Targeting cytokine and chemokine signaling pathways for cancer therapy.

Cytokines are critical in regulating immune responses and cellular behavior, playing dual roles in both normal physiology and the pathology of diseases such as cancer. These molecules, including interleukins, interferons, tumor necrosis factors, chemokines, and growth factors like TGF-ß, VEGF, and EGF, can promote or inhibit tumor growth, influence the tumor microenvironment, and impact the efficacy of cancer treatments. Recent advances in targeting these pathways have shown promising therapeutic potential, offering new strategies to modulate the immune system, inhibit tumor progression, and overcome resistance to conventional therapies. In this review, we summarized the current understanding and therapeutic implications of targeting cytokine and chemokine signaling pathways in cancer. By exploring the roles of these molecules in tumor biology and the immune response, we highlighted the development of novel therapeutic agents aimed at modulating these pathways to combat cancer. The review elaborated on the dual nature of cytokines as both promoters and suppressors of tumorigenesis, depending on the context, and discussed the challenges and opportunities this presents for therapeutic intervention. We also examined the latest advancements in targeted therapies, including monoclonal antibodies, bispecific antibodies, receptor inhibitors, fusion proteins, engineered cytokine variants, and their impact on tumor growth, metastasis, and the tumor microenvironment. Additionally, we evaluated the potential of combining these targeted therapies with other treatment modalities to overcome resistance and improve patient outcomes. Besides, we also focused on the ongoing research and clinical trials that are pivotal in advancing our understanding and application of cytokine- and chemokine-targeted therapies for cancer patients.

Novel Mito-Nuclear Combinations Facilitate the Global Invasion of a Major Agricultural Crop Pest.

A fundamental understanding of the underlying mechanisms involved in biological invasions is crucial to developing effective risk assessment and control measures against invasive species. The fall armyworm (FAW), Spodoptera frugiperda, is a highly invasive pest that has rapidly spread from its native Americas into much of the Eastern Hemisphere, with a highly homogeneous nuclear genetic background. However, the exact mechanism behind its rapid introduction and propagation remains unclear. Here, a systematic investigation is conducted into the population dynamics of FAW in China from 2019 to 2021 and found that FAW individuals carrying "rice" mitochondria (FAW-mR) are more prevalent (>98%) than that with "corn" mitochondria (FAW-mC) at the initial stage of the invasion and in newly-occupied non-overwintering areas. Further fitness experiments show that the two hybrid-strains of FAW exhibit different adaptions in the new environment in China, and this may have been facilitated by amino acid changes in mitochondrial-encoded proteins. FAW-mR used increases energy metabolism, faster wing-beat frequencies, and lower wing loadings to drive greater flight performance and subsequent rapid colonization of new habitats. In contrast, FAW-mC individuals adapt with more relaxed mitochondria and shuttle energetics into maternal investment, observed as faster development rate and higher fecundity. The presence of two different mitochondria types within FAW has the potential to significantly expand the range of damage and enhance competitive advantage. Overall, the study describes a novel invasion mechanism displayed by the FAW population that facilitates its expansion and establishment in new environments.

Retrotransposon-mediated disruption of a chitin synthase gene confers insect resistance to Bacillus thuringiensis Vip3Aa toxin.

The vegetative insecticidal protein Vip3Aa from Bacillus thuringiensis (Bt) has been produced by transgenic crops to counter pest resistance to the widely used crystalline (Cry) insecticidal proteins from Bt. To proactively manage pest resistance, there is an urgent need to better understand the genetic basis of resistance to Vip3Aa, which has been largely unknown. We discovered that retrotransposon-mediated alternative splicing of a midgut-specific chitin synthase gene was associated with 5,560-fold resistance to Vip3Aa in a laboratory-selected strain of the fall armyworm, a globally important crop pest. The same mutation in this gene was also detected in a field population. Knockout of this gene via CRISPR/Cas9 caused high levels of resistance to Vip3Aa in fall armyworm and 2 other lepidopteran pests. The insights provided by these results could help to advance monitoring and management of pest resistance to Vip3Aa.

Beyond success: unveiling the hidden potential of radiotherapy and immunotherapy in solid tumors.

Immunotherapy, particularly with immune checkpoint inhibitors, has significantly transformed cancer treatment. Despite its success, many patients struggle to respond adequately or sustain long-lasting clinical improvement. A growing consensus has emerged that radiotherapy (RT) enhances the response rate and overall efficacy of immunotherapy. Although combining RT and immunotherapy has been extensively investigated in preclinical models and has shown promising results, establishing itself as a dynamic and thriving area of research, clinical evidence for this combination strategy over the past five years has shown both positive and disappointing results, suggesting the need for a more nuanced understanding. This review provides a balanced and updated analysis of the combination of immunotherapy and RT. We summarized the preclinical mechanisms through which RT boosts antitumor immune responses and mainly focused on the outcomes of recently updated clinical trials, including those that may not have met expectations. We investigated the optimization of the therapeutic potential of this combined strategy, including key challenges, such as fractionation and scheduling, lymph node irradiation, and toxicity. Finally, we offered insights into the prospects and challenges associated with the clinical translation of this combination therapy, providing a realistic perspective on the current state of research and potential future directions.

Abundance and Seasonal Migration Patterns of Green Lacewings (Neuroptera: Chrysopidae) across the Bohai Strait in Eastern Asia.

Many insects, including green lacewings, migrate seasonally to exploit suitable breeding and winter habitats. Green lacewings are important natural enemies of insect pests worldwide. Here, four dominant green lacewing species, Chrysoperla nipponensis (Okamoto), Chrysopa pallens (Rambur), Chrysoperla furcifera (Okamoto), and Chrysopa formosa Brauer, were investigated for their ability to migrate between northern and northeastern China across the Bohai Strait from late May to late October each year. Furthermore, there were significant interannual and seasonal differences in the number of migratory green lacewings collected. The number of green lacewings in spring was significantly lower than that in summer and autumn, and the highest average number of green lacewings occurred in June. In addition, there were differences in the sex ratio of migrating green lacewings between months, with a greater proportion of females than males. Finally, the seasonal migration trajectories simulated by the HYSPLIT model revealed that the green lacewings captured on Beihuang Island primarily originated from Shandong Province. Accordingly, these findings contribute to our understanding of green lacewing migration in eastern Asia and aid its incorporation within integrated pest management (IPM) packages for several crop pests. Furthermore, long-term tracking of migrant insect populations can reveal ecosystem services and trophic dynamic processes at the macroscale.

Migration Activity of Spodoptera litura (Lepidoptera: Noctuidae) between China and the South-Southeast Asian Region.

The common cutworm, Spodoptera litura (F.), feeds on a wide variety of food and cash crops and is one of the most widespread and destructive agricultural pests worldwide. Migration is the biological basis of its regional population outbreaks but the seasonal movement of this pest between east and south Asia regions remains unknown. In this study, searchlight traps were used to monitor the seasonal migration of S. litura from 2019 to 2023 in Ruili City (Yunnan, China), located along the insect migratory route between China and the south Asia region. The results showed that migratory activity could occur throughout the year, with the main periods found in spring (April-May) and autumn (October-December). The ovarian development and mating status of the trapped females indicated that most individuals were in the middle or late stages of migration and that Ruili City was located in the transit area of the long-distance migration of the pest. In the migration trajectory simulation, populations of S. litura moved from northeast India, Bangladesh, and northern Myanmar to southwestern China along the southern margin of the Himalayas in spring and returned to the south Asia region in autumn. Our findings clarify the seasonal migration patterns of S. litura in China and South Asia and facilitate the development of regional cross-border monitoring and management systems for this pest.

Field evaluation the effect of two transgenic Bt maize events on predatory arthropods in the Huang-Huai-Hai summer maize-growing region of China.

To illustrate the impact of genetically modified (GM) Bt maize on the natural enemy communities in the Huang-Huai-Hai summer maize-growing region in China, the abundance of 7 common predator taxa (Geocoris pallidipennis Costa, Harmonia axyridis (Pallas), lacewings, Orius sauteri (Poppius), Propylea japonica (Thunberg), spiders, and Staphylinidae) was quantitatively evaluated by comparing Bt-Cry1Ab DBN9936 and Bt-Cry1Ab/Cry2Aj Ruifeng 125 events to their near non-Bt isolines during the growing season from 2016 to 2019. A total of 10,302, 19,793, 13,536, and 5,672 individuals were observed during 4 years, and the abundance of each taxa on Bt maize varied between sample dates among those arthropod taxa. Shannon-Wiener diversity index of predator communities from 7 taxa showed very similar temporal dynamics and principal response curve analyses to examine community-level effects showed no significant differences in predator abundance in Bt maize compared with non-Bt maize. We conclude that the 2 Bt maize hybrids did not adversely affect the predator community in the Huang-Huai-Hai summer maize-growing region of China.

The enhanced antitumor activity of bispecific antibody targeting PD-1/PD-L1 signaling.

The programmed cell death 1 (PD-1) signaling pathway, a key player in immune checkpoint regulation, has become a focal point in cancer immunotherapy. In the context of cancer, upregulated PD-L1 on tumor cells can result in T cell exhaustion and immune evasion, fostering tumor progression. The advent of PD-1/PD-L1 inhibitor has demonstrated clinical success by unleashing T cells from exhaustion. Nevertheless, challenges such as resistance and adverse effects have spurred the exploration of innovative strategies, with bispecific antibodies (BsAbs) emerging as a promising frontier. BsAbs offer a multifaceted approach to cancer immunotherapy by simultaneously targeting PD-L1 and other immune regulatory molecules. We focus on recent advancements in PD-1/PD-L1 therapy with a particular emphasis on the development and potential of BsAbs, especially in the context of solid tumors. Various BsAb products targeting PD-1 signaling are discussed, highlighting their unique mechanisms of action and therapeutic potential. Noteworthy examples include anti-TGFß × PD-L1, anti-CD47 × PD-L1, anti-VEGF × PD-L1, anti-4-1BB × PD-L1, anti-LAG-3 × PD-L1, and anti-PD-1 × CTLA-4 BsAbs. Besides, we summarize ongoing clinical studies evaluating the efficacy and safety of these innovative BsAb agents. By unraveling the intricacies of the tumor microenvironment and harnessing the synergistic effects of anti-PD-1/PD-L1 BsAbs, there exists the potential to elevate the precision and efficacy of cancer immunotherapy, ultimately enabling the development of personalized treatment strategies tailored to individual patient profiles.

Insecticidal Effects of Transgenic Maize Bt-Cry1Ab, Bt-Vip3Aa, and Bt-Cry1Ab+Vip3Aa against the Oriental Armyworm, Mythimna separata (Walker) in Southwest China.

The oriental armyworm, Mythimna separata (Walker), an important migratory pest of maize and wheat, is posing a severe threat to maize production in Asian countries. As source areas of spring-summer emigratory populations, the control of M. separata in southwestern China is of great significance for East Asian maize production. To assess the toxicity of Bt maize against the pest, bioassays of Bt-(Cry1Ab+Vip3Aa) maize (event DBN3601T), Bt-Cry1Ab maize (event DBN9936), and Bt-Vip3Aa maize (event DBN9501) were conducted in Yunnan province of southwest China. There were significant differences in insecticidal activity between the three Bt maize events, and DBN3601T presented the highest insecticidal role. The results also indicated that the insecticidal effect of various Bt maize tissues took an order in leaf > kernel > silk, which is highly consistent with the expression amounts of Bt insecticidal protein in leaf (69.69 ± 1.18 µg/g), kernel (11.69 ± 0.75 µg/g), and silk (7.32 ± 0.31 µg/g). In field trials, all larval population densities, plant damage rates, and leaf damage levels of DBN3601T maize were significantly lower than the conventional maize. This research indicated that the DBN3601T event had a high control efficiency against M. separata and could be deployed in southwest China for the management of M. separata.

Nutritional Status, Sex, and Ambient Temperature Modulate the Wingbeat Frequency of the Diamondback Moth Plutella xylostella.

The diamondback moth, Plutella xylostella L. (Lepidoptera: Plutellidae), is a cosmopolitan horticultural pest that is undergoing a fast, climate-driven range expansion. Its wide geographic distribution, pest status, and high incidence of insecticide resistance are directly tied to long-distance migration. Wingbeat frequency (WBF) is a key aspect of P. xylostella migratory behavior, but has received limited scientific attention. Here, we investigated the effects of environmental parameters, age, adult nutrition, and sex on P. xylostella WBF. Across experimental regimes, WBF ranged from 31.39 Hz to 78.87 Hz. Over a 10-35 °C range, the WBF of both male and female moths increased with temperature up to 62.96 Hz. Though male WBF was unaffected by humidity, females exhibited the highest WBF at 15% relative humidity (RH). WBF was unaffected by adult age, but adult nutrition exerted important impacts. Specifically, the WBF of moths fed honey water (54.66 Hz) was higher than that of water-fed individuals (49.42 Hz). Lastly, males consistently exhibited a higher WBF than females. By uncovering the biological and (nutritional) ecological determinants of diamondback moth flight, our work provides invaluable guidance to radar-based monitoring, migration forecasting, and the targeted deployment of preventative mitigation tactics.

Toxic Effects of Bt-(Cry1Ab+Vip3Aa) Maize on Storage Pest Paralipsa gularis (Zeller).

Paralipsa gularis (Zeller) is a storage pest; however, in recent years it has evolved into a considerable maize pest during the late growth stage in the border region between China and other Southeast Asian countries. Bt transgenic insect-resistant maize is an effective measure in controlling a wide range of lepidopteran pests, but there is a lack of research on the toxic effects of storage pests. We tested the toxicity of Bt-Cry1Ab, Vip3Aa, and their complex proteins against P. gularis via bioassay and investigated the efficiency of Bt-(Cry1Ab+Vip3Aa) maize in controlling P. gularis during the late growth stage of maize in the period 2022-2023. The bioassay results show that the susceptibilities of P. gularis to the two Bt proteins and their complex proteins were significantly different. The LC50 values of DBNCry1Ab ("DBN9936" event), DBNVip3Aa ("DBN9501" event), DBN Cry1Ab+Vip3Aa ("DBN3601T" event), and Syngenta Cry1Ab+Vip3Aa ("Bt11" event × "MIR162" event) were 0.038 µg/g, 0.114 µg/g, 0.110 µg/g, and 0.147 µg/g, and the GIC50 values were 0.014 µg/g, 0.073 µg/g, 0.027 µg/g, and 0.026 µg/g, respectively. Determination of the expression content of the insecticidal protein in different tissues of Bt-(Cry1Ab+Vip3Aa) maize shows that the total Bt protein content in different tissues was in the following order: stalk > bract > cob > kernel. However, the bioassay results show that the mortalities of P. gularis feeding on Bt-(Cry1Ab+Vip3Aa) maize in different tissues at different growth stages were all above 93.00%. The field trial indicates that the occurrence density of larvae and plant damage rate for conventional maize were 422.10 individuals/100 plants and 94.40%, respectively, whereas no larvae were found on Bt-(Cry1Ab+Vip3Aa) maize. In summary, this study implies that Bt-(Cry1Ab+Vip3Aa) maize has a high potential for control of P. gularis, providing a new technical measure for the management of the pest.

Simultaneous inhibition of FAK and ROS1 synergistically repressed triple-negative breast cancer by upregulating p53 signalling.

BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype lacking effective targeted therapies, necessitating innovative treatment approaches. While targeting ROS proto-oncogene 1 (ROS1) with crizotinib has shown promise, resistance remains a limitation. Recent evidence links focal adhesion kinase (FAK) to drug resistance, prompting our study to assess the combined impact of FAK inhibitor IN10018 and crizotinib in TNBC and elucidate the underlying mechanisms. METHODS: We employed the Timer database to analyze FAK and ROS1 mRNA levels in TNBC and adjacent normal tissues. Furthermore, we investigated the correlation between FAK, ROS1, and TNBC clinical prognosis using the GSE database. We conducted various in vitro assays, including cell viability, colony formation, flow cytometry, EdU assays, and western blotting. Additionally, TNBC xenograft and human TNBC organoid models were established to assess the combined therapy's efficacy. To comprehensively understand the synergistic anti-tumor mechanisms, we utilized multiple techniques, such as RNA sequencing, immunofluorescence, cell flow cytometry, C11-BODIPY staining, MDA assay, and GSH assay. RESULTS: The Timer database revealed higher levels of FAK and ROS1 in TNBC tissues compared to normal tissues. Analysis of GEO databases indicated that patients with high FAK and ROS1 expression had the poorest prognosis. Western blotting confirmed increased p-FAK expression in crizotinib-resistant TNBC cells. In vitro experiments showed that the combination therapy down-regulated cyclin B1, p-Cdc2, and Bcl2 while up-regulating BAX, cleaved-Caspase-3, cleaved-Caspase-9, and cleaved PARP. In TNBC xenograft models, the tumor volume in the combination therapy group was 73% smaller compared to the control group (p < 0.0001). Additionally, the combination therapy resulted in a 70% reduction in cell viability in human TNBC organoid models (p < 0.0001). RNA sequencing analysis of TNBC cells and xenograft tumor tissues highlighted enrichment in oxidative stress, glutathione metabolism, and p53 pathways. The combined group displayed a fivefold rise in the reactive oxygen species level, a 69% decrease in the GSH/GSSG ratio, and a sixfold increase in the lipid peroxidation in comparison to the control group. Western blotting demonstrated p53 upregulation and SCL7A11 and GPX4 downregulation in the combination group. The addition of a p53 inhibitor reversed these effects. CONCLUSION: Our study demonstrates that the combination of IN10018 and crizotinib shows synergistic antitumor effects in TNBC. Mechanistically, this combination inhibits cell proliferation, enhances apoptosis, and induces ferroptosis, which is associated with increased p53 levels.

Pest Status, Bio-Ecology, and Area-Wide Management of Mirids in East Asia.

Mirids (Hemiptera: Heteroptera: Miridae) feed upon a wide variety of cultivated and wild plants and can be economically important crop pests. They have traditionally been perceived as innocuous herbivores in East Asia; however, population levels of various mirid species have dramatically increased over the past decades. High-profile pests such as Apolygus spp., Adelphocoris spp., and Lygus spp. are now widely distributed across the region, and their infestation pressure is associated with climate, agroecological conditions, and farming practices. This review outlines how an in-depth understanding of pest biology, a systems-level characterization of pest ecology, and a comprehensive evaluation of integrated pest management tactics have enabled sustainable management of mirids across crop boundaries and harvest cycles. This work underscores how more holistic, integrative research approaches can accelerate the implementation of area-wide management of generalist pests, effectively prevent pest population build-up and yield impact, and shrink the environmental footprint of agriculture. In addition to highlighting the merits of interdisciplinary systems approaches, we discuss prospects and challenges for the sustainable management of polyphagous mirid pests in landscape matrices.

S100A8/A9 as a risk factor for breast cancer negatively regulated by DACH1.

BACKGROUND: S100A8 and S100A9 are members of Ca2+-binding EF-hand superfamily, mainly expressed by macrophages and neutrophils. Limited by the poor stability of homodimers, they commonly exist as heterodimers. Beyond acting as antibacterial cytokines, S100A8/A9 is also associated with metabolic and autoimmune diseases such as obesity, diabetes, and rheumatoid arthritis. While the involvement of S100A8/A9 in breast cancer development has been documented, its prognostic significance and the precise regulatory mechanisms remain unclear. METHODS: S100A8/A9 protein in breast cancer samples was evaluated by immunohistochemistry staining with tumor tissue microarrays. The serum S100A8 concentration in patients was measured by enzyme-linked immunosorbent assay (ELISA). The S100A8 secreted by breast cancer cells was detected by ELISA as well. Pooled analyses were conducted to explore the relationships between S100A8/A9 mRNA level and clinicopathological features of breast cancer patients. Besides, the effects of S100A8/A9 and DACH1 on patient outcomes were analyzed by tissue assays. Finally, xenograft tumor assays were adopted to validate the effects of DACH1 on tumor growth and S100A8/A9 expression. RESULTS: The level of S100A8/A9 was higher in breast cancer, relative to normal tissue. Increased S100A8/A9 was related to poor differentiation grade, loss of hormone receptors, and Her2 positive. Moreover, elevated S100A8/A9 predicted a worse prognosis for breast cancer patients. Meanwhile, serum S100A8 concentration was upregulated in Grade 3, basal-like, and Her2-overexpressed subtypes. Additionally, the results of public databases showed S100A8/A9 mRNA level was negatively correlated to DACH1. Stable overexpressing DACH1 in breast cancer cells significantly decreased the generation of S100A8. The survival analysis demonstrated that patients with high S100A8/A9 and low DACH1 achieved the shortest overall survival. The xenograft models indicated that DACH1 expression significantly retarded tumor growth and downregulated S100A8/A9 protein abundance. CONCLUSION: S100A8/A9 is remarkedly increased in basal-like and Her2-overexpressed subtypes, predicting poor prognosis of breast cancer patients. Tumor suppressor DACH1 inhibits S100A8/A9 expression. The combination of S100A8/A9 and DACH1 predicted the overall survival of breast cancer patients more preciously.

New insights into the stemness of adoptively transferred T cells by γc family cytokines.

T cell-based adoptive cell therapy (ACT) has exhibited excellent antitumoral efficacy exemplified by the clinical breakthrough of chimeric antigen receptor therapy (CAR-T) in hematologic malignancies. It relies on the pool of functional T cells to retain the developmental potential to serially kill targeted cells. However, failure in the continuous supply and persistence of functional T cells has been recognized as a critical barrier to sustainable responses. Conferring stemness on infused T cells, yielding stem cell-like memory T cells (TSCM) characterized by constant self-renewal and multilineage differentiation similar to pluripotent stem cells, is indeed necessary and promising for enhancing T cell function and sustaining antitumor immunity. Therefore, it is crucial to identify TSCM cell induction regulators and acquire more TSCM cells as resource cells during production and after infusion to improve antitumoral efficacy. Recently, four common cytokine receptor γ chain (γc) family cytokines, encompassing interleukin-2 (IL-2), IL-7, IL-15, and IL-21, have been widely used in the development of long-lived adoptively transferred TSCM in vitro. However, challenges, including their non-specific toxicities and off-target effects, have led to substantial efforts for the development of engineered versions to unleash their full potential in the induction and maintenance of T cell stemness in ACT. In this review, we summarize the roles of the four γc family cytokines in the orchestration of adoptively transferred T cell stemness, introduce their engineered versions that modulate TSCM cell formation and demonstrate the potential of their various combinations. Video Abstract.

Cross-Regional Pollination Behavior of Trichoplusia ni between China and the Indo-China Peninsula.

Noctuid moths, a group of "non-bee" pollinators, are essential but frequently underappreciated. To elucidate their roles in cross-regional pollination, this study selected the agriculturally significant species, cabbage looper (CL) Trichoplusia ni, as a representative model. From 2017 to 2021, this study was conducted on Yongxing Island, situated at the center of the South China Sea. We investigated the flower-visiting activities of CL, including its occurrence, potential host species, and geographic distribution in the surrounding areas of the South China Sea. First, the potential transoceanic migratory behavior and regional distribution of CL were systematically monitored through a comprehensive integration of the data obtained from a searchlight trap. The transoceanic migratory behavior of CL was characterized by intermittent occurrence, with the major migratory periods and the peak outbreak yearly. Furthermore, trajectory analysis confirmed the ability of CL to engage in periodic, round-trip, migratory flights between Southeast Asian countries and China. More importantly, an observation of pollen on the body surface demonstrated that 95.59% (130/136) of the migrating individuals carried pollen. The proboscis and compound eyes were identified as the primary pollen-carrying parts, with no observable gender-based differences in pollen-carrying rates. Further, identifying the pollen carried by CL using morphological and molecular methods revealed a diverse range of pollen types from at least 17 plant families and 31 species. Notably, CL predominantly visited eudicot and herbaceous plants. In conclusion, this pioneering study has not only revealed the long-distance migration activities of these noctuid moths in the East Asian region but also provided direct evidence supporting their role as potential pollinators. These findings offer a critical theoretical basis to guide the development of scientific management strategies.

Exploiting innate immunity for cancer immunotherapy.

Immunotherapies have revolutionized the treatment paradigms of various types of cancers. However, most of these immunomodulatory strategies focus on harnessing adaptive immunity, mainly by inhibiting immunosuppressive signaling with immune checkpoint blockade, or enhancing immunostimulatory signaling with bispecific T cell engager and chimeric antigen receptor (CAR)-T cell. Although these agents have already achieved great success, only a tiny percentage of patients could benefit from immunotherapies. Actually, immunotherapy efficacy is determined by multiple components in the tumor microenvironment beyond adaptive immunity. Cells from the innate arm of the immune system, such as macrophages, dendritic cells, myeloid-derived suppressor cells, neutrophils, natural killer cells, and unconventional T cells, also participate in cancer immune evasion and surveillance. Considering that the innate arm is the cornerstone of the antitumor immune response, utilizing innate immunity provides potential therapeutic options for cancer control. Up to now, strategies exploiting innate immunity, such as agonists of stimulator of interferon genes, CAR-macrophage or -natural killer cell therapies, metabolic regulators, and novel immune checkpoint blockade, have exhibited potent antitumor activities in preclinical and clinical studies. Here, we summarize the latest insights into the potential roles of innate cells in antitumor immunity and discuss the advances in innate arm-targeted therapeutic strategies.

Downregulation of a transcription factor associated with resistance to Bt toxin Vip3Aa in the invasive fall armyworm.

Transgenic crops producing insecticidal proteins from Bacillus thuringiensis (Bt) have revolutionized control of some major pests. However, more than 25 cases of field-evolved practical resistance have reduced the efficacy of transgenic crops producing crystalline (Cry) Bt proteins, spurring adoption of alternatives including crops producing the Bt vegetative insecticidal protein Vip3Aa. Although practical resistance to Vip3Aa has not been reported yet, better understanding of the genetic basis of resistance to Vip3Aa is urgently needed to proactively monitor, delay, and counter pest resistance. This is especially important for fall armyworm (Spodoptera frugiperda), which has evolved practical resistance to Cry proteins and is one of the world's most damaging pests. Here, we report the identification of an association between downregulation of the transcription factor gene SfMyb and resistance to Vip3Aa in S. frugiperda. Results from a genome-wide association study, fine-scale mapping, and RNA-Seq identified this gene as a compelling candidate for contributing to the 206-fold resistance to Vip3Aa in a laboratory-selected strain. Experimental reduction of SfMyb expression in a susceptible strain using RNA interference (RNAi) or CRISPR/Cas9 gene editing decreased susceptibility to Vip3Aa, confirming that reduced expression of this gene can cause resistance to Vip3Aa. Relative to the wild-type promoter for SfMyb, the promoter in the resistant strain has deletions and lower activity. Data from yeast one-hybrid assays, genomics, RNA-Seq, RNAi, and proteomics identified genes that are strong candidates for mediating the effects of SfMyb on Vip3Aa resistance. The results reported here may facilitate progress in understanding and managing pest resistance to Vip3Aa.

Regional Pollination Activity by Moth Migration in Athetis lepigone.

Nocturnal moths (Lepidoptera) are important pollinators of a wide range of plant species. Understanding the foraging preferences of these insects is essential for their scientific management. However, this information is lacking for most moth species. The present study was therefore conducted to delineate the host plant feeding and pollination ranges of an agriculturally important nocturnal moth species Athetis lepigone by identifying the pollen species adhering to their bodies during long-distance migration. Pollen grains were dislodged from 1871 A. lepigone migrants captured on Beihuang Island in the Bohai Strait between 2020 and 2021. This region is a key seasonal migration pathway for A. lepigone in northern China. Almost 20% of all moths sampled harbored pollens, providing direct evidences that this moth species may serve as pollinators. Moreover, at least 39 pollen taxa spanning 21 plant families and 31 genera were identified, with a preference for Asteraceae, Amaranthaceae, and Pinaceae. Additionally, the pollen adherence ratios and taxa varied with moth sex, inter-annual changes, and seasonal fluctuations. Most importantly, the pollen taxa were correlated with insect migration stages and indicated that A. lepigone bidirectionally migrates between central China (Shandong, Hebei, and Henan Provinces) and northeastern China (Liaoning Province). Overall, the findings of the present work provide valuable information on the pollination behavior, geographical origins, and pollination regions of A. lepigone moths and could facilitate the design and optimization of efficacious local and regional management strategies for this important insect.

Focal adhesion kinase: from biological functions to therapeutic strategies.

Focal adhesion kinase (FAK), a nonreceptor cytoplasmic tyrosine kinase, is a vital participant in primary cellular functions, such as proliferation, survival, migration, and invasion. In addition, FAK regulates cancer stem cell activities and contributes to the formation of the tumor microenvironment (TME). Importantly, increased FAK expression and activity are strongly associated with unfavorable clinical outcomes and metastatic characteristics in numerous tumors. In vitro and in vivo studies have demonstrated that modulating FAK activity by application of FAK inhibitors alone or in combination treatment regimens could be effective for cancer therapy. Based on these findings, several agents targeting FAK have been exploited in diverse preclinical tumor models. This article briefly describes the structure and function of FAK, as well as research progress on FAK inhibitors in combination therapies. We also discuss the challenges and future directions regarding anti-FAK combination therapies.