Dual-Functional Nanodroplet for Tumor Vasculature Ultrasound Imaging and Tumor Immunosuppressive Microenvironment Remodeling.

Accurately evaluating tumor neoangiogenesis and conducting precise interventions toward an immune-favorable microenvironment are of significant clinical importance. In this study, a novel nanodroplet termed as the nanodroplet-based ultrasound contrast agent and therapeutic (NDsUCA/Tx) is designed for ultrasound imaging and precise interventions of tumor neoangiogenesis. Briefly, the NDsUCA/Tx shell is constructed from an engineered CMs containing the tumor antigen, vascular endothelial growth factor receptor 1 (VEGFR1) extracellular domain 2-3, and CD93 ligand multimerin 2. The core is composed of perfluorohexane and the immune adjuvant R848. After injection, NDsUCA/Tx is found to be enriched in the tumor vasculature with high expression of CD93. When triggered by ultrasound, the perfluorohexane in NDsUCA/Tx underwent acoustic droplet vaporization and generated an enhanced ultrasound signal. Some microbubbles exploded and the resultant debris (with tumor antigen and R848) together with the adsorbed VEGF are taken up by nearby cells. This cleared the local VEGF for vascular normalization, and also served as a vaccine to activate the immune response. Using a syngeneic mouse model, the satisfactory performance of NDsUCA/Tx in tumor vasculature imaging and immune activation is confirmed. Thus, a multifunctional NDsUCA/Tx is successfully developed for molecular imaging of tumor neoangiogenesis and precise remodeling of the tumor microenvironment.

Lysosome-Targeting Bacterial Outer Membrane Vesicles for Tumor Specific Degradation of PD-L1.

Increased expression of immune check point genes, such as PD-L1, is one of the main reasons for immunosuppression, especially for colon cancer. Development of novel therapeutic strategies is of great importance to improve the prognosis. In this study, outer membrane vesicles (OMV) derived from Gram-negative bacteria are engineered to immune checkpoint blockade nanosystem for efficient elicitation of anti-tumor immunity. Briefly, the OMVs are engineered with Lyp1-Traptavidin (S52G, R53D mutant of streptavidin) fusion protein displayed on the surface. The Lyp-1 endows the OMV with the capacity to target tumor tissues, while the Traptavidin ensures easy decoration of biotinylated anti-PD-L1 and biotinylated M6P (mannose 6-phosphate). The simultaneously anchored anti-PD-L1 and M6P (ligand for cation-independent mannose 6-phosphate receptor) on the engineered OMVs coordinately direct the membrane PD-L1 to lysosome for degradation, and thus unleash the anti-tumor immunity. With syngeneic tumor model, the engineered OMVs are confirmed to boost immunity, inhibit cancer growth, and thus prolong survival. Together, A proposed OMV-based modular nanosystem that enables assembly of biotinylated anti-PD-L1 and M6P on the surface for tumor-targeted immune checkpoint blockade.

Pancreatic Cancer-Derived Exosomal miR-Let-7b-5p Stimulates Insulin Resistance in Skeletal Muscle Cells Through RNF20/STAT3/FOXO1 Axis Regulation.

Background: Cancers trigger systemic metabolic disorders usually associated with glucose intolerance, which is an initially apparent phenomenon. One of the features of pancreatic cancer (PC) metabolic reprogramming is the crosstalk between PC and peripheral tissues (skeletal muscle and adipose tissues), emphasized by insulin resistance (IR). Our previous study reported that mice pancreatic cancer-derived exosomes could induce skeletal muscle cells (C2C12) IR, and exosomal microRNAs (miRNAs) may exert an important effect. However, the underlying mechanism remains to be further elucidated. Methods: qPCR was used to determine the expression of let-7b-5p in normal pancreatic islet cells and PC cells. Exosomes were purified from PC cell culture medium by ultracentrifugation. The role let-7b-5p on IR-mediated by PC cells-derived exosomes was asses by Oil Red O staining using miRNA inhibitor. Western blot assay was performed to examine the expression of IR-related genes and the activation of signaling pathways. A Luciferase experiment was applied to confirm how let-7b-5p regulated the expression of RNF20. IP/WB analysis further determined whether RNF20 promoted STAT3 ubiquitination. Rescue experiment using RNF20 overexpression plasmid was performed to confirm the role of RNF20 on IR-mediated using PC cell-derived exosomes in C2C12 myotube cells. Results: miRNA-let-7b-5p was identified as the key exosomal miRNA, which could promote the IR in C2C12 myotube cells supported the lipid accumulation, the activation of STAT3/FOXO1 axis, and the decreased expression of IRS-1 and GLUT4. RNF20, an E3 ubiquitin ligase, was confirmed as the target gene of let-7b-5p and was found to improve IR by downregulating STAT3 protein expression via ubiquitination-mediated protein degradation. The ectopic expression of RNF20 could effectively attenuate the IR mediated by the pancreatic cancer-derived exosomes in C2C12 myotube cells. Conclusion: Our data suggest that exosomal miRNA-let-7b-5p may promote IR in C2C12 myotube cells by targeting RNF20 to activate the STAT3/FOXO1 axis.

LncRNA SNHG20 silencing inhibits hepatocellular carcinoma progression by sponging miR-5095 from MBD1.

OBJECTIVE: Long non-coding RNAs (lncRNAs) may have a significant regulatory effect on the progression of hepatocellular carcinoma (HCC), according to recent data. This study aims to investigate how SNHG20, a small nucleolar RNA host gene, contributes to the development of HCC. METHODS: LncRNA SNHG20, miR-5095, and MBD1 gene levels were determined using reverse transcription qPCR (RT-qPCR). Huh-7 and HepG2 cell bioactivities were evaluated using the CCK-8 kit, EdU, flow cytometry, and wound-healing migration tests. To assess the metastasis of Huh-7 and HepG2 cells, a transwell assay was used. The amounts of invasion- and proliferation-associated proteins were determined using western blot. Using the miRDB (www.mirdb.org) software, the possible target genes of lncRNA and miRNA were predicted, and this prediction was then verified by a twofold luciferase reporter test. To determine the pathologic alteration and Ki67 level in tumor tissues, H&E staining and IHC were employed. TUNEL was conducted to assess the presence of apoptotic bodies in the tumor tissues. RESULTS: lncRNA SNHG20 exhibited a high expression in HCC cells (P<0.01). LncRNA SNHG20 knockdown inhibited HCC cell metastasis (P<0.01) and accelerated apoptosis (P<0.01). LncRNA SNHG20 acted as a sponge of miR-5095 in HCC. In addition, miR-5095 overexpression inhibited HCC cell metastasis (P<0.01) and accelerated apoptosis (P<0.01); and miR-5095 negatively targeted MBD1. Furthermore, LncRNA SNHG20 regulated HCC progression through the miR-5095/MBD1 axis, and LncRNA SNHG20 knockdown inhibited HCC growth. CONCLUSION: LncRNA SNHG20 accelerates HCC progression by the miR-5095/MBD1 axis, indicating lncRNA SNHG20 can be used as a biomarker for patients with HCC.

Eutrophication decreases ecological resilience by reducing species diversity and altering functional traits of submerged macrophytes.

Positive feedback is key to producing alternative stable states and largely determines ecological resilience in response to external perturbations. Understanding the positive feedback mechanisms in macrophyte-dominated lakes is crucial for resilience-based management and restoration. Based on the field investigation of submerged macrophyte communities in 35 lakes in China, we found that morphological complexity (MC) and morphological plasticity (MP) are correlated with the stoichiometric homeostasis of phosphorus (HP ) and are related to ecosystem structure, functioning, and stability. We also found that the positive feedback strength of lakes dominated by macrophytes is biomass- and diversity-dependent. Eutrophication can decrease the community biomass by decreasing community MC, MP, and HP and the species diversity through low-light availability, ultimately decreasing the positive feedback strength and resilience of clear water states. We argue that functional traits and species diversity should be considered to build more resilient ecosystems in future changing environment scenarios.

Sequential therapy for pancreatic cancer patients with synchronous oligo-hepatic metastatic lesions.

BACKGROUND: Treatments for patients suffering from pancreatic cancer with oligo-hepatic metastasis have always been a cause of certain controversy. Herein, we reported 15 pancreatic cancer patients with oligo-hepatic metastasis who accepted sequential therapy of chemotherapy, radiofrequency ablation (RFA), and radical resection of the primary tumor. METHODS: A total of 87 pancreatic cancer patients with synchronous oligo-metastatic hepatic lesions who received treatments in the 2nd Affiliated Hospital of Zhejiang University between January 2017 and July 2020 were enrolled. The chemotherapy regimens included modified folfirinox (54/87) and gemcitabine plus nab-paclitaxel (33/87). Test of blood tumor markers and contrast-enhanced computed tomography (CT) or magnetic resonance (MR) scan was performed at diagnosis and after eight weeks of chemotherapy. RESULTS: Thirty-five patients received just chemotherapy because of poor reaction to the first round of chemotherapy(Overall survival (OS), 6.47±1.80 months); 15 patients reassessed as stable disease (SD)/partial response (PR) continued chemotherapy (OS, 10.35±3.15); nine patients reassessed as progressive disease (PD) after RFA and continued chemotherapy (OS, 10.90±2.60). The primary tumors in 13 patients were unresectable after chemotherapy and RFA (OS, 12.92±2.47), while 15 patients completed the sequential therapy of chemotherapy, radio-frequency ablation, and radical resection (OS, 16.76±6.55). CONCLUSIONS: Sequential chemotherapy and RFA is a good treatment strategy to select the best candidates for surgical treatment among patients with pancreatic cancer with oligo-hepatic metastasis.

Anti-PD-1-based immunotherapy plus lenvatinib to treat advanced gallbladder cancer in the elderly: a case series and review of current literature.

BACKGROUND: Gallbladder cancer (GBC) is a rare malignant tumour of the bile duct. Due to the lack of typical clinical manifestations in the early stage, it is basically at an advanced stage when discovered. Radical resection remains the only curative therapy for patients with GBC. The resection rate is relatively low due to tumour invasion and metastasis, and the overall prognosis is poor. For most patients with unresectable lesions, chemotherapy has been the only recommended treatment for decades. Immunotherapy combined with TKIs (tyrosine kinase inhibitors) was proven to be effective in patients with hepatocellular carcinoma and cholangiocarcinoma. Some physicians have attempted to apply immunotherapy and TKIs combined with traditional chemotherapy in patients with advanced GBC. However, the outcomes were not clear because limited cases were reported. CASE PRESENTATION: We present a case series of four elderly patients with advanced GBC who received tislelizumab and lenvatinib combined with chemotherapy. All four patients responded to this treatment approach. Tumour responses were better in Patient 1 (TMB-H, MSS), Patient 2 (low TMB, MSS), and Patient 3 (low TMB, MSI-H) than in Patient 4 (low TMB, MSS), in whom metastasis occurred during the later stage of treatment. CONCLUSION: The combination of tislelizumab and lenvatinib may be a promising treatment for patients with advanced GBC. The efficacy and safety need further confirmation.

Combination of Metformin and Sorafenib Induces Ferroptosis of Hepatocellular Carcinoma Through p62-Keap1-Nrf2 Pathway.

Hepatocellular carcinoma (HCC) is one of the most lethal cancers in the world. Sorafenib is the first small-molecule multi-kinase inhibitors approved by FDA for treatment of advanced HCC. Metformin has been demonstrated to have benefit for preventing cancer progression. In human recurrent HCCs, NF-E2-related factor 2 (Nrf2) was overexpressed and associated with poor survival. Nrf2 related signaling pathway plays central role to mediate cellular resistance to sorafenib through protecting HCC cells from ferroptosis. The effect of Combination treatment for HCC cells and the intrinsic mechanism have not been reported. In this study, metformin augmented the anti-tumor effect of sorafenib for HCC through ferroptosis induction by inhibiting Nrf2 related pathway. Based on the results of Nrf2 knockdown and p62 knockdown study, the combination of sorafenib and metformin suppressed proliferation of HCC cells through p62-Keap1-Nrf2/HO1 signaling way. Size of xenografts treated with the combination of sorafenib and metformin was smaller than other groups in vivo. Moreover, the combination treatment greatly induced ferroptosis in HCC cells through inhibiting Nrf2 expression. Based on our findings, the combination treatment suppressed proliferation of HCC cells through ferroptosis induction, by p62-Keap1-Nrf2/HO1 signaling way.

Linking the network topology of plant traits with community structure, functioning, and adaptive strategies of submerged macrophytes.

Plant trait network analysis can calculate the topology of trait correlations and clarify the complex relationships among traits, providing new insights into ecological topics, including trait dimensions and phenotypic integration. However, few studies have focused on the relationships between network topology and community structure, functioning, and adaptive strategies, especially in natural submerged macrophyte communities. In this study, we collected 15 macrophyte community-level traits from 12 shallow lakes in the Yangtze River Basin in the process of eutrophication and analyzed the changes in trait network structure (i.e., total phosphorus, TP) by using a moving window method. Our results showed that water TP significantly changed the topology of trait networks. Specifically, under low or high nutrient levels, the network structure was more dispersed, with lower connectance and higher modularity than that found at moderate nutrient levels. We also found that network connectance was positively correlated with community biomass and homeostasis, while network modularity was negatively correlated with community biomass and homeostasis. In addition, modules and hub traits also changed with the intensity of eutrophication, which can reflect the trait integration and adaptation strategies of plants in a stressful environment. At low or high nutrient levels, more modules were differentiated, and those modules with higher strength were related to community nutrition. Our results clarified the dynamics of community structure and functioning from a new perspective of plant trait networks, which is key to predicting the response of ecosystems to environmental changes.

Phosphorus accelerate the sulfur cycle by promoting the release of malodorous volatile organic sulfur compounds from Microcystis in freshwater lakes.

Volatile organic sulfur compounds (VSCs) released by algae are of great significance in sulfur cycle, climate regulation and biological information transmission, and they also caused taste and odor in freshwaters. However, the categories, sources, and environmental regulatory factors of VSCs in freshwaters were less known. Here, we show that eight common freshwater cyanobacterium Microcystis, which bloom in freshwaters over the world, are found to be important producers of VSCs. Dimethyl sulfide (DMS), dimethyl disulfide (DMDS) and isopropyl methyl sulfide (IPMS) are the main VSCs with the highest concentrations 184.81 nmol/L, 162.01 nmol/L and 101.55 nmol/L, respectively. The amount of VSCs released from those Microcystis varied greatly, M. elabens, M. panniformis and M. flos-aquae released the largest amount of VSCs (1260.52 nmol S/L, 1154.75 nmol S/L and 670.58 nmol S/L), and M. wesenbergii had the smallest release amount. We also found for the first time that phosphorus (P) was one of the important factors for the regulation VSCs from most Microcystis. P can elevate the release of DMS by promoting the biomass and DMS yields of most Microcystis in the range 0.05 mg/L to 0.5 mg/L. Similar results were also found in 16 lakes at three different spatiotemporal scales. Overall, we revealed that the common freshwater Microcystis were able to release diverse thioethers, and the major VSCs were significantly influenced by water P concentrations. In the context of global freshwater eutrophication and Microcystis bloom, freshwater cyanobacteria driven sulfur cycle and water odor will probably be further strengthened.

Efficacy and safety of FOLFIRINOX as second-line chemotherapy for advanced pancreatic cancer after gemcitabine-based therapy: A systematic review and meta-analysis.

OBJECTIVE: To undertake a meta-analysis of the treatment effects of different second-line chemotherapy regimens compared with FOLFIRINOX (FOL [folinic acid], F [fluorouracil], IRIN [irinotecan], OX [oxaliplatin]) after failure of gemcitabine-based first-line therapy in patients with pancreatic cancer. METHODS: This meta-analysis searched electronic databases, including Embase®, Medline, PubMed® and the Cochrane library, for eligible studies that reported the use of FOLFIRINOX and other drug regimens as second-line chemotherapy after failure of gemcitabine-based chemotherapy. Pooled analyses for progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and grade 3/4 treatment-emergent adverse events (TRAEs) were undertaken. RESULTS: The analysis included six studies with a total of 858 patients. Compared with the three other second-line regimens, FOLFIRINOX had a significantly longer PFS (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.52, 0.89) and OS (HR 0.71, 95% CI 0.59, 0.86); and a significantly better ORR (HR 0.43, 95% CI 0.23, 0.80) and DCR (HR 0.71, 95% CI 0.58, 0.88). However, grade 3/4 adverse events were more frequently reported in patients administered FOLFIRINOX compared with the other three regimens. CONCLUSION: FOLFIRINOX is recommended as a second-line chemotherapy regimen for patients with pancreatic cancer that have failed on gemcitabine-based first-line therapy.Research Registry number: reviewregistry1300.

Microwave ablation versus laparoscopic resection as first-line therapy for solitary 3-5-cm HCC.

BACKGROUND AND AIMS: The study objective was to compare the effectiveness of microwave ablation (MWA) and laparoscopic liver resection (LLR) on solitary 3-5-cm HCC over time. APPROACH AND RESULTS: From 2008 to 2019, 1289 patients from 12 hospitals were enrolled in this retrospective study. Diagnosis of all lesions were based on histopathology. Propensity score matching was used to balance all baseline variables between the two groups in 2008-2019 (n = 335 in each group) and 2014-2019 (n = 257 in each group) cohorts, respectively. For cohort 2008-2019, during a median follow-up of 35.8 months, there were no differences in overall survival (OS) between MWA and LLR (HR: 0.88, 95% CI 0.65-1.19, p = 0.420), and MWA was inferior to LLR regarding disease-free survival (DFS) (HR 1.36, 95% CI 1.05-1.75, p = 0.017). For cohort 2014-2019, there was comparable OS (HR 0.85, 95% CI 0.56-1.30, p = 0.460) and approached statistical significance for DFS (HR 1.33, 95% CI 0.98-1.82, p = 0.071) between MWA and LLR. Subgroup analyses showed comparable OS in 3.1-4.0-cm HCCs (HR 0.88, 95% CI 0.53-1.47, p = 0.630) and 4.1-5.0-cm HCCs (HR 0.77, 95% CI 0.37-1.60, p = 0.483) between two modalities. For both cohorts, MWA shared comparable major complications (both p > 0.05), shorter hospitalization, and lower cost to LLR (all p < 0.001). CONCLUSIONS: MWA might be a first-line alternative to LLR for solitary 3-5-cm HCC in selected patients with technical advances, especially for patients unsuitable for LLR.

Phosphorus enrichment affects trait network topologies and the growth of submerged macrophytes.

Significant differences in the morphological and physiological characteristics of submerged macrophytes have been studied following nutrient addition, but little research has investigated the changes in plant trait network topology structures and trait interactions at the whole-plant perspective along nutrient gradients. Plant trait interactions and coordination strongly determine ecosystem structure and functioning. Thirty plant traits were collected from a three-month experiment to construct plant trait networks to clarify the variations in trait connections and network organization arising from five total phosphorus (TP) addition concentrations in water, including a control (CK), 0.1 (TP1), 0.2 (TP2), 0.4 (TP3), and 0.8 (TP4) mg L-1. Nonmetric multidimensional scaling analysis showed a clear difference in the distribution of plant trait space among the different TP treatments. Distinct network structures showed that water TP-deficiency and TP-repletion changed the plant trait network into loose assemblages of more modules, which was related to low plant carbohydrate levels. Most plant functions involving biomass accumulation and carbohydrate synthesis were reduced under high TP conditions compared to moderate TP enrichment. Moreover, the percentage of significant relationships between plant functions and corresponding network modules was lower in the CK and TP4 treatments. These results suggested that low plant carbohydrates in high TP environments induced by high water chlorophyll a and tissue phosphorus could not support rapid resource transport among organs and thus inefficiently performed plant functions. Plant carbohydrates were a vital variable that impacted the network edge density, trait interactions, and plant growth. In summary, we demonstrated that high water TP enrichment reduces plant trait network connectedness and plant functional potentials, which may be correlated with reducing tissue carbohydrates. This study explores the correlations between plant trait network topology and functions to improve our understanding of physiological and ecological rules regulating trait interactions among organs and plant growth under eutrophic conditions.

Stoichiometric and physiological mechanisms that link hub traits of submerged macrophytes with ecosystem structure and functioning.

Eutrophication strongly influences plant stoichiometric characteristics and physiological status by altering nutrient and light availability in the water column. However, the mechanisms linking plant functional traits with ecosystem structure and functioning to clarify the decline of submerged macrophytes have not been fully elucidated to date. Therefore, based on a field investigation of 26 macrophytic shallow lakes on the Yangtze Plain, we first constructed a plant trait network at the whole-plant level to determine the hub traits of submerged macrophytes that play central regulatory roles in plant phenotype. Our results suggested that organ (leaf, stem, and root) phosphorus (P), starch, and total nonstructural carbohydrate (TNC) contents were hub traits. Organ starch and TNC were consistent with those in the experiment-based network obtained from a three-month manipulation experiment. Next, the mechanisms underlying the relationships between the hub traits and vital aspects of ecological performance were carefully investigated using field investigation data. Specifically, stoichiometric homeostasis of P (HP), starch, and TNC were positively associated with dominance and biomass at the species level, and community biomass at the community level. Additionally, structural equation modeling clarified not only a hypothesized pathway from eutrophication to water clarity and community TNC, but also combined effects of community TNC and HP on community biomass. That is, ecosystems dominated by more homeostatic communities tended to have more carbon (C)-rich compounds in relatively oligotrophic conditions, which promoted the primary production of macrophytes. Eutrophication was determined to affect community structure by inhibiting the predominance of more homeostatic species and the production of carbohydrates. Finally, reduced community biomass and increased nutrient contents and nutrient:C ratios in plants induced by eutrophication implied a decrease in the C sink in biomass and may potentially lead to an enhancement of litter decomposition rates and nutrient cycling rates. By adjusting plant responses to eutrophication, stoichiometric and physiological mechanisms linking plant traits with ecosystem structure have important implications for understanding ecosystem processes, and these results may contribute to practical management to achieve the restoration of submerged macrophytes and ecosystem services.

Clinical Study on Electronic Medical Neuroelectric Stimulation Based on the Internet of Things to Treat Epilepsy Patients with Anxiety and Depression.

With the continuous development and improvement of the level of medical technology in our country in recent years, the treatment of epilepsy has been constantly updated and developed. Nerve electrical stimulation is considered to be a very effective method for treating epilepsy with anxiety and depression. There are many traditional methods for the treatment of epilepsy. For example, vagus nerve stimulation (VNS) has been applied earlier, and the therapeutic effect has been confirmed, but it will cause serious complications and is easier to be uncomfortable; deep brain stimulation for epilepsy is still in the immature stage, and there is no final conclusion. Therefore, this article proposes a clinical study on the treatment of patients with epilepsy with anxiety and depression based on the electronic medical nerve stimulation of the Internet of Things. First of all, this article uses the literature method to study the causes of epilepsy and previous treatment methods. Then, we designed an experimental study of epilepsy with depression based on the Internet of Things electronic medical neuroelectric stimulation therapy and selected the core quality of life questionnaire, SDS, and SAS as observation indicators. Finally, the comparison of epilepsy symptoms and depression and anxiety between the control group and the observation group before and after treatment was analyzed. The results of the experiment showed that, among the 50 subjects in the study, the observation group that used electrical nerve stimulation therapy had 5 people who stopped seizures after treatment, accounting for 10%, while in the control group of traditional drug treatment methods, after treatment, only one person stopped the seizure, accounting for 2%. In addition, the SAS and SDS scores of the observation group were also lower than those of the control group. Therefore, the use of nerve electrical stimulation to treat epilepsy with anxiety and depression symptoms has better performance and can help patients recover as soon as possible.

Carbon, Nitrogen, and Phosphorus Allocation Strategy Among Organs in Submerged Macrophytes Is Altered by Eutrophication.

The allocation of limiting elements among plant organs is an important aspect of the adaptation of plants to their ambient environment. Although eutrophication can extremely alter light and nutrient availability, little is known about nutrient partitioning among organs of submerged macrophytes in response to eutrophication. Here, we analyzed the stoichiometric scaling of carbon (C), nitrogen (N), and phosphorus (P) concentrations among organs (leaf, stem, and root) of 327 individuals of seven common submerged macrophytes (three growth forms), sampled from 26 Yangtze plain lakes whose nutrient levels differed. Scaling exponents of stem nutrients to leaf (or root) nutrients varied among the growth forms. With increasing water total N (WTN) concentration, the scaling exponents of stem C to leaf (or root) C increased from <1 to >1, however, those of stem P to root P showed the opposite trend. These results indicated that, as plant nutrient content increased, plants growing in low WTN concentration accumulated leaf C (or stem P) at a faster rate, whereas those in high WTN concentration showed a faster increase in their stem C (or root P). Additionally, the scaling exponents of stem N to leaf (or root) N and stem P to leaf P were consistently large than 1, but decreased with a greater WTN concentration. This suggested that plants invested more N and P into stem than leaf tissues, with a higher investment of N in stem than root tissues, but eutrophication would decrease the allocation of N and P to stem. Such shifts in plant nutrient allocation strategies from low to high WTN concentration may be attributed to changed light and nutrient availability. In summary, eutrophication would alter nutrient allocation strategies of submerged macrophytes, which may influence their community structures by enhancing the competitive ability of some species in the process of eutrophication.

Radiofrequency ablation versus traditional liver resection and chemotherapy for liver metastases from gastric cancer.

OBJECTIVE: To compare the short- and long-term outcomes of radiofrequency ablation (RFA) versus liver resection and chemotherapy for liver metastases from gastric cancer. METHODS: We retrospectively evaluated 50 patients who underwent curative gastrectomy and local treatments for liver metastases (RFA, n = 20; liver resection, n = 20; and chemotherapy, n = 10) from 2008 to 2018. RESULTS: The short- and long-term outcomes of each local treatment were evaluated. The median overall survival (OS) after RFA was similar to that after liver resection (20 vs. 20 months, respectively) and longer than that after chemotherapy (20 vs. 10 months, respectively). The 3-year OS and progression-free survival (PFS) rates after RFA were 20% and 10%, respectively, while those in the liver resection group were 23.5% and 23.5%, respectively. The 3-year OS rate after chemotherapy was 10%. The size and number of metastases were prognostic factors for patients with gastric cancer with liver metastasis without statistical significance. CONCLUSIONS: Among patients with liver metastasis from gastric cancer, OS and PFS were satisfactory and comparable between RFA and liver resection but better than those of chemotherapy. RFA is an appropriate option for patients with gastric cancer who have a solitary liver metastasis measuring ≤3.0 cm.

The micropeptide LEMP plays an evolutionarily conserved role in myogenesis.

In recent years, micropeptides have been increasingly identified as important regulators in various biological processes. However, whether micropeptides are functionally conserved remains largely unknown. Here, we uncovered a micropeptide with evolutionarily conserved roles in myogenesis. RNA-seq data analysis of proliferating mouse satellite cells (SCs) and differentiated myotubes identified a previously annotated lncRNA, MyolncR4 (1500011K16RIK), which is upregulated during muscle differentiation. Significantly, MyolncR4 is highly conserved across vertebrate species. Multiple lines of evidence demonstrate that MyolncR4 encodes a 56-aa micropeptide, which was named as LEMP (lncRNA encoded micropeptide). LEMP promotes muscle formation and regeneration in mouse. In zebrafish, MyolncR4 is enriched in developing somites and elimination of LEMP results in impaired muscle development, which could be efficiently rescued by expression of the mouse LEMP. Interestingly, LEMP is localized at both the plasma membrane and mitochondria, and associated with multiple mitochondrial proteins, suggestive of its involvement in mitochondrial functions. Together, our work uncovers a micropeptide that plays an evolutionarily conserved role in skeletal muscle differentiation, pinpointing the functional importance of this growing family of small peptides.

Successful treatment of a huge hepatic carcinoma with right portal vein thrombosis: A case report.

INTRODUCTION: Unlike the traditional associating liver partition and portal vein ligation for staged hepatectomy, it is still controversial whether patients with portal vein thrombosis can receive benefits from liver partition. PATIENT CONCERNS: Right upper abdominal distension for 2 months. DIAGNOSIS: Hepatocellular carcinoma with portal vein invasion INTERVENTION:: Radiofrequency-assisted liver partition with portal vein ligation (RALPP) OUTCOMES:: Disease-free survival: 3 months, overall survival: 7 months CONCLUSION:: Our results advocate this variation of RALPP for use in patients with huge HCC with portal vein invasion, without enough future liver remnant. Patients can receive benefits from the operation, including a shorter operation time, better recovery, and lower overall costs of the 2-stage procedure.

ALYREF links 3'-end processing to nuclear export of non-polyadenylated mRNAs.

The RNA-binding protein ALYREF plays key roles in nuclear export and also 3'-end processing of polyadenylated mRNAs, but whether such regulation also extends to non-polyadenylated RNAs is unknown. Replication-dependent (RD)-histone mRNAs are not polyadenylated, but instead end in a stem-loop (SL) structure. Here, we demonstrate that ALYREF prevalently binds a region next to the SL on RD-histone mRNAs. SL-binding protein (SLBP) directly interacts with ALYREF and promotes its recruitment. ALYREF promotes histone pre-mRNA 3'-end processing by facilitating U7-snRNP recruitment through physical interaction with the U7-snRNP-specific component Lsm11. Furthermore, ALYREF, together with other components of the TREX complex, enhances histone mRNA export. Moreover, we show that 3'-end processing promotes ALYREF recruitment and histone mRNA export. Together, our results point to an important role of ALYREF in coordinating 3'-end processing and nuclear export of non-polyadenylated mRNAs.