Tertiary lymphoid structures as potential biomarkers for cancer prediction and prognosis.

Tertiary lymphoid structures (TLSs) are ectopic lymphocyte aggregates formed in non-lymphoid tissues, including cancers, and are loci for the generation of in situ anti-tumor immune responses, which play a crucial role in cancer control. The state of TLS presence in cancer and its composition can significantly impact the treatment response and prognosis of patients. TLSs have the potential to serve as predictive and prognostic biomarkers for cancer. However, the mechanisms underlying TLS formation in cancer and how the essential components of TLSs affect cancer are not fully understood. In this review, we summarized TLS formation in cancer, the value of the TLS in different states of existence, and its key constituents for cancer prediction and prognosis. Finally, we discussed the impact of cancer treatment on TLSs.

Tertiary Lymphoid Structure in Tumor Microenvironment and Immunotherapy of Lung Cancer.

Immune checkpoint inhibitors have opened an era of lung cancer therapy. However, a notable disparity exists in the efficacy of immunotherapy among individual patients. The tertiary lymphoid structure (TLS) is an ectopic lymphocyte aggregation that appears under pathological conditions and is the primary site of action for anti-tumor immunity. It is commonly reported that the presence of TLS within the tumor microenvironment (TME) relates to a favorable clinical prognosis and an excellent response to immunotherapy in lung cancer patients. A thorough understanding of TLS and its dynamic changes in TME has become an attractive focus for optimizing immunotherapy strategies for lung cancer. In this review, we comprehensively generalize the composition, formation, mechanism, detection methods of TLS, and summarize the role of TLS in lung cancer immunotherapy. Finally, induction of TLS is also discussed, which may provide more effective therapeutic strategies for lung cancer therapy.

Enhancing cassava beer quality: Extrusion-induced modification of cassava starch structure boosts fermentable sugar content in wort.

The high starch content and cost-effectiveness of cassava make it an attractive adjunct in beer brewing, with the fine structure of starch playing a crucial role in determining the composition of fermentable sugars (FS) and overall beer quality. This study investigated the effect of extrusion-induced changes in the starch structure of cassava flour on the FS profile of the wort and, consequently, on the quality attributes of cassava beer. The findings revealed that the shear stress during extrusion significantly reduced the molecular weight to 1.20 × 105g/mol and the branching degree of amylopectin. Simultaneously, there was an increase in the concentrations of short- and intermediate- chain amylose by 5.61% and 42.72%, respectively. These structural changes enhanced the enzymatic hydrolysis of extruded cassava flour (ECF), resulting in a higher total fermentable sugars content (22.00g/100 mL) in the ECF wort, predominantly composed of maltose and glucose. Furthermore, the altered FS profile led to an increased production of higher alcohols and esters in extruded cassava beer (ECB), particularly noted for the elevation of 2-phenylethyl alcohol levels, which imparted a distinctive rose aroma to the ECB. Consequently, the sensory profile of ECB showed significant improvement. This study offers critical insight into optimizing cassava beer quality and broadens the potential applications of cassava flour in the brewing industry.

Incorporating whole soybean pulp into wheat flour for nutrient-enriched steamed bread: Exploring the impact on physical and nutritional characteristics.

This research explored the impact of incorporating various levels of whole soybean pulp (WSP) (10%, 20%, 30%, 40%, and 50%) into wheat flour on the physical and nutritional qualities of steamed bread. In comparison with the traditional steamed bread, the substitution of up to 20% WSP did not significantly alter the specific volume, hardness, and chewiness of the steamed bread. Additionally, the crumb texture of the steamed bread with 20% WSP maintained small and uniform pores, with optimal springiness and cohesiveness. Nutritionally, the substitution of 10%-50% WSP enhanced total dietary fiber, total phenolics, and protein by 9.40%-89.79%, 14.96%-116.31%, and 3.45%-34.36%, respectively. Isoflavones in the steamed bread increased markedly from 22.92 µg/g to a range of 140.12-997.12 µg/g. The expected glycemic index showed a decrease from 90.24 to between 85.85 and 70.75, whereas amino acid scores improved from 59.22 to a range of 64.58-65.08, with lysine (Lys) scores notably increasing from 59.22 to between 64.96 and 88.80. In conclusion, partially replacing wheat flour with WSP is an effective method for enhancing the nutritional profile and addressing the essential amino acid imbalance in steamed bread. PRACTICAL APPLICATION: This study partially replaced flour with WSP to improve the steamed bread's nutritional quality. The optimal substitution level was determined to be 20% WSP, which improves the bread's nutritional value without significantly impacting its physical qualities. Furthermore, WSP is produced from soaked soybeans through hot water milling. This process simplifies soybean processing, lowers energy consumption and costs, and reduces pollution. It also effectively retains essential nutrients, such as protein, dietary fiber, polyphenols, and soy isoflavones, ensuring the full utilization of soybeans.

The HD-ZIP II gene PaHAT14 increases cuticle deposition by down-regulating ERF gene PaERF105 in Phalaenopsis.

To analyze the gene involved in orchid floral development, a HD-Zip II gene PaHAT14, which specifically and highly expressed in perianth during early flower development was identified from Phalaenopsis. Transgenic Arabidopsis plants expressing 35S::PaHAT14 and 35S::PaHAT14+SRDX (fused with the repressor motif SRDX) exhibited similar altered phenotypes, including small leaves, early flowering, and bending petals with increased cuticle production. This suggests that PaHAT14 acts as a repressor. In contrast, transgenic Arabidopsis plants expressing 35S::PaHAT14+VP16 (fused with the activation domain VP16) exhibited curled leaves, late flowering, and folded petals with decreased cuticle production within hardly opened flowers. Additionally, the expression of the ERF gene DEWAX2, which negatively regulates cuticular wax biosynthesis, was down-regulated in 35S::PaHAT14 and 35S::PaHAT14+SRDX transgenic Arabidopsis, while it was up-regulated in 35S::PaHAT14+VP16 transgenic Arabidopsis. Furthermore, transient overexpression of PaHAT14 in Phalaenopsis petal/sepal increased cuticle deposition due to the down-regulation of PaERF105, a Phalaenopsis DEWAX2 orthologue. On the other hand, transient overexpression of PaERF105 decreased cuticle deposition, whereas cuticle deposition increased and the rate of epidermal water loss was reduced in PaERF105 VIGS Phalaenopsis flowers. Moreover, ectopic expression of PaERF105 not only produced phenotypes similar to those in 35S::PaHAT14+VP16 Arabidopsis but also compensated for the altered phenotypes observed in 35S::PaHAT14 and 35S::PaHAT14+SRDX Arabidopsis. These results suggest that PaHAT14 promotes cuticle deposition by negatively regulating downstream gene PaERF105 in orchid flowers.

Mature tertiary lymphoid structures: important contributors to anti-tumor immune efficacy.

Tertiary lymphoid structures (TLS) represent the ectopic aggregations of immune cells arising during chronic inflammation or tumor progression. In cancer, TLS are often associated with beneficial clinical outcomes in patients undergoing immunotherapy, underscoring their prognostic and predictive significance. Mature TLS, characterized by germinal centers and areas of T-cell and B-cell aggregation, are considered primary locations for activating and maintaining both humoral and cellular anti-tumor immune effects. Despite their recognized importance, the mechanisms driving the formation of mature TLS in cancer and their influence on the immune response within tumors remain insufficiently understood. Therefore, this review aims to comprehensively explore the structural composition, development mechanisms, maturity impact factors, immunological function, and innovative therapeutic strategies of mature TLS within the tumor microenvironment. The research summarized herein offers novel insights and considerations for therapeutic approaches to promote TLS generation and maturation in patients with cancer, representing a promising avenue for future cancer therapies.

A Novel Approach for Preparing Sepiolite Micron Powder Based on Steam Pressure Changes.

As a common method for preparing micron powder in industrial operations, the mechanical extrusion method simply pursues the particle size without considering the microstructure characteristics of sepiolite, which leads to problems such as bundles of sepiolite not being effectively dispersed, and thus the disruption of fibers is inevitably caused. In this work, a new micronization method for disaggregating these bundles while preserving the original structural integrity of the fibers is proposed based on steam pressure changes. The effects of steam pressure changes on the particle size distribution, microstructure, and properties of treated sepiolite are studied using X-ray fluorescence spectrometer (XRF), X-ray diffractometer (XRD), Field Emission Scanning Electron Microscopy (FESEM), Transmission Electron Microscopy (TEM), and a specific surface area and aperture analyzer (BET). The experimental results show that the particle size of sepiolite powder depends greatly on steam pressure, and sepiolite powder with mass ratio of 91.6% and a particle size D97 of 21.27 µm is obtained at a steam pressure of 0.6 MPa. Compared to the sepiolite after mechanical extrusion, the sepiolite treated with steam pressure changes can maintain the integrity of its crystalline structure. The specific surface area of sepiolite enhanced from 80.15 m2 g-1 to 141.63 m2 g-1 as the steam pressure increased from 0.1 to 0.6 MPa, which is about 1.6 times that of the sample treated with mechanical extrusion.

Allogeneic CD19-targeted CAR-T therapy in patients with severe myositis and systemic sclerosis.

Allogeneic chimeric antigen receptor (CAR)-T cells hold great promise for expanding the accessibility of CAR-T therapy, whereas the risks of allograft rejection have hampered its application. Here, we genetically engineered healthy-donor-derived, CD19-targeting CAR-T cells using CRISPR-Cas9 to address the issue of immune rejection and treated one patient with refractory immune-mediated necrotizing myopathy and two patients with diffuse cutaneous systemic sclerosis with these cells. This study was registered at ClinicalTrials.gov (NCT05859997). The infused cells persisted for over 3 months, achieving complete B cell depletion within 2 weeks of treatment. During the 6-month follow-up, we observed deep remission without cytokine release syndrome or other serious adverse events in all three patients, primarily shown by the significant improvement in the clinical response index scores for the two diseases, respectively, and supported by the observations of reversal of inflammation and fibrosis. Our results demonstrate the high safety and promising immune modulatory effect of the off-the-shelf CAR-T cells in treating severe refractory autoimmune diseases.

An investigation of the molecular characterization of the tripartite motif (TRIM) family and primary validation of TRIM31 in gastric cancer.

Most TRIM family members characterized by the E3-ubiquitin ligases, participate in ubiquitination and tumorigenesis. While there is a dearth of a comprehensive investigation for the entire family in gastric cancer (GC). By combining the TCGA and GEO databases, common TRIM family members (TRIMs) were obtained to investigate gene expression, gene mutations, and clinical prognosis. On the basis of TRIMs, a consensus clustering analysis was conducted, and a risk assessment system and prognostic model were developed. Particularly, TRIM31 with clinical prognostic and diagnostic value was chosen for single-gene bioinformatics analysis, in vitro experimental validation, and immunohistochemical analysis of clinical tissue microarrays. The combined dataset consisted of 66 TRIMs, of which 52 were differentially expressed and 43 were differentially prognostic. Significant survival differences existed between the gene clusters obtained by consensus clustering analysis. Using 4 differentially expressed genes identified by multivariate Cox regression and LASSO regression, a risk scoring system was developed. Higher risk scores were associated with a poorer prognosis, suppressive immune cell infiltration, and drug resistance. Transcriptomic data and clinical sample tissue microarrays confirmed that TRIM31 was highly expressed in GC and associated with a poor prognosis. Pathway enrichment analysis, cell migration and colony formation assay, EdU assay, reactive oxygen species (ROS) assay, and mitochondrial membrane potential assay revealed that TRIM31 may be implicated in cell cycle regulation and oxidative stress-related pathways, contribute to gastric carcinogenesis. This study investigated the whole functional and expression profile and a risk score system based on the TRIM family in GC. Further investigation centered around TRIM31 offers insight into the underlying mechanisms of action exhibited by other members of its family in the context of GC.

Rh(III)-catalyzed C(sp2)-H functionalization/[4+2] annulation of oxadiazolones with iodonium ylides to access diverse fused-isoquinolines and fused-pyridines.

In this study, a Rh(III)-catalyzed C-H/N-H [4+2] annulation of oxadiazolones with iodonium ylides has been developed, which afforded a series of diverse fused-isoquinolines and fused-pyridines in moderate to high yields. These divergent synthesis protocols featured mild conditions, broad substrate scope, and functional-group compatibility. In addition, scale-up synthesis, related applications and preliminary mechanistic explorations were also accomplished.

Immune-related adverse events in non-small cell lung cancer: Occurrence, mechanisms and therapeutic strategies.

The emergence of immune checkpoint inhibitors (ICIs) has heralded a transformative era in the therapeutic landscape of non-small cell lung cancer (NSCLC). While ICIs have demonstrated clinical efficacy in a portion of patients with NSCLC, these treatments concurrently precipitate a spectrum of immune-related adverse events (irAEs), encompassing mild to severe manifestations, collectively posing a risk of significant organ damage. Consequently, there exists an imperative to augment our comprehension of the pathophysiological underpinnings of irAEs and to formulate more efficacious preventive and ameliorative strategies. In this comprehensive review, we delineate the clinical presentation of organ-specific irAEs in patients with NSCLC and provide an in-depth analysis of recent advancements in understanding the mechanisms driving ICI-induced toxicity. Furthermore, we discuss potential strategies and targets for ameliorating these irAEs. Ultimately, this review aims to furnish valuable insights to guide further research endeavours in the context of irAEs in NSCLC patients.

The role of immune cells and inflammation in pulmonary hypertension: mechanisms and implications.

Pulmonary hypertension (PH) is a malignant disease with progressive increase of pulmonary vascular pressure, which eventually leads to right heart failure. More and more evidences show that immune cells and inflammation play an important role in the occurrence and development of PH. In the context of pulmonary vascular diseases, immune cells migrate into the walls of the pulmonary vascular system. This leads to an increase in the levels of cytokines and chemokines in both the bloodstream and the surrounding tissues of the pulmonary vessels. As a result, new approaches such as immunotherapy and anti-inflammatory treatments are being considered as potential strategies to halt or potentially reverse the progression of PH. We reviewed the potential mechanisms of immune cells, cytokines and chemokines in PH development. The potential relationship of vascular cells or bone morphogenetic protein receptor 2 (BMPR2) in immune regulation was also expounded. The clinical application and future prospect of immunotherapy were further discussed.

The radiological characteristics, tertiary lymphoid structures, and survival status associated with EGFR mutation in patients with subsolid nodules like stage I-II LUAD.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) recommended for the patients with subsolid nodule in early lung cancer stage is not routinely. The clinical value and impact in patients with EGFR mutation on survival outcomes is further needed to be elucidated to decide whether the application of EGFR-TKIs was appropriate in early lung adenocarcinoma (LUAD) stage appearing as subsolid nodules. MATERIALS AND METHODS: The inclusion of patients exhibiting clinical staging of IA-IIB subsolid nodules. Clinical information, computed tomography (CT) features before surgical resection and pathological characteristics including tertiary lymphoid structures of the tumors were recorded for further exploration of correlation with EGFR mutation and prognosis. RESULTS: Finally, 325 patients were enrolled into this study, with an average age of 56.8 ± 9.8 years. There are 173 patients (53.2%) harboring EGFR mutation. Logistic regression model analysis showed that female (OR = 1.944, p = 0.015), mix ground glass nodule (OR = 2.071, p = 0.003, bubble-like lucency (OR = 1.991, p = 0.003) were significant risk factors of EGFR mutations. Additionally, EGFR mutations were negatively correlated with TLS presence and density. Prognosis analysis showed that the presence of TLS was associated with better recurrence-free survival (RFS)(p = 0.03) while EGFR mutations were associated with worse RFS(p = 0.01). The RFS in patients with TLS was considerably excel those without TLS within EGFR wild type group(p = 0.018). Multivariate analyses confirmed that EGFR mutation was an independent prognostic predictor for RFS (HR = 3.205, p = 0.037). CONCLUSIONS: In early-phase LUADs, subsolid nodules with EGFR mutation had specific clinical and radiological signatures. EGFR mutation was associated with worse survival outcomes and negatively correlated with TLS, which might weaken the positive impact of TLS on prognosis. Highly attention should be paid to the use of EGFR-TKI for further treatment as agents in early LUAD patients who carrying EGFR mutation.

Nortriptyline hydrochloride, a potential candidate for drug repurposing, inhibits gastric cancer by inducing oxidative stress by triggering the Keap1-Nrf2 pathway.

Effective drugs for the treatment of gastric cancer (GC) are still lacking. Nortriptyline Hydrochloride (NTP), a commonly used antidepressant medication, has been demonstrated by numerous studies to have antitumor effects. This study first validated the ability of NTP to inhibit GC and preliminarily explored its underlying mechanism. To begin with, NTP inhibits the activity of AGS and HGC27 cells (Human-derived GC cells) in a dose-dependent manner, as well as proliferation, cell cycle, and migration. Moreover, NTP induces cell apoptosis by upregulating BAX, BAD, and c-PARP and downregulating PARP and Bcl-2 expression. Furthermore, the mechanism of cell death caused by NTP is closely related to oxidative stress. NTP increases intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels, decreasing the mitochondrial membrane potential (MMP) and inducing glucose (GSH) consumption. While the death of GC cells can be partially rescued by ROS inhibitor N-acetylcysteine (NAC). Mechanistically, NTP activates the Kelch-like ECH-associated protein (Keap1)-NF-E2-related factor 2 (Nrf2) pathway, which is an important pathway involved in oxidative stress. RNA sequencing and proteomics analysis further revealed molecular changes at the mRNA and protein levels and provided potential targets and pathways through differential gene expression analysis. In addition, NTP can inhibited tumor growth in nude mouse subcutaneous tumor models constructed respectively using AGS and MFC (mouse-derived GC cells), providing preliminary evidence of its effectiveness in vivo. In conclusion, our study demonstrated that NTP exhibits significant anti-GC activity and is anticipated to be a candidate for drug repurposing.

Anterior transposition and positioning via helix sling method in cubital tunnel syndrome: An open-label, retrospective trial of maximum 5-year follow-up.

Background: Ulnar nerve transposition is used for cubital tunnel syndrome (CuTS) with nerve instability. The aim is to report a modified technique for ulnar nerve transposition using medial intermuscular septum and Osborne's ligament as a double-strand helix sling to recreate a sliding channel for the ulnar nerve and the functional outcomes at follow-ups. Methods: Twenty-five patients with persistent CuTS underwent nerve release and subcutaneous transposition from January 2017 to January 2022 in our institute. Among them, 9 patients were excluded due to incomplete medical records, lack of follow-up history, or bilateral limb numbness. The medial intermuscular septum with one end attached was excised to rebuild a tension-free double-strand helix sling by anchoring at the residue of Osborne's ligament. The modified Mc-Gowan classification was applied to evaluate the disease severity preoperatively. The quick disability of arm and shoulder and hand (quickDASH) questionnaire and visual analogue scale (VAS) scores were used to evaluate pre- and postoperative symptoms. Ultrasound imaging was utilized for nerve structure evaluation before surgery and at follow-ups. Results: Sixteen out of twenty-five patients received follow-ups postoperatively (ranging from 9 to 69 months, 36 months in average). No findings indicated subluxation of ulnar nerve or recompression by ultrasound imaging examination. According to quickDASH and VAS scores and physical examination, 14 out of 16 patients showed postoperative improvement in symptoms and function at final follow-ups. Interpretation: In this modified technique, the medial intermuscular septum and Osborne's ligament can create tension-free helix sling for stable and smooth sliding and preventing subluxation after nerve transposition, which is highly effective and safe for CuTS treatment.

Influence of magnetic field on gluten aggregation behavior and quality characteristics of dough enriched with potato pulp.

This study investigated the effect of varying magnetic field intensities (ranging from 0 to 10 mT) on the quality characteristics of dough with 40 % potato pulp substitution (DPP). The results indicated that the DPP fermented with a 4 mT magnetic field exhibited a significant enhancement in the combination of water and substrate, thereby elevating the viscoelastic properties of DPP through reinforcing the stability of gluten network. Meanwhile, DPP treated with a 4 mT magnetic field exhibited the highest amount of disulfide bonds (11.64 µmol SS/g sample). This is accompanied by a prominent cross-linkage structure, as evidenced by SDS-PAGE and CLSM. Notably, the application of a magnetic field substantially augments the dough's capacity to retain gas during fermentation. In addition, the application of magnetic field significantly increased the wet gluten content (20.85 %, P < 0.05) in DPP, which improved tensile properties and an acceptable color profile. The introduction of a magnetic field induces gluten aggregation, which in turn results in heightened particle size distribution and ζ-potential values. In conclusion, this study emphasize the potential of magnetic field technology as a viable method to enhance the overall quality attributes of dough enriched with potato pulp substitution.

Free peroneal artery perforator flap for reconstruction of traumatic limb soft tissue defects: A retrospective case series study.

BACKGROUND: The free peroneal artery perforator (FPAP) flap is used for soft tissue defects after burns and trauma. However, the use of FPAP flaps to repair limb soft tissue defects for immediate reconstruction was rarely reported previously. Therefore, the purpose of this report is to evaluate free peroneal artery perforator flap to reconstruct traumatic limb soft tissue defects for immediate reconstruction. PATIENTS AND METHODS: A total of 25 cases of limb soft tissue defects undergoing immediate reconstruction of FPAP flap transfer were retrospectively evaluated from January 2019 to June 2019 in our institute. The locations of defects included the palm (10 cases), finger (5 cases), foot (7 cases), ankle (2 cases) and wrist (1 case). The sizes of defect varied from 3 × 2 cm to 15 × 7 cm (54.1 cm2 in average). Flaps were harvested based on the peroneal perforator vessels, initially marked using hand-held Doppler. RESULTS: Average size of harvested flap was 9.7 × 6.2 cm (ranging from 3.5 × 2 cm to 16 × 8 cm). All perforators were harvested from the peroneal artery and the arterial diameter ranged from 0.8 to 1.7 mm. The average pedicle length was 3.04 cm (range, 1.85-4.75 cm). Five vascular thrombosis were found including three cases of arterial thrombosis and two cases of venous thrombosis which were successfully salvaged by re-operation and vein graft. Satisfying functional outcome and acceptable appearance were achieved at 6 months or longer after surgery (range, 6-15 months, 12 months in average). All flaps survived at the end-point. CONCLUSIONS: The FPAP flap is a reliable and thin fasciocutaneous flap, which can be used for repairing limb soft tissue defects. The FPAP flap can be used for covering defects with various appearances, locations, and sizes.

CRCS: An automatic image processing pipeline for hormone level analysis of Cushing's disease.

Due to the abnormal secretion of adreno-cortico-tropic-hormone (ACTH) by tumors, Cushing's disease leads to hypercortisonemia, a precursor to a series of metabolic disorders and serious complications. Cushing's disease has high recurrence rate, short recurrence time and undiscovered recurrence reason after surgical resection. Qualitative or quantitative automatic image analysis of histology images can potentially in providing insights into Cushing's disease, but still no software has been available to the best of our knowledge. In this study, we propose a quantitative image analysis-based pipeline CRCS, which aims to explore the relationship between the expression level of ACTH in normal cell tissues adjacent to tumor cells and the postoperative prognosis of patients. CRCS mainly consists of image-level clustering, cluster-level multi-modal image registration, patch-level image classification and pixel-level image segmentation on the whole slide imaging (WSI). On both image registration and classification tasks, our method CRCS achieves state-of-the-art performance compared to recently published methods on our collected benchmark dataset. In addition, CRCS achieves an accuracy of 0.83 for postoperative prognosis of 12 cases. CRCS demonstrates great potential for instrumenting automatic diagnosis and treatment for Cushing's disease.

The response of LncRNAs associated with photosynthesis-and pigment synthesis-related genes to green light in Chlamydomonas reinhardtii.

The quality of light is an important abiotic factor that affects the growth and development of green plants. Ultraviolet, red, blue, and far-red light all have demonstrated roles in regulating green plant growth and development, as well as light morphogenesis. However, the mechanism underlying photosynthetic organism responses to green light throughout the life of them are not clear. In this study, we exposed the unicellular green alga Chlamydomonas reinhardtii to green light and analyzed the dynamics of transcriptome changes. Based on the whole transcriptome data from C. reinhardtii, a total of 9974 differentially expressed genes (DEGs) were identified under green light. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that these DEGs were mainly related to "carboxylic acid metabolic process," "enzyme activity," "carbon metabolism," and "photosynthesis and other processes." At the same time, 253 differentially expressed long non-coding RNAs (DELs) were characterized as green light responsive. We also made a detailed analysis of the responses of photosynthesis- and pigment synthesis-related genes in C. reinhardtii to green light and found that these genes exhibited obvious dynamic expression. Lastly, we constructed a co-expression regulatory network, comprising 49 long non-coding RNAs (lncRNAs) and 20 photosynthesis and pigment related genes, of which 9 mRNAs were also the predicted trans/cis-targets of 8 lncRNAs, these results suggested that lncRNAs may affect the expression of mRNAs related to photosynthesis and pigment synthesis. Our findings give a preliminary explanation of the response mechanism of C. reinhardtii to green light at the transcriptional level.

Comparison of Azvudine and Nirmatrelvir/Ritonavir and Combined Use in Patients with COVID-19.

Purpose: To compare the effectiveness of azvudine and nirmatrelvir/ritonavir for the treatment of coronavirus disease (COVID-19). Patients and Methods: We conducted a retrospective analysis of data from 576 patients with COVID-19, comprising 195 patients without antiviral therapy, 226 patients treated with azvudine, 114 patients treated with nirmatrelvir/ritonavir, and 41 patients were treated with azvudine and nirmatrelvir/ritonavir concurrently. We compared their symptoms, mortality rates, and the length and cost of hospitalization. Results: The incidence of symptoms was similar in patients treated with azvudine and in those treated with nirmatrelvir/ritonavir. However, among patients experiencing weakness, the duration of weakness was significantly shorter in the azvudine group than in the nirmatrelvir/ritonavir group (P=0.029). Mortality did not differ significantly between the azvudine group and the nirmatrelvir/ritonavir group (18.14% vs.10.53%, P=0.068). Among "severe patients", the mortality rate was markedly lower in patients treated with nirmatrelvir/ritonavir than in patients treated with azvudine (16.92% vs.32.17%, P=0.026). In patients with hepatic insufficiency, those treated with nirmatrelvir/ritonavir had substantially lower mortality than those treated with azvudine (15.09% vs.34.25%, P=0.016). In addition, patients treated with nirmatrelvir/ritonavir had longer hospital stays (P=0.002) and higher hospital costs (P<0.001) than those receiving azvudine. Compared with patients treated with nirmatrelvir/ritonavir or azvudine alone, patients taking nirmatrelvir/ritonavir and azvudine concurrently had no significant improvement in survival (P>0.05), length of stay (P>0.05), or hospital costs (P>0.05). Conclusion: Azvudine is recommended for patients with non-severe COVID-19 with weakness. Nirmatrelvir/ritonavir is recommended for patients with severe COVID-19, to reduce mortality, and it could be the best choice for patients with hepatic insufficiency. The concurrent use of nirmatrelvir/ritonavir and azvudine in patients with COVID-19 could be not recommended.