Para-aortic and pelvic lymphadenectomy in locally advanced cervical cancer with pelvic lymph node metastasis.

OBJECTIVE: This study sought to explore the efficiency of para-aortic and pelvic lymphadenectomy in the treatment of locally advanced cervical cancer (LACC) with pelvic lymph node (PLN) metastasis. METHODS: A total of 171 LACC patients with imaging-confirmed pelvic lymph node metastasis were included in this study. These patients were divided into two groups: the surgical staging group, comprising 58 patients who had received para-aortic and pelvic lymphadenectomy (surgical staging) along with concurrent chemoradiation therapy (CCRT), and the imaging staging group, comprising 113 patients who had received only CCRT. The two groups' progression-free survival (PFS), overall survival (OS) and treatment-related complications were compared. RESULTS: The surgical staging group started radiotherapy 10.2 days (range 9-12 days) later than the imaging staging group. The overall incidence of lymphatic cysts was 9.30%. In the surgical staging group, para-aortic lymph node metastasis was identified in 34.48% (20/58) of patients, while pathology-negative PLN was observed in 12.07% (7/58). Over a median follow-up period of 52 months, no significant differences in PFS and OS rates were found between the two groups (p > 0.05). Subgroup analysis of patients with lymph node diameters of ≥ 1.5 cm revealed a five-year PFS rate of 75.0% and an OS rate of 80.0% in the surgical staging group, compared to 41.5% and 50.1% in the imaging staging group, respectively, showing statistically significant differences (p = 0.022, HR:0.34 [0.13, 0.90] and p = 0.038, HR: 0.34 [0.12,0.94], respectively for PFS and OS). Additionally, in patients with two or more metastatic lymph nodes, the five-year PFS and OS rates were 69.2% and 73.1% in the surgical staging group, versus 41.0% and 48.4% in the imaging staging group, with these differences also being statistically significant (p = 0.025, HR: 0.41[0.19,0.93] and p = 0.046, HR: 0.42[0.18,0.98], respectively). CONCLUSION: Performing surgical staging before CCRT is safe and delivers accurate lymph node details crucial for tailoring radiotherapy. This approach merits further investigation, particularly in women with pelvic lymph nodes measuring 1.5 cm or more in diameter or patients with two or more imaging-positive PLNs.

Prolonged course of Paxlovid administration in a centenarian with COVID-19: A case report.

BACKGROUND: According to the population statistics in 2023, there were 110000 people aged over 100 years in China, and the experience of using Paxlovid (nirmatrelvir/ritonavir) for centenarians is particularly valuable. This article reports our experience of using Paxlovid in a centenarian with the novel coronavirus disease 2019 (COVID-19) infection. CASE SUMMARY: A 103-year-old female with mild COVID-19 and renal insufficiency was given sufficient Paxlovid for 2 days and a half dose for 3 days. During treatment, the patient was complicated with lung infection and heart failure, and nucleic acid remained positive. After expert consultation, a full dose of Paxlovid was given again on the 9th day of admission for 2 days and a half dose for 3 days. Meanwhile, anti-heart failure and antibiotics were administered; the heart failure and pulmonary infection were improved. Finally, on the 33th day of admission, nucleic acid turned negative, body temperature returned to normal, cough and sputum, fatigue, poor appetite and other symptoms basically improved. The patient was given Paxlovid via nasal feeding for 2 courses without deterioration of liver and kidney function, diarrhea, nausea and vomiting, myalgia, chest tightness and other side effects, and was discharged from hospital with good recovery. CONCLUSION: This case suggests that Paxlovid can be used cautiously in centenarians with renal insufficiency and two courses of treatment can be considered in patients with persistent positive nucleic acid.

Biodegradation of phthalic acid esters by a novel marine bacterial strain RL-BY03: Characterization, metabolic pathway, bioaugmentation and genome analysis.

Biodegradation is recognized as the main route for the decomposition of phthalic acid esters (PAEs) in nature, but the fate of PAEs in marine ecosystems is not well understood. Herein, a novel marine bacterium, Gordonia sihwaniensis RL-BY03, was identified and analyzed for its ability to degrade PAEs. Furthermore, the metabolic mechanism of di-(2-ethylhexyl) phthalate (DEHP) was examined through UPLC-MS/MS and genomic analysis. RL-BY03 could rely solely on several types of PAEs as its sole carbon source. Initial pH and temperature for DEHP degradation were optimized as 8.0 and 30 °C, respectively. Surprisingly, RL-BY03 could simultaneously degrade ethyl acetate and DEHP and they could increase the cell surface hydrophobicity. DEHP degradation kinetics fitted well with the first-order decay model. The metabolic pathway of DEHP was deduced following the detection of five metabolic intermediates. Further, genes that are related to DEHP degradation were identified through genomic analysis and their expression levels were validated through RT-qPCR. A co-related metabolic pathway at biochemical and molecular level indicated that DEHP was turned into DBP and DEP by ß-oxidation, which was further hydrolyzed into phthalic acid. Phthalic acid was utilized through catechol branch of ß-ketoadipate pathway. Additionally, RL-BY03 exhibited excellent bioremediation potential for DEHP-contaminated marine samples. In general, these findings have the potential to enhance our understanding of the fate of PAEs in marine ecosystems.

Epidemiology, pathogenesis, clinical characteristics, and treatment of mucormycosis: a review.

AIM: This review aims to summarize the epidemiology, etiology, pathogenesis, clinical manifestations, and current diagnostic and therapeutic approaches for mucormycosis. The goal is to improve understanding of mucormycosis and promote early diagnosis and treatment to reduce mortality. METHODS: A comprehensive literature review was conducted, focusing on recent studies and data on mucormycosis. The review includes an analysis of the disease's epidemiology, etiology, and pathogenesis, as well as current diagnostic techniques and therapeutic strategies. RESULTS: Mucormycosis is increasingly prevalent due to the growing immunocompromised population, the COVID-19 pandemic, and advances in detection methods. The pathogenesis is closely associated with the host immune status, serum-free iron levels, and the virulence of Mucorales. However, the absence of typical clinical manifestations complicates diagnosis, leading to missed or delayed diagnoses and higher mortality. CONCLUSION: An enhanced understanding of the epidemiology, pathogenesis, and clinical presentation of mucormycosis, along with the adoption of improved diagnostic and therapeutic approaches, is essential for reducing mortality rates associated with this opportunistic fungal infection. Early diagnosis and prompt treatment are critical to improving patient outcomes.

The incidence of mucormycosis has increased following the COVID-19 pandemic.The presence of the halo sign and reverse halo sign may indicate the onset of pulmonary mucormycosis.Early implementation of molecular diagnostic methods, such as mNGS and qPCR, may improve the early diagnosis rate of mucormycosis.Isavuconazole and posaconazole can also be considered as first-line treatments for the initial management of mucormycosis.

Nomogram predicting overall and cancer specific prognosis for poorly differentiated lung adenocarcinoma after resection based on SEER cohort analysis.

The prognosis of poorly differentiated lung adenocarcinoma (PDLA) is determined by many clinicopathological factors. The aim of this study is identifying prognostic factors and developing reliable nomogram to predict the overall survival (OS) and cancer-specific survival (CSS) in patients with PDLA. Patient data from the Surveillance, Epidemiology and End Results (SEER) database was collected and analyzed. The SEER database was used to screen 1059 eligible patients as the study cohort. The whole cohort was randomly divided into a training cohort (n = 530) and a test cohort (n = 529). Cox proportional hazards analysis was used to identify variables and construct a nomogram based on the training cohort. C-index and calibration curves were performed to evaluate the performance of the model in the training cohort and test cohorts. For patients with PDLA, age at diagnosis, gender, tumor size were independent prognostic factors both for overall survival (OS) and cancer-specific survival (CSS), while race and number of nodes were specifically related to OS. The calibration curves presented excellent consistency between the actual and nomogram-predict survival probabilities in the training and test cohorts. The C-index values of the nomogram were 0.700 and 0.730 for OS and CSS, respectively. The novel nomogram provides new insights of the risk of each prognostic factor and can assist doctors in predicting the 1-year, 3-year and 5-year OS and CSS in patients with PDLA.

Baicalin methyl ester prevents the LPS - induced mice intestinal barrier damage in vivo and in vitro via P65/TNF-α/MLCK/ZO-1 signal pathway.

The effect of baicalin methyl ester (BME) on the regulation of mice intestinal barrier in the inflammatory response was studied in vivo and in vitro. Thirty six C57/BL mice were randomly divided into six groups (n = 6): control group; LPS group (LPS 3.5 mg/kg given intraperitoneal [ip] on day 7 of the study only), PBS group, and three BME groups (low: 50 mg/kg; medium: 100 mg/kg; high: 200 mg/kg) orally dosed with BME for 7d and LPS ip on day 7. All mice were sacrificed on day 8, and jejunum tissue collected for histopathology (H&E and PAS staining), protein expression of pro-inflammatory factors (TNF-α, IL-6, IL-8, IFN-γ) by ELISA, and intestinal tight junction proteins (ZO-1, occludin, claudin-1 and claudin-4) by Western Blot. Compared with the control group, LPS significantly increased the serum cytokines DAO (p < 0.01) and DLA (p < 0.01), upregulated the expression of pro-inflammatory factors, MLCK proteins (p <0.05) and increased the MLCK/ZO-1ratio (p <0.001). LPS also decreased the expression of claudin-4 (p < 0.01) in the jejunum and induced an inflammatory response damaging the jejunal mucosal barrier. Pretreatment with BME (100-200 mg/kg) significantly decreased the cytokines DAO (p < 0.05) and DLA (p < 0.01) in the serum, pro-inflammatory factors in the jejunum, significantly down-regulated the expression of MLCK (p <0.05) and the ratio of MLCK/ZO-1(p <0.001) but upregulated the expressions of ZO-1(p < 0.01), occludin (p < 0.05), claudin-1(p < 0.05) and claudin-4 (p < 0.05), and thereby restored the intestinal tissue structure, suggestive of alleviation of LPS-induced intestinal inflammation by BME. In vitro, MODE-K cells (derived from mice intestinal epithelium) were exposed to BME at 0 (control group-No LPS), 10, 20 and 40 µM BME for 24 h prior to LPS addition at 50 µg/mL for 2 h. LPS significantly increased the expression of pro-inflammatory factors, MLCK (p < 0.01) and the ratio of MLCK/ZO-1(p <0.001), decreased the expressions of ZO-1 (p < 0.05), occludin (p < 0.01), claudin-1 (p < 0.01) and claudin-4 (p < 0.01) in MODE-K cells compared with the control group. Compared with the LPS group, BME (10 - 40 µM) significantly decreased the expression of pro-inflammatory factors, MLCK (p < 0.05) and the ratio of MLCK/ZO-1(p <0.01) but increased the expressions of ZO-1(p < 0.01), occludin (p < 0.05) and claudin-4(p < 0.01) indicating an up-regulation of the expression of tight junction proteins by BME. On addition of extrinsic TNF-α plus LPS, the TNF- α level increased (p < 0.001) in MODE-K cells and the protein expression of MLCK (p < 0.01) was markedly up-regulated. Molecular docking predicted BME interacted with P65 by forming hydrogen bonds. IP-WB further confirmed that BME was directly bound to P65 protein in MODE-K cells. In conclusion, BME was able to restore the intestinal barrier through the P65 / TNF-α / MLCK / ZO-1 signaling pathway.

Impact of pre-delivery medication treatment on delivery outcome in patients with primary immune thrombocytopenia: a cohort study.

BACKGROUND: Clinical research data showed a series of adverse events in the delivery period of primary immune thrombocytopenia (ITP) patients, including high cesarean section rate. Consensus report proposed that for patients with platelet count below 50 × 109/L, prednisone or intravenous immunoglobulins (IVIg) can be given to raise the platelet count in third trimester in preparation for labor. OBJECTIVES: To evaluate the effect of low-dose prednisone or IVIg therapy on delivery outcomes in patients with ITP. STUDY DESIGN: This was a cohort study that included pregnant women with ITP from January 2017 to December 2022. Patients with platelet counts of (20-50) ×109/L at the time of delivery (≥34 weeks) and who had not received any medication before were enrolled in the study. Patients were divided into the pre-delivery medication group (oral prednisone or IVIg) and untreated group according to their preferences. The differences in vaginal delivery rate, postpartum bleeding rate, and platelet transfusion volume between the two groups were compared using t-test, Wilcoxon rank-sum test, and χ2 test. Logistic regression analysis was used to identify the factors affecting vaginal delivery rate and postpartum bleeding rate, and multiple linear regression analysis was used to identify the factors affecting platelet transfusion volume. RESULTS: During the study period, a total of 96 patients with ITP were enrolled, including 70 in the pre-delivery medication group and 26 in the untreated group. The platelet count of pre-delivery medication group was 54.8 ± 34.5 × 109/L, which was significantly higher than that of untreated group 34.4 ± 9.0 × 109/L (p = .004). The vaginal delivery rate of the medication group was higher than the untreated group [60.0% (42/70) vs. 30.8% (8/26), χ2 = 6.49, p = .013]. After adjusting for the proportion of multiparous women and gestational weeks, the results showed that medication therapy during the peripartum period was associated with vaginal delivery (OR = 4.937, 95% CI: 1.511-16.136, p = .008). The postpartum bleeding rates were 22.9% (16/70) and 26.9% (7/26) in the medication group and untreated group, respectively, with no significant difference between the two groups (χ2 = 0.17, p = .789), while the platelet transfusion volume was lower in the medication group than untreated group [(1.1 ± 1.0) vs. (1.6 ± 0.8) U]. CONCLUSION: Pre-delivery medication therapy can increase vaginal delivery rate, reduce platelet transfusion volume, but does not decrease the incidence of postpartum hemorrhage.

What is the context?The high cesarean section rate has always been a prominent pregnancy issue in ITP patients. The data shows that the reason for cesarean section in most ITP patients may be related to early induced labor due to thrombocytopenia or patients' concerns of bleeding events during delivery. The study of treatment during the perinatal period is expected to further increase platelet count and prepare for safer delivery.What is new?To date, no study has focused on pre-delivery treatment for pregnant ITP patients. In this study, patients with a platelet count<50 × 109/L after 34 weeks can experience a significant increase in platelet count after receiving immunoglobulin or prednisone therapy. The results of this study preliminarily demonstrate IVIg or prednisone is a promising pre-delivery treatment for pregnant ITP patients in preparation for labor. The pre-delivery medication therapy can improve the rate of successful vaginal delivery and reduce the consumption of blood products.What is the impact?This study provides further evidence that the target threshold for platelets should be raised in late third trimester, with a platelet count above 50 × 109/L as the standard for delivery, in order to further reduce the cesarean section rate and blood product infusion in ITP patients.

Rhodium(III) Complex Noncanonically Potentiates Antitumor Immune Responses by Inhibiting Wnt/ß-Catenin Signaling.

Metal-based chemoimmunotherapy has recently garnered significant attention for its capacity to stimulate tumor-specific immunity beyond direct cytotoxic effects. Such effects are usually caused by ICD via the activation of DAMP signals. However, metal complexes that can elicit antitumor immune responses other than ICD have not yet been described. Herein, we report that a rhodium complex (Rh-1) triggers potent antitumor immune responses by downregulating Wnt/ß-catenin signaling with subsequent activation of T lymphocyte infiltration to the tumor site. The results of mechanistic experiments suggest that ROS accumulation following Rh-1 treatment is a critical trigger of a decrease in ß-catenin and enhanced secretion of CCL4, a key mediator of T cell infiltration. Through these properties, Rh-1 exerts a synergistic effect in combination with PD-1 inhibitors against tumor growth in vivo. Taken together, our work describes a promising metal-based antitumor agent with a noncanonical mode of action to sensitize tumor tissues to ICB therapy.

Myo-inositol oxygenase CgMIOX3 alleviates S-RNase-induced inhibition of incompatible pollen tubes in pummelo.

Pummelo (Citrus grandis L. Osbeck) exhibits S-RNase-based self-incompatibility (SI), during which S-RNase cytotoxicity inhibits pollen tubes in an S-haplotype-specific manner. The entry of S-RNase into self-pollen tubes triggers a series of reactions. However, these reactions are still poorly understood in pummelo. In the present study, we used S-RNases as baits to screen a pummelo pollen cDNA library and characterized a myo-inositol oxygenase (CgMIOX3) that physically interacts with S-RNases. CgMIOX3 is highly expressed in pummelo pollen tubes, and its downregulation leads to a reduction in pollen tube growth. Upon entering pollen tubes, S-RNases increase the expression of CgMIOX3 and enhance its activity by directly binding to it in an S-haplotype-independent manner. CgMIOX3 improves pollen tube growth under oxidative stress through ascorbic acid (AsA) accumulation and increases the length of self-pollen tubes. Furthermore, over-expression of CgMIOX3 increases the relative length of self-pollen tubes growing in the style of petunia (Petunia hybrida). This study provides intriguing insights into the pumelo SI system, revealing a regulatory mechanism mediated by CgMIOX3 that plays an important role in the resistance of pollen tubes to S-RNase cytotoxicity.

Enhanced Parkinson's gait, reduced fall risk, and improved cognitive function through multimodal rehabilitation combined with rivastigmine treatment.

OBJECTIVE: This study aimed to examine the effects of combined rehabilitation and rivastigmine treatment on patients with Parkinson's disease (PD). METHODS: Gait parameters were assessed using the Gibbon Gait Analyzer in fifteen patients. Baseline gait data and cognitive assessments were collected. Each patient underwent external counterpulsation therapy, transcranial magnetic stimulation therapy, and exercise therapy for one hour per day, five days a week for three weeks. Post-intervention, gait and cognitive data were re-evaluated. Alongside their standard PD medications, all participants were administered rivastigmine throughout the study period. RESULTS: The intervention significantly enhanced motor function in the single-task test, evidenced by marked improvements in gait metrics such as stride width and walking speed, and a substantial reduction in fall risk. Cognitive function, assessed by mini-mental state examination and Montreal cognitive assessment, showed an improvement trend after the three-week intervention. Improvements in dual-task walking function were observed, although these changes did not reach statistical significance. CONCLUSION: Multimodal exercise training combined with rivastigmine treatment significantly improves certain gait parameters in the single-task test, enhances balance, and reduces the risk of falling in patients with PD. Cognitive function also demonstrated improvement.

Cu(II) complex that synergistically potentiates cytotoxicity and an antitumor immune response by targeting cellular redox homeostasis.

Developing anticancer drugs with low side effects is an ongoing challenge. Immunogenic cell death (ICD) has received extensive attention as a potential synergistic modality for cancer immunotherapy. However, only a limited set of drugs or treatment modalities can trigger an ICD response and none of them have cytotoxic selectivity. This provides an incentive to explore strategies that might provide more effective ICD inducers free of adverse side effects. Here, we report a metal-based complex (Cu-1) that disrupts cellular redox homeostasis and effectively stimulates an antitumor immune response with high cytotoxic specificity. Upon entering tumor cells, this Cu(II) complex enhances the production of intracellular radical oxidative species while concurrently depleting glutathione (GSH). As the result of heightening cellular oxidative stress, Cu-1 gives rise to a relatively high cytotoxicity to cancer cells, whereas normal cells with low levels of GSH are relatively unaffected. The present Cu(II) complex initiates a potent ferroptosis-dependent ICD response and effectively inhibits in vivo tumor growth in an animal model (c57BL/6 mice challenged with colorectal cancer). This study presents a strategy to develop metal-based drugs that could synergistically potentiate cytotoxic selectivity and promote apoptosis-independent ICD responses through perturbations in redox homeostasis.

Global research progress on radiofrequency ablation in cardiology: A bibliometric analysis (2004-2023).

In recent years, significant advancements in radiofrequency ablation technology have notably enhanced arrhythmia treatment in cardiology. Technological advancements and increasing clinical adoption have made radiofrequency ablation a key therapy in improving life quality for patients with conditions like atrial fibrillation (AF). Consequently, there has been a marked increase in research output, underscoring the technology's significance and its potential in cardiology. Aims to comprehensively analyze cardiology's radiofrequency ablation research trends, identifying leading countries and institutions in international collaborations, key researchers' contributions, and evolving research hotspots. The study, based on the Web of Science Core Collection database, reviewed the literatures from 2004 to 2023. CiteSpace 6.2.R7 Basic was used for bibliometric analysis, which examined annual publication trends, international collaboration networks, key authors, leading research institutions, major journals, keyword co-occurrence and clustering trends. Analyzing 3423 relevant articles, this study reveals a consistent growth in cardiology radiofrequency ablation research since 2004. The analysis shows that the United States, Germany, and France hold central roles in the international collaboration network, with leading authors from premier US and European institutions. Keyword cluster analysis identifies "atrial flutter" and "ventricular tachycardia" as current research focal points. Cardiology radiofrequency ablation research shows a growth trend, led by the United States and European countries. Research hotspots are concentrated on the diverse applications of radiofrequency ablation technology and the treatment of AF. Future studies may increasingly focus on technological innovation and the deepening of clinical applications.

Hierarchical Composite with Self-Adaptive Anisotropic Deformation for Thermal Protection System.

Rigid thermal protection materials such as ultra-high-temperature ceramics are desirable for applications in aerospace vehicles, but few materials can currently satisfy the emerging high-temperature sealing requirements for dynamic gaps created by the mismatch of the thermal expansion of different protection layers. Here, we design and fabricate a flexible biomimetic anisotropic deformation composite by multilayer cocuring onto fiber fabrics. It displays superior anisotropic deformation, whose longitudinal expansion ratio is 48 times greater than the transverse expansion ratio at specific temperatures. Furthermore, the ordered carbon structure created by transition-metal-catalyzed graphitization and the C/Si synergistic effect resulting from the combination of biomimetic fiber fabrics and SR enable the in situ formation of a high-temperature-resistant SiC crystalline phase within the char layer, ultimately resulting in exceptional thermal protection properties. By constructing hollow structures in situ, the back temperature of the composite, which is only 4.33 mm thick, is stabilized at 140 °C under the condition of continuous butane flame ablation (1300 °C) for 420 s. Multilayer structure and flexible features can facilitate large-scale preparation and arbitrary cutting and bending, adapted to different thermal protection areas.

A risk score based on polyamine metabolism and chemotherapy-related genes predicts prognosis and immune cells infiltration of lung adenocarcinoma.

We aimed to explore whether the genes associated with both platinum-based therapy and polyamine metabolism could predict the prognosis of LUAD. We searched for the differential expression genes (DEGs) associated with platinum-based therapy, then we interacted them with polyamine metabolism-related genes to obtain hub genes. Subsequently, we analysed the main immune cell populations in LUAD using the scRNA-seq data, and evaluated the activity of polyamine metabolism of different cell subpopulations. The DEGs between high and low activity groups were screened to identify key DEGs to establish prognostic risk score model. We further elucidated the landscape of immune cells, mutation and drug sensitivity analysis in different risk groups. Finally, we got 10 hub genes associated with both platinum-based chemotherapy and polyamine metabolism, and found that these hub genes mainly affected signalling transduction pathways. B cells and mast cells with highest polyamine metabolism activity, while NK cells were found with lowest polyamine metabolism activity based on scRNA-seq data. DEGs between high and low polyamine metabolism activity groups were identified, then 6 key genes were screened out to build risk score, which showed a good predictive power. The risk score showed a universal negative correlation with immunotherapy checkpoint genes and the cytotoxic T cells infiltration. The mutation rates of EGFR in low-risk group was significantly higher than that of high-risk group. In conclusion, we developed a risk score based on key genes associated with platinum-based therapy and polyamine metabolism, which provide a new perspective for prognosis prediction of LUAD.

Comparative analysis of codon usage bias in chloroplast genomes of ten medicinal species of Rutaceae.

Rutaceae family comprises economically important plants due to their extensive applications in spices, food, oil, medicine, etc. The Rutaceae plants is able to better utilization through biotechnology. Modern biotechnological approaches primarily rely on the heterologous expression of functional proteins in different vectors. However, several proteins are difficult to express outside their native environment. The expression potential of functional genes in heterologous systems can be maximized by replacing the rare synonymous codons in the vector with preferred optimal codons of functional genes. Codon usage bias plays a critical role in biogenetic engineering-based research and development. In the current study, 727 coding sequences (CDSs) obtained from the chloroplast genomes of ten Rutaceae plant family members were analyzed for codon usage bias. The nucleotide composition analysis of codons showed that these codons were rich in A/T(U) bases and preferred A/T(U) endings. Analyses of neutrality plots, effective number of codons (ENC) plots, and correlations between ENC and codon adaptation index (CAI) were conducted, which revealed that natural selection is a major driving force for the Rutaceae plant family's codon usage bias, followed by base mutation. In the ENC vs. CAI plot, codon usage bias in the Rutaceae family had a negligible relationship with gene expression level. For each sample, we screened 12 codons as preferred and high-frequency codons simultaneously, of which GCU encoding Ala, UUA encoding Leu, and AGA encoding Arg were the most preferred codons. Taken together, our study unraveled the synonymous codon usage pattern in the Rutaceae family, providing valuable information for the genetic engineering of Rutaceae plant species in the future.

[Research progress of non-coding RNA involved in glycolysis regulation of hepatocellular carcinoma].

Liver cancer is a common tumor of digestive system. Hepatocellular carcinoma (HCC) is a common type of liver cancer, which has a high degree of malignancy and ranks among the top causes of cancer-related death in the world. Metabolic reprogramming is considered to be an important marker of carcinogenesis. Glucose metabolism is one of the main ways for cells to produce energy. Glycolysis, as the basic reaction of glucose metabolism, plays an important role in cell metabolism. Therefore, the regulation of glycolysis is of great significance to the proliferation and evolution of tumors. More and more non-coding RNAs (ncRNA) have been proved to play an important role in the regulation of tumor glycolysis. This article reviews the role of ncRNA in the regulation of HCC glycolysis and its related mechanisms. At the same time, the prospect of targeted therapy for HCC based on the related mechanisms of glycolysis regulation is put forward.

miR-185-5p May Modulate the Chemosensitivity of LUSC to Cisplatin via Targeting PCDHA11: Multi-omics Analysis and Experimental Validation.

Drug resistance is the major difficulty in treatment of lung squamous cell carcinoma (LUSC). This study aims to explore drug response-related miRNAs (DRmiRNAs) based on multi-omics research. We identified DRmiRNAs of LUSC with a multi-omics integrated system that combines expression data of microRNA, lncRNA, mRNA, methylation levels, somatic mutations. After identifying DRmiRNAs, we screened and validated of the target mRNAs of DRmiRNAs through Targetscan and the miRDB database. Then, Real-time PCR and Western blot assays were used to estimate the expression of DRmiRNAs and target protein, and the dual-luciferase assays were used to confirm the interaction of DRmiRNAs and target mRNA. Furthermore, CCK-8 (Cell Counting Kit-8) assays were used to evaluate cell proliferation and drug sensitivity. After integrated analysis, hsa-miR-185-5p was identified as DRmiRNA based on multi-omics data. Through Targetscan and miRDB database, the possible target mRNAs were obtained and PCDHA11 was validated as a target mRNA of miR-185-5p by real-time PCR, Western blot assays and dual-luciferase assays. CCK-8 assays and clone formation assays showed that the proliferation of miR-185-5p mimics was significantly slower than that of miR-185-5p inhibitors, which means overexpression of miR-185-5p enhanced the anticancer effects of cisplatin, whereas the downregulation of miR-185-5p reduced the effects. Furthermore, the proliferation of silencing PCDHA11 was significantly slower than that of overexpression of PCDHA11, which means PCDHA11 overexpression weakened the anticancer effects of cisplatin, and silencing PCDHA11 enhanced the effects. This study demonstrated that miR-185-5p was involved in chemoresistance of LUSC cells to cisplatin partly via down-regulating PCDHA11, which may promote understanding the underlying molecular mechanisms of drug response.

An S-locus F-box protein as pollen S determinant targets non-self S-RNase underlying self-incompatibility in Citrus.

Self-incompatibility (SI) is a crucial mechanism that prevents self-fertilization and inbreeding in flowering plants. Citrus exhibits SI regulated by a polymorphic S-locus containing an S-RNase gene and multiple S-locus F-box (SLF) genes. It has been documented that S-RNase functions as the pistil S determinant, but there is no direct evidence that the SLF genes closely linked with S-RNase function as pollen S determinants in Citrus. This study assembled the genomes of two pummelo (Citrus grandis) plants, obtained three novel complete and well-annotated S-haplotypes, and isolated 36 SLF or SLF-like alleles on the S-loci. Phylogenetic analysis of 138 SLFs revealed that the SLF genes were classified into 12 types, including six types with divergent or missing alleles. Furthermore, transformation experiments verified that the conserved S6-SLF7a protein can lead to the transition of SI to self-compatibility by recognizing non-self S8-RNase in 'Mini-Citrus' plants (S7S8 and S8S29, Fortunella hindsii), a model plant for citrus gene function studies. In vitro assays demonstrated interactions between SLFs of different S haplotypes and the Skp1-Cullin1-F-box subunit CgSSK1 protein. This study provides direct evidence that SLF controls the pollen function in Citrus, demonstrating its role in the 'non-self recognition' SI system.

A 12-Vertex Metallacarborane of Silver(I).

The discovery of ferrocene in 1951 was a significant landmark in the field of organometallic chemistry, and since then, numerous sandwich- or half-sandwich metallic complexes have been reported. However, silver stands as an intriguing exception in this regard, and knowledge of its bonding situation has remained undisclosed. Herein, unprecedented 12-vertex metallacarboranes of Ag(I) (2a and 2b) were synthesized through the reaction of sodium hexamethyldisilazide (NaHMDS) with the mixture of nido-C2B9 carborane anion-supported N-heterocyclic carbene precursors (1a and 1b) and [Ag(PPh3)Cl]4. The X-ray structural analysis of the resulting metallacarboranes revealed a unique "slipped" half-sandwich structure, which is a rarity among cyclopentadienyl analogues. DFT calculations provided insights into the asymmetric π-interactions between the pentagonal C2B3 face and the silver ion.