Abiotic stresses substantially affect the growth and development of plants. Plants have evolved multiple strategies to cope with the environmental stresses, among which transcription factors play an important role in regulating the tolerance to abiotic stresses. Basic leucine zipper transcription factors (bZIP) are one of the largest gene families. The stability and activity of bZIP transcription factors could be regulated by different post-translational modifications (PTMs) in response to various intracellular or extracellular stresses. This paper introduces the structural feature and classification of bZIP transcription factors, followed by summarizing the PTMs of bZIP transcription factors, such as phosphorylation, ubiquitination and small ubiquitin-like modifier (SUMO) modification, in response to abiotic stresses. In addition, future perspectives were prospected, which may facilitate cultivating excellent stress-resistant crop varieties by regulating the PTMs of bZIP transcription factors.
Basic-Leucine Zipper Transcription Factors/genetics* ; Protein Processing, Post-Translational ; Phosphorylation ; Transcription Factors/genetics* ; Stress, Physiological/genetics*

The coronavirus disease 2019 (COVID-19) pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection. So far, a few small-molecule antiviral drugs, including nirmatrelvir-ritonavir (Paxlovid), remdesivir, and molnupiravir have been marketed for the treatment of COVID-19. Nirmatrelvir-ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate COVID-19. However, the existing treatment options have limitations, and effective treatment strategies that are cost-effective and convenient for tackling COVID-19 are still needed. To date, four domestically developed oral anti-COVID-19 drugs have been granted conditional market approval in China. These drugs include azvudine, simnotrelvir-ritonavir (Xiannuoxin), leritrelvir, and mindeudesivir (VV116). Preclinical and clinical studies have explored the efficacy and tolerability of mindeudesivir and supported its early use in mild-to-moderate COVID-19 cases at high risk for progression. In this review, we discuss the most recent findings regarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule antiviral agents for COVID-19. These findings will expand our understanding and highlight the potential widespread application of China's homegrown anti-COVID-19 drugs.
Humans ; Ritonavir/therapeutic use* ; COVID-19 ; Antiviral Agents/therapeutic use* ; China ; Nitriles ; Lactams ; Proline ; Adenosine/analogs & derivatives* ; Leucine

Artemisia argyi is an important medicinal and economic plant in China, with the effects of warming channels, dispersing cold, and relieving pain, inflammation, and allergy. The essential oil of this plant is rich in volatile terpenoids and widely used in moxi-bustion and healthcare products, with huge market potential. The bZIP transcription factors compose a large family in plants and are involved in the regulation of plant growth and development, stress response, and biosynthesis of secondary metabolites such as terpenoids. However, little is known about the bZIPs and their roles in A. argyi. In this study, the bZIP transcription factors in the genome of A. argyi were systematically identified, and their physicochemical properties, phylogenetic relationship, conserved motifs, and promoter-binding elements were analyzed. Candidate AarbZIP genes involved in terpenoid biosynthesis were screened out. The results showed that a total of 156 AarbZIP transcription factors were identified at the genomic level, with the lengths of 99-618 aa, the molecular weights of 11.7-67.8 kDa, and the theoretical isoelectric points of 4.56-10.16. According to the classification of bZIPs in Arabidopsis thaliana, the 156 AarbZIPs were classified into 12 subfamilies, and the members in the same subfamily had similar conserved motifs. The cis-acting elements of promoters showed that AarbZIP genes were possibly involved in light and hormonal pathways. Five AarbZIP genes that may be involved in the regulation of terpenoid biosynthesis were screened out by homologous alignment and phylogenetic analysis. The qRT-PCR results showed that the expression levels of the five AarbZIP genes varied significantly in different tissues of A. argyi. Specifically, AarbZIP29 and AarbZIP55 were highly expressed in the leaves and AarbZIP81, AarbZIP130, and AarbZIP150 in the flower buds. This study lays a foundation for the functional study of bZIP genes and their regulatory roles in the terpenoid biosynthesis in A. argyi.
Gene Expression Profiling ; Phylogeny ; Artemisia/genetics* ; Basic-Leucine Zipper Transcription Factors/metabolism* ; Terpenes ; Gene Expression Regulation, Plant

Microcystin-leucine arginine (MC-LR), a potentially carcinogenic toxin, is produced by Cyanobacteria such as Microcystis and Ananabacteria during water bloom. Increasing evidence demonstrated that MC-LR induces male reproductive toxicity, mainly by inducing germ cell apoptosis, destroying cell cytoskeleton, interfering with DNA damage repair pathway, and damaging blood-testicular barrier (BTB), which eventually lead to male sterility. Testicular Sertoli cells are the somatic cells that directly contact with spermatogenic cells in seminiferous tubules. They not only regulate immune response to maintain testicular immune homeostasis by secreting a variety of cytokines and immunosuppressive factors, but also provide the protective effects of spermatogenic cells by forming BTB. MC-LR induces inflammation and apoptosis of Sertoli cells, and destroys the integrity of the BTB, and then causes spermatogenesis dysfunction.
Male ; Humans ; Sertoli Cells ; Leucine/pharmacology* ; Arginine/pharmacology* ; Microcystins/metabolism* ; Immunity

Leucine-rich repeats containing 4 ( LRRC4 , also named netrin-G ligand 2 [NGL-2]) is a member of the NetrinGs ligands (NGLs) family. As a gene with relatively high and specific expression in brain, it is a member of the leucine-rich repeat superfamily and has been proven to be a suppressor gene for gliomas, thus being involved in gliomagenesis. LRRC4 is the core of microRNA-dependent multi-phase regulatory loops that inhibit the proliferation and invasion of glioblastoma (GB) cells, including LRRC4/NGL2-activator protein 2 (AP2)-microRNA (miR) 182-LRRC4 and LRRC4-miR185-DNA methyltransferase 1 (DNMT1)-LRRC4/specific protein 1 (SP1)-DNMT1-LRRC4. In this review, we demonstrated LRRC4 as a new member of the partitioning-defective protein (PAR) polarity complex that promotes axon differentiation, mediates the formation and plasticity of synapses, and assists information input to the hippocampus and storage of memory. As an important synapse regulator, aberrant expression of LRRC4 has been detected in autism, spinal injury and GBs. LRRC4 is a candidate susceptibility gene for autism and a neuro-protective factor in spinal nerve damage. In GBs, LRRC4 is a novel inhibitor of autophagy, and an inhibitor of protein-protein interactions involving in temozolomide resistance, tumor immune microenvironment, and formation of circular RNA.
Humans ; Cell Line, Tumor ; Glioblastoma/metabolism* ; Leucine ; Leucine-Rich Repeat Proteins/genetics* ; MicroRNAs ; Nerve Tissue Proteins/genetics* ; Tumor Microenvironment

Humans ; Hemangioendothelioma, Epithelioid/pathology* ; Trans-Activators ; Transcription Factors ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; Hemangioendothelioma

Objective: To investigate the clinicopathological features of pulmonary granular cell tumors (pGCTs) and to improve the diagnostic accuracy of the tumor. Methods: A total of 5 pGCTs were diagnosed from February 2016 to January 2022 at Shanghai Pulmonary Hospital, Tongji University School of Medicine and Fudan University Shanghai Cancer Center, China. Immunohistochemical staining, and analysis of the clinicopathological characteristics were performed. Results: The average age of the pGCTs patients was 46 years (ranging from 24 to 54 years), with 3 females and 2 males. One case occurred in the bronchus with multiple nodules in the lung, 2 cases occurred in the bronchial opening, and 2 cases were solitary nodules in the lung. The maximum diameter of the tumors ranged from 12 to 15 mm (mean size 14 mm). Microscopically, the tumor showed infiltrative growth and consisted of round, oval or polygonal cells. Abundant eosinophilic cytoplasm was noted, and the nucleoli were prominent. None of the 5 cases showed any mitosis or necrosis. Immunohistochemical and histochemical study showed positive staining for S-100 (5/5), SOX10 (5/5), Vimentin (5/5), TFE3 (4/5), PAS (3/5), and amylase-digested-PAS (3/5), while 4 cases were negative for CD68. TFE3 FISH analyses on 2 cases showed that no signal abnormality was detected in these 2 cases. The average proliferation index of Ki-67 was 2.2% (range 0-5%). There was no recurrence in 4 cases of pGCTs with a follow-up time ranging from 2 months to 60 months. Conclusions: pGCTs are very rare tumors, most likely originating from Schwann cells. Immunohistochemical staining is the conventional diagnostic tool for pGCTs diagnosis. Recognition of this entity is essential for pathologists to avoid misdiagnosis and unnecessary treatments.
Female ; Humans ; Male ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; Biomarkers, Tumor ; Bronchi ; China ; Granular Cell Tumor/surgery* ; Lung ; S100 Proteins ; Adult ; Middle Aged

Objective: Differential flora and differential metabolites shared by the intestinal and respiratory tracts of rats were screened to analyze the possible role of changes in intestinal flora and metabolites in the progression of pneumoconiosis in rats. Methods: In April 2020, 18 SD rats were randomly divided into three groups (control group, coal mine dust group and silica group, 6 in each group) , rats in the coal mine dust group and silica group were perfused with 1 ml of 50 mg/ml coal mine well dust suspension and silica suspension by nontracheal exposure, respectively. While rats in the control group were perfused with an equal dose of sterilized normal saline. Twenty four weeks after dust staining, rat feces, throat swabs, and lung lavages were collected. 16SrDNA gene sequencing and UHPLC-QTOF-MS untargeted metabolomics were used to analyze the flora and metabolites in feces, throat swabs and lung lavage fluid of rats in each group, to screen for shared differential flora and shared differential metabolites in intestinal and respiratory tract, and the correlation analysis between the differential flora and metabolites was performed using Spearman's statistics. Results: Compared with the control group, a total of 9 species shared differential flora between intestinal and respiratory tract were screened at phylum level, and a total of 9 species shared differential genus between intestinal and respiratory tract were screened at genus level in the coal mine dust group, mainly Firmicutes, Actinobacteria, Streptococcus, Lactobacillus, etc. Compared with the control group, a total of 9 shared differential flora were screened at the phylum level, and a total of 5 shared differential genus were screened at the genus level in the silica group, mainly Proteobacteria, Actinobacteria, Allobactera, Mucilaginibacter, etc. Compared with the control group, a total of 7 shared differential metabolites were screened for up-regulation of Stigmatellin, Linalool oxide and Isoleucine-leucine in both intestinal and respiratory tract in the coal mine dust group. Compared with the control group , a total of 19 shared differential metabolites werescreened in the silica group, of which Diethanolamine, 1-Aminocyclopropanecarboxylic acid, Isoleucine-leucine, Sphingosine, Palmitic acid, D-sphinganine, 1, 2-dioleoyl-sn-glycero-3-phosphatidylcholine, and 1-Stearoyl-2-oleoyl-sn-glycerol 3-phosphocholine were up-regulated in both the intestinal and respiratory tract. Conclusion: There is a translocation of intestinal and respiratory flora in pneumoconiosis rats, and rats have an imbalance of lipid metabolism during the progression of pneumoconiosis.
Rats ; Animals ; Isoleucine ; Leucine ; Coal Mining ; Rats, Sprague-Dawley ; Pneumoconiosis ; Dust/analysis* ; Silicon Dioxide ; Coal

Objective: To investigate the clinicopathological features of perivascular epithelioid cell tumor (PEComa) of the lung. Methods: Eight PEComa cases of the lung diagnosed at the First Affiliated Hospital of Soochow University, Suzhou, China from July 2008 to December 2021 were collected and subject to immunohistochemical staining, fluorescence in situ hybridization and next generation sequencing. The relevant literature was reviewed and the clinicopathological features were analyzed. Results: There were 5 males and 3 females, aged from 18 to 70 years (mean 39 years). There were 3 cases of the right upper lung, 3 cases of the left lower lung, 1 case of the left upper lung and 1 case of the right middle lung. Seven cases were solitary and 1 case was multifocal (4 lesions). Seven cases were benign while one was malignant. The tumors were all located in the peripheral part of the lung, with a maximum diameter of 0.2-4.0 cm. Grossly, they were oval and well circumscribed. Microscopically, the tumor cells were oval, short spindle-shaped, arranged in solid nests, acinar or hemangiopericytoma-like patterns, with clear or eosinophilic cytoplasm. The stroma was rich in blood vessels with hyalinization. Coagulated necrosis and high-grade nuclei were seen in the malignant case, and calcification was seen in 2 cases. Immunohistochemically, the tumor cells were positive for Melan A (8/8), HMB45 (7/8), CD34 (6/8), TFE3 (4/7), and SMA (3/8). All cases were negative for CKpan and S-100. TFE3 (Xp11.2) gene fusion was examined using the TFE3 break-apart fluorescence in situ hybridization in 5 cases, in which only the malignant case was positive. The next generation sequencing revealed the SFPQ-TFE3 [t(X;1)(p11.2;p34)] fusion. Follow-up of the patients ranged from 12 to 173 months while one patient was lost to the follow-up. The malignant case had tumor metastasis to the brain 4 years after the operation and then received radiotherapy. Other 6 cases had no recurrence and metastasis, and all the 7 patients survived. Conclusions: Most of the PEComas of the lung are benign. When there are malignant morphological features such as necrosis, high-grade nuclei or SFPQ-TFE3 gene fusion, close follow-up seems necessary.
Male ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Perivascular Epithelioid Cell Neoplasms/pathology* ; Lung/pathology* ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics* ; Necrosis ; Biomarkers, Tumor/analysis*

Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics* ; Biomarkers, Tumor ; Humans ; Perivascular Epithelioid Cell Neoplasms/surgery* ; Stomach