Astaxanthin, a ketone carotenoid known for its high antioxidant activity, holds significant potential for application in nutraceuticals, aquaculture, and cosmetics. The increasing market demand necessitates a higher production of astaxanthin using Phaffia rhodozyma. Despite extensive research efforts focused on optimizing fermentation conditions, employing mutagenesis treatments, and utilizing genetic engineering technologies to enhance astaxanthin yield in P. rhodozyma, progress in this area remains limited. This review provides a comprehensive summary of the current understanding of rough metabolic pathways, regulatory mechanisms, and preliminary strategies for enhancing astaxanthin yield. However, further investigation is required to fully comprehend the intricate and essential metabolic regulation mechanism underlying astaxanthin synthesis. Specifically, the specific functions of key genes, such as crtYB, crtS, and crtI, need to be explored in detail. Additionally, a thorough understanding of the action mechanism of bifunctional enzymes and alternative splicing products is imperative. Lastly, the regulation of metabolic flux must be thoroughly investigated to reveal the complete pathway of astaxanthin synthesis. To obtain an in-depth mechanism and improve the yield of astaxanthin, this review proposes some frontier methods, including: omics, genome editing, protein structure-activity analysis, and synthetic biology. Moreover, it further elucidates the feasibility of new strategies using these advanced methods in various effectively combined ways to resolve these problems mentioned above. This review provides theory and method for studying the metabolic pathway of astaxanthin in P. rhodozyma and the industrial improvement of astaxanthin, and provides new insights into the flexible combined use of multiple modern advanced biotechnologies.

Comprehending the structure and function of rhizobacteria components and their regulation are crucial for sustainable agricultural management. However, obtaining comprehensive species information for most bacteria in the natural environment, particularly rhizobacteria, presents a challenge using traditional culture methods. To obtain diverse and pure cultures of rhizobacteria, this study primarily reviews the evolution of rhizobacteria culturomics and associated culture methods. Furthermore, it explores new strategies for enhancing the application of culturomics, providing valuable insights into efficiently enriching and isolate target bacterial strains/groups from the environment. The findings will help improve rhizobacteria\'s culturability and enrich the functional bacterial library.

暂无摘要。

Immunotherapy of cancer has made tremendous progress in recent years, as demonstrated by the remarkable clinical responses obtained from adoptive cell transfer (ACT) of patient-derived tumor infiltrating lymphocytes, chimeric antigen receptor (CAR)-modified T cells (CAR-T) and T cell receptor (TCR)-engineered T cells (TCR-T). TCR-T uses specific TCRS optimized for tumor engagement and can recognize epitopes derived from both cell-surface and intracellular targets, including tumor-associated antigens, cancer germline antigens, viral oncoproteins, and tumor-specific neoantigens (neoAgs) that are largely sequestered in the cytoplasm and nucleus of tumor cells. Moreover, as TCRS are naturally developed for sensitive antigen detection, they are able to recognize epitopes at far lower concentrations than required for CAR-T activation. Therefore, TCR-T holds great promise for the treatment of human cancers. In this focused review, we summarize basic, translational, and clinical insights into the challenges and opportunities of TCR-T. We review emerging strategies used in current ACT, point out limitations, and propose possible solutions. We highlight the importance of targeting tumor-specific neoAgs and outline a strategy of combining neoAg vaccines, checkpoint blockade therapy, and adoptive transfer of neoAg-specific TCR-T to produce a truly tumor-specific therapy, which is able to penetrate into solid tumors and resist the immunosuppressive tumor microenvironment. We believe such a combination approach should lead to a significant improvement in cancer immunotherapies, especially for solid tumors, and may provide a general strategy for the eradication of multiple cancers.

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the paradigm in hematological malignancies treatment, driving an ever-expanding number of basic research and clinical trials of genetically engineering T cells to treat solid tumors. CAR T-cell therapies based on the antibodies targeting Mesothelin, CEA, EGFR, EGFR, MUC1, DLL3, and emerging novel targets provide promising efficacy for lung cancer patients. However, clinical application of CAR T-cell therapy against lung cancer remains limited on account of physical and immune barriers, antigen escape and heterogeneity, on-target off-tumor toxicity, and many other reasons. Understanding the evolution of CAR structure and the generalizable requirements for manufacturing CAR T cells as well as the interplay between lung tumor immunology and CAR T cells will improve clinical translation of this therapeutic modality in lung cancer. In this review, we systematically summarize the latest advances in CAR T-cell therapy in lung cancer, focusing on the CAR structure, target antigens, challenges, and corresponding new strategies.

Meningiomas are the most commonly diagnosed benign intracranial adult tumors. Subsets of meningiomas that present with extensive invasion into surrounding brain areas have high recurrence rates, resulting in difficulties for complete resection, substantially increased mortality of patients, and are therapeutically challenging for neurosurgeons. Exciting new data have provided insights into the understanding of the molecular machinery of invasion. Moreover, clinical trials for several novel approaches have been launched. Here, we will highlight the mechanisms which govern brain invasion and new promising therapeutic approaches for brain-invasive meningiomas, including pharmacological approaches targeting three major aspects of tumor cell invasion: extracellular matrix degradation, cell adhesion, and growth factors, as well as other innovative treatments such as immunotherapy, hormone therapy, Tumor Treating Fields, and biodegradable copolymers (wafers), impregnated chemotherapy. Those ongoing studies can offer more diversified possibilities of potential treatments for brain-invasive meningiomas, and help to increase the survival benefits for patients.

Introduction: Akt is a widely known serine threonine kinase involved in a series of critical cellular pathways like cell survival and proliferation. With the development of small-molecule Akt inhibitors, new strategies such as covalent, peptide-based, and PROTAC (Proteolysis Targeting Chimera) strategies have also been used the design of Akt inhibitors. On the other hand, due to the specificity of the Akt pathway, the use of Akt modulators in combination therapy and immunotherapy has been disclosed in the past 5 years.Areas covered: This review focuses on the patent literature covering small-molecule inhibitors of Akt kinase and their applications from 2016-present.Expert opinion: Although Akt inhibitors\' progress has been somewhat slow over the past five years, new strategies still provide new opportunities for the development of Akt inhibitors. Combination with Akt pathway inhibitors for tumor therapy has also been widely disclosed in patents in the last 5 years. Notably, combination strategies of Akt inhibitors and immunotherapy have started to emerge in recent years. While the clinical indications of Akt modulators should not be limited to anti-cancer, it is still worth trying the treatment of other diseases. Within the next years, current drug development around Akt inhibitors should be fascinating.

The incidence of cancer is increasing year by year. Cancer has become one of the health threats of modern people. Simply relying on the surgery, chemotherapy or radiotherapy, not only the survival rate is not high, but also the quality of life of patients is not much better. Fortunately, the emergence and rapid development of cancer immunotherapy have brought more and more exciting results. However, when scientists think it is possible to overcome cancer, they find that not all cancer patients can benefit from immunotherapy, that is to say, the overall efficiency of immunotherapy is not high. Drug resistance and side effects of immunotherapy cannot be ignored. In order to overcome these difficulties, scientists continue to improve the strategy of immunotherapy and find that combination therapy can effectively reduce the incidence of drug resistance. They also found that by reprogramming tumor blood vessels, activating ferroptosis, utilizing thioredoxin, FATP2 and other substances, the therapeutic effect can be improved and side effects can be alleviated. This article reviews the principles of immunotherapy, new strategies to overcome drug resistance of cancer immunotherapy, and how to improve the efficacy of immunotherapy and reduce side effects.

OBJECTIVE: Numerous corrective methods have been successfully applied in concha-type microtia reconstruction over the past several decades, and autogenous rib cartilage grafting has become a routine technique in a two or three-stage operation. However, it still remains a challenge due to the effective use of the large volume of the remnant cartilage and skin involved. The objective of this study was to clarify how this remnant cartilage and skin could be manipulated for new suitable treatment strategies without autogenous costal cartilage grafting.
METHODS: A total of 424 patients with concha-type microtia operated at our Center from January of 2012 to June of 2019 have been reviewed and analyzed cases. At the same time, a classification system for grading the severity of concha-type microtia was created on the basis of anatomical findings and ear size.
RESULTS: A total of 436 ear cases (involving 424 patients), showing concha-type microtia, were included in our study and reviewed through medical records, photographs, analysis of surgical methods, and postoperative outcomes. The concha-type microtia were classified into four graded types: Grade I (n = 151), Grade II (n = 101), Grade III (n = 93), and Grade IV (n = 79). A total of 352 ears in 345 patients with Grade I to III concha-type microtia were followed up for 1 month to 7 years (average, 14.7 months). 329 patients (95.4%) were satisfied with the aesthetic outcomes of the corrected ear.
CONCLUSIONS: Individual corrective methods and aesthetic outcomes for patients with Grade I to III of deformity were described in this study. The authors present new suitable approaches according to a progressive classification system which provide conservative and individualized methods of treatment in early stages of life.

Patients with low response rates to cancer vaccines, short duration of anti-tumor response after vaccination, and relatively weak curative effects are problems that have not been resolved effectively during the development and application of cancer vaccines. With the continuous improvement of knowledge and awareness regarding the immune system and cancer cells, many researches have helped to explain the reasons for poor vaccine efficacy. Input from researchers accompanied by some newly emerged strategies could bring hope to improve the therapeutic effects of vaccines.
Data were collected from Web of Science, Medline, Pubmed, through searching of these keywords: \"cancer vaccine\", \"cancer stem cell\", \"targeted agent\", \"immune checkpoint blockade\" and \"neoantigen\".
It may be more effective in immunotherapy of human cancers, including cancer stem cell vaccines, combination vaccines with targeted agents or immune checkpoint blockade, and neoantigen-based vaccines.
Personalized vaccines will become the mainstream solution of cancer treatment program with the continuous improvement of human understanding of the immune system and the progress of related experiments.