Gastrodin attenuates high fructose-induced sweet taste preference decrease by inhibiting hippocampal neural stem cell ferroptosis.

INTRODUCTION: High fructose intake has been implicated as a risk factor for behavioral disorders, potentially through cell ferroptosis induction in the central nervous system. Neural stem cells (NSCs) are crucial for maintaining hippocampal neurogenesis to resist behavioral alterations. Gastrodin, derived from the traditional Chinese herb Gastrodia elata, has neuroprotective effect. OBJECTIVES: This study aimed to elucidate the underlying mechanism by which high fructose induces sweet taste preference and assesses the impact of gastrodin on hippocampal NSC ferroptosis. METHODS: Mice and cultured NSCs were treated with high fructose and/or gastrodin, respectively. NSC ferroptosis was evaluated by assay of lipid peroxidation and DNA double-strand breaks. Transcriptome sequencing (RNA-seq), Western blotting, and chromatin immunoprecipitation (ChIP) were employed to explore the potential mechanism underlying high fructose-induced NSC ferroptosis and the modulation of gastrodin. Simultaneously, specific gene expression was regulated by lentivirus injection into the hippocampus of mice. RESULTS: Our data showed that gastrodin mitigated sweet taste preference decline and hippocampal NSC ferroptosis in high fructose-fed mice, being consistent with reduction of reactive oxygen species (ROS) and iron accumulation in hippocampal NSC mitochondria. Mechanistically, we identified CDGSH iron-sulfur domain 1 (CISD1) as a mediator of NSC ferroptosis, with its expression being augmented by high fructose. Overexpression of Zic family member 2 (ZIC2) increased the transcription of Cisd1 gene. Additionally, overexpression of Zic2 with lentiviral vectors in hippocampus showed the decreased sweet taste preference in mice, consistently up-regulated CISD1 protein expression and reduced hippocampal NSC number. Gastrodin downregulated ZIC2 expression to inhibit CISD1 transcription in its attenuation of high fructose-induced NSC ferroptosis and sweet taste preference decrease. CONCLUSION: Collectively, high fructose can drive hippocampal NSC ferroptosis by upregulating ZIC2 and CISD1 expression, thereby contributing to the decline in sweet taste preference. Gastrodin emerges as a promising agent for mitigating NSC ferroptosis and improving sweet taste preference.

Discovering Effective Chiral Dipeptides against Aß(1-42) Aggregation by the Computational Screening Strategy.

The ß-sheet-breaker (BSB) peptides inhibiting amyloidogenic aggregation have been extensively studied. However, the inhibition efficacy of ultrashort chiral dipeptides remains inadequately understood. In this study, we proposed a computational screening strategy to identify chiral dipeptides as BSB with optimal antiaggregation performance against Aß(1-42) aggregation. We constructed a complete dipeptide library encompassing all possible chiral sequence arrangements and then filtered the library by cascaded molecular docking-molecular dynamics (MD) simulation. Our screening strategy discovered dipeptide DWDP (superscript for chirality) that displayed strong interactions with Aß fibrils and inhibitory effects on Aß aggregation, validated by subsequent experiments. Mechanistic investigation by both MD and replica-exchange molecular dynamics (REMD) simulations revealed that DWDP interacts with Aß by hydrophobic contacts and hydrogen bonds and thus inhibits Aß intermolecular contacts and salt bridge formation, therefore inhibiting Aß aggregation and disrupting Aß aggregates. Totally, our strategy presents a viable approach to discover potential dipeptides with effective antiaggregation ability as potential therapeutic agents for Alzheimer's disease.

The Regulation of Solid Electrolyte Interphase on Composite Lithium Anodes in Solid-State Batteries.

Solid-state lithium metal batteries (SSLMBs) with solid polymer electrolyte (SPE) are highly promising for next-generation energy storage due to their enhanced safety and energy density. However, the stability of the solid electrolyte interphase (SEI) on the lithium metal/SPE interface is a major challenge, as continuous SEI degradation and regeneration during cycling lead to capacity fading. This article investigates the SEI formation on lithium anodes (l-SEI) and composite lithium anodes (c-SEI) in solid-state lithium metal batteries. The composite anodes form a uniform Li2S-rich inorganic SEI layer and a thinner organic SEI layer, effectively passivating the interface for enhanced cycling stability. Specifically, the full cells with c-SEI anodes sustain over 400 cycles at 0.5 C under a high areal capacity of 2.0 mAh cm-2. Moreover, the reversible high-loading solid-state pouch cells exhibit exceptional safety even after curling and cutting. These findings offer valuable insights into developing composite electrodes with robust SEI for solid-state polymer-based lithium metal batteries.

A MYC-STAMBPL1-TOE1 positive feedback loop mediates EGFR stability in hepatocellular carcinoma.

The role of STAM binding protein-like 1 (STAMBPL1), a Lys-63 linkage-specific deubiquitinase, in hepatocellular carcinoma has remained elusive. Here, we report the functions of STAMBPL1 in modulating the stability of the protein and mRNA of the epidermal growth factor receptor (EGFR). STAMBPL1 deficiency attenuates liver tumorigenesis in vitro and in vivo. STAMBPL1 removes K63-linked ubiquitin chains from EGFR to avoid lysosome degradation upon EGF stimulation. STAMBPL1 augments RNA efficient splicing of EGFR to avoid intron retention by activating cleavage of the K63-linked ubiquitin chain on the target of EGR1 protein 1 (TOE1). Moreover, the EGFR-MYC axis has a positive feedback regulation on the transcription of STAMBPL1, and depletion of STAMBPL1 in vivo blunts MYC-driven liver tumorigenesis. Inhibition of STAMBPL1 or TOE1 synergistically improves the antitumor activity of lenvatinib. Our work shows the mechanism of STAMBPL1 in liver cancer and suggests it as a potential therapeutic target for liver cancer treatment.

Siwu tablet attenuates high fructose-induced glomerular podocyte senescence in rats through increasing Nup155 to promote INO80 mRNA nuclear export.

ETHNOPHARMACOLOGICAL RELEVANCE: Siwu tablet (SWT), derived from a traditional Chinese medicinal formula named Siwu decoction, is widely used for blood deficiency syndrome. Siwu decoction and its derived formulas have been proven to improve renal anemia and prevent senescence. Whether SWT prevents glomerular podocyte senescence and the underlying molecular mechanism remains unknow. AIM OF THE STUDY: To elucidate the protective effect and possible mechanism of SWT on glomerular podocyte senescence. MATERIAL AND METHODS: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to characterize components of SWT. Male Sprague-Dawley rats were given 10% fructose drinking water for 16 weeks. SWT (810 and 1620 mg/kg) was administered orally for the last 8 weeks. The assays of senescence-associated beta-galactosidase (SA-ß-gal) staining, immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot as well as enzyme linked immunosorbent assay were performed to evaluate rat glomerular podocyte senescence. The mRNA and protein levels of nucleoporin 155 (Nup155) and inositol requiring mutant 80 (INO80) in rat glomeruli were detected by qRT-PCR, Western blot and immunofluorescence. Foot processes and nuclear pore complexes (NPCs) of rat glomerular podocytes were visualized by transmission electron microscopy. RESULTS: One hundred and fifty-nine components were preliminarily identified in SWT. The results of animal experiments showed that SWT decreased the activity of SA-ß-gal, protein levels of p16, p21, p53 and phosphorylated histone H2AX (γ-H2AX), and mRNA levels of interleukin-1ß (IL-1ß), IL-6 and tumor necrosis factor-α (TNF-α) in glomeruli of high fructose-fed rats. As expected, SWT increased renal cortex erythropoietin mRNA expression and serum erythropoietin concentration in this animal model. SWT reduced urine albumin-to-creatinine ratio and serum levels of uric acid, creatinine and blood urea nitrogen, and recovered glomerular structure injury in high fructose-fed rats. It up-regulated mRNA and protein levels of Nup155 and the number of podocyte NPCs, and subsequently reinforced mRNA nuclear export and protein expression of INO80 in rat glomeruli under high fructose stimulation. CONCLUSIONS: SWT ameliorates glomerular podocyte senescence in high fructose-fed rats possibly by increasing Nup155 to promote INO80 mRNA nuclear export.

Global property rights and land use efficiency.

The study investigates the global impact of land property rights on land use efficiency (LUE), as measured by the key indicator for United Nations Sustainable Development Goal 11.3.1, namely Land Consumption Rate to Population Growth Rate. By utilizing human-land change data from 165 countries spanning the period between 1990 and 2020, we have developed a fixed effects model and employed legal origins as an instrumental variable to examine the influence of land property rights security on LUE. Our findings demonstrate that the security of land property rights significantly influences LUE, with common law countries exhibiting higher levels of LUE compared to civil law countries while controlling for other variables. Stability in property rights encourages long-term investments in infrastructure and sustainable land management practices, thereby enhancing land productivity and mitigating urban sprawl. Furthermore, safeguarding property rights limits governments' power to expropriate lands, facilitating rational and efficient land transactions that contribute towards achieving Sustainable Development Goals.

Intracellular C5aR1 inhibits ferroptosis in glioblastoma through METTL3-dependent m6A methylation of GPX4.

Glioblastoma (GBM) is the most common primary intracranial malignant tumor. Recent literature suggests that induction of programmed death has become a mainstream cancer treatment strategy, with ferroptosis being the most widely studied mode. Complement C5a receptor 1 (C5aR1) is associated with both tumorigenesis and tumor-related immunity. However, knowledge regarding the role of C5aR1 in GBM progression is limited. In the present study, we observed significant upregulation of C5aR1 in glioma tissue. In addition, C5aR1 expression was found to be closely associated with patient prognosis and survival. Subsequent experimental verification demonstrated that C5aR1 promoted the progression of GBM mainly by suppressing ferroptosis induction, inhibiting the accumulation of lipid peroxides, and stabilizing the expression of the core antiferroptotic factor glutathione peroxidase 4 (GPX4). Aberrant N6-methyladenosine (m6A) modification of GPX4 mRNA contributes significantly to epigenetic tumorigenesis, and here, we report that selective methyltransferase-like 3 (METTL3)-dependent m6A methylation of GPX4 plays a key role in C5AR1 knockdown-induced ferroptosis induction. Mechanistically, ERK1/2 signaling pathway activation increases the METTL3 protein abundance in GBM cells. This activation then increases the stability of METTL3-mediated m6A modifications on GPX4, enabling it to fulfill its transcriptional function. More importantly, in an intracranial xenograft mouse model, PMX205, a C5aR1 inhibitor, promoted alterations in ferroptosis in GBM cells and inhibited GBM progression. In conclusion, our findings suggest that C5aR1 inhibits ferroptosis in GBM cells and promotes MettL3-dependent GPX4 expression through ERK1/2, thereby promoting glioma progression. Our study reveals a novel mechanism by which the intracellular complement receptor C5aR1 suppresses ferroptosis induction and promotes GBM progression. These findings may facilitate the identification of a potential therapeutic target for glioma.

Rnf111 has a pivotal role in regulating development of definitive hematopoietic stem and progenitor cells through the Smad2/3-Gcsfr/NO axis in zebrafish.

The ubiquitination or SUMOylation of hematopoietic related factors plays pivotal roles in hematopoiesis. RNF111, known as a ubiquitin ligase (Ubl), is a newly discovered SUMO-targeted ubiquitin ligase (STUbl) involved in multiple signaling pathways mediated by TGF-ß family members. However, its role in hematopoiesis remains unclear. Herein, a heritable Rnf111 mutant zebrafish line was generated by CRISPR/Cas9-mediated genome editing. Impaired hematopoietic stem and progenitor cells (HSPC) of definitive hematopoiesis was found in Rnf111 deficient mutants. Ablation of Rnf111 resulted in decreased phosphorylation of Smad2/3 in HSPC. Definitive endoderm 2 inducer (IDE2), which specifically activates TGF-ß signaling and downstream Smad2 phosphorylation, can restore the definitive hematopoiesis in Rnf111-deficient embryos. Further molecular mechanism studies revealed that Gcsfr/NO signaling was an important target pathway of Smad2/3 involved in Rnf111-mediated HSPC development. In conclusion, our study demonstrated that Rnf111 contributes to the development of HSPC by maintaining Smad2/3 phosphorylation and the Gcsfr/NO signaling pathway activation. Keywords: Rnf111, Ubiquitin ligase (UbL), HSPC, Smad2/3, Gcsfr/NO.

Preparation and characterization ofcarvacrol/soybean protein isolate composite film with efficient antimicrobial and antioxidant activities and its application in grape preservation.

There is an urgent need for a simple and effective method to enhance the freshness of fruits during transportation. In this study, we developed a composite antibacterial film (CAR film) using carvacrol and soy protein isolate (SPI). The mechanical properties, hydrophobicity, antibacterial activity, and antioxidant capacity of the film were characterized. The results demonstrated that, compared to the soy protein isolate film, the film with 2.5 % carvacrol content exhibited superior mechanical properties (tear strength decreased by approximately 37 %, elongation at break increased by about 108 %), hydrophobicity (water vapor permeability decreased by 38 %), antibacterial activity (inhibition zone diameters against E. coli and S. aureus were 14.21 mm and 11.83 mm, respectively), antioxidant capacity (increased by 5 to 6 times), and biocompatibility (cell survival rate exceeded 90 %). Grape preservation experiments further confirmed that the CAR film effectively prolongs shelf life. Therefore, CAR film is a promising packaging material for fruit preservation.

Cognitive impairment in adolescent and adult-onset psychosis: a comparative study.

BACKGROUND: Cognitive impairment presents in both adolescent-onset(ado-OP) and adult-onset psychosis(adu-OP). Age and neurodevelopmental factors likely contribute to cognitive differences. This study aimed to characterize cognitive functions in ado-OP compared to adu-OP in a clinical population with drug-naive first-episode psychosis(FEP). METHODS: A total of 788 drug-naive patients with FEP and 774 sex- and age-matched healthy controls(HCs) were included. Participants were divided into four groups by whether they were under or over 21 years of age: adolescent-onset FEP(ado-FEP, n = 380), adult-onset FEP(adu-FEP, n = 408), adolescent HC(ado-HC, n = 334), and adult HC(adu-HC, n = 440). Comprehensive cognitive assessments were performed using the MATRICS Cognitive Consensus Battery(MCCB), covers six cognitive domains: speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning, and problem-solving. Data analyses were conducted using correlation analyses and binary logistic regression. RESULTS: The patterns of cognitive domain differences between ado-FEP and adu-FEP were found to be similar to those between ado-HC and adu-HC, whereas cognitive impairments appeared to be more pronounced in patients with adu-OP than ado-OP. The mazes subtest had the maximum effect size(ES) in the FEP(ES = 0.37) and HC(ES = 0.30) groups when comparing the adolescent and adult groups. Cognitive subtests were mostly significantly correlated with negative symptoms, especially for adolescents with FEP, in which all the subtests were significantly correlated with negative symptoms in the ado-FEP group. Better performance in the domains of spatial cognition and problem-solving abilities was more likely in the ado-FEP group than in the adu-FEP group. CONCLUSIONS: These findings suggest cognitive differences between adolescents and adults but similar patterns of affected domains in HCs and patients with FEP. Therefore, the development of targeted cognitive interventions tailored to the specific needs of different age groups appears warranted.

Identification of isoquinoline alkaloids from Corydalis mucronifera and their acetylcholinesterase inhibitory effects.

Four new spirobenzylisoquinoline mucroniferanines N - Q (1-4) and a rare chlorinated isoquinoline mucroniferanine R (5) were isolated from Corydalis mucronifera Maxim. Their structures were elucidated based on extensive spectroscopic data analysis of HRESIMS, 1D and 2D NMR, and their absolute configurations were confirmed by ECD data. The isolated compounds were evaluated for acetylcholinesterase (AChE) inhibitory activities. Mucroniferanine R showed significant activities with IC50 values of 0.78 µM compared to galanthamine (1.34 µM). The AChE inhibitory activity was further supported by the molecular docking analysis that exhibited the accommodation of mucroniferanine R in the active site of human AChE.

Palmatine as a potent immunomodulator: Enhancing resistance to Micropterus salmoides rhabdovirus in largemouth bass through innate immune activation and viral suppression.

Micropterus salmoides rhabdovirus (MSRV) poses a significant threat to aquaculture, causing substantial economic losses. In this study, we evaluated the antiviral efficacy and immunomodulatory potential of palmatine, a plant-derived monomer, against MSRV infection in largemouth bass. Our results demonstrated that palmatine significantly inhibited MSRV replication, with a reduction in viral nucleoprotein expression by 85 % at a safe concentration. Additionally, palmatine pre-treatment of EPC cells enhanced their antiviral capacity, with a maximum inhibition rate of 82 % following 24 h pre-incubation. Palmatine also effectively reduced MSRV-induced cytopathic effects, protecting cellular integrity and maintaining mitochondrial membrane potential. In vivo studies revealed that palmatine immersion at 80 mg/L was non-toxic and significantly suppressed MSRV replication in largemouth bass, increasing survival rates by 53 % over 15 d. Furthermore, palmatine pre-treatment enhanced the fish's resistance to MSRV, with a 78 % inhibition rate of viral replication and a 46 % increase in survival rate. Mechanistically, palmatine activated key immune genes, including IRF3, IRF7, and IFN, indicating its role in boosting innate immune responses. The compound also reduced horizontal transmission of MSRV in a cohabitation model, decreasing viral spread by up to 78 % over nine days. These findings highlight palmatine's potential as a small-molecule immunomodulator in aquaculture, offering a sustainable approach to disease management and enhancing fish health and welfare. Integrating palmatine into fish diets as an immunostimulant could provide a continuous, proactive defense against viral outbreaks, promoting more resilient and sustainable aquaculture practices.

Reproductive Disorders in Donkeys: Current Evidence and Update.

Reproductive disorders in donkeys present a significant challenge to their health and welfare, impacting their roles in agriculture, conservation, and companionship. With the development of large-scale donkey farming in recent years, reproductive disorders have become a limiting factor for the expansion of the donkey population. In general, donkeys suffer from a similar array of diseases like horses, but little is known about the specificities of donkey reproductive disorders. This review synthesizes current knowledge on the pathogenesis, distribution, presentation, diagnosis, treatment, and prognosis of a diverse array of reproductive disorders affecting donkeys. There are similar infectious and non-infectious causes for infertility and pregnancy loss in jennies compared with mares, but a difference in disease susceptibility does exist, which may be attributed to genetic influence, pathogen specificity, the environment, and reproductive management practices. Diagnostic and treatment plans need to be tailored towards the particularities of donkey reproductive disorders to increase donkey populations and to enhance the standard of care for this species. Enhancing reproductive health in donkeys not only ensures their sustainable use but also promotes their welfare and longevity in diverse human-animal interactions.

Identification and expression patterns of voltage-gated sodium channel genes with intron retentions in different strains of Bactrocera dorsalis.

Pyrethroid are the primary insecticides used for controlling of Bactricera dorsalis, a highly destructive and invasive fruit pest. Field populations have developed serious resistance, especially to ß-cypermethrin. While mutations in the voltage-gated sodium channel (Vgsc) are a common mechanism of pyrethroid resistance, variations in BdVgsc associated with ß-cypermethrin resistance remain unclear. Here, we reported the resistance levels of five field populations from China, with resistance ratio ranging from 1.54 to 21.34-fold. Cloning the full length of BdVgsc revealed no specific or known amino acid mutations between the most resistant population and the susceptible strain. However, three types of partial intron retention (IRE4-5, IRE19-f and IREL-24) were identified in BdVgsc transcripts, with these intron retentions containing stop codons. The expression of IRE4-5 transcripts and total BdVgsc showed different trends across developmental stages and tissues. Exposure to ß-cypermethrin led to increased expression of IRE4-5. Comparison of genomic and transcriptional sequences reveled that IRE4-5 transcripts had two types (IRE4-5.5 T and IRE4-5.6 T) caused by genomic variations. Both field and congenic strains indicated that homozygotes for IRE4-5.5 T had lower IRE4-5 transcript levels than homozygotes for IRE4-5.6 T. However, congenic and field strains exhibited inconsistent results about the association of expression levels of IRE4-5 transcripts with sensitivity to ß-cypermethrin. In summary, this study is the first to identify intron retention transcripts in the Vgsc gene from B. dorsalis and to examine their expression patterns across different developmental stages, tissues, and strains with varying sensitivities to ß-cypermethrin. The potential role of the intron retentions of BdVgsc in insecticide toxicity is also discussed.

Dual role of triglyceride structures facilitates anti-tumor drug delivery: Both as a self-assembling module and a responsive module.

Small molecule prodrugs self-assembled nano-delivery systems with tumor responsive linkages are emerging as an effective platform. However, the heterogeneity of tumor microenvironment may limit the anti-tumor effect of prodrug nanomedicines with a single response module. Here, we chose disulfide bond as the response module and branched chain alcohol as the self-assembly modification module to construct a single-responsive prodrug. We also constructed a double-responsive paclitaxel prodrug combining triglyceride and disulfide bond, taking into account of the highly expressed lipase and glutathione levels in tumor cells. The results showed that the anti-tumor effect of single-responsive branched chain alcohol modified prodrug nanoparticles was inferior to triglyceride prodrug nanoparticles with dual response modules. The triglyceride structure can not only serve as a self-assembly modification module, but also serve as a response module for intelligent drug release in tumor. Such dual roles will facilitate the efficient delivery of small molecule self-assembled prodrugs to tumor sites.

Discovery of SILA-123 as a Highly Potent FLT3 Inhibitor for the Treatment of Acute Myeloid Leukemia with Various FLT3 Mutations.

The FLT3-ITD (internal tandem duplication) mutant has been a promising target for acute myeloid leukemia (AML) drug discovery but is now facing the challenge of resistance due to point mutations. Herein, we have discovered a type II FLT3 inhibitor, SILA-123. This inhibitor has shown highly potent inhibitory effects against FLT3-WT (IC50 = 2.1 nM) and FLT3-ITD (IC50 = 1.0 nM), tumor cells with the FLT3-ITD mutant such as MOLM-13 (IC50 = 0.98 nM) and MV4-11 (IC50 = 0.19 nM), as well as BaF3 cells associated with the FLT3-ITD mutant and point mutations like BaF3-FLT3-ITD-G697R (IC50 = 3.0 nM). Moreover, SILA-123 exhibited promising kinome selectivity against 310 kinases (S score (10) = 0.06). In in vivo studies, SILA-123 significantly suppressed the tumor growth in MV4-11 (50 mg/kg/d, TGI = 87.3%) and BaF3-FLT3-ITD-G697R (50 mg/kg/d, TGI = 60.0%) cell-inoculated allograft models. Our data suggested that SILA-123 might be a promising drug candidate for FLT3-ITD-positive AML.

Band alignment of one-dimensional transition-metal dichalcogenide heterotubes.

One-dimensional (1D) van der Waals (vdW) heterotubes, where different kinds of 1D nanotubes coaxially nest inside each other, offer a flexible platform for promising applications. The various properties of these 1D heterotubes depend on their diameter. Here, we present a systematic theoretical investigation into the structural and electronic properties of two kinds of 1D transition-metal dichalcogenide (TMD) heterotubes. We demonstrate that the thermodynamic stability of 1D heterotubes is determined by their interlayer distance. Additionally, we establish that the band alignment transition changes from type I to type II in 1D TMD heterotubes. We identify two distinct transition mechanisms, originating from the exchange of either the valence band maximum or the conduction band minimum. According to an electrostatic model, the band alignment transition is attributed to the interlayer electric field effect, which depends on the heterotube diameter. The findings in this work provide valuable physical insights into the band alignment transition in 1D heterotubes and are instrumental for their potential applications in nanotechnology.

Performance and microbial mechanism in sulfide-driven autotrophic denitrification by different inoculation sources in face of various sulfide and sulfate stress.

To develop a reliable sulfide (S2-) autotrophic denitrification (SAD) process under S2- and SO42- salinity stresses, the biofilm performance and microbial mechanisms were comparatively studied using different inocula of activated sludge (AS) and intertidal sediment (IS). Biofilm IS enriched more denitrification genes (0.34 %) and S2- oxidation genes (0.29 %) than those with AS. Higher denitrification performance was obtained under S2- (100 mg/L) and SO42- (5-15 g/L Na2SO4) stresses, but no significantly differences were observed under levels of 0-200 mg/L S2- and 30 g/L Na2SO4. Notably, biofilm samples in SAD systems with IS still had more S2- oxidation genes at high S2- levels of 100-200 mg/L and Na2SO4 level of 30 g/L. The key functional genus Thiobacillus accumulated well at 30 g/L Na2SO4, but was strongly inhibited at 200 mg/L S2-. The findings were advantage to SAD application under sulfide and salinity stresses.

Efficacy and safety of ramucirumab in gastric or gastroesophageal cancer: A systematic review and meta-analysis.

BACKGROUND: Ramucirumab is considered a potential treatment for gastric or gastroesophageal cancer; however, its safety has not been evaluated. This meta-analysis aimed to evaluate the efficacy and safety of ramucirumab for treating gastric or gastroesophageal cancer. METHODS: The databases of PubMed, Embase, and Cochrane Library were searched through October 2023. The search focused on randomized controlled trials (RCTs) comparing ramucirumab (with or without chemotherapy) to a placebo (with or without chemotherapy) in patients with gastric or gastroesophageal cancer. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were pooled. RESULTS: Seven RCTs with a total of 2613 patients were included. Compared with placebo (with or without chemotherapy), ramucirumab (with or without chemotherapy) significantly improved OS (HR: 0.90, 95% CI: 0.82-0.99, p = 0.030), PFS (HR: 0.74, 95% CI: 0.60-0.90, p = 0.003), ORR (OR: 1.39, 95% CI: 1.15-1.67, p < 0.001), and DCR (OR: 1.91, 95% CI: 1.38-2.63, p < 0.001). However, ramucirumab (with or without chemotherapy) also increased the incidence of decreased appetite (OR: 1.29, 95% CI: 1.09-1.53, p = 0.004), diarrhea (OR: 1.39, 95% CI: 1.01-1.91, p = 0.05), hypertension (OR: 3.13, 95% CI: 2.03-4.83, p < 0.00001), and bleeding or hemorrhage (OR: 2.34, 95% CI: 1.93-2.85, p < 0.00001). CONCLUSIONS: Ramucirumab (with or without chemotherapy) can improve OS, PFS, ORR and DCR in patients with gastric or gastroesophageal cancer. However, it may also increase the incidence of specific AEs.

How did the floating Ulva prolifera develop into the world's largest green tide?

It has been 16 years since the world's largest Ulva bloom appeared in the Yellow Sea. However, it remains unclear how the floating Ulva prolifera developed into the immense green tide within two months especially considering that source control measures have been conducted since 2019. In this study, we investigated the growth mechanism of the floating population by examining the production and regeneration of U. prolifera explants and constructing a growth model. The results showed that U. prolifera explants exhibited rapid regeneration mainly through branches at 15, 20 and 25 °C. Algivore feeding and sporulation (at 20-25 °C) contributed to mass production of explants. The growth of floating population could be attributed to the coupling of mass production and rapid regeneration of explants through multiple cycles, which accounted for the outbreak of floating green tide. This finding presented a novel population growth model to elucidate macroalgal bloom occurrences.