Chilling stress response in tobacco seedlings: insights from transcriptome, proteome, and phosphoproteome analyses.

Tobacco (Nicotiana tabacum L.) is an important industrial crop, which is sensitive to chilling stress. Tobacco seedlings that have been subjected to chilling stress readily flower early, which seriously affects the yield and quality of their leaves. Currently, there has been progress in elucidating the molecular mechanisms by which tobacco responds to chilling stress. However, little is known about the phosphorylation that is mediated by chilling. In this study, the transcriptome, proteome and phosphoproteome were analyzed to elucidate the mechanisms of the responses of tobacco shoot and root to chilling stress (4 °C for 24 h). A total of 6,113 differentially expressed genes (DEGs), 153 differentially expressed proteins (DEPs) and 345 differential phosphopeptides were identified in the shoot, and the corresponding numbers in the root were 6,394, 212 and 404, respectively. This study showed that the tobacco seedlings to 24 h of chilling stress primarily responded to this phenomenon by altering their levels of phosphopeptide abundance. Kyoto Encyclopedia of Genes and Genomes analyses revealed that starch and sucrose metabolism and endocytosis were the common pathways in the shoot and root at these levels. In addition, the differential phosphopeptide corresponding proteins were also significantly enriched in the pathways of photosynthesis-antenna proteins and carbon fixation in photosynthetic organisms in the shoot and arginine and proline metabolism, peroxisome and RNA transport in the root. These results suggest that phosphoproteins in these pathways play important roles in the response to chilling stress. Moreover, kinases and transcription factors (TFs) that respond to chilling at the levels of phosphorylation are also crucial for resistance to chilling in tobacco seedlings. The phosphorylation or dephosphorylation of kinases, such as CDPKs and RLKs; and TFs, including VIP1-like, ABI5-like protein 2, TCP7-like, WRKY 6-like, MYC2-like and CAMTA7 among others, may play essential roles in the transduction of tobacco chilling signal and the transcriptional regulation of the genes that respond to chilling stress. Taken together, these findings provide new insights into the molecular mechanisms and regulatory networks of the responses of tobacco to chilling stress.

Effectiveness of prognostic nutritional index in predicting overall survival and evaluating immunotherapy response in anaplastic thyroid carcinoma.

BACKGROUND: The prognostic value of nutritional status in anaplastic thyroid carcinoma (ATC) remains unclear. The Prognostic Nutritional Index (PNI) is a reliable indicator of overall nutritional and immune status, and it has emerged as a significant prognostic factor in various malignancies. This study aimed to explore the utility of PNI in ATC. METHODS: We systematically reviewed ATC patients in our institute from January 2000 to June 2023 and categorized them into high and low PNI groups based on the median PNI value. Kaplan-Meier analysis and Cox regression were employed to assess the impact of PNI on overall survival, while ROC curve analysis evaluated the predictive value of PNI. Mimics software was used for three-dimensional reconstruction of pre- and post-immunotherapy tumor volumes, enabling the assessment of treatment response. RESULTS: A total of 77 ATC patients were included in this study. Low baseline PNI was associated with significantly shorter overall survival (1-year survival rate: 5.26% vs 30.77%; median survival time: 5.30 months vs 8.87 months). The 1-year, 2-year, and 3-year AUC values for PNI were 0.82, 0.79, and 0.77, respectively. In the multivariate analysis, both PNI and tumor size emerged as independent prognostic factors for patient overall survival. Among ATC patients receiving 2-3 cycles of immunotherapy, an increase in post-treatment PNI levels was positively correlated with a reduction in tumor volume. CONCLUSION: PNI is an independent predictor of overall survival and holds the potential to serve as a valuable indicator for assessing and predicting immunotherapy efficacy in ATC patients.

Risk factors of transient and permanent hypoparathyroidism after thyroidectomy: a systematic review and meta-analysis.

BACKGROUND: Postoperative hypoparathyroidism (hypoPT) is a common complication following thyroid surgery. However, current research findings on the risk factors for post-thyroid surgery hypoPT are not entirely consistent, and the same risk factors may have different impacts on transient and permanent hypoPT. Therefore, there is a need for a comprehensive study to summarize and explore the risk factors for both transient and permanent hypoPT after thyroid surgery. MATERIALS AND METHODS: Two databases (PubMed and Embase) were searched from inception to 2024. The Newcastle-Ottawa Scale was used to rate study quality. Pooled odds ratios (OR) were used to calculate the relationship of each risk factor with transient and permanent hypoPT. Subgroup analyses were conducted for hypoPT with different definition-time (6 or 12 mo). Publication bias was assessed using Begg's test, and Egger's test. RESULTS: A total of 19 risk factors from the 93 studies were included in the analysis. Among them, sex and parathyroid autotransplantation were the most frequently reported risk factors. Meta-analysis demonstrated that sex (female vs. male), cN stage, central neck dissection, lateral neck dissection, extent of central neck dissection (bilateral vs. unilateral), surgery (total thyroidectomy (TT) vs. lobectomy), surgery type (TT vs. sub-TT), incidental parathyroidectomy, and pathology (cancer vs. benign) were significantly associated with transient and permanent hypoPT. Preoperative calcium and parathyroid autotransplantation were only identified as risk factors for transient hypoPT. Additionally, node metastasis and parathyroid in specimen were associated with permanent hypoPT. CONCLUSION: The highest risk of hypoPT occurs in female thyroid cancer patients with lymph node metastasis undergoing TT combined with neck dissection. The key to preventing postoperative hypoPT lies in the selection of surgical approach and intraoperative protection.

Retrospective assessment of neoadjuvant camrelizumab combined with induction chemotherapy: efficacy in laryngeal preservation for advanced hypopharyngeal and laryngeal squamous cell carcinoma.

BACKGROUND: Hypopharyngeal and laryngeal squamous cell carcinoma (SCC) account for 25-30% of head and neck SCC. Total laryngectomy, while effective, compromises the quality of life. Immune checkpoint inhibitors such as Camrelizumab offer potential in laryngeal preservation. The study investigated Camrelizumab combined with TP regimen as a neoadjuvant therapy for laryngeal preservation in advanced hypopharyngeal and laryngeal SCC. METHODS: A retrospective study was conducted at Sun Yat-sen University Cancer Center on patients diagnosed with locally advanced SCC of the hypopharynx and larynx from October 1, 2019, to October 25, 2022. The efficacy of a first-line treatment combining Camrelizumab (200 mg) and TP regimen (Albumin-bound paclitaxel at 260 mg/m2 and Cisplatin at 60 mg/m2) was evaluated using RECIST 1.1 criteria. Outcomes included overall survival (OS), progression-free survival (PFS), laryngectomy-free survival (LFS), and response rates. RESULTS: Of the 71 included patients, the median age was 60.7 years. Post the first-line treatment, 90.1% demonstrated an overall response. The one-year and two-year OS rates were 91.5% and 84.3%, respectively. One-year and two-year PFS rates were 92.9% and 83.9%, respectively, with LFS at 85.6% and 73.2%. The initial T4 stage as significantly associated with reduced OS and LFS. Skin reaction was the predominant adverse event. CONCLUSION: The Camrelizumab-TP regimen demonstrated promising results for advanced hypopharyngeal/laryngeal SCC patients, exhibiting high response rates, OS, and LFS, positioning it as a potential primary option for laryngeal preservation. Further comprehensive, randomized controlled studies are imperative to validate these initial observations and elucidate the regimen's full clinical efficacy in optimizing laryngeal outcomes.

The FJQR Has Synergistic Effect with Fluoropyrimidine in the Maintenance Treatment for HER-2 Negative Gastric Cancer.

INTRODUCTION: Maintenance therapy aimed to strengthen the first-line chemotherapy and improve quality of life is needed for gastric cancer (GC). Currently, many clinical studies have confirmed the important role of fluoropyrimidine in the maintenance stage. Our team has created patented prescriptions "Fuzheng jiedu Quyu Method" recipe (FJQR), which was considered as an adjuvant therapeutic scheme (reduce toxicity and increase the efficacy of chemotherapy). This study aimed to evaluate the efficacy and safety of FJQR combined with fluoropyrimidine as a maintenance treatment in HER-2 negative GC patients. METHODS: We performed the analysis of 129 patients with HER-2 negative GC who entered the maintenance stage in our hospital and Tianjin Cancer Hospital between January 2018 and December 2020. Out of the 129 eligible patients, 64 were categorized into the maintenance treatment group with FJQR+fluoropyrimidine, and 65 patients were assigned to the control group if they received fluoropyrimidine alone. Capecitabine was orally 1000mg/m2, Qd, half an hour after meals, and FGQR was 15g Bid after capecitabine. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), overall remission rate (ORR), quality of Life (QOL), TCM syndrome and safety. RESULTS: The mPFS in the treatment group was significantly prolonged compared with the control group (6.3 vs. 5.0 months, p = 0.03), while the mOS was not substantially improved (11.4 vs. 10.5 months, p = 0.38). Gastrointestinal symptoms and pain became better in the treatment group. The number of distant metastatic organs, first-line chemotherapy cycles, and lymph node metastasis were independent risk predictors for PFS. Blood stasis syndrome may be the protective factor. In terms of safety, treatment-related adverse events (AEs) in the treatment group were relatively lighter, and the incidence of grade III-IV AEs could be significantly reduced. CONCLUSION: FJQR and fluoropyrimidine have synergistic effects as maintenance treatment in HER-2 negative GC, with good efficacy and safety.

Comparative physiological and transcriptome analysis between potassium-deficiency tolerant and sensitive sweetpotato genotypes in response to potassium-deficiency stress.

BACKGROUND: Sweetpotato is a typical ''potassium (K+) favoring'' food crop, which root differentiation process needs a large supply of potassium fertilizer and determine the final root yield. To further understand the regulatory network of the response to low potassium stress, here we analyze physiological and biochemical characteristics, and investigated root transcriptional changes in two sweetpotato genotypes, namely, - K tolerant "Xu32" and - K susceptible"NZ1". RESULT: We found Xu32 had the higher capability of K+ absorption than NZ1 with better growth performance, higher net photosynthetic rate and higher chlorophyll contents under low potassium stress, and identified 889 differentially expressed genes (DEGs) in Xu32, 634 DEGs in NZ1, 256 common DEGs in both Xu32 and NZ1. The Gene Ontology (GO) term in molecular function enrichment analysis revealed that the DEGs under low K+ stress are predominately involved in catalytic activity, binding, transporter activity and antioxidant activity. Moreover, the more numbers of identified DEGs in Xu32 than that in NZ1 responded to K+-deficiency belong to the process of photosynthesis, carbohydrate metabolism, ion transport, hormone signaling, stress-related and antioxidant system may result in different ability to K+-deficiency tolerance. The unique genes in Xu32 may make a great contribution to enhance low K+ tolerance, and provide useful information for the molecular regulation mechanism of K+-deficiency tolerance in sweetpotato. CONCLUSIONS: The common and distinct expression pattern between the two sweetpotato genotypes illuminate a complex mechanism response to low potassium exist in sweetpotato. The study provides some candidate genes, which can be used in sweetpotato breeding program for improving low potassium stress tolerance.

An Improved Spectral Subtraction Method for Eliminating Additive Noise in Condition Monitoring System Using Fiber Bragg Grating Sensors.

The additive noise in the condition monitoring system using fiber Bragg grating (FBG) sensors, including white Gaussian noise and multifrequency interference, has a significantly negative influence on the fault diagnosis of rotating machinery. Spectral subtraction (SS) is an effective method for handling white Gaussian noise. However, the SS method exhibits poor performance in eliminating multifrequency interference because estimating the noise spectrum accurately is difficult, and it significantly weakens the useful information components in measured signals. In this study, an improved spectral subtraction (ISS) method is proposed to enhance its denoising performance. In the ISS method, a reference noise signal measured by the same sensing system without working loads is considered the estimated noise, the same sliding window is used to divide the power spectrums of the measured and reference noise signals into multiple frequency bands, and the formula of spectral subtraction in the standard SS method is modified. A simulation analysis and an experiment are executed by using simulated signals and establishing a vibration test rig based on the FBG sensor, respectively. The statistical results demonstrate the effectiveness and feasibility of the ISS method in simultaneously eliminating white Gaussian noise and multifrequency interference while well maintaining the useful information components.

Experimental observation on a new chimney-shaped mechanical valve completely implanted above the mitral annulus in animals.

Current commercially available prosthetic valves suffer from limited size, high requirements for implantation technique, subvalvular structural destruction, and valve dysfunction due to proliferation of fibrous endothelial tissue. This study aims to perform the preclinical large animal experiments for surgically implanting a chimney-shaped artificial mechanical heart valve with zero left ventricular occupancy, which fully accommodates the movement of the valve leaflets in the valve frame and realizes completely supra-annular surgical implantation. A total of 7 sheep underwent the replacement of artificial valve, and 5 sheep survived normally until anatomical examination. The mechanical properties of these artificial mitral valves remain functionally normal. There was no obvious thromboembolism around the artificial valve and in the important organs. The tissue layer of suture ring was completely organized and endothelialized, and the thickness of tissue layer was about 0.6-1.0 mm. The follow-up of echocardiography showed that the left ventricular ejection fraction was normal (60-70%) before and 6 months after operation. The results of transvalvular pressure gradient and blood flow velocity of artificial valve were normal. Left ventricular retrograde angiography showed that the artificial valve was completely located in the left atrium with good position and normal opening and closing. There was no obvious perivalvular leakage and other abnormalities. At 3 and 6 months, there were no obvious abnormalities in blood routine test, liver and kidney function, and other indexes. The new chimney-shaped artificial mechanical valve implanted completely above the mitral annulus had good wear resistance, histocompatibility, and antithrombotic and hemodynamic performance.

Intratumor microbiome: selective colonization in the tumor microenvironment and a vital regulator of tumor biology.

The polymorphic microbiome has been proposed as a new hallmark of cancer. Intratumor microbiome has been revealed to play vital roles in regulating tumor initiation and progression, but the regulatory mechanisms have not been fully uncovered. In this review, we illustrated that similar to other components in the tumor microenvironment, the reside and composition of intratumor microbiome are regulated by tumor cells and the surrounding microenvironment. The intratumor hypoxic, immune suppressive, and highly permeable microenvironment may select certain microbiomes, and tumor cells may directly interact with microbiome via molecular binding or secretions. Conversely, the intratumor microbiomes plays vital roles in regulating tumor initiation and progression via regulating the mutational landscape, the function of genes in tumor cells and modulating the tumor microenvironment, including immunity, inflammation, angiogenesis, stem cell niche, etc. Moreover, intratumor microbiome is regulated by anti-cancer therapies and actively influences therapy response, which could be a therapeutic target or engineered to be a therapy weapon in the clinic. This review highlights the intratumor microbiome as a vital component in the tumor microenvironment, uncovers potential mutual regulatory mechanisms between the tumor microenvironment and intratumor microbiome, and points out the ongoing research directions and drawbacks of the research area, which should broaden our view of microbiome and enlighten further investigation directions.

miR-30e-5p-mediated FOXD1 promotes cell proliferation by blocking cellular senescence and apoptosis through p21/CDK2/Rb signaling in head and neck carcinoma.

Forkhead box D1 (FOXD1) belongs to the FOX protein family, which has been found to function as a oncogene in multiple cancer types, but its role in head and neck squamous cell carcinoma (HNSCC) requires further investigation. Our research aimed to investigate the function of FOXD1 in HNSCC. Bioinformatics analysis indicated that mRNA level of FOXD1 was highly expressed in HNSCC tissues, and over-expressed FOXD1 was related to poor prognosis. Moreover, FOXD1 knockdown increased the ratio of senescent cells but decreased the proliferation ability, while FOXD1 overexpression obtained the opposite results. In vitro experiments revealed that FOXD1 bound to the p21 promoter and inhibited its transcription, which blocked the cyclin dependent kinase 2 (CDK2)/retinoblastoma (Rb) signaling pathway, thus preventing senescence and accelerating proliferation of tumor cells. CDK2 inhibitor could reverse the process to some extent. Further research has shown that miR-3oe-5p serves as a tumor suppressant by repressing the translation of FOXD1 through combining with the 3'-untranslated region (UTR). Thus, FOXD1 resists cellular senescence and facilitates HNSCC cell proliferation by affecting the expression of p21/CDK2/Rb signaling, suggesting that FOXD1 may be a potential curative target for HNSCC.

The Role of IAA in Regulating Root Architecture of Sweetpotato (Ipomoea batatas [L.] Lam) in Response to Potassium Deficiency Stress.

Plants can adapt to the spatial heterogeneity of soil nutrients by changing the morphology and architecture of the root system. Here, we explored the role of auxin in the response of sweetpotato roots to potassium (K+) deficiency stress. Two sweetpotato cultivars, Xushu 32 (low-K-tolerant) and Ningzishu 1 (low-K-sensitive), were cultured in low K+ (0.1 mmol L-1, LK) and normal K+ (10 mmol L-1, CK) nutrient solutions. Compared with CK, LK reduced the dry mass, K+ content, and K+ accumulation in the two cultivars, but the losses of Xushu 32 were smaller than those of Ningzishu 1. LK also affected root growth, mainly impairing the length, surface area, forks number, and crossings number. However, Xushu 32 had significantly higher lateral root length, density, and surface area than Ningzishu 1, closely related to the roots' higher indole-3-acetic acid (IAA) content. According to the qPCR results, Xushu 32 synthesized more IAA (via IbYUC8 and IbTAR2) in leaves but transported and accumulated in roots through polar transport (via IbPIN1, IbPIN3, and IbAUX1). It was also associated with the upregulation of auxin signaling pathway genes (IbIAA4 and IbIAA8) in roots. These results imply that IAA participates in the formation of lateral roots and the change in root architecture during the tolerance to low K+ stress of sweetpotato, thus improving the absorption of K+ and the formation of biomass.

Advances in immune checkpoint inhibitors therapy for small cell lung cancer.

BACKGROUND: As one of the most aggressive neuroendocrine tumors, small cell lung cancer (SCLC) has the most disappointing prognosis of all lung cancers. Although SCLC responds well to initial chemotherapy, the majority of patients experience disease recurrence within one year, and patient survival is poor. It is still necessary to explore the application of ICIs in SCLC since the beginning of the road to immunotherapy, which broke the 30-year treatment deadlock of SCLC. METHODS: We searched PubMed, Web of Science, and Embase with search terms such as "SCLC", "ES-SCLC", "ICIs", and "ICBs", and categorized and summarized the relevant literature obtained, and we compiled the latest progress about the application of ICIs in SCLC. RESULTS: We listed 14 clinical trials on ICIs, including 8 clinical trials on first-line SCLC treatment, 2 clinical trials on second-line SCLC treatment, 3 clinical trials on third-line SCLC treatment, and 1 clinical trial on SCLC maintenance treatment. CONCLUSION: ICIs in combination with chemotherapy can improve OS in SCLC patients, but the extent to which SCLC patients can benefit from ICIs is limited, and ICIs' combination treatment strategies still need to be continuously explored.

Femtosecond Laser-Induced Nano-Joining of Volatile Tellurium Nanotube Memristor.

Nanowire/nanotube memristor devices provide great potential for random-access high-density resistance storage. However, fabricating high-quality and stable memristors is still challenging. This paper reports multileveled resistance states of tellurium (Te) nanotube based on the clean-room free femtosecond laser nano-joining method. The temperature for the entire fabrication process was maintained below 190 °C. A femtosecond laser joining technique was used to form nanowire memristor units with enhanced properties. Femtosecond (fs) laser-irradiated silver-tellurium nanotube-silver structures resulted in plasmonic-enhanced optical joining with minimal local thermal effects. This produced a junction between the Te nanotube and the silver film substrate with enhanced electrical contacts. Noticeable changes in memristor behavior were observed after fs laser irradiation. Capacitor-coupled multilevel memristor behavior was observed. Compared to previous metal oxide nanowire-based memristors, the reported Te nanotube memristor system displayed a nearly two-order stronger current response. The research displays that the multileveled resistance state is rewritable with a negative bias.

Immune checkpoint inhibitors for RET fusion non-small cell lung cancer: hopes and challenges.

Immune ch eckpoint inhibitors (ICIs) represent a milestone in advanced nonsmall cell lung cancer (NSCLC). Nevertheless, NSCLC with known oncogenic drivers has been overlooked in most studies evaluating anti-programmed death-1/programmed death ligand 1. Rearranged during transfection proto-oncogene (RET) gene fusion was identified in 1-2% of NSCLC patients. More recently, two selective RET inhibitors, selpercatinib and pralsetinib, demonstrated higher efficacy and good tolerability. In contrast, the activity of ICIs in RET fusion NSCLC has not been well characterized. Here, we analyzed the clinical data of ICIs and discussed the suitable time to introduce ICIs in RET fusion NSCLC. Finally, we put forward future strategies to adequately maximize the efficacy of ICIs treatment in patients with RET fusion NSCLC in the upcoming era of combination immunotherapies.

Advances in Antibody-Drug Conjugates in the Treatment of HER2-Positive Breast Cancer.

Although targeted drugs improved the therapeutic effect of HER2-positive breast cancer, the long-term prognosis was still poor. In this regard, the research and development of antibody-drug conjugates (ADCs) came into being and made a lot of progress. ADCs had the characteristics of both chemotherapeutic agents and targeted agents by combining chemotherapeutic agents and targeted agents through a linker. It not only had a strong anti-tumor effect on HER2-positive breast cancer, but also had certain anti-tumor effects on HER2-low and even HER2-negative patients. In addition, the clinical researches of ADCs combined with immune checkpoint inhibitors (ICIs) therapy had also made a great breakthrough. This review aimed to summarize the clinical progress of ADCs, in particular the two drugs approved by the US Food and Drug Administration (FDA) for HER2-positive metastatic breast cancer as well as to summarize the current status of ADCs in combination with ICIs.

The Clinical Observation of Acupuncture Combined With Antiemetic Drugs in the Prevention and Treatment of CINV in Breast Cancer Patients.

Objective: The present study aimed to explore the effectiveness of acupuncture combined with antiemetic drugs in prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) among breast cancer patients receiving postoperative adjuvant chemotherapy. Methods: We retrospectively collected the clinical records of 81 postoperative breast cancer patients at our hospital from January 2021 to December 2021. These patients were divided into the acupuncture group and the control group. The efficacy of the antiemetic drugs combined with acupuncture for CINV was analysed. The primary endpoints were total, acute, and delayed nausea and vomiting grade and remission rate. Safety and overall patient quality of life were secondary endpoints. Results: During the whole observation period, compared with the control group, the frequency of nausea and vomiting was decreased in the acupuncture group (P=0.034). And the ECOG-PS score in the acupuncture group was significantly improved (P=0.004). In addition, the adverse events, such as abdominal (12.2% vs. 5.0%, P=0.252), distention (19.5% vs. 5.0%, P=0.049), and diarrhea (9.7% vs. 0, P=0.044), were decreased by acupuncture. Conclusions: Acupuncture combined with antiemetics could reduce the incidence of CINV, improve the quality of life of patients and reduce the incidence of adverse side effects of antiemetic drugs.

Research Progress on RET Fusion in Non-Small-Cell Lung Cancer.

Great progress has been made in the treatment of driver gene-positive Non- Small Cell Lung Cancer (NSCLC) in recent years. RET fusion was seen in 0.7% to 2% of NSCLC and was associated with younger age and never-smoker status. The pralsetinib and selpercatinib for RET fusion NSCLC was recommended by the 2021 NSCLC treatment guidelines. This review outlines the research progress in the treatment of RET fusion NSCLC, identifies current challenges and describes proposals for improving the outlook for these patients.

KLF4 prevented angiotensin II-induced smooth muscle cell senescence by enhancing autophagic activity.

BACKGROUND: Vascular aging is an important risk factor for various cardiovascular diseases. Transcription factor krüppel-like factor 4 (KLF4) could regulate the phenotypic transformation of the vascular smooth muscle cell (VSMC) in the pathogenesis of aortic diseases. The present study aimed to explore the role and mechanism of KLF4 in angiotensin II (Ang II)-induced VSMC senescence. METHODS: The VSMC senescence mouse model was induced by sustained release of Ang II (1.0 µg/kg/min) for 4 weeks. The premature senescent VSMCs were induced by Ang II (0.1 µmol/L) for 72 h. Cellular senescence was measured by senescence-associated ß-galactosidase (SA-ß-gal) activity and p53/p16 expression. The autophagic activity was evaluated by autophagic flux and autophagic marker expression. RESULTS: The expression of KLF4 was extremely increased in abdominal aorta tissues after 1-week Ang II stimulation (p < .01) but began to decrease in later periods. Decreased expression of KLF4 was also detected in premature senescent VSMCs. Overexpression of KLF4 could enhance the antisenescence ability of VSMCs. Significantly decreased amounts of SA-ß-gal-positive cells and lower p53/p16 expression were detected in KLF4-overexpressing VSMCs (p < .01). Next, telomerase reverse transcriptase (TERT) was identified as a direct downstream target of KLF4 in VSMCs. Overexpression of KLF4 in VSMCs prevented the decreased expression of TERT under Ang II stimulation condition, which could in turn, contribute to the enhanced autophagic activity, and ultimately to the improved antisenescence ability of VSMCs. CONCLUSIONS: Our results demonstrated that overexpression of KLF4 prevented Ang II-induced VSMC senescence by promoting TERT-mediated autophagy. These findings provided novel potential targets for the prevention and therapy of vascular aging.

Sucrose nonfermenting-1-related protein kinase 1 regulates sheath-to-panicle transport of nonstructural carbohydrates during rice grain filling.

The remobilization of nonstructural carbohydrates (NSCs) reserved in rice (Oryza sativa) sheaths is essential for grain filling. This assimilate distribution between plant tissues and organs is determined by sucrose non-fermenting-1-related protein kinase 1 (SnRK1). However, the SnRK1-mediated mechanism regulating the sheath-to-panicle transport of NSCs in rice remains unknown. In this study, leaf cutting treatment was used to accelerate NSC transport in the rice sheaths. Accelerated NSC transport was accompanied by increased levels of OsSnRK1a mRNA expression, SnRK1a protein expression, catalytic subunit phosphorylation of SnRK1, and SnRK1 activity, indicating that SnRK1 activity plays an important role in sheath NSC transport. We also discovered that trehalose-6-phosphate, a signal of sucrose availability, slightly reduced SnRK1 activity in vitro. Since SnRK1 activity is mostly regulated by OsSnRK1a transcription in response to low sucrose content, we constructed an snrk1a mutant to verify the function of SnRK1 in NSC transport. NSCs accumulated in the sheaths of snrk1a mutant plants and resulted in a low seed setting rate and grain weight, verifying that SnRK1 activity is essential for NSC remobilization. Using phosphoproteomics and parallel reaction monitoring, we identified 20 SnRK1-dependent phosphosites that are involved in NSC transport. In addition, the SnRK1-mediated phosphorylation of the phosphosites directly affected starch degradation, sucrose metabolism, phloem transport, sugar transport across the tonoplast, and glycolysis in rice sheaths to promote NSC transport. Therefore, our findings reveal the importance, function, and possible regulatory mechanism of SnRK1 in the sheath-to-panicle transport of NSCs in rice.

Early postoperative calcitonin-to-preoperative calcitonin ratio as a predictive marker for structural recurrence in sporadic medullary thyroid cancer: A retrospective study.

Background: Calcitonin (Ctn) is widely used as a marker in the diagnosis, prognosis, and postoperative follow-up of patients with medullary thyroid carcinoma (MTC). The prognostic value of postoperative calcitonin-to-preoperative calcitonin ratio (CR), reflecting the change in Ctn level of response to initial treatment, remains uncertain in long-term disease outcomes. This study aims to determine the cut-off value of CR for predicting structural recurrence and assess the prognostic role of CR in patients with MTC. Methods: We retrospectively reviewed patients with MTC in Sun Yat-sen University Cancer Center (SYSUCC) between 2000 and 2022. CR is defined as the ratio of postoperative Ctn level on the day of discharge divided by preoperative Ctn level. In order to determine the optimal cut-off value of CR, the receiver operating characteristic (ROC) analysis was performed. We evaluate the effect of CR on recurrence-free survival (RFS) by using the Kaplan-Meier method and Cox regression analysis. Then, a nomogram based on CR was constructed. Results: In total, 112 sporadic MTC patients were included in this study. The optimal cut-off value of CR that predicted disease recurrence was 0.125. Patients with CR≥0.125 showed significantly worse RFS than patients with CR <0.125, respectively (3-years RFS rate of 63.1 vs. 94.7%, 5-years RFS rate of 50.7 vs. 90.3%, P < 0.001). In the multivariate analysis, CR was the strongest independent predictor of structural recurrence (HR: 5.050, 95% CI: 2.247-11.349, P <0.001). Tumor size (HR: 1.321, 95% CI: 1.010-1.726, P =0.042), multifocality (HR: 2.258, 95% CI: 1.008-5.058, P =0.048) and metastasized lymph nodes (HR: 3.793, 95% CI: 1.617-8.897, P <0.001) were also independent predictors of structural recurrence. The uncorrected concordance index (c-index) of the nomogram was 0.827 (95% CI, 0.729-0.925) for RFS, and bias-corrected c-index were similar. As compared to TNM stage, the nomogram based on CR provided better discrimination accuracy. Conclusions: We demonstrate that CR is a strong prognostic marker to predict structural recurrence in patients with sporadic MTC. The nomogram incorporating CR provided useful prediction of RFS for patients with sporadic MTC to provide personalized treatment.