Inetetamab combined with tegafur as second-line treatment for human epidermal growth factor receptor-2-positive gastric cancer: A case report.

BACKGROUND: Human epidermal growth factor receptor-2 (HER-2) plays a vital role in tumor cell proliferation and metastasis. However, the prognosis of HER2-positive gastric cancer is poor. Inetetamab, a novel anti-HER2 targeting drug independently developed in China, exhibits more potent antibody-dependent cell-mediated cytotoxicity than trastuzumab, which is administered as the first-line treatment for HER2-positive gastric cancer in combination with chemotherapy. In this case, the efficacy and safety of inetetamab combined with tegafur was investigated as a second-line treatment for HER2-positive gastric cancer. CASE SUMMARY: A 52-year-old male patient with HER2-positive gastric cancer presented with abdominal distension, poor appetite, and fatigue two years after receiving six cycles of oxaliplatin combined with tegafur as first-line treatment after surgery, followed by tegafur monotherapy for six months. The patient was diagnosed with postoperative recurrence of gastric adenocarcinoma. He received 17 cycles of a combination of inetetamab, an innovative domestically developed anti-HER2 monoclonal antibody, and tegafur chemotherapy as the second-line treatment (inetetamab 200 mg on day 1, every 3 wk combined with tegafur twice daily on days 1-14, every 3 wk). Evaluation of the efficacy of the second-line treatment revealed that the patient achieved a stable condition and progression-free survival of 17 months. He tolerated the treatment well without exhibiting any grade 3-4 adverse events. CONCLUSION: Inetetamab combined with chemotherapy for the treatment of metastatic HER2-positive gastric cancer demonstrates significant survival benefits and acceptable safety.

MicroRNA397 promotes rice flowering by regulating the photorespiration pathway.

The precise timing of flowering plays a pivotal role in ensuring successful plant reproduction and seed production. This process is intricately governed by complex genetic networks that integrate internal and external signals. This study delved into the regulatory function of microRNA397 (miR397) and its target gene LACCASE-15 (OsLAC15) in modulating flowering traits in rice (Oryza sativa). Overexpression of miR397 led to earlier heading dates, decreased number of leaves on the main stem, and accelerated differentiation of the spikelet meristem. Conversely, overexpression of OsLAC15 resulted in delayed flowering and prolonged vegetative growth. Through biochemical and physiological assays, we uncovered that miR397-OsLAC15 had a profound impact on carbohydrate accumulation and photosynthetic assimilation, consequently enhancing the photosynthetic intensity in miR397-overexpressing rice plants. Notably, we identified that OsLAC15 is at least partially localized within the peroxisome organelle, where it regulates the photorespiration pathway. Moreover, we observed that a high CO2 concentration could rescue the late flowering phenotype in OsLAC15-overexpressing plants. These findings shed valuable insights into the regulatory mechanisms of miR397-OsLAC15 in rice flowering and provided potential strategies for developing crop varieties with early flowering and high-yield traits through genetic breeding.

Hammered silver appearance of the corneal endothelium in Fuchs uveitis syndrome: A case report.

BACKGROUND: Hammered silver appearance of the corneal endothelium is considered a characteristic change in iridocorneal-endothelial syndrome. Herein we report an interesting case of hammered silver appearance of the corneal endothelium in Fuchs uveitis syndrome (FUS). CASE SUMMARY: A 49-year-old man with progressive vision loss in the right eye for one year was admitted to our hospital. The clinical manifestations of the patient's right eye were mild conjunctival hyperemia, scattered stellate keratic precipitates on the corneal endothelium, normal depth anterior chamber, 2+ cellular reaction in the aqueous humor, diffuse iris depigmentation, absence of synechia, Koeppe nodules, opalescent lens, and vitreous opacity. FUS and a complicated cataract were diagnosed based on the typical clinical manifestations. The corneal endothelial changes were recorded in detail by slit-lamp examination, specular microscopy, and in vivo confocal microscopy before cataract extraction, revealing a hammered silver appearance of the corneal endothelium in the affected eye, a wide-band dark area, as well as irregular corneal endothelial protuberances and dark bodies of various sizes. Subsequently, the patient underwent phacoemulsification combined with intraocular lens implantation, and his postoperative visual acuity recovered to 1.0. CONCLUSION: Hammered silver appearance of the corneal endothelium in FUS, which is considered a more serious manifestation of endothelial damage, is rare and may be caused by many irregular protrusions in the corneal endothelium.

Short-Chain Fatty Acids Ameliorate Depressive-like Behaviors of High Fructose-Fed Mice by Rescuing Hippocampal Neurogenesis Decline and Blood-Brain Barrier Damage.

Excessive fructose intake is associated with the increased risk of mental illness, such as depression, but the underlying mechanisms are poorly understood. Our previous study found that high fructose diet (FruD)-fed mice exhibited neuroinflammation, hippocampal neurogenesis decline and blood-brain barrier (BBB) damage, accompanied by the reduction of gut microbiome-derived short-chain fatty acids (SCFAs). Here, we found that chronic stress aggravated these pathological changes and promoted the development of depressive-like behaviors in FruD mice. In detail, the decreased number of newborn neurons, mature neurons and neural stem cells (NSCs) in the hippocampus of FruD mice was worsened by chronic stress. Furthermore, chronic stress exacerbated the damage of BBB integrity with the decreased expression of zonula occludens-1 (ZO-1), claudin-5 and occludin in brain vasculature, overactivated microglia and increased neuroinflammation in FruD mice. These results suggest that high fructose intake combined with chronic stress leads to cumulative negative effects that promote the development of depressive-like behaviors in mice. Of note, SCFAs could rescue hippocampal neurogenesis decline, improve BBB damage and suppress microglia activation and neuroinflammation, thereby ameliorate depressive-like behaviors of FruD mice exposed to chronic stress. These results could be used to develop dietary interventions to prevent depression.

Bidirectional Brain-gut-microbiota Axis in increased intestinal permeability induced by central nervous system injury.

Central nervous system injuries may lead to the disorders of the hypothalamic-pituitary-adrenal axis, autonomic nervous system, and enteric nervous system. These effects then cause the changes in the intestinal microenvironment, such as a disordered intestinal immune system as well as alterations of intestinal bacteria. Ultimately, this leads to an increase in intestinal permeability. Inflammatory factors produced by the interactions between intestinal neurons and immune cells as well as the secretions and metabolites of intestinal flora can then migrate through the intestinal barrier, which will aggravate any peripheral inflammation and the central nervous system injury. The brain-gut-microbiota axis is a complex system that plays a crucial role in the occurrence and development of central nervous system diseases. It may also increase the consequences of preventative treatment. In this context, here we have summarized the factors that can lead to the increased intestinal permeability and some of the possible outcomes.

A high-throughput and untargeted lipidomics approach reveals new mechanistic insight and the effects of salvianolic acid B on the metabolic profiles in coronary heart disease rats using ultra-performance liquid chromatography with mass spectrometry.

High-throughput lipidomics provides the possibility for the development of new therapeutic drugs. Accordingly, herein, we reveal the protective role of salvianolic acid B (Sal B) in rats with coronary heart disease (CHD) and propose a new mechanism for its action through a high-throughput and non-targeted lipidomics strategy. A CHD animal model was induced by consecutive high-fat diet feeding with vitamin D3 injection. At the end of the 8th week, the serum sample was analyzed to explore the metabolic biomarker and pathway changes using untargeted lipidomics based on ultra-performance liquid chromatography with mass spectrometry (UPLC/MS). In addition, blood and heart tissue samples were collected and processed for the detection of biochemical indicators and liver histological observation. After salvianolic acid B treatment, the levels of LDH, CK, CK-MB, MYO, CTn1, TG, TC, LDL-c, and Apo(b) were significantly lower than that in the model group, while the levels of HDL-c and Apo(a1) were significantly higher than that in the model group. Furthermore, the histological features of fibrosis and steatosis were also evidently relieved in the model group. A total of twenty-six potential biomarkers were identified to express the lipid metabolic turbulence in the CHD animal models, of which twenty-two were regulated by salvianolic acid B trending to the normal state, including TG(20:0/20:4/o-18:0), PC(20:4/18:1(9Z)), PC(18:3/20:2), PA(18:0/18:2), LysoPE(18:2/0:0), SM(d18:0/22:1), PE(22:6/0:0), LysoPE (20:4/0:0), sphinganine, Cer(d18:0/18:0), PS(14:0/14:1), PC (18:0/16:0), LysoPC(17:0), PE(22:2/20:1), PC(20:3/20:4), PE(20:4/P-16:0), PS(20:3/18:0), cholesterol sulfate, TG(15:0/22:6/18:1), prostaglandin E2, arachidonic acid and sphingosine-1-phosphate. According to the metabolite enrichment and pathway analyses, the pharmacological activity of salvianolic acid B on CHD is mainly involved in three vital metabolic pathways including glycerophospholipid metabolism, sphingolipid metabolism and arachidonic acid metabolism. Thus, based on the lipidomics-guided biochemical analysis of the lipid biomarkers and pathways, Sal B protects against CHD with good therapeutic effect by regulating glycerophospholipid metabolism, sphingolipid metabolism and arachidonic acid metabolism, inhibiting oxidative stress damage and lipid peroxidation.

Large-scale rewiring of innate immunity circuitry and microRNA regulation during initial rice blast infection.

Rice blast is a recurrent fungal disease, and resistance to fungal infection is a complex trait. Therefore, a comprehensive examination of rice transcriptome and its variation during fungal infection is necessary to understand the complex gene regulatory networks. In this study, adopting Next-Generation Sequencing we profiled the transcriptomes and microRNAomes of rice varieties, one susceptible and the other resistant to M. oryzae, at multiple time points during the fungal infection. Our results revealed a substantial variation in the plant transcriptome and microRNAome as well as change to rice innate immunity during fungal infection. A number of putative R gene candidates were identified from a perturbed rice transcriptome analysis. The expression of genes and non-coding RNA molecules changed in both fungal resistant and susceptible plants during M. oryzae invasion discovered distinct pathways triggered in the susceptible and resistant plants. In addition, a number of fungus genes in the susceptible and resistant plants were constantly expressed at different time points, suggesting that they were likely to be the potential AVR genes. Our results revealed large-scale rewiring of innate immunity circuitry and microRNA regulation during initial rice blast infection, which would help to develop more robust blast-resistant rice plants.

MiR397b regulates both lignin content and seed number in Arabidopsis via modulating a laccase involved in lignin biosynthesis.

Plant laccase (LAC) enzymes belong to the blue copper oxidase family and polymerize monolignols into lignin. Recent studies have established the involvement of microRNAs in this process; however, physiological functions and regulation of plant laccases remain poorly understood. Here, we show that a laccase gene, LAC4, regulated by a microRNA, miR397b, controls both lignin biosynthesis and seed yield in Arabidopsis. In transgenic plants, overexpression of miR397b (OXmiR397b) reduced lignin deposition. The secondary wall thickness of vessels and the fibres was reduced in the OXmiR397b line, and both syringyl and guaiacyl subunits are decreased, leading to weakening of vascular tissues. In contrast, overexpression of miR397b-resistant laccase mRNA results in an opposite phenotype. Plants overexpressing miR397b develop more than two inflorescence shoots and have an increased silique number and silique length, resulting in higher seed numbers. In addition, enlarged seeds and more seeds are formed in these miR397b overexpression plants. The study suggests that miR397-mediated development via regulating laccase genes might be a common mechanism in flowering plants and that the modulation of laccase by miR397 may be potential for engineering plant biomass production with less lignin.

Isolation, expression, and characterization of a hydroperoxide lyase gene from cucumber.

A full-length cDNA coding for hydroperoxide lyase (CsHPL) was isolated from cucumber fruits of No. 26 (Southern China type) and No.14-1 (Northern China type), which differed significantly in fruit flavor. The deduced amino acid sequences of CsHPL from both lines show the same and significant similarity to known plant HPLs and contain typical conserved domains of HPLs. The recombinant CsHPL was confirmed to have 9/13-HPL enzymatic activity. Gene expression levels of CsHPL were measured in different organs, especially in fruits of different development stages of both lines. The HPL activities of fruit were identified basing on the catalytic action of crude enzyme extracts incubating with 13-HPOD (13-hydroperoxy-(9Z,12E)-octadecadienoic acid) and 13-HPOD + 9-HPOD (9-hydroperoxy-(10E,12Z)-octadecadienoic acid), and volatile reaction products were analyzed by GC-MS (gas chromatography-mass spectrometry). CsHPL gene expression in No. 26 fruit occurred earlier than that of total HPL enzyme activity and 13-HPL enzyme activity, and that in No. 14-1 fruit was consistent with total HPL enzyme activity and 9-HPL enzyme activity. 13-HPL enzyme activities decreased significantly and the 9-HPL enzyme activities increased significantly with fruit ripening in both lines, which accounted for the higher content of C6 aldehydes at 0-6 day post-anthesis (dpa) and higher content of C9 aldehydes at 9-12 dpa.

Overexpression of microRNA OsmiR397 improves rice yield by increasing grain size and promoting panicle branching.

Increasing grain yields is a major focus of crop breeders around the world. Here we report that overexpression of the rice microRNA (miRNA) OsmiR397, which is naturally highly expressed in young panicles and grains, enlarges grain size and promotes panicle branching, leading to an increase in overall grain yield of up to 25% in a field trial. To our knowledge, no previous report has shown a positive regulatory role of miRNA in the control of plant seed size and grain yield. We determined that OsmiR397 increases grain yield by downregulating its target, OsLAC, whose product is a laccase-like protein that we found to be involved in the sensitivity of plants to brassinosteroids. As miR397 is highly conserved across different species, our results suggest that manipulating miR397 may be useful for increasing grain yield not only in rice but also in other cereal crops.

[Study on degradation of polycyclic aromatic hydrocarbons (PAHs) with different additional carbon sources in aged contaminated soil].

This study was conducted with different additional carbon sources (such as: glucose, DL-malic acid, citrate, urea and ammonium acetate) to elucidate the degradation of polycyclic aromatic hydrocarbons (PAHs) in aged contaminated soil under an indoor simulation experiment. The results showed that the quantity of CO2 emission in different additional carbon sources treatments was obviously much more than that of check treatment in the first week, and the quantity of CO2 emission in DL-malic acid treatment was the largest. The average CO2 production decreased in an order urea > glucose approximately citrate approximately DL-malic acid approximately ammonium acetate > check. Meanwhile, the amount of volatized PAHs in applied carbon sources treatments was significantly less than that in check treatment. The amount of three volatized PAHs decreased in an order phenanthrene > fluoranthene > benzo(b)fluoranthene. Compared with the check treatment, the average degradation rates of the three PAHs were significantly augmented in the supplied carbon sources treatments, in which rates of the three PAHs were much higher in DL-malic acid and urea treatments than those in other treatments. The largest proportion of residual was benzo(b)fluoranthene (from 72% to 81%) among three PAHs compounds, followed by fluoranthene (from 53% to 70% ) and phenanthrene (from 27% to 44%).

Sculpting the meristem: the roles of miRNAs in plant stem cells.

The whole structure of higher plants is generated dynamically throughout the life cycle by the activity of stem cell niches at the apex of shoot and root. Hormone molecules and many transcription factors cooperate to balance the stem cell maintenance and differentiation. It is becoming increasingly clear that microRNA (miRNA) molecules are also participants in these processes. Here, we highlight the advances that have been made in regarding the roles of miRNAs in plant stem cell control. These advances provide a framework for our understanding of how signals are integrated to specify and position the stem cell niches in plants.

Expression analysis of phytohormone-regulated microRNAs in rice, implying their regulation roles in plant hormone signaling.

Twenty-two conserved miRNAs were chosen to investigate the expression pattern in response to phytohormone treatments, in which the effects of five classic plant hormone stresses were surveyed in Oryza sativa. The results showed that 11 miRNAs were found to be dysregulated by one or more phytohormone treatments. The target genes of these miRNAs were validated in vivo and their expression profiling were revealed. We also analyzed the promoter regions of the 22 conserved miRNAs for phytohormone-responsive elements and the existence of the elements provided further evidences supporting our results. These findings enable us to further investigate the role of miRNAs in phytohormone signaling.

[Characters of soil-vegetable transfer and accumulation of polycyclic aromatic hydrocarbons].

The transfer and accumulation of polycyclic aromatic hydrocarbons (PAHs) from aged contaminated agricultural soil to vegetable was studied. The results show that the positive correlation between the PAHs concentrations in tested vegetables and those in the corresponding soils is present. The PAHs concentrations in contaminated soils are significantly (p < 0.05) higher than that in roots, stems and leaves of vegetables, and the PAHs concentrations in roots are also significantly (p < 0.05) higher than that in stems and leaves. The ratio of sum of low molecular weight PAHs to total PAHs concentrations (Sigma LMW-PAHs/Sigma PAHs) in polluted vegetable roots is higher than that in corresponding soils (p < 0.05), and LMW-PAHs are more easily accumulated in vegetable roots than HMW-PAHs (high molecular weitht PAHs). The distinction of PAHs concentrations among the four selected leafy vegetables in the same tested soils does not achieve the significant level.