Identification of NR3C2 as a functional diagnostic and prognostic biomarker and potential therapeutic target in non-small cell lung cancer.

Background: Non-small cell lung cancer (NSCLC), including the lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) subtypes, is a malignant tumor type with a poor 5-year survival rate. The identification of new powerful diagnostic biomarkers, prognostic biomarkers, and potential therapeutic targets in NSCLC is urgently required. Methods: The UCSC Xena, UALCAN, and GEO databases were used to screen and analyze differentially expressed genes, regulatory modes, and genetic/epigenetic alterations in NSCLC. The UCSC Xena database, GEO database, tissue microarray, and immunohistochemistry staining analyses were used to evaluate the diagnostic and prognostic values. Gain-of-function assays were performed to examine the roles. The ESTIMATE, TIMER, Linked Omics, STRING, and DAVID algorithms were used to analyze potential molecular mechanisms. Results: NR3C2 was identified as a potentially important molecule in NSCLC. NR3C2 is expressed at low levels in NSCLC, LUAD, and LUSC tissues, which is significantly related to the clinical indexes of these patients. Receiver operating characteristic curve analysis suggests that the altered NR3C2 expression patterns have diagnostic value in NSCLC, LUAD, and especially LUSC patients. Decreased NR3C2 expression levels can help predict poor prognosis in NSCLC and LUAD patients but not in LUSC patients. These results have been confirmed both with database analysis and real-world clinical samples on a tissue microarray. Copy number variation contributes to low NR3C2 expression levels in NSCLC and LUAD, while promoter DNA methylation is involved in its downregulation in LUSC. Two NR3C2 promoter methylation sites have high sensitivity and specificity for LUSC diagnosis with clinical application potential. NR3C2 may be a key participant in NSCLC development and progression and is closely associated with the tumor microenvironment and immune cell infiltration. NR3C2 co-expressed genes are involved in many cancer-related signaling pathways, further supporting a potentially significant role of NR3C2 in NSCLC. Conclusions: NR3C2 is a novel potential diagnostic and prognostic biomarker and therapeutic target in NSCLC.

Global Burden of Stroke Attributable to Low Physical Activity/High Body Mass Index Among People Aged 55 Years and Older.

BACKGROUND: This study aimed to quantify the global stroke burden attributable to low physical activity and high body mass index in adults aged ≥55 years using data from the Global Burden of Disease 2019 study. METHODS: We extracted data on stroke mortality, disability-adjusted life years, and risk factor exposure from the Global Burden of Disease 2019 study for people aged ≥55 years. We calculated the population-attributable fraction and absolute number of stroke cases and disability-adjusted life years attributable to low physical activity and high body mass index by location, age group, sex, and year. RESULTS: Globally, body mass index and physical inactivity-attributable stroke burden have declined modestly since 1990, but with diverging escalatory regional trajectories. Population growth and aging drive this rising burden. CONCLUSIONS: Multidimensional, context-specific strategies focused on modifiable lifestyle risks are imperative to address the modest declines and escalatory regional trajectories in body mass index and physical inactivity-attributable stroke burden.

Dual-molecular targeting nanomedicine upregulates synergistic therapeutic efficacy in preclinical hepatoma models.

Advanced hepatocellular carcinoma (HCC) is one of the most challenging cancers because of its heterogeneous and aggressive nature, precluding the use of curative treatments. Sorafenib (SOR) is the first approved molecular targeting agent against the mitogen-activated protein kinase (MAPK) pathway for the noncurative therapy of advanced HCC; yet, any clinically meaningful benefits from the treatment remain modest, and are accompanied by significant side effects. Here, we hypothesized that using a nanomedicine platform to co-deliver SOR with another molecular targeting drug, metformin (MET), could tackle these issues. A micelle self-assembled with amphiphilic polypeptide methoxy poly(ethylene glycol)-block-poly(L-phenylalanine-co-l-glutamic acid) (mPEG-b-P(LP-co-LG)) (PM) was therefore designed for combinational delivery of two molecular targeted drugs, SOR and MET, to hepatomas. Compared with free drugs, the proposed, dual drug-loaded micelle (PM/SOR+MET) enhanced the drugs' half-life in the bloodstream and drug accumulation at the tumor site, thereby inhibiting tumor growth effectively in the preclinical subcutaneous, orthotopic and patient-derived xenograft hepatoma models without causing significant systemic and organ toxicity. Collectively, these findings demonstrate an effective dual-targeting nanomedicine strategy for treating advanced HCC, which may have a translational potential for cancer therapeutics. STATEMENT OF SIGNIFICANCE: Treatment of advanced hepatocellular carcinoma (HCC) remains a formidable challenge due to its aggressive nature and the limitations inherent to current therapies. Despite advancements in molecular targeted therapies, such as Sorafenib (SOR), their modest clinical benefits coupled with significant adverse effects underscore the urgent need for more efficacious and less toxic treatment modalities. Our research presents a new nanomedicine platform that synergistically combines SOR with metformin within a specialized diblock polypeptide micelle, aiming to enhance therapeutic efficacy while reducing systemic toxicity. This innovative approach not only exhibits marked antitumor efficacy across multiple HCC models but also significantly reduces the toxicity associated with current treatments. Our dual-molecular targeting approach unveils a promising nanomedicine strategy for the molecular treatment of advanced HCC, potentially offering more effective and safer treatment alternatives with significant translational potential.

Association between vitamin B2 intake and prostate-specific antigen in American men: 2003-2010 National Health and Nutrition Examination Survey.

BACKGROUND: Accumulating evidence suggests a pivotal role of vitamin B2 in the pathogenesis and progression of prostate cancer (PCa). Vitamin B2 intake has been postulated to modulate the screening rate for PCa by altering the concentration of prostate-specific antigen(PSA). However, the relationship between vitamin B2 and PSA remains indeterminate. Hence, we conducted a comprehensive evaluation of the association between vitamin B2 intake and PSA levels, utilizing data from the National Health and Nutrition Examination Survey (NHANES) database. METHODS: From a pool of 20,371 participants in the NHANES survey conducted between 2003 and 2010, a cohort of 2,323 participants was selected for the present study. The male participants were classified into four distinct groups based on their levels of vitamin B2 intake. We employed a multiple linear regression model and a non-parametric regression method to investigate the relationship between vitamin B2 and PSA levels. RESULTS: The study cohort comprised of 2,323 participants with a mean age of 54.95 years (± 11.73). Our findings revealed a statistically significant inverse correlation between vitamin B2 intake (mg) and PSA levels, with a reduction of 0.13 ng/ml PSA concentration for every unit increase in vitamin B2 intake. Furthermore, we employed a fully adjusted model to construct a smooth curve to explore the possible linear relationship between vitamin B2 intake and PSA concentration. CONCLUSIONS: Our study in American men has unveiled a notable inverse association between vitamin B2 intake and PSA levels, potentially posing a challenge for the identification of asymptomatic prostate cancer. Specifically, our findings suggest that individuals with higher vitamin B2 intake may be at a greater risk of being diagnosed with advanced prostate cancer in the future, possibly indicating a detection bias. These results may offer a novel explanation for the observed positive correlation between vitamin B2 intake and prostate cancer.

Templated Synthesis of Copper Nanoclusters with a Hybrid Lysozyme-Polymer Material for Enhanced Fluorescence.

Hybrid materials that combine organic polymers and biomacromolecules offer unique opportunities for precisely controlling 3D chemical environments. Although biological or organic templates have been separately used to control the growth of inorganic nanoclusters, hybrid structures represent a relatively unexplored approach to tailoring nanocluster properties. Here, we demonstrate that a molecularly defined lysozyme-polymer resin material acts as a structural scaffold for the synthesis of copper nanoclusters (CuNCs) with well controlled size distributions. The resulting CuNCs have significantly enhanced fluorescence compared with syntheses based on polymeric or biological templates alone. The synergistic approach described here is appealing for the synthesis of biocompatible fluorescent labels with improved photostability.

Esculin suppresses the PERK-eIF2α-CHOP pathway by enhancing SIRT1 expression in oxidative stress-induced rat chondrocytes, mitigating osteoarthritis progression in a rat model.

OBJECTIVE: Osteoarthritis (OA) is a degenerative disease characterized by the gradual degeneration of chondrocytes, involving endoplasmic reticulum (ER) stress. Esculin is a natural compound with antioxidant, anti-inflammatory and anti-tumor properties. However, its impact on ER stress in OA therapy has not been thoroughly investigated. We aim to determine the efficiency of Esculin in OA treatment and its underlying mechanism. METHODS: We utilized the tert-butyl hydroperoxide (TBHP) to establish OA model in chondrocytes. The expression of SIRT1, PERK/eIF2α pathway-related proteins, apoptosis-associated proteins and ER stress-related proteins were detected by Western blot and Real-time PCR. The apoptosis was evaluated by flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. X-ray imaging, Hematoxylin & Eosin staining, Safranin O staining and immunohistochemistry were used to assess the pharmacological effects of Esculin in the anterior cruciate ligament transection (ACLT) rat OA model. RESULTS: Esculin downregulated the expression of PERK/eIF2α pathway-related proteins, apoptosis-associated proteins and ER stress-related proteins, while upregulated the expression of SIRT1 and Bcl2 in the TBHP-induced OA model in vitro. It was coincident with the results of TUNEL staining and flow cytometry. We further confirmed the protective effect of Esculin in the rat ACLT-related model. CONCLUSION: Our results suggest the potential therapeutic value of Esculin on osteoarthritis. It probably inhibits the PERK-eIF2α-ATF4-CHOP pathway by upregulating SIRT1, thereby mitigating endoplasmic reticulum stress and protecting chondrocytes from apoptosis.

Global, regional and national epidemiology of allergic disorders in children from 1990 to 2019: findings from the Global Burden of Disease study 2019.

OBJECTIVE: This modelling study aimed to estimate the burden for allergic diseases in children during a period of 30 years. DESIGN: Population-based observational study. MAIN OUTCOMES AND MEASURES: The data on the incidence, mortality and disability-adjusted life years (DALYs) for childhood allergic diseases, such as atopic dermatitis (AD) and asthma, were retrieved from the Global Burden of Disease study 2019 online database. This data set spans various groups, including different regions, ages, genders and Socio-Demographic Indices (SDI), covering the period from 1990 to 2019. RESULTS: In 2019, there were approximately 81 million children with asthma and 5.6 million children with AD worldwide. The global incidence of asthma in children was 20 million. Age-standardised incidence rates showed a decrease of 4.17% for asthma, from 1075.14 (95% uncertainty intervals (UI), 724.63 to 1504.93) per 100 000 population in 1990 to 1030.33 (95% UI, 683.66 to 1449.53) in 2019. Similarly, the rates for AD decreased by 5.46%, from 594.05 (95% UI, 547.98 to 642.88) per 100 000 population in 1990 to 561.61 (95% UI, 519.03 to 608.29) in 2019. The incidence of both asthma and AD was highest in children under 5 years of age, gradually decreasing with age. Interestingly, an increase in SDI was associated with a rise in the incidence of both conditions. However, the mortality rate and DALYs for asthma showed a contrasting trend. CONCLUSIONS: Over the past three decades, there has been a worldwide increase in new asthma and AD cases, even though mortality rates have significantly declined. However, the prevalence of these allergic diseases among children varies considerably across regions, countries and age groups. This variation highlights the need for precise prevalence assessments. These assessments are vital in formulating effective strategies for prevention and treatment.

Separation of Nanoparticle Seed Pseudoisomers via Amplification of Their Crystallographic Differences.

Seed-mediated syntheses rely on small nanoparticle (NP) precursors that act as templates for growth but are often inhomogeneous with respect to their internal twinning structures (e.g., single crystalline, multiply twinned), leading to nonuniform product morphologies. To address this, we developed a method for separating seed NPs of the same approximate size (∼ 10 nm) but with different interior twinning (i.e., NP "pseudoisomers") by exaggerating their crystallographic differences through heteroexpitaxial metal overgrowth. Specifically, single crystalline and pentatwinned Au seeds that are natively inseparable via traditional methods exhibit drastically different Ag shell morphologies that allow for their selective precipitation through colloidal depletion forces. Oxidation of the Ag shell from separated particles results in seeds that are both size uniform and crystallographically pure (>99%), allowing for the controlled synthesis of a library of Oh- and D5h-symmetric gold NPs bearing {111}, {110}, {730}, {310}, {720}, and {100} facets, several of which have no precedent in the literature. These results lay the foundation for precision nanosynthesis by establishing a new paradigm for the purification of NP precursors.

Analysis of the global burden of disease study highlights the global, regional, and national trends of idiopathic epilepsy epidemiology from 1990 to 2019.

Epilepsy is a profound disorder, accounting for roughly 1% of the global disease burden. It can result in premature death and significant disability. To comprehensively understand the current dynamics and trends of idiopathic epilepsy, a deep insight into its epidemiological attributes is vital. We evaluated the incidence, prevalence, mortality, and disability-adjusted life years associated with idiopathic epilepsy from 1990 to 2019 using data and methodologies from the Global Burden of Disease Study. In 2019, there were approximately 2,898,222 individuals diagnosed with idiopathic epilepsy. Intriguingly, from 1990 to 2019, the age-standardized incidence rate of idiopathic epilepsy was consistently lower in women compared to men. Over these three decades, global mortality connected to idiopathic epilepsy increased by 13.95%. However, within the same period, age-standardized death rates for idiopathic epilepsy decreased from 1.94 per 100,000 population to 1.46 per 100,000 population. Predictions indicate an increase in the incidence of idiopathic epilepsy across all age brackets through 2035, especially among the elderly aged 80 and above. Mortality rates are projected to climb for those aged 80 and above while remaining relatively unchanged in other age demographics. Idiopathic epilepsy continues to be a significant contributor to both disability and death. The findings of our study underscore the critical importance of incorporating idiopathic epilepsy management into modern healthcare frameworks. Such strategic inclusion can enhance public awareness of relevant risk factors and the range of available therapeutic interventions.

Brucellosis involving the aorta and iliac arteries: a systematic review of 130 cases.

Objective: Brucellosis, the most common bacterial zoonosis, poses a serious threat to public health in endemic regions. Cardiovascular complications of brucellosis, mostly pericarditis or endocarditis, are the leading cause of brucellosis-related death. Complications involving the aorta and iliac arteries are extremely rare but can be life-threatening. Our objective was to identify and review all reported cases of aortic and iliac involvement in brucellosis to provide a deep, up-to-date understanding of the clinical characteristics and management of the disease. Methods: Online searches in PubMed, Web of Science, China National Knowledge Infrastructure, and the Chinese Wanfang database were conducted to collect articles reporting cases of brucellosis with aortic and iliac artery involvement. All data in terms of patient demographics, diagnostic methods, clinical manifestations, and treatment regimens and outcomes were extracted and analyzed in this systematic review. Results: A total of 79 articles were identified, reporting a total of 130 cases of brucellosis with aortic and iliac artery involvement. Of the 130 cases, 110 (84.5%) were male individuals and 100 (76.9%) were over 50 years old. The patients had an overall mortality rate of 12.3%. The abdominal aorta was most commonly involved, followed by the ascending aorta, iliac artery, and descending thoracic aorta. Arteriosclerosis, hypertension, and smoking were the most common comorbidities. There were 71 patients (54.6%) who presented with systemic symptoms of infection at the time of admission. Endovascular therapy was performed in 56 patients (43.1%), with an overall mortality rate of 3.6%. Open surgery was performed in 52 patients (40.0%), with an overall mortality rate of 15.4%. Conclusion: Aortic and iliac involvement in brucellosis is extremely rare but can be life-threatening. Its occurrence appears to be associated with the male gender, an older age, arteriosclerosis, and smoking. Although the number of reported cases in developing countries has increased significantly in recent years, its incidence in these countries may still be underestimated. Early diagnosis and therapeutic intervention are critical in improving patient outcomes. Endovascular therapy has become a preferred surgical treatment in recent years, and yet, its long-term complications remain to be assessed.

The cytotoxicity of γδT cells in non-small cell lung cancer mediated via coordination of the BCL-2 and AKT pathways.

The effectiveness and mechanisms of γδT-cell immunotherapy in lung cancer remain unclear. In this study, we assessed the effects of continuous, low-dose γδT-cell intervention on lung cancer cells. We cultured γδT cells with a lung cancer cell line (A549) and replaced the γδT-cell population every 48 hours. The killing effect of γδTcells on A549 cells and the Half-maximal inhibitory concentration (IC50) value were detected by the cholecystokinin octapeptide (CCK-8) method. The levels of perforin, granzyme B and the inflammatory factors interleukin-6 (IL-6), interferon (IFN)-γ, and tumor necrosis factor-alpha (TNF-a), in the supernatants of cocultured cells were measured by ELISA. The protein expression of Bcl-2, Bax, PI3K and Akt was detected by western blotting. Our results indicated that γδT-cell treatment decreased the protein expression of Bcl-2, PI3K, and AKT but upregulated that of Bax. Moreover, γδT-cell treatment increased perforin and granzyme B release related to the Bax/Bcl-2 signaling pathway. In addition, γδT-cell-mediated cytolysis for A549 cells involved the PI3K/AKT pathway. In vivo results were consistent with the in vitro results. γδT-cell immunotherapy integrated regulation of a signaling pathway network involving the mutual regulation of apoptosis and proliferation. γδT-cell immunotherapy could be used to enhance the cytotoxic killing of lung cancer cells.

Clinical effect of endovascular repair of complex aortic lesions using optimized Octopus surgery.

Objective: Complex aortic lesions, especially those involving branches of the visceral artery, remain a challenge to treat. A single-center study using the Octopus technique to evaluate the safety and short-term effects of endovascular repair of complex aortic lesions was reported and documented. Methods: The data of six cases who underwent optimized Octopus surgery in our center from August 2020 to February 2022 were analyzed retrospectively. The choice of operation scheme, operation time, operation complications, and follow-up data were analyzed among them. Results: The average age of the six patients undergoing optimized Octopus surgery was 55.1 ± 17.2 years. Two cases were diagnosed as pararenal aortic aneurysms; four cases were aortic dissection involving the visceral artery. All cases achieved technical success; all visceral arteries were reconstructed as planned. A total of 17 visceral arteries were planned to be reconstructed; five celiac arteries were embolized. Three cases of gutter endoleak were found during the operation without embolization but with follow-up observation. There were two cases of slight damage to renal function and two cases of perioperative death. Other complications, such as intestinal ischemia and spinal cord ischemia, did not occur. Follow-up ranged from 6 months to 30 months. One patient died of gastrointestinal bleeding 6 months after the operation. At the 6 months follow-up, computed tomographic angiography showed that all internal leaks had disappeared. The patency rate of the visceral artery was 100%, and no complications, such as stent displacement and occlusion, occurred during the follow-up period. Conclusion: With fenestrated and branched stent grafts technology not widely available, and off label use not a viable option, Octopus technology for treating complex aortic lesions should be considered. The Octopus technique is an up-and-coming surgical method, but we should recognize its operation difficulty, operation-related complications, and long-term prognosis. We should pay attention to and continue to optimize Octopus technology.

Human descending aorta injury caused by brucellosis: A case report.

BACKGROUND: Brucellosis is one of the most common zoonotic diseases in the world. Although cardiovascular complications of human brucellosis account for only 3% of morbidity, they are the leading cause of death. Peripheral vascular disease due to brucellosis is rare and under-reported in the literature. CASE PRESENTATION: Two patients with previous brucellosis, both of whom had been treated with anti-brucellosis, were admitted to vascular surgery for thoracic aortic ulcer and abdominal aortic pseudoaneurysm, respectively, with positive IgG antibody to brucellosis and negative IgM antibody to brucellosis, tube agglutination test, and blood culture. These 2 patients were successfully treated with aortic stent-graft implantation and followed up for 8 and 10 weeks without complications. CONCLUSIONS: Chronic damage to human blood vessels by brucellosis may not disappear with brucellosis treatment, and peripheral blood vessels should be examined annually in people previously diagnosed with brucellosis. Clinicians in related departments should pay attention to peripheral vascular complications of brucellosis.

Treatment of abdominal aortic pseudoaneurysm caused by brucellosis with endovascular aneurysm repair.

Peripheral vascular disease caused by brucellosis is rarely seen around the world; thus, it is easily ignored by patients and doctors, leading to a lack of corresponding screening and delayed comprehensive treatment. Currently, there is no standard or guideline for diagnosing and treating peripheral arterial disease caused by brucellosis. From June 2021 to December 2022, four cases of abdominal aortic pseudoaneurysm caused by brucellosis disease were treated with endovascular aneurysm repair This study reported treatment results as follows and reviewed the incidence, treatment, and prognosis of abdominal aortic pseudoaneurysm caused by brucellosis.

Genic male and female sterility in vegetable crops.

Vegetable crops are greatly appreciated for their beneficial nutritional and health components. Hybrid seeds are widely used in vegetable crops for advantages such as high yield and improved resistance, which require the participation of male (stamen) and female (pistil) reproductive organs. Male- or female-sterile plants are commonly used for production of hybrid seeds or seedless fruits in vegetables. In this review we will focus on the types of genic male sterility and factors affecting female fertility, summarize typical gene function and research progress related to reproductive organ identity and sporophyte and gametophyte development in vegetable crops [mainly tomato (Solanum lycopersicum) and cucumber (Cucumis sativus)], and discuss the research trends and application perspectives of the sterile trait in vegetable breeding and hybrid production, in order to provide a reference for fertility-related germplasm innovation.

Pollen tube emergence is mediated by ovary-expressed ALCATRAZ in cucumber.

Pollen tube guidance within female tissues of flowering plants can be divided into preovular guidance, ovular guidance and a connecting stage called pollen tube emergence. As yet, no female factor has been identified to positively regulate this transition process. In this study, we show that an ovary-expressed bHLH transcription factor Cucumis sativus ALCATRAZ (CsALC) functions in pollen tube emergence in cucumber. CsALC knockout mutants showed diminished pollen tube emergence, extremely reduced entry into ovules, and a 95% reduction in female fertility. Further examination showed two rapid alkalinization factors CsRALF4 and CsRALF19 were less expressed in Csalc ovaries compared to WT. Besides the loss of male fertility derived from precocious pollen tube rupture as in Arabidopsis, Csralf4 Csralf19 double mutants exhibited a 60% decrease in female fertility due to reduced pollen tube distribution and decreased ovule targeting efficiency. In brief, CsALC regulates female fertility and promotes CsRALF4/19 expression in the ovary during pollen tube guidance in cucumber.

Natural variation in CRABS CLAW contributes to fruit length divergence in cucumber.

Fruit length is a key domestication trait that affects crop yield and appearance. Cucumber (Cucumis sativus) fruits vary from 5 to 60 cm in length. Despite the identification of several regulators and multiple quantitative trait loci (QTLs) underlying fruit length, the natural variation, and molecular mechanisms underlying differences in fruit length are poorly understood. Through map-based cloning, we identified a nonsynonymous polymorphism (G to A) in CRABS CLAW (CsCRC) as underlying the major-effect fruit size/shape QTL FS5.2 in cucumber. The short-fruit allele CsCRCA is a rare allele that has only been found in round-fruited semi-wild Xishuangbanna cucumbers. A near-isogenic line (NIL) homozygous for CsCRCA exhibited a 34∼39% reduction in fruit length. Introducing CsCRCG into this NIL rescued the short-fruit phenotype, and knockdown of CsCRCG resulted in shorter fruit and smaller cells. In natural cucumber populations, CsCRCG expression was positively correlated with fruit length. Further, CsCRCG, but not CsCRCA, targets the downstream auxin-responsive protein gene CsARP1 to regulate its expression. Knockout of CsARP1 produced shorter fruit with smaller cells. Hence, our work suggests that CsCRCG positively regulates fruit elongation through transcriptional activation of CsARP1 and thus enhances cell expansion. Using different CsCRC alleles provides a strategy to manipulate fruit length in cucumber breeding.

CsIAGLU Regulates the Angle of Leaf Petiole by Affecting Endogenous Content of Auxin in Cucumber (Cucumis sativus L.).

The leaf angle is an important factor determining plant shoot architecture that may boost crop yield by increasing photosynthetic efficiency and facilitating high-density planting. Auxin is an important phytohormone involved in leaf angle regulation. Here, we identified two Single-Nucleotide Polymorphisms (SNPs) in the Indoleacetic Acid (IAA) glucosyltransferase gene CsIAGLU in 80 re-sequenced cucumber lines, of which the CsIAGLU717G,1234T is the dominant allele associated with a small leaf pedicle angle (LPA), whereas CsIAGLU717C,1234A is linked with a large LPA. CsIAGLU was highly expressed in leaves and petioles. In natural cucumber populations, the expression of CsIAGLU was negatively correlated with the LPA. The mutation of CsIAGLU induced by the CRISPR-Cas9 system resulted in elevated free IAA levels and enlarged cell expansion on the adaxial side of the petiole base, thus producing a greater LPA. Consistently, exogenous IAA treatment led to increased LPA and cell size. Therefore, our findings suggest that CsIAGLU functions as a negative regulator of LPA development via auxin-mediated cell expansion in cucumber, providing a valuable strategy for cucumber breeding with small LPAs.

Immunosuppressive adenosine-targeted biomaterials for emerging cancer immunotherapy.

Immunotherapy has paved the way for the future of cancer therapy, but there are still significant challenges to be overcome, such as the occurrence of immune escape or suppression. Adenosine is essential in modulating the immune responses of immune cells and maintaining immune tolerance. Emerging adenosine pathway inhibitors are considered a breakthrough in cancer immunotherapy, with emphasis first being placed on the top-down blockade of adenosine signaling axis, followed by combination therapy. However, these therapeutic strategies rely on adenosine inhibitors, mainly small molecules or antibody proteins, which are limited by a single route of administration and off-target toxicity. Therefore, synergistic nanomedicine with accurate delivery targeting deeper tumors is focused on in preclinical studies. This review discusses how adenosine reshapes immunosuppressive microenvironments through its effects on immune cells, including lymphocytes and myeloid cells. Additionally, it will be the first discussion of a comprehensive strategy of biomaterials in modulating the adenosine signaling pathway, including inhibition of adenosine production, inhibition of adenosine binding to immune cells, and depletion of adenosine in the microenvironments. Furthermore, biomaterials integrating multiple therapeutic modalities with adenosine blocking are also discussed as a promising strategy for promoting cancer immunotherapy.