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Allergic rhinitis is a common non-infectious inflammatory disease that affects approximately 15 % of people worldwide and has a complex and unclear aetiology. In recent years, pyroptosis has been found to play a role in the development of allergic rhinitis. IL-9, pyroptosis, serum and glucocorticoid-induced protein kinase 1 (SGK1), NOD-like receptor 3 (NLRP3), and nuclear factor kappa B (NF-κB) have been shown to influence each other. Herein, we aimed to explore the role of IL-9 neutralising antibody in pyroptosis involving IL-9, SGK1, NF-κB, and NLRP3 in allergic rhinitis. We observed a decrease in cytokines involved in pyroptosis and gasdermin D (GSDMD) compared with those in mice with allergic rhinitis. Further, phosphorylation of NF-κB/p65 decreased compared with that in mice with allergic rhinitis; NLRP3 and ASC also decreased, although the levels were higher than those in controls. SGK1 levels decreased compared with that in mice with allergic rhinitis and increased after using IL-9 neutralising antibodies, thus demonstrating its negative regulatory effects. The IL-9 neutralising antibody reduced the inflammatory and pyroptosis responses via SGK1 and NF-κB/NLRP3/GSDMD pathway. Our research results indicate that IL-9 regulates allergic rhinitis via the influence of SGK1 and NF-κB/NLRP3/GSDMD signalling pathway, providing new insights for developing novel drugs to treat allergic rhinitis.

The purpose of this study was to explore the effect of Semaglutide on intrauterine adhesions and discover new drugs for such adhesions. In this study, the cell model was simulated by TGF-β1-induced human endometrial epithelial cells, and the animal model was established through mechanical curettage and inflammatory stimulation. After co-culturing with TGF-β1 with or without different concentrations of Semaglutide for 48 h, cells were collected for RT-qPCR and Western blotting analyses. Three doses were subcutaneously injected into experimental mice once a day for two weeks, while the control group received sterile ddH2O. The serum and uterine tissues of the mice were collected. HE and Masson staining were used for the uterine histomorphological and pathological analyses. RT-qPCR and Western blotting were used for mRNA and protein expression analyses. Serum indicators were detected using ELISA kits. The results showed that Semaglutide significantly reduced the mRNA levels of fibrosis indicators ACTA2, COL1A1, and FN and inflammatory indicators TNF-α, IL-6, and NF-κB in the two models. Semaglutide improved endometrium morphology, increased the number of endometrial glands, and reduced collagen deposition in IUA mice. The results also showed that Semaglutide could inhibit vimentin, E-Cadherin, and N-Cadherin in the two models. In summary, Semaglutide can ameliorate fibrosis and inflammation of intrauterine adhesions as well as inhibit epithelial–mesenchymal transition in IUA models.

The Three River Headwater Region (TRHR) is an important river source area providing important ecological functions. Decades ago, climate change and human activities severely degraded the ecosystem in the TRHR. To restore vegetation, a series of ecological projects have been implemented since 1989. Using net primary productivity (NPP) data from 1988 to 2012, a sequential Mann–Kendall trend test (SQ-MK) method was applied to identify the turning point of vegetation NPP. This approach was able to represent the critical response time of the vegetation to important disturbances. A 3-year time window was set after the implementation of one ecological project to detect and analyze its short-term effects. The ecological projects included the Yangtze River Basin Shelterbelt System Construction Project (YRCP), the TRHR Nature Reserve Construction Project (TNR), the Returning Grazing Land to Grassland Project (RGLGP), and the first phase of the Ecological Conservation and Restoration Project of the TRHR (ECRP). Our results showed that the vegetation in the TRHR responded positively to restoration: 89% of pixels showed an increasing trend and 54% of pixels underwent an abrupt change. The accelerated growth type accounted for the highest proportion among all types of detected turning points. In the ECRP’s window, the positive turns rose rapidly, from 41% in 2005 to 86% in 2008, and it showed the most balanced restoration effects across grasslands. The alpine meadow and montane meadow restoration was largely influenced by the ECRP and the RGLGP (both >40%). The alpine steppe restoration was mainly attributed to the ECRP (68%). On the county scale, the positive turns in Yushu at the source of the Yangtze River mainly benefited from the RGLGP (56%), while the positive turns in Maduo at the source of the Yellow River benefited from the ECRP (77%). Nangqian, Tanggula and Zaduo County were still in need of intervention for restoration (< 3%). The results of the study can enhance our understanding of the spatio–temporal distribution of the short-term ecological benefits of different ecological projects, thus provide a scientific and timely reference for future planning and adjustment of the conservation and restoration projects.

Abstract Background As one of the most important staple food crops, rice produces large of agronomic biomass residues that contain lots of secondary cell walls (SCWs). Membrane trafficking plays key roles in SCWs biosynthesis, but information association membrane trafficking and SCWs formation in plants is limited. Results In this study, we report the function characterization of a rice mutant, c ulm e asily f ragile 3 (cef3), that exhibits growth retardation and fragile culm phenotype with significantly altered cell wall composition and reduced secondary wall thickness. Map-based cloning revealed that CEF3 encodes a homologous protein of Arabidopsis STOMATAL CYTOKINESIS DEFECTIVE2 (SCD2). The saccharification assays revealed that CEF3 mutation can improve biomass enzymatic saccharification. Expression pattern analysis indicated that CEF3 is ubiquitously expressed in many organs at different developmental stages. Subcellular localization revealed that CEF3 is a Golgi-localized protein. The FM4-64 uptake assay revealed CEF3 is involved in endocytosis. Furthermore, mutation of CEF3 not only affected cellulose synthesis-related genes expression, but also altered the abundance of cellulose synthase catalytic subunit 9 (OsCESA9) in the PM and in the endomembrane systems. Conclusions This study has demonstrated that CEF3 participates in the membrane trafficking that is essential for normal cellulose and other polysaccharides biosynthesis of the secondary cell wall, thereby manipulation of CEF3 could alter cellulose content and enhance biomass enzymatic saccharification in rice plants. Therefore, the study of the function of CEF3 can provide a strategy for genetic modification of SCWs in bioenergy crops.

The high altitude in mountainous regions results in lower atmospheric pressure, oxygen concentration and temperature, leading to lower combustion efficiency in motor vehicles. Therefore, there may be differences in carbon dioxide (CO2), carbon monoxide (CO), and nitrogen oxides (NOx) emissions characteristics at different altitudes. In this study, a portable emission measurement system was used to investigate the effects of varying elevations on the emission factors of CO2, CO, and NOx on diesel and gasoline-powered vehicles at altitudes ranging from 2270 to 4540 m in the Qinghai–Tibet Plateau of China. Additionally, the influencing factors of CO2, CO, and NOx emissions were studied. Results showed that the CO2, CO, and NOx emission factors for diesel vehicles varied in the range of 161.83–195.54, 0.59–0.77, and 4.61–6.58 g/km; the population means with 90% confidence intervals were 178.54, 0.68, and 5.60 g/km, respectively. For gasoline vehicles, the CO2, CO, and NOx emission factors varied in the range of 161.66–181.98, 0.95–1.06, and 0.12–0.25 g/km; the population means with 90% confidence intervals were 171.82, 1.01, and 0.19 g/km, respectively. Overall, the emission factors of diesel vehicles were higher than those of gasoline vehicles, and the emissions increased with increasing altitude. Atmospheric pressure was identified as the primary environmental factor affecting CO2, CO, and NOx emissions. As the speed of motor vehicles increased, the emission of CO2 also increased, while there was a quadratic relationship with acceleration. This study provides a reference and guidance for vehicle pollution control in high-altitude regions.

Grain weight is a major determinant in rice yield, which is tightly associated with grain size. However, the underlying molecular mechanisms that control this trait remain unclear. Here, we report a rice (Oryza sativa) mutant, low grain weight (lgw), which shows that reduced grain length is caused by decreased cell elongation and proliferation. Map-based cloning revealed that all mutant phenotypes resulted from a nine-base pair (bp) deletion in LGW, which encodes the kinesin-like protein BRITTLE CULM12 (BC12). Protein sequence alignment analysis revealed that the mutation site was located at the nuclear localization signal (NLS) of LGW/BC12, resulting in the lgw protein not being located in the nucleus. LGW is preferentially expressed in both culms and roots, as well as in the early developing panicles. Overexpression of LGW increased the grain length, indicating that LGW is a positive regulator for regulating grain length. In addition, LGW/BC12 is directly bound to the promoter of GW7 and activates its expression. Elevating the GW7 expression levels in lgw plants rescued the small grain size phenotype. We conclude that LGW regulates grain development by directly binding to the GW7 promoter and activating its expression. Our findings revealed that LGW plays an important role in regulating grain size, and manipulation of this gene provides a new strategy for regulating grain weight in rice.

Allergic rhinitis is mainly mediated by IgE after specific individuals are exposed to allergens. It is a common nasal mucosa disease of non-infectious chronic inflammatory disease and is often accompanied by asthma and conjunctivitis. In the study of allergic asthma, it was found that IL-9 participates in the pathogenic development of asthma. Because asthma and allergic rhinitis have the same airway and the same disease, it is inferred that IL-9 may also play an important role in allergic rhinitis. BALB/c mice received intranasal stimulation of ovalbumin (OVA) treatment at different times. The nasal mucosa of the mice were then sliced and stained with Sirius red and Toluidine blue, and eosinophils and mast cells in the mucosa were counted. ELISA was used to detect the expression of OVA-IgE in peripheral blood. The Th2 cell fraction in the mouse spleen was detected by flow cytometry. The expressions of IL-4, IL-5, IL-9, and IL-13 and their mRNA in mucosa were detected by real-time PCR and flow cytometry bead array analysis. Finally, the expression changes of Thymic stromal lymphopoietin related proteins and its mRNA, JAK1/2, and STAT5 proteins were detected by real-time PCR and Western blot. After the intervention with the IL-9 neutralizing antibody, the symptoms of allergic rhinitis in mice were significantly reduced. The expression of OVA-IgE in the peripheral blood of mice was inhibited, the fraction of Th2 cells in the spleen decreased, the related cytokines (IL-4, IL-5, and IL-13) were inhibited, and their functions decreased. The TSLP-OX40/OX40L signal pathway and JAK1/2-STAT5 signal are inhibited. IL-9 neutralizing antibody has a good therapeutic effect on the mouse model of allergic rhinitis, which may be related to the TSLP-OX40/OX40L pathway and JAK1/2-STAT5 signaling.

Cultivating rice varieties with lower cellulose content in the bran layer has the potential to enhance both the nutritional value and texture of brown rice. This study aims to establish a rapid and accurate method to quantify cellulose content in the bran layer utilizing near-infrared spectroscopy (NIRS), thereby providing a technical foundation for the selection, screening, and breeding of rice germplasm cultivars characterized by a low cellulose content in the bran layer. To ensure the accuracy of the NIR spectroscopic analysis, the potassium dichromate oxidation (PDO) method was improved and then used as a reference method. Using 141 samples of rice bran layer (rice bran without germ), near-infrared diffuse reflectance (NIRdr) spectra, near-infrared diffuse transmittance (NIRdt) spectra, and fusion spectra of NIRdr and NIRdt were used to establish cellulose quantitative analysis models, followed by a comparative evaluation of these models’ predictive performance. Results indicate that the optimized PDO method demonstrates superior precision compared to the original PDO method. Upon examining the established models, their predictive capabilities were ranked in the following order: the fusion model outperforms the NIRdt model, which in turn surpasses the NIRdr model. Of all the fusion models developed, the model exhibiting the highest predictive accuracy utilized fusion spectra (NIRdr-NIRdt (1st der)) derived from preprocessed (first derivative) diffuse reflectance and transmittance spectra. This model achieved an external predictive R2p of 0.903 and an RMSEP of 0.213%. Using this specific model, the rice mutant O2 was successfully identified, which displayed a cellulose content in the bran layer of 3.28%, representing a 0.86% decrease compared to the wild type (W7). The utilization of NIRS enables quantitative analysis of the cellulose content within the rice bran layer, thereby providing essential technical support for the selection of rice varieties characterized by lower cellulose content in the bran layer.

Abstract Background Gastric cancer is one of the most common malignant tumors of the digestive system. However, its targeted therapy develops at a slow pace. Thus, exploring the mechanisms of the malignant behavior of gastric cancer cells is crucial to exploit its treatment. Mammalian never-in-mitosis A (NIMA)-related kinases (NEKs) are considered to play a significant role in cancer cell proliferation. However, no study has reported on NIMA family proteins in gastric cancer. Methods Bioinformatics analysis was employed to clarify the expression patterns of NEK1–NEK11 and their effects on prognosis. The effects of NEK7 on immune infiltration and NEK7 related pathways were also analyzed. At the cell level, 5-ethynyl-2-deoxyuridine, cell cycle, and Cell Counting Kit-8 assays were utilized to clarify the effect of NEK7 on gastric cancer cell proliferation. A mouse subcutaneous model revealed the regulating effect of NEK7 on gastric cancer cell proliferation in vivo. Results Bioinformatics analysis revealed that NEK7 is upregulated in gastric cancer and is related to poor prognosis. NEK7 is also related to T-stage, which is closely associated with cell proliferation. Further analysis showed that NEK7 was correlated with infiltration of multiple immune cells as well as gastric cancer-related pathways. Cell experiments indicated the promoting effect of NEK7 on cell proliferation, while the absence of NEK7 could lead to inhibition of gastric cancer proliferation and G1/S arrest. Conclusion NEK7 exerts a regulatory effect on cell proliferation and is closely related to tumor immune infiltration.

Unique ecosystems distributed in alpine areas of the Qinghai–Tibetan Plateau play important roles in climate change mitigation, local food supply, and conservation of species diversity. To understand the water use efficiency (WUE) of this fragile and sensitive region, this study combined observed data from the eddy covariance system and the Shuttleworth–Wallace (S-W) model to measure the continuous mass exchange, including gross primary productivity (GPP), evapotranspiration (ET), and canopy transpiration (T) throughout 2 or 3 years (2016–2018) in three common alpine ecosystems (i.e., alpine steppe, alpine meadow, and alpine swamp). These ecosystems represent a water availability gradient and thus provide the opportunity to quantify environmental and biological controls on WUE at various spatiotemporal scales. We analyzed the ecosystem WUE (WUEe; defined as the ratio of GPP to ET) and canopy WUE (WUEc; defined as the ratio of GPP and canopy T). It was found that the yearly WUEe was 1.40, 1.63, and 2.16 g C kg–1 H2O, and the yearly WUEc was 8.93, 2.46, and 5.19 g C kg–1 H2O in the three typical ecosystems, respectively. The controlling factors of yearly WUE diverged between WUEe and WUEc. We found that plant functional group proportion (e.g., gramineous and Cyperaceae) highly explained the yearly WUEe variation across sites, and a good correlation was observed between community species diversity and WUEc. These findings suggest that community composition and trait change are critical in regulating WUEe and WUEc across different alpine ecosystems and that the regulation mechanisms may differ fundamentally between WUEe and WUEc.

Wood vinegar, a by-product of wood pyrolysis, is mostly discarded. Wood vinegar has a phytotoxic effect and could be potentially used as a naturally derived herbicide for weed control. The objective of this research was to evaluate the efficacy of wood vinegar from the pyrolysis of apple (Malus × domestica Borkh.) tree branch wastes to control weeds. The wood vinegar concentrations required to inhibit 50% motherwort (Leonurus cardiaca L.), redroot pigweed (Amaranthus retroflexus L.), Spanish needles (Bidens pilosa L.), and tall fescue (Festuca arundinacea L.) seed germination measured 0.51%, 0.48%, 0.16%, and 1.1%, respectively. The wood vinegar application rates (spray volume) required to provide 50% control of motherwort and Spanish needles measured 1911 L ha−1 and 653 L ha−1, respectively, while the highest evaluated rate at 4000 L ha−1 controlled 35% tall fescue by 10 days after treatment (DAT). Common purslane (Portulaca oleracea L.) control increased as the wood vinegar application rate increased from 500 L ha−1 to 2000 L ha−1. Wood vinegar was more effective in dark than light conditions for controlling common purslane. By 5 DAT, averaged over application rates, wood vinegar provided 95% and 87% control of common purslane in dark and light conditions, respectively. These findings suggest that wood vinegar obtained from the pyrolysis of apple tree branches could be used for weed management.

Objective To determine whether aldehyde dehydrogenase 1 (ALDH1) immunostaining in axillary lymph node metastases in patients with breast cancer is associated with poor clinical prognosis. Methods This retrospective study reviewed data from the medical records of patients with immunohistochemistry-confirmed invasive ductal carcinoma (IDC) and 1–3 metastatic lymph nodes in the ipsilateral axilla between December 2012 and July 2015. The association between ALDH1 immunostaining in axillary lymph node metastases and clinical parameters and prognosis was analysed using χ 2 -test, Kaplan–Meier survival analysis, univariate and multivariate Cox regression analyses. Results A total of 229 patients with IDC were enrolled in the study. The median follow-up was 61 months (range, 20–89 months). Patients with ALDH1-positive axillary lymph node metastases had significantly shorter relapse-free survival and overall survival compared with those with ALDH1-negative axillary lymph node metastases. ALDH1 immunostaining in axillary lymph node metastases was a significant predictor of poor prognosis in univariate and multivariate analyses. Conclusion This large study with long-term follow-up suggests that ALDH1 immunostaining in axillary lymph node metastases is an independent predictor of poor prognosis in patients with breast cancer. The clinical relevance of this finding should be confirmed in further well-designed prospective studies.

Breast cancer (BC) is the most common gynecologic tumor worldwide where aberrant expression of microRNAs (miRNAs) is frequently involved. Here, we evaluated the function of miR-375 on BC development and the molecules implicated. Differentially expressed genes between tumor and paired normal tissues from BC patients were screened out by microarray analyses. miR-375 was abundantly expressed in BC tissues and cells, and it was correlated with the poor prognosis of patients. Downregulation of miR-375 was introduced into BC cell lines MCF-7 and HCC1954, after which the viability, colony formation, migration, and invasion were suppressed, while the apoptosis of cells was increased, and the xenograft tumors in nude mice were reduced as well. EZH2 increased methylation and phosphorylation of signal transducer and activator of transcription 3 (STAT3) and increased transcription activity of miR-375, while miR-375 directly targeted FOXO1. Either overexpression of EZH2 or downregulation of FOXO1 blocked the functions of anti-miR-375 in cells and animals. FOXO1 was found as an activator of the p53 signaling pathway. This study showed that miR-375 is an important oncogene in BC. EZH2 is an upstream regulator of miR-375 through mediating the methylation of STAT3, while FOXO1 is a downstream target mRNA of miR-375 that activates the p53 signaling pathway to suppress BC development.

Objective To assess the impact of a regional rapid response system (RRS) implemented in a Chinese Joint Commission International Hospital on the timely treatment of patients with serious adverse events (SAEs). Methods Clinical SAEs, activation periods, reasons for RSS activation, and patient outcomes were assessed using SAE response sheets at admission to the hospital and over 31 months of follow-up. Results We found that 192 events were called by medical staff and 6 were called by auxiliary staff. Reasons for the 385 RRS activations included: unconsciousness (133; 34.5%), and airway obstruction and absent carotid pulse (49 each; 12.7%). The average arrival time of the medical emergency team was 2.4 ± 0.1 minutes. There were 123 (62.1%) RRS activations during daytime working hours (8:00–17:00); CPR was performed in 86 (43.4%) cases. Outcomes of RRS were: vital signs stabilized in 82 (41.4%) patients and 61 (30.8%) patients were transferred to ICU. Conclusion Our experience showed that the regional RRS has led to better integrated multidisciplinary cooperation and reduced time for treating patients with SAEs, resulting in success of the RRS.

Background: Due to similar symptoms of abdominal pain, acute pancreatitis (AP) is often difficult to differentiate from acute aortic dissection (AAD) in clinical practice. It is unknown whether serum amylase and coagulation function indices can be used to distinguish AP from AAD. Methods: In this retrospective study, 114 AP patients (AP group) and 48 cases with AAD (AAD group) admitted for acute abdominal pain were enrolled for a final analysis. The levels of serum amylase and coagulation function indices, including prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (FIB), and D-dimer (DD), were tested before or on admission and compared between the two groups. Student's t-test was adopted for comparing the mean. Model discrimination was evaluated by using the area under the receiver operating characteristic curve (AUC). Comparison of AUC was performed by using the Z-test. Results: Compared with the AAD group, amylase and FIB were both significantly increased, while DD was significantly lower in the AP group (all p < 0.01). There were no statistically significant differences of PT, INR, and APTT between AP and AAD (all p > 0.05). The AUCs in distinguishing AP from AAD were 0.913, 0.854, and 0.837 for amylase, FIB, and DD, respectively, but there were no significant differences observed among amylase, FIB, and DD (all p > 0.05). Finally, the cutoff values (specificity, sensitivity, and Youden index) in distinguishing between AP and AAD were 114 μ/L (80.70%, 95.83%, 0.765) for amylase, 2.62 g/L (76.32%, 85.42%, 0.617) for FIB, and 2.74 mg/L (95.61%, 62.50%, 0.581) for DD, respectively. Conclusions: Amylase, FIB, and DD can demonstrate accurate and reliable diagnostic values, suggesting that they are useful and potential biomarkers in distinguishing AP from AAD. [ABSTRACT FROM AUTHOR]

Urine provides an ideal source for disease biomarker discovery. High-adhesion contaminants such as urobilin, which are difficult to remove from urine, can severely interfere with urinary proteomic analysis. Here, we aimed to establish a strategy based on single-pot, solid-phase-enhanced sample preparation (SP3) technology to prepare samples for urinary proteomics analysis that almost completely eliminates the impact of urobilin. A systematic evaluation of the effects of two urinary protein precipitation methods, two types of protein lysis buffers, and different ratios of magnetic digestion beads on the identification and quantification of the microscale urinary proteome was conducted. Our results indicate that methanol–chloroform precipitation, coupled with efficient lysis facilitated by urea, and subsequent enzymatic digestion using a mix of hydrophilic and hydrophobic magnetic beads offers the best performance. Further applying this strategy to the urine of patients with benign prostatic hyperplasia, prostate cancer and healthy individuals, combined with a narrow window of data-independent acquisition, FGFR4, MYLK, ORM2, GOLM1, SPP1, CD55, CSF1, DLD and TIMP3 were identified as potential biomarkers to discriminate benign prostatic hyperplasia and prostate cancer patients. [ABSTRACT FROM AUTHOR]

Abstract Background Astragalus membranaceus (Fisch.) Bunge is one of the most well-known tonic herbs in traditional Chinese medicine, renowned for its remarkable medicinal value in various clinical contexts. The corresponding chloroplast (cp) and nuclear genomes have since been accordingly sequenced, providing valuable information for breeding and phylogeny studies. However, the mitochondrial genome (mitogenome) of A. membranaceus remains unexplored, which hinders comprehensively understanding the evolution of its genome. Results For this study, we de novo assembled the mitogenome of A. membranaceus (Fisch.) Bunge var. mongholicus (Bunge) P. K. Hsiao using a strategy integrating Illumina and Nanopore sequencing technology and subsequently performed comparative analysis with its close relatives. The mitogenome has a multi-chromosome structure, consisting of two circular chromosomes with a total length of 398,048 bp and an overall GC content of 45.3%. It encodes 54 annotated functional genes, comprising 33 protein-coding genes (PCGs), 18 tRNA genes, and 3 rRNA genes. An investigation of codon usage in the PCGs revealed an obvious preference for codons ending in A or U (T) bases, given their high frequency. RNA editing identified 500 sites in the coding regions of mt PCGs that exhibit a perfect conversion of the base C to U, a process that tends to lead to the conversion of hydrophilic amino acids into hydrophobic amino acids. From the mitogenome analysis, a total of 399 SSRs, 4 tandem repeats, and 77 dispersed repeats were found, indicating that A. membranaceus possesses fewer repeats compared to its close relatives with similarly sized mitogenomes. Selection pressure analysis indicated that most mt PCGs were purifying selection genes, while only five PCGs (ccmB, ccmFc, ccmFn, nad3, and nad9) were positive selection genes. Notably, positive selection emerged as a critical factor in the evolution of ccmB and nad9 in all the pairwise species comparisons, suggesting the extremely critical role of these genes in the evolution of A. membranaceus. Moreover, we inferred that 22 homologous fragments have been transferred from cp to mitochondria (mt), in which 5 cp-derived tRNA genes remain intact in the mitogenome. Further comparative analysis revealed that the syntenic region and mt gene organization are relatively conserved within the provided legumes. The comparison of gene content indicated that the gene composition of Fabaceae mitogenomes differed. Finally, the phylogenetic tree established from analysis is largely congruent with the taxonomic relationships of Fabaceae species and highlights the close relationship between Astragalus and Oxytropis. Conclusions We provide the first report of the assembled and annotated A. membranaceus mitogenome, which enriches the genetic resources available for the Astragalus genus and lays the foundation for comprehensive exploration of this invaluable medicinal plant.

Abstract Tumor-infiltrating lymphocyte (TIL) therapy in adoptive T-cell therapy (ACT) has already caused durable regression in a variety of cancer types due to T-cell persistence, clinical activity, and duration of objective response and safety. TILs are composed of polyclonal effector T-cells specific to heterogenetic tumor antigens, reasonably providing a promising means for tumor therapy. In addition, their expansion in vitro can release them from the suppressive tumor microenvironment. Even though significant advances have been made in the procedure of TIL therapy, from TIL isolation, modification, expansion, and infusion back to the patient to target the tumor, strategy optimization is always ongoing to overcome drawbacks such as a complex process, options for the lineage differentiation status of TILs, and sufficient trafficking of TILs to the tumor. In this review, we summarize the current advances of TIL therapy, raise problem-based optimization strategies, and provide future perspectives on next-generation TIL therapy as a potential avenue for enhancing cell-based immunotherapy.