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Abstract In the last decade, messenger ribonucleic acid (mRNA)-based drugs have gained great interest in both immunotherapy and non-immunogenic applications. This surge in interest can be largely attributed to the demonstration of distinct advantages offered by various mRNA molecules, alongside the rapid advancements in nucleic acid delivery systems. It is noteworthy that the immunogenicity of mRNA drugs presents a double-edged sword. In the context of immunotherapy, extra supplementation of adjuvant is generally required for induction of robust immune responses. Conversely, in non-immunotherapeutic scenarios, immune activation is unwanted considering the host tolerability and high expression demand for mRNA-encoded functional proteins. Herein, mainly focused on the linear non-replicating mRNA, we overview the preclinical and clinical progress and prospects of mRNA medicines encompassing vaccines and other therapeutics. We also highlight the importance of focusing on the host-specific variations, including age, gender, pathological condition, and concurrent medication of individual patient, for maximized efficacy and safety upon mRNA administration. Furthermore, we deliberate on the potential challenges that mRNA drugs may encounter in the realm of disease treatment, the current endeavors of improvement, as well as the application prospects for future advancements. Overall, this review aims to present a comprehensive understanding of mRNA-based therapies while illuminating the prospective development and clinical application of mRNA drugs.

Abstract The yield of pearl millet, a resilient cereal crop crucial for African food security, is severely impacted by the root parasitic weed Striga hermonthica, which requires host-released hormones, called strigolactones (SLs), for seed germination. Herein, we identify four SLs present in the Striga-susceptible line SOSAT-C88-P10 (P10) but absent in the resistant 29Aw (Aw). We generate chromosome-scale genome assemblies, including four gapless chromosomes for each line. The Striga-resistant Aw lacks a 0.7 Mb genome segment containing two putative CARLACTONOIC ACID METHYLTRANSFERASE1 (CLAMT1) genes, which may contribute to SL biosynthesis. Functional assays show that P10CLAMT1b produces the SL-biosynthesis intermediate methyl carlactonoate (MeCLA) and that MeCLA is the precursor of P10-specific SLs. Screening a diverse pearl millet panel confirms the pivotal role of the CLAMT1 section for SL diversity and Striga susceptibility. Our results reveal a reason for Striga susceptibility in pearl millet and pave the way for generating resistant lines through marker-assisted breeding or direct genetic modification.

The use of strigolactone (SL) analogs as suicidal germination agents to control the seed banks of the parasitic weed Striga hermonthica has gained interest for field applications in recent years. However, concerns about the environmental safety of these SL analogs remain. In this study, we evaluated the mutagenic potential of two selected SL analogs, Methyl Phenlactonoate 3 (MP3) and Nijmegen-1, across concentrations ranging from 1.5 to 5000 μg per plate. We conducted this assessment using five histidine-deficient mutant tester strains of Salmonella typhimurium. After incubating the SL analogs with the tester strains, we observed no significant increase in the number of revertants, with and without the S9 mix, compared to both negative and positive laboratory controls. These results suggest that MP3 and Nijmegen-1 are non-mutagenic according to the bacterial reverse mutation test, supporting their potential as environmentally safe agents for managing Striga populations.

Obsessional slowness (OS) is characterized by a syndrome of extreme slowness in doing ordinary, day-to-day activities. Several scholars regarded OS as secondary to obsessive compulsive disorder (OCD). Therefore, it is commonly thought to be the consequence of extensive rituals and has been paid minimal attention in its own right. A combination of behavior therapy and aromatherapy are recommended for treatment of this condition. However, the outcome is often frustrating. Reports of surgical management for OS are limited. Patient concerns:She had symptoms characterized by repeated checking and progressive slowness in self-care behavior. Diagnosis:At the age of 19, the patient had the first presentation. The patient was diagnosed with a case of OCD with obsessional slowness according to the International Classification of Diseases and Related Health Problems (ICD-10).Interventions:Considering the lack of a response to pharmacotherapy and cognitive behavioral therapy (CBT), we treated this case with anterior capsulotomy and accumbensotomy. Outcomes: Moderate somnolence, urticaria, juvenile behavior, mild short-term memory impairment and slight nonsense were noted during the first postoperative days. At 10 months, the patient’s OCD symptoms recovered nearly to her preoperative level. The OS symptom also had an obvious rebound at 10 months. Through comprehensive judgment, we decided to choose accumbensotomy. At 9 months after the accumbensotomy, the OCD symptoms started to rebound. Soon after, the OS symptoms also recurred. At the last timepoint of 30 months, the patient’s OCD and OS symptoms had completely rebounded. This time, the patient and parents refused any treatment. Conclusion: This case suggests that OCD with OS, as a special category, might not be suitable for stereotactic neurosurgery. Furthermore, multiple surgeries in this kind of OCD patient should be considered with as much caution as much as possible.

Abstract Invasion and migration are the key hallmarks of cancer, and aggressive growth is a major factor contributing to treatment failure and poor prognosis in glioblastoma. Protein arginine methyltransferase 6 (PRMT6), as an epigenetic regulator, has been confirmed to promote the malignant proliferation of glioblastoma cells in previous studies. However, the effects of PRMT6 on glioblastoma cell invasion and migration and its underlying mechanisms remain elusive. Here, we report that PRMT6 functions as a driver element for tumor cell invasion and migration in glioblastoma. Bioinformatics analysis and glioma sample detection results demonstrated that PRMT6 is highly expressed in mesenchymal subtype or invasive gliomas, and is significantly negatively correlated with their prognosis. Inhibition of PRMT6 (using PRMT6 shRNA or inhibitor EPZ020411) reduces glioblastoma cell invasion and migration in vitro, whereas overexpression of PRMT6 produces opposite effects. Then, we identified that PRMT6 maintains the protein stability of EZH2 by inhibiting the degradation of EZH2 protein, thereby mediating the invasion and migration of glioblastoma cells. Further mechanistic investigations found that PRMT6 inhibits the transcription of TRAF6 by activating the histone methylation mark (H3R2me2a), and reducing the interaction between TRAF6 and EZH2 to enhance the protein stability of EZH2 in glioblastoma cells. Xenograft tumor assay and HE staining results showed that the expression of PRMT6 could promote the invasion of glioblastoma cells in vivo, the immunohistochemical staining results of mouse brain tissue tumor sections also confirmed the regulatory relationship between PRMT6, TRAF6, and EZH2. Our findings illustrate that PRMT6 suppresses TRAF6 transcription via H3R2me2a to enhance the protein stability of EZH2 to facilitate glioblastoma cell invasion and migration. Blocking the PRMT6-TRAF6-EZH2 axis is a promising strategy for inhibiting glioblastoma cell invasion and migration.

Background: G protein-coupled receptor 68 (GPR68), an orphan receptor, has emerged as a promising therapeutic target for mitigating neuronal inflammation and oxidative damage. This study explores the protective mechanisms of GPR68 in cerebral ischemia-reperfusion injury (CIRI). Methods: An in vivo middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model was established. Mice received intraperitoneal injections of Ogerin, a selective GPR68 agonist. In vitro, GPR68 was overexpressed in SH-SY5Y and HMC3 cells, and the effects of oxygen-glucose deprivation/reperfusion (OGD/R) on cell viability were assessed using real-time quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and flow cytometry. Results: The expression of GPR68 was suppressed in cells subjected to OGD/R treatment, whereas its upregulation conferred protection to SH-SY5Y and HMC3 cells. In vivo, levels of GPR68 were reduced in brain tissues affected by MCAO/R, correlating with oxidative stress, inflammation, and neurological damage. Treatment with a GPR68 agonist decreased brain infarction, apoptosis, and dysregulated gene expression induced by MCAO/R. Mechanistically, GPR68 agonist treatment may inhibit the activation of the NF-κB/Hif-1α pathway, thereby reducing oxidative and inflammatory responses and enhancing protection against CIRI. Conclusions: This study confirms that the GPR68/NF-κB/Hif-1α axis modulates apoptosis, inflammation, and oxidative stress in CIRI, indicating that GPR68 is a potential therapeutic target for CIRI.

Plants adapt to cold stress through a tightly regulated process involving metabolic reprogramming and tissue remodeling to enhance tolerance within a short timeframe. However, the precise differences and interconnections among various organs during cold adaptation remain poorly understood. This study employed dynamic transcriptomic and metabolite quantitative analyses to investigate cold adaptation and subsequent de-adaptation in Artemisia annua, a species known for its robust resistance to abiotic stress. Our findings revealed distinct expression patterns in most differentially expressed genes (DEGs) encoding transcription factors and components of the calcium signal transduction pathway within the two organs under cold stress. Notably, the long-distance transport of carbon sources from source organs (leaves) to sink organs (roots) experienced disruption followed by resumption, while nitrogen transport from roots to leaves, primarily in the form of amino acids, exhibited acceleration. These contrasting transport patterns likely contribute to the observed differences in cold response between the two organs. The transcriptomic analysis further indicated that leaves exhibited increased respiration, accumulated anti-stress compounds, and initiated the ICE-CBF-COR signaling pathway earlier than roots. Differential expression of genes associated with cell wall biosynthesis suggests that leaves may undergo cell wall thickening while roots may experience thinning. Moreover, a marked difference was observed in phenylalanine metabolism between the two organs, with leaves favoring lignin production and roots favoring flavonoid synthesis. Additionally, our findings suggest that the circadian rhythm is crucial in integrating temperature fluctuations with the plant’s internal rhythms during cold stress and subsequent recovery. Collectively, these results shed light on the coordinated response of different plant organs during cold adaptation, highlighting the importance of inter-organ communication for successful stress tolerance.

Immunotherapy represents a promising strategy for cancer treatment that utilizes immune cells or drugs to activate the patient’s own immune system and eliminate cancer cells. One of the most exciting advances within this field is the targeting of neoantigens, which are peptides derived from non-synonymous somatic mutations that are found exclusively within cancer cells and absent in normal cells. Although neoantigen-based therapeutic vaccines have not received approval for standard cancer treatment, early clinical trials have yielded encouraging outcomes as standalone monotherapy or when combined with checkpoint inhibitors. Progress made in high-throughput sequencing and bioinformatics have greatly facilitated the precise and efficient identification of neoantigens. Consequently, personalized neoantigen-based vaccines tailored to each patient have been developed that are capable of eliciting a robust and long-lasting immune response which effectively eliminates tumors and prevents recurrences. This review provides a concise overview consolidating the latest clinical advances in neoantigen-based therapeutic vaccines, and also discusses challenges and future perspectives for this innovative approach, particularly emphasizing the potential of neoantigen-based therapeutic vaccines to enhance clinical efficacy against advanced solid tumors.

BackgroundDespite significant benefits from targeted therapy in patients with driver mutations, inevitable drug resistance usually occurred in non-small cell lung cancer, highlighting the necessity for sequential treatments to prolong overall survival. Unfortunately, durable drug response has not been reported in posterior-line therapy of cases with acquired EML4-ALK fusion after resistance to osimertinib, urging the need of referable decision-making in clinical management.Case presentationWe present a case of a 71-year-old Chinese female, never smoker, diagnosed with invasive adenocarcinoma in the left inferior lobe of her lung, with metastases in regional lymph nodes. She received erlotinib treatment after the detection of coexistent EGFR L858R/G719S and BRAF V600E via next-generation sequencing of resected tumor tissue. Routine imaging revealed disease progression approximately 14 months after starting erlotinib treatment, followed by the detection of EGFR L858R through non-invasive liquid biopsy. Subsequently, osimertinib was administered, showing clinical activities for nearly 19 months until the emergence of an EML4-ALK fusion. Given the EML4-ALK fusion, a relatively rare resistance mechanism to osimertinib, she received third-line ensartinib treatment. One month later, alleviated tumor lesions plus normal serum marker levels demonstrated the effectiveness of ensartinib in overcoming resistance to osimertinib. Of note, the clinical response to ensartinib persisted for more than 14 months, superior to the previously reported efficacy of aletinib and crizotinib in osimertinib-failure cases. As of the last follow-up in July 2022, the patient showed no signs of recurrence and maintained a good life quality.ConclusionWe reported a third-line ensartinib therapy in a patient with lung adenocarcinoma who developed an acquired EML4-ALK fusion after sequential treatment with erlotinib and osimertinib. Given the rarity of the EML4-ALK fusion as a resistance mechanism to osimertinib, ensartinib emerges as a promising treatment option for this specific clinical challenge, offering superior efficacy and good safety.

Abstract Obesity often leads to severe medical complications. However, existing FDA-approved medications to combat obesity have limited effectiveness in reducing adiposity and often cause side effects. These medications primarily act on the central nervous system or disrupt fat absorption through the gastrointestinal tract. Adipose tissue enlargement involves adipose hyperplasia and hypertrophy, both of which correlate with increased reactive oxygen species (ROS) and hyperactivated X-box binding protein 1 (XBP1) in (pre)adipocytes. In this study, we demonstrate that KT-NE, a nanoemulsion loaded with the XBP1 inhibitor KIRA6 and α-Tocopherol, simultaneously alleviates aberrant endoplasmic reticulum stress and oxidative stress in (pre)adipocytes. As a result, KT-NE significantly inhibits abnormal adipogenic differentiation, reduces lipid droplet accumulation, restricts lipid droplet transfer, impedes obesity progression, and lowers the risk of obesity-associated non-alcoholic fatty liver disease in female mice with obesity. Furthermore, diverse administration routes of KT-NE impact its in vivo biodistribution and contribute to localized and/or systemic anti-obesity effectiveness.

Abstract Climate changes and the rapid expanding human population have become critical concerns for global food security. One of the promising solutions is the employment of plant growth regulators (PGRs) for increasing crop yield and overcoming adverse growth conditions, such as desert climate. Recently, the apocarotenoid zaxinone and its two mimics (MiZax3 and MiZax5) have shown a promising growth-promoting activity in cereals and vegetable crops under greenhouse and field conditions. Herein, we further investigated the effect of MiZax3 and MiZax5, at different concentrations (5 and 10 µM in 2021; 2.5 and 5 µM in 2022), on the growth and yield of the two valuable vegetable crops, potato and strawberry, in the Kingdom of Saudi of Arabia. Application of both MiZax significantly increased plant agronomic traits, yield components and total yield, in five independent field trials from 2021 to 2022. Remarkably, the amount of applied MiZax was far less than humic acid, a widely applied commercial compound used here for comparison. Hence, our results indicate that MiZax are very promising PGRs that can be applied to promote the growth and yield of vegetable crops even under desert conditions and at relatively low concentrations.

Abstract Background Hepatic ischemia–reperfusion injury (IRI) in donation after cardiac death (DCD) donors is a major determinant of transplantation success. Endoplasmic reticulum (ER) stress plays a key role in hepatic IRI, with potential involvement of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway and the antiapoptotic protein hematopoietic-lineage substrate-1-associated protein X-1 (HAX1). In this study, we aimed to investigate the effects of hypothermic oxygenated perfusion (HOPE), an organ preservation modality, on ER stress and apoptosis during hepatic IRI in a DCD rat model. Methods To investigate whether HOPE could improve IRI in DCD livers, levels of different related proteins were examined by western blotting and quantitative real-time polymerase chain reaction. Further expression analyses, immunohistochemical analyses, immunofluorescence staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and transmission electron microscopy were conducted to analyze the effects of HOPE on ER stress and apoptosis. To clarify the role of the JAK2/STAT3 pathway and HAX1 in this process, AG490 inhibitor, JAX1 plasmid transfection, co-immunoprecipitation (CO-IP), and flow cytometry analyses were conducted. Results HOPE reduced liver injury and inflammation while alleviating ER stress and apoptosis in the DCD rat model. Mechanistically, HOPE inhibited unfolded protein responses by activating the JAK2/STAT3 pathway, thus reducing ER stress and apoptosis. Moreover, the activated JAK2/STAT3 pathway upregulated HAX1, promoting the interaction between HAX1 and SERCA2b to maintain ER calcium homeostasis. Upregulated HAX1 also modulated ER stress and apoptosis by inhibiting the inositol-requiring enzyme 1 (IRE1) pathway. Conclusions JAK2/STAT3-mediated upregulation of HAX1 during HOPE alleviates hepatic ER stress and apoptosis, indicating the JAK2/STAT3/HAX1 pathway as a potential target for IRI management during DCD liver transplantation. Graphical Abstract

Abstract The combination of PD-1 blockade with neoadjuvant chemotherapy (NAC) has achieved unprecedented clinical success in non-small cell lung cancer (NSCLC) compared to NAC alone, but the underlying mechanisms by which PD-1 blockade augments the effects of chemotherapy remain incompletely elucidated. Single-cell RNA sequencing was performed on CD45+ immune cells isolated from surgically resected fresh tumors of seven NSCLC patients receiving NAC or neoadjuvant pembrolizumab and chemotherapy (NAPC). Multiplex fluorescent immunohistochemistry was performed on FFPE tissues before and after NAC or NAPC from 65 resectable NSCLC patients, and results were validated with GEO dataset. NAC resulted in an increase only of CD20+ B cells, whereas NAPC increased the infiltration of CD20+ B cells, CD4+ T cells, CD4+CD127+ T cells, CD8+ T cells, CD8+CD127+ and CD8+KLRG1+ T cells. Synergistic increase in B and T cells promotes favorable therapeutic response after NAPC. Spatial distribution analysis discovered that CD8+ T cells and their CD127+ and KLRG1+ subsets were in closer proximity to CD4+ T/CD20+ B cells in NAPC versus NAC. GEO dataset validated that B-cell, CD4, memory, and effector CD8 signatures correlated with therapeutic responses and clinical outcomes. The addition of PD-1 blockade to NAC promoted anti-tumor immunity through T and B cells recruitment in the tumor microenvironment and induced tumor-infiltrating CD8+ T cells skewed toward CD127+ and KLRG1+ phenotypes, which may be assisted by CD4+ T cells and B cells. Our comprehensive study identified key immune cell subsets exerting anti-tumor responses during PD-1 blockade therapy and that may be therapeutically targeted to improve upon existing immunotherapies for NSCLC.

The cleavage of plant carotenoids leads to apocarotenoids, a group of metabolites including precursors of the hormones strigolactones (SLs) and abscisic acid, regulatory and signaling molecules. Zaxinone is a recently discovered apocarotenoid growth regulator that improves growth and suppress SL biosynthesis in rice (Oryza sativa). To test if zaxinone also counteracts the growth regulatory effects of SLs in rice, we co-supplied zaxinone and the synthetic SL analog rac-GR24 to the rice SL-deficient DWARF17 (d17) mutant. Results showed that co-application of GR24 and zaxinone still rescued d17 phenotype, indicating that zaxinone and GR24 act independently in regulating root and shoot growth and development in rice.

Background and objective At present, robotic surgery is widely used in thoracic surgery, which has higher maneuverability, precision, and stability, especially for small space complex operations and reconstructive surgery. The advantages of robotic lung segment resection under full orifice artificial pneumothorax are obvious. Methods Based on a large number of clinical practices, we established a set of surgical methods for 4-arm robotic lung segment resection under a port-only artificial pneumothorax. 98 cases of robotic lung segment resection were performed with this method from January 2019 to August 2022. The clinical experience was summarized. Results Robotic lung segment resection under port-only artificial pneumothorax has obvious advantages in the anatomy of lung segment vessels and bronchi. It is characterized by less bleeding, shorter operation time, adequate exposure, and flexible operation. Conclusion This surgical model we propose optimizes the operation mode and technique of lung segment resection, makes each step procedural, reduces collateral damage, and is easy to learn and master, which is believed to cure more lung cancer patients with less trauma.

Abstract Background Immunotherapy has been proved to have a large effect on extensive‐stage small cell lung cancer, but the role of immunotherapy in limited‐stage small‐cell lung cancer (LS‐SCLC) is still unknown. Methods A retrospective study of six patients with LS‐SCLC who were treated with neoadjuvant chemoimmunotherapy (durvalumab plus etoposide combined with cisplatin) was performed. Patients were evaluated by the safety, feasibility and pathologic responses of neoadjuvant chemoimmunotherapy. Results Neoadjuvant durvalumab combined chemotherapy was associated with few immediate adverse events and did not delay planned surgery. All patients achieved partial pathologic response (pPR) instead of major pathologic response, or pathologic complete response. No association was observed between programmed death‐ligand 1 expression in tumor specimens and the pathologic response. However, tumors with high expression of immune cells such as CD4+ T cells, CD8+ T cells and FoxP3+ Tregs tended to have better pathologic responses than tumors with low expression of immune cells. Conclusions Neoadjuvant durvalumab combined chemotherapy could induce pPR with few side effects in resectable LS‐SCLC. The immune cells in the tumor microenvironment might play an important role in neoadjuvant chemoimmunotherapy in resectable LS‐SCLC.

Background: Neoadjuvant immunotherapy, the focus of current research and treatment modality for long-term survival, has become one of the main options in supporting primary treatment interventions in early NSCLC. Methods: This was a retrospective analysis of patients with locally resectable NSCLC who received the neoadjuvant drug pembrolizumab combined with chemotherapy and underwent surgical resection. Pathological responses, PFS and OS in the whole sample and subgroups were analyzed. Results: Of the 61 patients included in this retrospective analysis, 31 (50.82%) achieved a pCR, and 38 (62.30%) obtained an MPR. Patients with a pCR had significantly higher OS than the non-pCR group (HR = 0.093, P = 0.0227); patients with an MPR also had significantly elevated OS compared with the non-MPR group (HR = 0.05357, P = 0.0169). Patients with lymph node metastasis after surgery had significantly reduced OS (HR = 0.01607, p = 0.0004) and PFS (HR = 0.08757, p = 0.0004) than those without lymph node metastasis. There was no significant difference in OS and PFS between squamous cell carcinomas (SCC) group and adenocarcinomas (AD) group. No significant differences in OS and PFS were found between patients administered 2 and 3 cycles of neoadjuvant therapy before surgery, between those administered ≤5 and > 5 cycles of adjuvant therapy post-surgery, and between patients with TPS 0.05). Conclusion: Neoadjuvant immunochemotherapy with pembrolizumab plus chemotherapy in non-small cell lung cancer is safe and tolerable. Both pCR and MPR were closely associated with OS and PFS, reflecting a good response of tumor tissues to drug therapy. Lymph node metastasis after surgery was a poor prognostic factor, reducing OS and PFS.

Abstract The combination of immune checkpoint inhibitors (ICIs) with chemotherapy (chemoimmunotherapy) in the neoadjuvant setting have achieved favorable clinical benefits in non-small cell lung cancer (NSCLC), but the mechanism of clinical responses remain unclear. We provide a rich resource of 186,477 individual immune cells from 48 samples of four treatment-naive and eight neoadjuvant chemoimmunotherapy treated IIIA NSCLC patients (responders versus non-responders) by single-cell RNA-seq and TCR-seq. We observed the synergistic increase of B cells and CD4+ T cells were associated with a positive therapeutic response of neoadjuvant chemoimmunotherapy. B cell IgG subclasses IgG1 and IgG3 played a critical role in anti-tumor immune response in tumor lesions, and this process was driven by increased IL-21 secreted by infiltrated T follicular helper (Tfh) cells after neoadjuvant chemoimmunotherapy. Furthermore, we uncovered several critical events for positive clinical outcomes, including the diminished activated TNFRSF4+ regulatory T cells (Tregs), increased LAMP3+ dendritic cells (DCs), and the expansion of intratumoral CD4+ T clones and peripheral C3-Cytotoxic CD8+ T clones. A validation cohort of 26 treatment-naive and 30 neoadjuvant chemoimmunotherapy treated IIIA/ IIIB NSCLC patients verified these findings. In total, our comprehensive study of the single-cell profile of immune cells provides insights into mechanisms underlying anti-PD-1-based therapies and identified potential predictive factors and therapeutic targets for improving the efficiency of neoadjuvant chemoimmunotherapy in NSCLC.

Abstract Adoptive cell therapy (ACT) was one of the most promising anti-tumor modalities that has been confirmed to be especially effective in treating hematological malignancies. However, the clinical efficacy of ACT on solid tumor was greatly hindered by the insufficient tumor-infiltration of cytotoxic CD8 + T cells. Herein, we constructed a nanoplatform termed dual-binding magnetic nanoparticles (DBMN) that comprised PEG-maleimide (Mal), hyaluronic acid (HA) and Fe3O4 for adoptive T cell-modification and ACT-sensitization. After a simple co-incubation, DBMN was anchored onto the cell membrane (Primary linking) via Michael addition reaction between the Mal and the sulfhydryl groups on the surface of T cells, generating magnetized T cells (DBMN-T). Directed by external magnetic field and in-structure Fe3O4, DBMN-T was recruited to solid tumor where HA bond with the highly expressed CD44 on tumor cells (Secondary Linking), facilitating the recognition and effector-killing of tumor cells. Bridging adoptive T cells with host tumor cells, our DBMN effectively boosted the anti-solid tumor efficacy of ACT in a mouse model and simultaneously reduced toxic side effects.

Abstract Long non-coding RNAs (lncRNAs) have been manifested to manipulate diverse biological processes, including tumor-induced immune tolerance. Thus, we aimed in this study to identify the expression pattern of lncRNA homeobox A cluster antisense RNA 2 (HOXA-AS2) in glioma and decipher its role in immune tolerance and glioma progression. We found aberrant upregulation of lncRNA HOXA-AS2, lysine demethylase 2A (KDM2A), and jagged 1 (JAG1) and a downregulation of microRNA-302a (miR-302a) in glioma specimens. Next, RNA immunoprecipitation, chromatin immunoprecipitation, and dual-luciferase reporter gene assay demonstrated that lncRNA HOXA-AS2 upregulated KDM2A expression by preventing miR-302a from binding to its 3′untranslated region. The functional experiments suggested that lncRNA HOXA-AS2 could promote regulatory T (Treg) cell proliferation and immune tolerance, which might be achieved through inhibition of miR-302a and activation of KDM2A/JAG1 axis. These findings were validated in a tumor xenograft mouse model. To conclude, lncRNA HOXA-AS2 facilitates KDM2A/JAG1 expression to promote Treg cell proliferation and immune tolerance in glioma by binding to miR-302a. These findings may aid in the development of novel antitumor targets.

A PCB spring terminal is a common type of connector found on the printed circuit board of electronic devices. Contact force is a crucial performance metric of this component that directly affects the product’s dependability. In actual production, the contact force is unstable, and the influencing factors are unknown, whereas conventional experimental research is restricted to costly and error-prone trial-and-error procedures. In this study, finite element simulation technology and Spearman rank correlation analysis are combined to determine the crucial factors controlling the contact force of the PCB spring terminals in the structural design parameters and the plating related parameters. The validity of the results is confirmed by the measured data. The results indicate that the thickness of the spring terminal is the most significant factor in controlling the contact force. According to the conclusion, the company has re-established the inspection standard and resolved production problems. This case shows that the combination of finite element simulation and correlation analysis can be used to find the most important design parameters of such components quickly, accurately, and cheaply.

Long noncoding RNAs (lncRNAs) participate in many pathophysiological processes after traumatic brain injury by mediating neuroinflammation and apoptosis. Homeobox A11 antisense RNA (HOXA11-AS) is a member of the lncRNA family that has been reported to participate in many inflammatory reactions; however, its role in traumatic brain injury remains unclear. In this study, we established rat models of traumatic brain injury using a weight-drop hitting device and injected LV-HOXA11-AS into the right lateral ventricle 2 weeks before modeling. The results revealed that overexpression of HOXA11-AS aggravated neurological deficits in traumatic brain injury rats, increased brain edema and apoptosis, promoted the secretion of proinflammatory factors interleukin-1β, interleukin-6, and tumor necrosis factor α, and promoted the activation of astrocytes and microglia. Microglia were treated with 100 ng/mL lipopolysaccharide for 24 hours to establish in vitro cell models, and then transfected with pcDNA-HOXA11-AS, miR-124-3p mimic, or sh-MDK. The results revealed that HOXA11-AS inhibited miR-124-3p expression and boosted MDK expression and TLR4-nuclear factor-κB pathway activation. Furthermore, lipopolysaccharide enhanced potent microglia-induced inflammatory responses in astrocytes. Forced overexpression of miR-124-3p or downregulating MDK repressed microglial activation and the inflammatory response of astrocytes. However, the miR-124-3p-mediated anti-inflammatory effects were reversed by HOXA11-AS. These findings suggest that HOXA11-AS can aggravate neuroinflammation after traumatic brain injury by modulating the miR-124-3p-MDK axis. This study was approved by the Animal Protection and Use Committee of Southwest Medical University (approval No. SMU-2019-042) on February 4, 2019.

Abstract Background Gene therapy shows great promise for a broad array of diseases. However, we found that hypoxic tumor microenvironment (TME) exerted significant inhibitory effects on transfection efficiency of a variety of gene vectors (such as Lipo 2000 and PEI) in an oxygen-dependent manner. Solid tumors inevitably resulted in acute hypoxic areas due to the rapid proliferation of tumor cells and the aberrant structure of blood vessels. Thus, the hypoxic TME severely limited the efficiency and application of gene therapy. Methods In our previous study, we constructed endoplasmic reticulum-targeted cationic liposomes, PAR-Lipo, which could effectively deliver genes and ensure high transfection efficiency under normoxia. Unsatisfactorily, the transfection efficiency of PAR-Lipo was rather poor under hypoxia. We believed that reoxygenation was the most direct and effective means to rescue the low transfection under hypoxia. Hence, we fabricated liposomes modified with perfluorooctyl bromide (PFOB@Lipo) to load oxygen and deliver it to tumor sites, which effectively alleviated the hypoxic nature of tumor. Then PAR-Lipo were applied to mediate high-efficiency delivery of tumor suppressor gene pTP53 to inhibit tumor progression. Results The results showed that such staged strategy augmented the expression of P53 protein in tumors and extremely suppressed tumor growth. Conclusion This work was the first attempt to utilize an oxygen nanocarrier to assist the therapeutic effect of gene therapy under hypoxia, providing a new reference for gene therapy in malignant tumors. Graphical Abstarct

Plants release a set of chemical compounds, called exudates, into the rhizosphere, under normal conditions and in response to environmental stimuli and surrounding soil organisms. Plant root exudates play indispensable roles in inhibiting the growth of harmful microorganisms, while also promoting the growth of beneficial microbes and attracting symbiotic partners. Root exudates contain a complex array of primary and specialized metabolites. Some of these chemicals are only found in certain plant species for shaping the microbial community in the rhizosphere. Comprehensive understanding of plant root exudates has numerous applications from basic sciences to enhancing crop yield, production of stress-tolerant crops, and phytoremediation. This review summarizes the metabolomics workflow for determining the composition of root exudates, from sample preparation to data acquisition and analysis. We also discuss recent advances in the existing analytical methods and future perspectives of metabolite analysis.

Strigolactones (SLs) are a plant hormone regulating different processes in plant development and adjusting plant’s architecture to nutrition availability. Moreover, SLs are released by plants to communicate with beneficial fungi in the rhizosphere where they are, however, abused as chemical cues inducing seed germination of root parasitic weeds, e.g. Striga spp., and guiding them towards host plants in their vicinity. Based on their structure, SLs are divided into canonical and non-canonical SLs. In this perspective, we describe the metabolism of root-released SLs and SL pattern in rice max1-900 mutants, which are affected in the biosynthesis of canonical SLs, and show the accumulation of two putative non-canonical SLs, CL+30 and CL+14. Using max1-900 and SL-deficient d17 rice mutants, we further investigated the metabolism of non-canonical SLs and their possible biological roles. Our results show that the presence and further metabolism of canonical and non-canonical SLs are particularly important for their role in rhizospheric interactions, such as that with root parasitic plants. Hence, we proposed that the root-released SLs are mainly responsible for rhizospheric communications and have low impact on plant architecture, which makes targeted manipulation of root-released SLs an option for rhizospheric engineering.

The apocarotenoid zaxinone is a recently discovered regulatory metabolite required for proper rice growth and development. In addition, zaxinone and its two mimics (MiZax3 and MiZax5) were shown to have a remarkable growth-promoting activity on crops and a capability to reduce infestation by the root parasitic plant Striga through decreasing strigolactone (SL) production, suggesting their potential for application in agriculture and horticulture. In the present study, we developed a new series of MiZax via structural modification of the two potent zaxinone mimics (MiZax3 and MiZax5) and evaluated their effect on plant growth and Striga infestation. In general, the structural modifications to MiZax3 and MiZax5 did not additionally improve their overall performance but caused an increase in certain activities. In conclusion, MiZax5 and especially MiZax3 remain the likely most efficient zaxinone mimics for controlling Striga infestation.

Wang et al. report zaxinone as a global regulator of the transcriptome and metabolome, as well as of hormonal and cellular composition of rice roots. This study shows that zaxinone promotes rice growth by enhancing root sugar uptake and metabolism and modulation of cytokinin content, indicating the potential application of this compound in increasing rice performance.

RNA secondary structure is important for viral replication, transcription and translation. Here the authors employ SPLASH method and map in vivo RNA interactions and dynamics of SARS-CoV-2 RNA genome in different viral life cycles.

Abstract Background Photothermal therapy (PTT) is a highly effective treatment for solid tumors and can induce long-term immune memory worked like an in situ vaccine. Nevertheless, PTT inevitably encounters photothermal resistance of tumor cells, which hinders therapeutic effect or even leads to tumor recurrence. Naïve CD8+ T cells are mainly metabolized by oxidative phosphorylation (OXPHOS), followed by aerobic glycolysis after activation. And the differentiate of effector CD8+ T cell (CD8+ Teff) into central memory CD8+ T cell (CD8+ TCM) depends on fatty acid oxidation (FAO) to meet their metabolic requirements, which is regulated by adenosine monophosphate activated protein kinase (AMPK). In addition, the tumor microenvironment (TME) is severely immunosuppressive, conferring additional protection against the host immune response mediated by PTT. Methods Metformin (Met) down-regulates NADH/NADPH, promotes the FAO of CD8+ T cells by activating AMPK, increases the number of CD8+ TCM, which boosts the long-term immune memory of tumor-bearing mice treated with PTT. Here, a kind of PLGA microspheres co-encapsulated hollow gold nanoshells and Met (HAuNS-Met@MS) was constructed to inhibit the tumor progress. 2-Deoxyglucose (2DG), a glycolysis inhibitor for cancer starving therapy, can cause energy loss of tumor cells, reduce the heat stress response of tumor cell, and reverse its photothermal resistance. Moreover, 2DG prevents N-glycosylation of proteins that cause endoplasmic reticulum stress (ERS), further synergistically enhance PTT-induced tumor immunogenic cell death (ICD), and improve the effect of immunotherapy. So 2DG was also introduced and optimized here to solve the metabolic competition among tumor cells and immune cells in the TME. Results We utilized mild PTT effect of HAuNS to propose an in situ vaccine strategy based on the tumor itself. By targeting the metabolism of TME with different administration strategy of 2DG and perdurable action of Met, the thermotolerance of tumor cells was reversed, more CD8+ TCMs were produced and more effective anti-tumor was presented in this study. Conclusion The Step-by-Step starving-photothermal therapy could not only reverse the tumor thermotolerance, but also enhance the ICD and produce more CD8+ TCM during the treatment. Graphical Abstract

Global food security is a critical concern that needs practical solutions to feed the expanding human population. A promising approach is the employment of biostimulants to increase crop production. Biostimulants include compounds that boost plant growth. Recently, mimics of zaxinone (MiZax) were shown to have a promising growth-promoting effect in rice (Oryza sativa). In this study, we investigated the effect of MiZax on the growth and yield of three dicot horticultural plants, namely, tomato (Solanum lycopersicum), capsicum (Capsicum annuum), and squash (Cucurbita pepo) in different growth environments, as well as on the growth and development of the monocot date palm (Phoenix dactylifera), an important crop in the Middle East. The application of MiZax significantly enhanced plant height, flower, and branch numbers, fruit size, and total fruit yield in independent field trials from 2020 to 2021. Importantly, the amount of applied MiZax was far less than that used with the commercial compound humic acid, a widely used biostimulant in horticulture. Our results indicate that MiZax have significant application potential to improve the performance and productivity of horticultural crops.

Summary: The plant hormone strigolactones (SLs) are secreted by plant roots to act as rhizospheric signals. Here, we present a protocol for characterizing plant-released SLs. We first outline all necessary steps required for collection, processing, and analysis of plant root exudates using the C18 column for SL extraction, followed by liquid chromatography-mass spectrometry (LC-MS) for SL quantification. We then describe image processing by SeedQuant, an open-source artificial-intelligence-based software, for measuring the biological activity of SLs in inducing root parasitic plant seed germination.For complete details on the use and execution of this protocol, please refer to Wang et al. (2019) and Braguy et al. (2021).

Abstract Background Brain abscess due to the Nocardia genus is rare and usually found in immunocompromised patients. The most common subtype implicated is Nocardia farcinica while brain abscess due to Nocardia brasiliensis is comparatively rare. Diagnosis of brain abscess is based mainly on bacteriological culture from pus collected at the site of infection, and brain imaging. Stereotaxic aspiration or surgical resection combined with adequate duration of treatment with antibiotics to which the bacteria are sensitive represent effective treatment strategies. Case presentation We report a rare case of brain abscess caused by Nocardia brasiliensis in a non-immunocompromised patient. He admitted to our hospital twice with a headache. Stereotaxic aspiration was performed at the patient’s first appointment at the hospital, and a craniotomy was used to excise the lesion during subsequent abscess recurrence. Conclusion Early diagnosis, reasonable surgical intervention, and adequate duration of treatment with effective antibiotics are critical for treating brain abscess.

Background and objective Da Vinci robotic system is currently widely used in thoracic surgery. The ports employment and procedures vary in different medical center in China. Usually, a small incision was used for assistant. Methods Based on clinical practice, we summarized domestic and foreign experience, combined with the characteristics of the Chinese body anatomy, employ portal technique and artificial pneumothorax, summarized a set of simplified and easier surgical method. Results Port-only artificial pneumothorax robot-assisted lobectomy has further improvement in anatomical safety, hemostatic effect and aesthetic appearance of the wound. Conclusion This study optimizes the procedure of port-only artificial pneumothorax robot-assisted lobectomy in order to serve lung cancer patients better.

The potential side effects of cabazitaxel (CBZ) in the field of cancer treatment have become a great limitation to its further clinical application. Liposomal delivery is a well-established approach to increase the therapeutic index of hydrophobic drugs. In this study, a PEG-modified liposome was developed for efficiently encapsulating CBZ, thus enhancing its specific tumor inhibition effect and reducing the systemic toxicity. It was found that the loading efficiency of CBZ into the liposome could be improved with the increase of lipophilic materials, as it could be over 80% under the weight ratio of 20:1 (total lipid: CBZ). The diameter of CBZ loaded liposome (CBZ@Lipo) was ∼100 nm. And the liposome suspending in aqueous medium was stable at 4 °C for at least one month, according to the change of its size distribution. The killing ability of CBZ@Lipo to cancer cells was significantly lower comparing to that of CBZ solution, which could be attributed to the slow release of CBZ from the liposomes. However, CBZ@Lipo could induce an obvious apoptosis of the cancer cells at low concentration. Furthermore, CBZ@Lipo exhibited an expressively enhanced tumor growth inhibition effect comparing to CBZ solution. More importantly, CBZ@Lipo showed an obviously higher biosafety proved by lower hemolysis probability, stable body weight of mice during the whole experiment and no obvious lesion in histology analysis. Our work provided a useful reference of the formulation of CBZ, which had potential for greater clinical application. Keywords: Cabazitaxel, Liposome, Stability, Apoptosis, Biosafety

Reactive oxygen species induced by endoplasmic reitculum stress can be exploited for cancer therapy. Here, nanoparticles are targetted to the endoplasmic reticulum and, when accompanied by PDT, produce stress resulting in calreticulin exposure on the cell surface, which activates dendritic cells.

Strigolactone and abscisic acid are carotenoid-derived plant hormones. Here the authors describe the identification of zaxinone, a further apocarotenoid metabolite, which down-regulates strigolactone content and is required for normal growth and development in rice.

Abstract The development of gene delivery has attracted increasing attention, especially when the introduction and application of the CRISPR/Cas9 gene editing system appears promising for gene therapy. However, ensuring biosafety and high gene editing efficiency at the same time poses a great challenge for its in vivo applications. Herein, a pardaxin peptide (PAR)‐modified cationic liposome (PAR‐Lipo) is developed. The results are indicative that significantly enhanced gene editing efficiency can be obtained through the mediation of PAR‐Lipos compared to non‐Lipos (non‐PAR‐modified liposomes) and Lipofectamine 2000, owing to its protection toward carried nucleotide by the prevention of lysosomal capture, prolongation of retention time in cells through the accumulation in the endoplasmic reticulum (ER), and more importantly, facilitation of the nuclear access via an ER‐nucleus route. Accumulation of PAR‐Lipos in the ER may improve the binding of Cas9 and sgRNA, thus further contributing to the eventually enhanced gene editing efficiency. Given their high biosafety, PAR‐Lipos are used to mediate the knockout of the oncogene CDC6 in vivo, which results in significant tumor growth inhibition. This work may provide a useful reference for enhancing the delivery of gene editing systems, thus improving the potential for their future clinical applications.

Carotenoids are ubiquitous precursors of important metabolites including hormones, such as strigolactones (SLs) and abscisic acid (ABA), and signaling and regulatory molecules, such as the recently discovered zaxinone. Strigolactones and ABA are key regulators of plant growth and development, adaptation to environmental changes and response to biotic and abiotic stress. Previously, we have shown that zaxinone, an apocarotenoid produced in rice by the enzyme zaxinone synthase (ZAS) that is common in mycorrhizal plants, is required for normal rice growth and development, and a negative regulator of SL biosynthesis. Zaxinone is also formed in Arabidopsis, which lacks ZAS, via an unknown route. In the present study, we investigated the biological activity of zaxinone in Arabidopsis, focusing on its effect on SL and ABA biosynthesis. For this purpose, we quantified the content of both hormones and determined the levels of related transcripts in Arabidopsis (Arabidopsis thaliana), roots upon zaxinone treatment. For SL quantification, we also employed Striga seed germination bioassay. Results obtained show that zaxinone application to hydroponically grown Arabidopsis seedlings enhanced transcript levels of key biosynthetic genes of both hormones, led to higher root ABA and SL (methyl carlactonoate, MeCLA) content, and increased SL release, even under sufficient phosphate supply. Using the SL insensitive (max2-1) and the ABA deficient (aba1-6, aba2-1, and nced3) mutants, we also show that zaxinone application reduced hypocotyl growth and that this effect is caused by increasing ABA content. Our results suggest that zaxinone is a regulatory metabolite also in Arabidopsis, which triggers the biosynthesis of both carotenoid-derived hormones, SLs and ABA, in roots. In the non-mycotrophic plant Arabidopsis, zaxinone does not increase growth and may be perceived as a stress signal, while it acts as a growth-promoting metabolite and suppressor of SL biosynthesis in rice.

Strigolactones (SLs) are a group of carotenoid derived plant hormones that play a key role in establishing plant architecture and adapting it to environmental changes, and are involved in plants response to biotic and abiotic stress. SLs are also released into the soil to serve as a chemical signal attracting beneficial mycorrhizal fungi. However, this signal also induces seed germination in root parasitic weeds that represent a major global threat for agriculture. This wide spectrum of biological functions has made SL research one of the most important current topics in fundamental and applied plant science. The availability of SLs is crucial for investigating SL biology as well as for agricultural application. However, natural SLs are produced in very low amounts, and their organic synthesis is quite difficult, which creates a need for efficient and easy-to-synthesize analogs and mimics. Recently, we have generated a set of SL analogs, Methyl Phenlactonoates (MPs), which resemble the non-canonical SL carlactonoic acid. In this paper, we describe the development and characterization of a new series of easy-to-synthesize MPs. The new analogs were assessed with respect to regulation of shoot branching, impact on leaf senescence, and induction of seed germination in different root parasitic plants species. Some of the new analogs showed higher efficiency in inhibiting shoot branching as well as in triggering parasitic seed germination, compared to the commonly used GR24. MP16 was the most outstanding analog showing high activity in different SL biological functions. In summary, our new analogs series contains very promising candidates for different applications, which include the usage in studies for understanding different aspects of SL biology as well as large scale field application for combating root parasitic weeds, such as Striga hermonthica that devastates cereal yields in sub-Saharan Africa.

The obligate hemiparasite Striga hermonthica is one of the major global biotic threats to agriculture in sub-Saharan Africa, causing severe yield losses of cereals. The germination of Striga seeds relies on host-released signaling molecules, mainly strigolactones (SLs). This dependency opens up the possibility of deploying SL analogs as “suicidal germination agents” to reduce the accumulated seed bank of Striga in infested soils. Although several synthetic SL analogs have been developed for this purpose, the utility of these compounds in realizing the suicidal germination strategy for combating Striga is still largely unknown. Here, we evaluated the efficacy of three potent SL analogs (MP3, MP16, and Nijmegen-1) under laboratory, greenhouse, and farmer’s field conditions. All investigated analogs showed around a 50% Striga germination rate, equivalent to a 50% reduction in infestation, which was comparable to the standard SL analog GR24. Importantly, MP16 had the maximum reduction of Striga emergence (97%) in the greenhouse experiment, while Nijmegen-1 appeared to be a promising candidate under field conditions, with a 43% and 60% reduction of Striga emergence in pearl millet and sorghum fields, respectively. These findings confirm that the selected SL analogs appear to make promising candidates as simple suicidal agents both under laboratory and real African field conditions, which may support us to improve suicidal germination technology to deplete the Striga seed bank in African agriculture.

Striga hermonthica, a member of the Orobanchaceae family, is an obligate root parasite of staple cereal crops, which poses a tremendous threat to food security, contributing to malnutrition and poverty in many African countries. Depleting Striga seed reservoirs from infested soils is one of the crucial approaches to minimize subterranean damage to crops. The dependency of Striga germination on the host-released strigolactones (SLs) has prompted the development of the “Suicidal Germination” strategy to reduce the accumulated seed bank of Striga. The success of aforementioned strategy depends not only on the activity of the applied SL analogs, but also requires suitable application protocol with simple, efficient, and handy formulation for rain-fed African agriculture. Here, we developed a new formulation “Emulsifiable Concentration (EC)” for the two previously field-assessed SL analogs Methyl phenlactonoate 3 (MP3) and Nijmegen-1. The new EC formulation was evaluated for biological activities under lab, greenhouse, mini-field, and field conditions in comparison to the previously used Atlas G-1086 formulation. The EC formulation of SL analogs showed better activities on Striga germination with lower EC50 and high stability under Lab conditions. Moreover, EC formulated SL analogs at 1.0 µM concentrations reduced 89–99% Striga emergence in greenhouse. The two EC formulated SL analogs showed also a considerable reduction in Striga emergence in mini-field and field experiments. In conclusion, we have successfully developed a desired formulation for applying SL analogs as suicidal agents for large-scale field application. The encouraging results presented in this study pave the way for integrating the suicidal germination approach in sustainable Striga management strategies for African agriculture.

Abstract Background Precision plant genome engineering holds much promise for targeted improvement of crop traits via unprecedented single-base level control over the genetic material. Strigolactones (SLs) are a key determinant of plant architecture, known for their role in inhibiting shoot branching (tillering). Results We used CRISPR/Cas9 in rice (Oryza sativa) for targeted disruption of CAROTENOID CLEAVAGE DIOXYGENASE 7 (CCD7), which controls a key step in SL biosynthesis. The ccd7 mutants exhibited a striking increase in tillering, combined with a reduced height, which could be rescued by application of the synthetic SL analog GR24. Striga germination assays and liquid chromatography–mass spectrometry analysis showed that root exudates of ccd7 mutants were also SL deficient. Conclusions Taken together, our results show the potential and feasibility of the use of the CRISPR/Cas9 system for targeted engineering of plant architecture and for elucidating the molecular underpinnings of architecture-related traits.

Photosensitizer, proper laser irradiation, and oxygen are essential components for effective photodynamic therapy (PDT) in clinical cancer therapy. However, native hypoxic tumoral microenvironment is a major barrier hindering photodynamic reactions in vivo. Thus, we have prepared biocompatible liposomes by loading complexes of oxygen-carrier (hemoglobin, Hb) and photosensitizer (indocyanine green, ICG) for enhanced PDT against hypoxic tumor. Ideal oxygen donor Hb, which is an oxygen-carried protein in red blood cells, makes such liposome which provide stable oxygen supply. ICG, as a photosensitizer, could transfer energy from lasers to oxygen to generate cytotoxic reactive oxygen species (ROS) for treatment. The liposomes loading ICG and Hb (LIH) exhibited efficient tumor homing upon intravenous injection. As revealed by T2-weighted magnetic resonance imaging and immunohistochemical analysis, the intratumoral hypoxia was greatly alleviated, and the level of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in tumor was obviously down-regulated. A weak PDT efficiency was found in cells incubated in simulated hypoxia condition in vitro, while PDT effect was dramatically enhanced in LIH treated hypoxia cells under near-infrared (NIR) laser, which was mainly attributed to massive generation of ROS with sufficient oxygen supply. ROS trigger oxidative damage of tumors and induce complete suppression of tumor growth and 100% survival rate of mice, which were also in good health condition. Our work highlights a liposome-based nanomedicine that could effectively deliver oxygen to tumor and alleviate tumor hypoxia state, inducing greatly improved efficacy compared to conventional cancer PDT and demonstrates the promise of modulating unfavorable tumor microenvironment with nanotechnology to overcome limitations of cancer therapies.

Plants utilize hormones and other small molecules to trigger and coordinate their growth and developmental processes, adapt and respond to environmental cues, and communicate with surrounding organisms. Some of these molecules originate from carotenoids that act as universal precursors of bioactive metabolites arising through oxidation of the carotenoid backbone. This metabolic conversion produces a large set of compounds known as apocarotenoids, which includes the plant hormones abscisic acid (ABA) and strigolactones (SLs) and different signaling molecules. An increasing body of evidence suggests a crucial role of previously identified and recently discovered carotenoid-derived metabolites in the communication with arbuscular mycorrhizal (AM) fungi and the establishment of the corresponding symbiosis, which is one of the most relevant plant–fungus mutualistic interactions in nature. In this review, we provide an update on the function of apocarotenoid hormones and regulatory metabolites in AM symbiosis, highlighting their effect on both partners.

Strigolactones (SLs) regulate plant development and induce seed germination in obligate root parasitic weeds, e.g. Striga spp. Because organic synthesis of natural SLs is laborious, there is a large need for easy-to-synthesize and efficient analogs. Here, we investigated the effect of a structural modification of the D-ring, a conserved structural element in SLs. We synthesized and investigated the activity of two analogs, MP13 and MP26, which differ from previously published AR8 and AR36 only in the absence of methylation at C-3′. The de-methylated MP13 and MP26 were much more efficient in regulating plant development and inducing Striga seed germination, compared with AR8. Hydrolysis assays performed with purified Striga SL receptor and docking of AR8 and MP13 to the corresponding active site confirmed and explained the higher activity. Field trials performed in a naturally Striga-infested African farmer’s field unraveled MP13 as a promising candidate for combating Striga by inducing germination in host’s absence. Our findings demonstrate that methylation of the C-3′ in D-ring in SL analogs has a negative impact on their activity and identify MP13 and, particularly, MP26 as potent SL analogs with simple structures, which can be employed to control Striga, a major threat to global food security.

Ecological adaptation plays an important role in the process of plant expansion, and genetics and epigenetics are important in the process of plant adaptation. In this study, genetic and epigenetic analyses and soil properties were performed on D. angustifolia of 17 populations, which were selected in the tundra zone on the western slope of the Changbai Mountains. Our results showed that the levels of genetic and epigenetic diversity of D. angustifolia were relatively low, and the main variation occurred among different populations (amplified fragment length polymorphism (AFLP): 95%, methylation sensitive amplification polymorphism (MSAP): 87%). In addition, DNA methylation levels varied from 23.36% to 35.70%. Principal component analysis (PCA) results showed that soil properties of different populations were heterogeneous. Correlation analyses showed that soil moisture, pH and total nitrogen were significantly correlated with genetic diversity of D. angustifolia, and soil temperature and pH were closely related to epigenetic diversity. Simple Mantel tests and partial Mantel tests showed that genetic variation significantly correlated with habitat or geographical distance. However, the correlation between epigenetic variation and habitat or geographical distance was not significant. Our results showed that, in the case of low genetic variation and genetic diversity, epigenetic variation and DNA methylation may provide a basis for the adaptation of D. angustifolia.