symptoms. METHODS: Women with breast cancer (n = 749) were enrolled the week prior to surgery and required to complete a demographic questionnaire, the Chinese version of Neuroticism subscale of NEO-Five Factor Inventory (CV-N-NEO-FFI), Anxiety Sensitivity Index-3 (CV-ASI-3), and Life Orientation Test-Revised (CV-LOT-R). Four weeks post-surgery, the Chinese version of Insomnia Severity Index (CV-ISI) was administered to evaluate insomnia symptoms. RESULTS: Neuroticism (ß = 0.317, p < 0.001), anxiety sensitivity (ß = 0.220, p < 0.001), and optimism (ß = - 0.332, p < 0.001) could predict post-surgery insomnia symptoms. When putting them together into one stepwise regression, optimism (ß = - 0.215, p < 0.001) became the statistically most important predictor for insomnia symptoms. Optimism suppressed the predictions of insomnia symptoms provided by neuroticism (ß = 0.114, p < 0.001) and anxiety sensitivity (ß = 0.079, p < 0.001). CONCLUSION: Neuroticism and anxiety sensitivity positively predicted insomnia, but optimism negatively predicted insomnia. In particular, optimism plays a more important role in post-surgery insomnia symptoms in women with breast cancer compared to neuroticism and anxiety sensitivity. Sleep intervention in women with breast cancer should focus on enhancing their optimism level.

Harnessing fold-to-wrinkle transition and hierarchical wrinkling on soft material surfaces by regulating substrate stiffness and sputtering flux.

Strain-induced complex surface patterns such as wrinkles, folds and hierarchical structures are quite useful in a wide range of practical applications. Although various surface patterns have been extensively investigated, precisely controlling the coexistence and transition of multimodal structures is still a challenge. In this work, we report on a facile technique to harness fold-to-wrinkle transition and hierarchical wrinkling on soft material surfaces by regulating substrate stiffness and sputtering flux. It is found that as the substrate stiffness or sputtering flux increases, the surface patterns successively evolve from networked folds to isolated folds (coexistence of folds and wrinkles) and finally to labyrinth-like wrinkles. For larger sputtering flux, two distinct wrinkling patterns (i.e., G1 wrinkling due to surface instability during sputtering and G2 wrinkling due to thermal compression after deposition) can coexist on the sample surfaces, resulting in the spontaneous formation of hierarchical wrinkles. The report in this work could promote better understanding of the sputtering effect on the spontaneous pattern formation for soft materials and controllable fabrication of multiple complex patterns by simply regulating substrate stiffness and sputtering flux.

Relationship between multifaceted body image and negative affect among women undergoing mastectomy for breast cancer: a longitudinal study.

The purpose of the current study was to investigate how post-surgery multifaceted body image predicts negative affect (NA) 6 months post-surgery among women undergoing mastectomy. In total, 310 Chinese women undergoing mastectomy were recruited from a hospital in the Hunan province between 2012 and 2013. Upon enrollment (T1), all women were administered the Chinese version of Body Image after Breast Cancer Questionnaire (BIBCQ) (BIBCQ-C), NA subscale of Positive and Negative Affect Schedule (PANAS), Multidimensional Scale of Perceived Social Support (MSPSS), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD). Two weeks later, BIBCQ-C was re-administered. Six months later (T2), the NA subscale was administered again. We first evaluated the psychometric properties of BIBCQ-C, and then investigated the long-term impact of different aspects of body image on NA using forced entry hierarchical regression analyses. The BIBCQ-C scores demonstrated acceptable internal consistency (all Cronbach's α > 0.70) and test-retest reliability (all ICC > 0.86). Confirmatory factor analysis supported the six-factor model (CFI = 0.93, TLI = 0.94, RMSEA = 0.04). Regression analysis showed that two dimensions of body image, vulnerability (ß = 0.217) and body concern (ß = 0.119) at T1, significantly predict NA at T2 (all p < 0.05). BIBCQ-C was a good instrument for measuring multifaceted body image. Improvement of vulnerability and body concern, two aspects of body image, may reduce post-surgery NA among Chinese women undergoing mastectomy.

Knocking down of Xkr8 enhances chemotherapy efficacy through modulating tumor immune microenvironment.

Scramblase Xk-related protein 8 (Xkr8) regulates the externalization of phosphatidylserine (PS) during apoptosis and holds a pivotal role in fostering tumor immunosuppression. Targeting Xkr8 in conjunction with chemotherapy demonstrated a novel avenue for amplifying antitumor immune response and overcoming chemo-immune resistance. Here we further evaluated this strategy by using a clinically relevant orthotopic model and elucidated the mechanism through in-depth single-cell RNA sequencing (scRNA-seq). We found that Xkr8 knockdown exhibited the potential to lead to immunogenic cell death (ICD) by impeding the normal clearance of apoptotic cells. Co-delivery of Xkr8 small interference RNA (siRNA) and a prodrug conjugate of 5-fluorouracil (5-Fu) and oxoplatin (FuOXP) showed remarkable therapeutic efficacy in an orthotopic pancreatic tumor model with increased infiltration of proliferative NK cells and activated macrophages in the tumor microenvironment (TME). Single-cell trajectory analysis further unveiled that tumor infiltrating CD8+ T cells are differentiated favorably to cytotoxic over exhausted phenotype after combination treatment. Our study sheds new light on the impact of Xkr8 knockdown on TME and solidifies the rationale of combining Xkr8 knockdown with chemotherapy to treat various types of cancers.

Hydrophobic Surface Array Structure Based on Laser-Induced Graphene for Deicing and Anti-Icing Applications.

The exceptional performance of graphene has driven the advancement of its preparation techniques and applications. Laser-induced graphene (LIG), as a novel graphene preparation technique, has been applied in various fields. Graphene periodic structures created by the LIG technique exhibit superhydrophobic characteristics and can be used for deicing and anti-icing applications, which are significantly influenced by the laser parameters. The laser surface treatment process was simulated by a finite element software analysis (COMSOL Multiphysics) to optimize the scanning parameter range, and the linear array surface structure was subsequently fabricated by the LIG technique. The generation of graphene was confirmed by Raman spectroscopy and energy-dispersive X-ray spectroscopy. The periodic linear array structure was observed by scanning electron microscopy (SEM) and confocal laser imaging (CLSM). In addition, CLSM testings, contact angle measurements, and delayed icing experiments were systematically performed to investigate the effect of scanning speed on surface hydrophobicity. The results show that high-quality and uniform graphene can be achieved using the laser scanning speed of 125 mm/s. The periodic linear array structures can obviously increase the contact angle and suppress delayed icing. Furthermore, these structures have the enhanced ability of the electric heating deicing, which can reach 100 °C and 240 °C within 15 s and within 60 s under the DC voltage power supply ranging from 3 to 7 V, respectively. These results indicate that the LIG technique can be developed to provide an efficient, economical, and convenient approach for preparing graphene and that the hydrophobic surface array structure based on LIG has considerable potential for deicing and anti-icing applications.

Knocking down of Xkr8 enhances chemotherapy efficacy through modulating tumor immune microenvironment.

Scramblase Xkr8 regulates the externalization of phosphatidylserine (PS) during apoptosis and holds a pivotal role in fostering tumor immunosuppression. Targeting Xkr8 in conjunction with chemotherapy demonstrated a novel avenue for amplifying antitumor immune response and overcoming chemo-immune resistance. Here we further evaluated this strategy by using a clinically relevant orthotopic model and elucidated the mechanism through in-depth single-cell RNA sequencing (scRNA-seq). We found that Xkr8 knockdown exhibited the potential to lead to immunogenic cell death (ICD) by impeding the normal clearance of apoptotic cells. Co-delivery of Xkr8 small interference RNA (siRNA) and chemo prodrug FuOXP showed remarkable therapeutic efficacy in an orthotopic pancreatic tumor model with an increase of proliferative NK cells and activated macrophages infiltration in the tumor microenvironment (TME). Single-cell trajectory analysis further unveiled that tumor infiltrating CD8+ T cells are differentiated favorably to cytotoxic over exhausted phenotype after combination treatment. Our study sheds new light on the impact of Xkr8 knockdown on TME and solidifies the rationale of combining Xkr8 knockdown with chemotherapy to treat various types of cancers.