Hippo cooperates with p53 to maintain foregut homeostasis and suppress the malignant transformation of foregut basal progenitor cells.

Basal progenitor cells serve as a stem cell pool to maintain the homeostasis of the epithelium of the foregut, including the esophagus and the forestomach. Aberrant genetic regulation in these cells can lead to carcinogenesis, such as squamous cell carcinoma (SCC). However, the underlying molecular mechanisms regulating the function of basal progenitor cells remain largely unknown. Here, we use mouse models to reveal that Hippo signaling is required for maintaining the homeostasis of the foregut epithelium and cooperates with p53 to repress the initiation of foregut SCC. Deletion of Mst1/2 in mice leads to epithelial overgrowth in both the esophagus and forestomach. Further molecular studies find that Mst1/2-deficiency promotes epithelial growth by enhancing basal cell proliferation in a Yes-associated protein (Yap)-dependent manner. Moreover, Mst1/2 deficiency accelerates the onset of foregut SCC in a carcinogen-induced foregut SCC mouse model, depending on Yap. Significantly, a combined deletion of Mst1/2 and p53 in basal progenitor cells sufficiently drives the initiation of foregut SCC. Therefore, our studies shed light on the collaborative role of Hippo signaling and p53 in maintaining squamous epithelial homeostasis while suppressing malignant transformation of basal stem cells within the foregut.

The development and stem cells of the esophagus.

The esophagus is derived from the anterior portion of the foregut endoderm, which also gives rise to the respiratory system. As it develops, the esophageal lining is transformed from a simple columnar epithelium into a stratified squamous cell layer, accompanied by the replacement of unspecified mesenchyme with layers of muscle cells. Studies in animal models have provided significant insights into the roles of various signaling pathways in esophageal development. More recent studies using human pluripotent stem cells (hPSCs) further demonstrate that some of these signaling pathways are conserved in human esophageal development. In addition, a combination of mouse genetics and hPSC differentiation approaches have uncovered new players that control esophageal morphogenesis. In this Review, we summarize these new findings and discuss how the esophagus is established and matures throughout different stages, including its initial specification, respiratory-esophageal separation, epithelial morphogenesis and maintenance. We also discuss esophageal muscular development and enteric nervous system innervation, which are essential for esophageal structure and function.

High-nitrogen fertilizer alleviated adverse effects of drought stress on the growth and photosynthetic characteristics of Hosta 'Guacamole'.

BACKGROUND: Several plants are facing drought stress due to climate change in recent years. In this study, we aimed to explore the effect of varying watering frequency on the growth and photosynthetic characteristics of Hosta 'Guacamole'. Moreover, we investigated the effect of high-nitrogen and -potassium fertilizers on alleviating the impacts of drought stress on the morphology, photosynthetic characteristics, chlorophyll fluorescence, fast chlorophyll a fluorescence transient, JIP-test parameters, and enzymatic and non-enzymatic scavenging system for reactive oxygen species (ROS) in this species. RESULTS: Leaf senescence, decreased chlorophyll contents, limited leaf area, and reduced photosynthetic characteristics and oxygen-evolving complex (OEC) activity were observed in Hosta 'Guacamole' under drought stress. However, high-nitrogen fertilizer (30-10-10) could efficiently alleviate and prevent the adverse effects of drought stress. High-nitrogen fertilizer significantly increased chlorophyll contents, which was higher by 106% than drought stress. Additionally, high-nitrogen fertilizer significantly improved net photosynthetic rate and water use efficiency, which were higher by 467% and 2900% than those under drought stress. It attributes that high-nitrogen fertilizer could reduce transpiration rate of leaf cells and stomatal opening size in drought stress. On the other hand, high-nitrogen fertilizer enhanced actual photochemical efficiency of PS II and photochemical quenching coefficient, and actual photochemical efficiency of PS II significantly higher by 177% than that under drought stress. Furthermore, high-nitrogen fertilizer significantly activated OEC and ascorbate peroxidase activities, and enhanced the performance of photosystem II and photosynthetic capacity compared with high-potassium fertilizers (15-10-30). CONCLUSIONS: High-nitrogen fertilizer (30-10-10) could efficiently alleviate the adverse effects of drought stress in Hosta 'Guacamole' via enhancing OEC activity and photosynthetic performance and stimulating enzymatic ROS scavenging system.

Efficacy and safety of different chemotherapy regimens concurrent with radiotherapy in the treatment of locally advanced cervical cancer.

BACKGROUND: Evaluate the efficacy and safety of different chemotherapy regimens concurrent with radiotherapy in treating locally advanced cervical cancer (LACC). METHODS: Retrospective data was collected from LACC patients who were treated at our institution. These patients were categorized into three groups: the single-agent cisplatin (DDP) chemoradiotherapy group, the paclitaxel plus cisplatin (TP) chemoradiotherapy group, and the nanoparticle albumin-bound (nab-) paclitaxel combined with cisplatin (nPP) chemoradiotherapy group. The primary endpoints were overall survival (OS) and progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR) and incidence of adverse events (AEs). RESULTS: A total of 124 patients were enrolled (32 in the DDP group, 41 in the TP group, and 51 in the nPP group). There were differences in OS (P = 0.041, HR 0.527, 95% CI 0.314-0.884) and PFS (P = 0.003, HR 0.517, 95% CI 0.343-0.779) between the three groups. Notably, the 2-year OS rate was significantly higher in the nPP group compared to the DDP group (92.2% vs. 85.4%, P = 0.012). The 2-year PFS rates showed a marked increase in the TP group (78.0% vs. 59.4%, P = 0.048) and the nPP group (88.2% vs. 59.4%, P = 0.001) relative to the DPP group, with multiple comparisons indicating that the 2-year PFS rate was significantly superior in the nPP group versus the DDP group (88.2% vs. 59.4%, P = 0.001). Moreover, the ORR was also significantly higher in the nPP group than in the DDP group (P = 0.013); and no statistically significant differences were found in the incidence of AEs among the groups (P > 0.05). CONCLUSIONS: In LACC treatment, the two cisplatin-based doublet chemotherapy regimens are associated with better outcomes, with the nab-paclitaxel plus cisplatin regimen showing better efficacy than the paclitaxel plus cisplatin regimen. Furthermore, the AEs associated with these regimens were deemed tolerable. These findings could provide a reference for the clinical treatment of LACC. However, further prospective studies are needed to verify it.

Efficacy of nimotuzumab in combination with immunotherapy for a young recurrent cervical cancer patient: a case report and literature review.

Cervical cancer is one of the most common malignant tumors in women, and more than one-third of the patients have already developed to a locally advanced stage at initial diagnosis. After standard concurrent chemoradiotherapy, recurrence still occurs in 29-38% of patients with locally advanced cervical cancer (LACC), and the 5-year survival rate of patients with recurrence is only 3.8-13.0%, resulting in a poor prognosis and limited therapeutic choices. Currently, the recommended first-line systemic treatment for recurrent metastatic cervical cancer involves cisplatin or carboplatin in combination with paclitaxel-based chemotherapy, supplemented with the antivascular agent bevacizumab and the immune checkpoint inhibitor pembrolizumab. The use of these drugs, however, is limited due to side effects such as myelosuppression, gastrointestinal perforation, and bleeding, so new treatment modalities need to be explored. Anti-EGFR (epithelial growth factor receptor, anti-surface growth factor receptor antibody) targeted drugs have been demonstrated to have a significant radiosensitizing effect on synchronous chemoradiotherapy in LACC and are now considered to have potential for the treatment of recurrent cervical cancer. We represented a LACC patient who relapsed 6 months after concurrent chemoradiotherapy. The patient received six cycles of nimotuzumab combined with camrelizumab, and the efficacy was evaluated to be partial remission after two or four cycles of treatment, with progression-free survival up to 9 months, without significant side effects. Until March 2024, the patient was still undergoing treatment. Promising efficacy and tolerable side effects of nimotuzumab in combination with camrelizumab were observed in this case.

BMP Signaling in Development, Stem Cells, and Diseases of the Gastrointestinal Tract.

The bone morphogenetic protein (BMP) pathway is essential for the morphogenesis of multiple organs in the digestive system. Abnormal BMP signaling has also been associated with disease initiation and progression in the gastrointestinal (GI) tract and associated organs. Recent studies using animal models, tissue organoids, and human pluripotent stem cells have significantly expanded our understanding of the roles played by BMPs in the development and homeostasis of GI organs. It is clear that BMP signaling regulates GI function and disease progression that involve stem/progenitor cells and inflammation in a tissue-specific manner. In this review we discuss these new findings with a focus on the esophagus, stomach, and intestine.

Clinical research of the value of high-risk CTV setting on intensity-modulated radiotherapy for stage IIB-IVA cervical cancer.

BACKGROUND: This study aims to evaluate the clinical efficacy and side effects of setting up a high-risk clinical target volume (CTV-hr) alongside simultaneous integrated boost intensity-modulated radiotherapy (IMRT-SIB) in patients diagnosed with stage IIB-IVA cervical cancer. METHODS: This study retrospectively analysed patients with stage IIB-IVA cervical cancer who received radical radiotherapy at the Affiliated Hospital of Qingdao University between November 2014 and September 2019. The patients were divided into experimental and control groups based on whether CTV-hr was set. All patients received a combined treatment of radiotherapy and chemotherapy. The dosage for paclitaxel was 135 mg/m2, while for cisplatin it was 75 mg/m2 or for carboplatin it was AUC 4-6, given in a cycle of 21 days. Radiotherapy (RT) included external beam radiation therapy (EBRT) and intracavitary brachytherapy (ICBT). In the control group, positive lymph nodes (GTV-n) were treated at a dose of 58-62 Gy/26-28 fractions(f), while clinical target volumes (CTV) were treated with a dose of 46-48 Gy/26-28f. The experimental group received a simultaneous integrated boost (SIB) to CTV-hr at a dose of 54-56 Gy/26-28f, with the same CTV and GTV-n as the control group. Both groups were combined with brachytherapy with a total dose (EQD2, the equivalent dose in 2 Gy/f) of 80-90 Gy. The study measured objective remission rate (ORR), 3-year progression-free survival (PFS) rate, 3-year overall survival (OS) rate, recurrence rate, and side effects as endpoints. RESULTS: The study enrolled 217 patients, with 119 in the experimental group and 98 in the control group. Results showed that the experimental group had a higher 3-year OS rate (87.4% vs. 71.4%, p = 0.001) and 3-year PFS rate (72.3% vs. 51.0%, p = 0.000) compared to the control group. Additionally, the experimental group had significantly lower rates of overall recurrence (26.1% vs. 50.0%, p = 0.003), in-field recurrence (15.1% vs. 36.7%, p = 0.000), and out-field recurrence(13.4% vs. 35.7%, p = 0.000) compared to the control group. All observed differences were found to be statistically significant. However, the experimental and control groups had no statistically significant difference in ORR and radiological side effects, such as radiation cystitis and enteritis (p > 0.05). CONCLUSIONS: Setting CTV-hr and performing IMRT-SIB on patients with stage IIB-IVA cervical cancer effectively increased the 3-year OS rate, 3-year PFS rate and reduced recurrence rate, with no significant differences in side effects.

Long-Term Organic Fertilization Strengthens the Soil Phosphorus Cycle and Phosphorus Availability by Regulating the pqqC- and phoD-Harboring Bacterial Communities.

The pqqC and phoD genes encode pyrroloquinoline quinone synthase and alkaline phosphomonoesterase (ALP), respectively. These genes play a crucial role in regulating the solubilization of inorganic phosphorus (Pi) and the mineralization of organic phosphorus (Po), making them valuable markers for P-mobilizing bacterial. However, there is limited understanding of how the interplay between soil P-mobilizing bacterial communities and abiotic factors influences P transformation and availability in the context of long-term fertilization scenarios. We used real-time polymerase chain reaction and high-throughput sequencing to explore the characteristics of soil P-mobilizing bacterial communities and their relationships with key physicochemical properties and P fractions under long-term fertilization scenarios. In a 38-year fertilization experiment, six fertilization treatments were selected. These treatments were sorted into three groups: the non-P-amended group, including no fertilization and mineral NK fertilizer; the sole mineral-P-amended group, including mineral NP and NPK fertilizer; and the organically amended group, including sole organic fertilizer and organic fertilizer plus mineral NPK fertilizer. The organically amended group significantly increased soil labile P (Ca2-P and enzyme-P) and Olsen-P content and proportion but decreased non-labile P (Ca10-P) proportion compared with the sole mineral-P-amended group, indicating enhanced P availability in the soil. Meanwhile, the organically amended group significantly increased soil ALP activity and pqqC and phoD gene abundances, indicating that organic fertilization promotes the activity and abundance of microorganisms involved in P mobilization processes. Interestingly, the organically amended group dramatically reshaped the community structure of P-mobilizing bacteria and increased the relative abundance of Acidiphilium, Panacagrimonas, Hansschlegelia, and Beijerinckia. These changes had a greater positive impact on ALP activity, labile P, and Olsen-P content compared to the abundance of P-mobilizing genes alone, indicating their importance in driving P mobilization processes. Structural equation modeling indicated that soil organic carbon and Po modulated the relationship between P-mobilizing bacterial communities and labile P and Olsen-P, highlighting the influence of SOC and Po on the functioning of P-mobilizing bacteria and their impact on P availability. Overall, our study demonstrates that organic fertilization has the potential to reshape the structure of P-mobilizing bacterial communities, leading to increased P mobilization and availability in the soil. These findings contribute to our understanding of the mechanisms underlying P cycling in agricultural systems and provide valuable insights for enhancing microbial P mobilization through organic fertilization.

Circulating Neuropeptide Y May Be a Biomarker for Diagnosing Atrial Fibrillation.

INTRODUCTION: Sympathetic nervous system disorder promotes atrial fibrillation (AF), and neuropeptide Y (NPY) is an important neurotransmitter. This study aimed to explore the predictive value of plasma NPY in patients with AF. METHODS: Five hundred seventy-six patients were divided into AF (including paroxysmal and long-standing persistent AF; 360) and sinus rhythm (SR) groups (216). NPY level was detected using enzyme-linked immunosorbent assay, and NPY mRNA expression level was detected using quantitative polymerase chain reaction. Logistic regression was used to analyse the risk factors for AF; the correlations between blood NPY level and age, body mass index (BMI), left ventricular ejection fraction, left atrial diameter (LAD), and European Heart rate Association (EHRA) score in patients with AF were determined. The receiver operating characteristic (ROC) curve was utilised to predict AF. RESULTS: Plasma NPY levels were found to be higher in patients with AF than in patients with SR and in patients with long-standing persistent AF than in patients with paroxysmal AF; blood NPY mRNA levels were higher in the paroxysmal and long-standing persistent AF groups compared to the SR group (p < 0.05). Increased age {odds ratio (OR) = 1.201 (95% confidence interval [CI]: 1.01, 1.427)} and high NPY [OR = 1.239 (95% CI: 1.022, 1.501)] were factors found to affect AF detrimentally. NPY was associated with BMI (r = 0.5856, p < 0.05), LAD (r = 0.4023, p < 0.05), and EHRA score (r = 0.898, p < 0.05). The ROC curve for the predictive value of plasma NPY levels for AF showed an area under the curve (AUC) value of 0.919 (p < 0.05), while that for long-standing persistent AF showed an AUC of 0.784 (p < 0.05). CONCLUSION: Circulating NPY may be a promising molecular biomarker of AF.

Development of EST-SSR markers based on transcriptome sequencing for germplasm evaluation of 65 lilies (Lilium).

BACKGROUND: Lilium genus consists of approximately 100 species and numerous varieties, many of which are interspecific hybrids, which result in a complicated genetic background. The germplasm identification, genetic relationship analysis, and breeding of Lilium rely on exploiting genetic information among different accessions. Hence, an attempt was made to develop new EST-SSR markers and study the molecular divergence among 65 genotypes of Lilium. METHODS AND RESULTS: A total of 5509 EST-SSRs were identified from the high-throughput sequencing database of L. 'Elodie'. After primer screening, six primer pairs with the most abundant polymorphic bands were selected from 100 primer pairs. Combined with the other 10 reported SSR primers, a total of 16 pairs detected genetic information with an average PIC value of 0.7583. The number of alleles per locus varied from four to 33, the expected heterozygosity varied from 0.3289 to 0.9231, and the observed heterozygosity varied from 0.2857 to 0.5122. Based on the phylogenic results, 22 Asiatic hybrids (A), seven Longiflorum × Asiatic hybrids (LA), as well as two native species were grouped. Eighteen Oriental hybrids (O) and nine Oriental × Trumpet (OT) hybrids, four native species, one LO, and one LL (L. pardalinum × L. longiflorum) variety were grouped. CONCLUSIONS: Two major clusters were reported and a large number of genotypes were grouped based on UPGMA and STRUCTURE analysis methods. The PIC value as well as other parameters revealed that the EST-SSR markers selected were informative. In addition, the clustering pattern displayed better agreement with the cultivar's pedigree. The newly identified SSRs in this study provides molecular markers for germplasm characterization and genetic diversity for Lilium.

Transitional basal cells at the squamous-columnar junction generate Barrett's oesophagus.

In several organ systems, the transitional zone between different types of epithelium is a hotspot for pre-neoplastic metaplasia and malignancy, but the cells of origin for these metaplastic epithelia and subsequent malignancies remain unknown. In the case of Barrett's oesophagus, intestinal metaplasia occurs at the gastro-oesophageal junction, where stratified squamous epithelium transitions into simple columnar cells. On the basis of a number of experimental models, several alternative cell types have been proposed as the source of this metaplasia but in all cases the evidence is inconclusive: no model completely mimics Barrett's oesophagus in terms of the presence of intestinal goblet cells. Here we describe a transitional columnar epithelium with distinct basal progenitor cells (p63+KRT5+KRT7+) at the squamous-columnar junction of the upper gastrointestinal tract in a mouse model. We use multiple models and lineage tracing strategies to show that this squamous-columnar junction basal cell population serves as a source of progenitors for the transitional epithelium. On ectopic expression of CDX2, these transitional basal progenitors differentiate into intestinal-like epithelium (including goblet cells) and thereby reproduce Barrett's metaplasia. A similar transitional columnar epithelium is present at the transitional zones of other mouse tissues (including the anorectal junction) as well as in the gastro-oesophageal junction in the human gut. Acid reflux-induced oesophagitis and the multilayered epithelium (believed to be a precursor of Barrett's oesophagus) are both characterized by the expansion of the transitional basal progenitor cells. Our findings reveal a previously unidentified transitional zone in the epithelium of the upper gastrointestinal tract and provide evidence that the p63+KRT5+KRT7+ basal cells in this zone are the cells of origin for multi-layered epithelium and Barrett's oesophagus.

Molecular and Metabolic Insights into Anthocyanin Biosynthesis for Spot Formation on Lilium leichtlinii var. maximowiczii Flower Petals.

Plants exhibit remarkable diversity in their petal colors through biosynthesis and the accumulation of various pigments. Lilium, an important cut and potted flower, has many coloring pattern variations, including bicolors and spots. To elucidate the mechanisms regulating spot formation in Lilium leichtlinii var. maximowiczii petals, we used multiple approaches to investigate the changes in petal carotenoids, spot anthocyanins, and gene expression dynamics. This included green petals without spots (D1-Pe and D1-Sp), yellow-green petals with purple spots (D2-Pe and D2-Sp), light-orange petals with dark-purple spots (D3-Pe and D3-Sp), and orange petals with dark-purple spots (D4-Pe and D4-Sp). D3-Pe and D4-Pe contained large amounts of capsanthin and capsorubin and small amounts of zeaxanthin and violaxanthin, which contributed to the orange color. In addition to cyanidin-3-O-glucoside, pelargonidin-3-O-rutinoside, cyanidin-3-O-rutinoside, and peonidin-3-O-rutinoside may also contribute to L. leichtlinii var. maximowiczii's petal spot colors. KEGs involved in flavonoid biosyntheses, such as CHS, DFR, and MYB12, were significantly upregulated in D2-Sp and D3-Sp, compared with D1-Sp, as well as in spots, compared with petals. Upregulated anthocyanin concentrations and biosynthesis-related genes promoted spot formation and color transition. Our results provide global insight into pigment accumulation and the regulatory mechanisms underlying spot formation during flower development in L. leichtlinii var. maximowiczii.

SWATH-MS-Based Proteomics Reveals the Regulatory Metabolism of Amaryllidaceae Alkaloids in Three Lycoris Species.

Alkaloids are a class of nitrogen-containing alkaline organic compounds found in nature, with significant biological activity, and are also important active ingredients in Chinese herbal medicine. Amaryllidaceae plants are rich in alkaloids, among which galanthamine, lycorine, and lycoramine are representative. Since the difficulty and high cost of synthesizing alkaloids have been the major obstacles in industrial production, particularly the molecular mechanism underlying alkaloid biosynthesis is largely unknown. Here, we determined the alkaloid content in Lycoris longituba, Lycoris incarnata, and Lycoris sprengeri, and performed a SWATH-MS (sequential window acquisition of all theoretical mass spectra)-based quantitative approach to detect proteome changes in the three Lycoris. A total of 2193 proteins were quantified, of which 720 proteins showed a difference in abundance between Ll and Ls, and 463 proteins showed a difference in abundance between Li and Ls. KEGG enrichment analysis revealed that differentially expressed proteins are distributed in specific biological processes including amino acid metabolism, starch, and sucrose metabolism, implicating a supportive role for Amaryllidaceae alkaloids metabolism in Lycoris. Furthermore, several key genes collectively known as OMT and NMT were identified, which are probably responsible for galanthamine biosynthesis. Interestingly, RNA processing-related proteins were also abundantly detected in alkaloid-rich Ll, suggesting that posttranscriptional regulation such as alternative splicing may contribute to the biosynthesis of Amaryllidaceae alkaloids. Taken together, our SWATH-MS-based proteomic investigation may reveal the differences in alkaloid contents at the protein levels, providing a comprehensive proteome reference for the regulatory metabolism of Amaryllidaceae alkaloids.

Wnt/Fgf crosstalk is required for the specification of basal cells in the mouse trachea.

Basal progenitor cells are crucial for the establishment and maintenance of the tracheal epithelium. However, it remains unclear how these progenitor cells are specified during foregut development. Here, we found that ablation of the Wnt chaperone protein Gpr177 (also known as Wntless) in mouse tracheal epithelium causes a significant reduction in the number of basal progenitor cells accompanied by cartilage loss in Shh-Cre;Gpr177loxp/loxp mutants. Consistent with the association between cartilage and basal cell development, Nkx2.1+p63+ basal cells are co-present with cartilage nodules in Shh-Cre;Ctnnb1DM/loxp mutants, which maintain partial cell-cell adhesion but not the transcription regulation function of ß-catenin. More importantly, deletion of Ctnnb1 in the mesenchyme leads to the loss of basal cells and cartilage, concomitant with reduced transcript levels of Fgf10 in Dermo1-Cre;Ctnnb1loxp/loxp mutants. Furthermore, deletion of Fgf receptor 2 (Fgfr2) in the epithelium also leads to significantly reduced numbers of basal cells, supporting the importance of Wnt/Fgf crosstalk in early tracheal development.

Use of hPSC-derived 3D organoids and mouse genetics to define the roles of YAP in the development of the esophagus.

Balanced progenitor activities are crucial for the development and maintenance of high turn-over organs such as the esophagus. However, the molecular mechanisms regulating these progenitor activities in the esophagus remain to be elucidated. Here, we demonstrated that Yap is required for the proliferation of esophageal progenitor cells (EPCs) in the developing murine esophagus. We found that Yap deficiency reduces EPC proliferation and stratification whereas persistent Yap activation increases cell proliferation and causes aberrant stratification of the developing esophagus. We further demonstrated that the role of YAP signaling is conserved in the developing human esophagus by utilizing 3D human pluripotent stem cell (hPSC)-derived esophageal organoid culture. Taken together, our studies combining loss/gain-of-function murine models and hPSC differentiation support a key role for YAP in the self-renewal of EPCs and stratification of the esophageal epithelium.

Optimizing organic amendment applications to enhance carbon sequestration and economic benefits in an infertile sandy soil.

A thorough understanding of the agricultural, ecological, and economic benefits of organic amendment (OA) application in infertile soils is crucial for facilitating agricultural sustainability. We conducted a three-year field study to evaluate the effects of OA application on soil organic carbon (SOC) sequestration, crop yields, and the net ecosystem economic benefit (NEEB) in a typical infertile sandy soil (with an initial SOC content of 2.56 g kg-1) of the ancient Yellow River alluvial plain. In addition to the control (CK; non-OA application), two types of OAs, namely, manure-based organic fertilizer (M) and spent mushroom residue (MR), were each applied at 12, 24, and 36 Mg ha-1 yr-1. Two scenarios of OA application practices, namely, conventional manual OA application (AMA) and mechanical OA application (AME), were considered in the economic evaluation. An increase of 1 g kg-1 SOC content could improve the crop yield by 2.25 Mg ha-1 yr-1. Compared with the CK, the application of OAs enhanced the SOC content and SOC stock by 14.6%-39.8% and 8.5%-28.2%, respectively. However, the SOC sequestration efficiency of the OAs tended to decrease under high rates of OA application. MR was observed to have greater potential than M in sequestering SOC and promoting soil aggregates. OA-induced SOC sequestration could neutralize 36.6%-97.8% of greenhouse gas emissions, which resulted in a reduction in the global warming potential and its cost by 0.62-2.68 Mg CO2-eq ha-1 yr-1 and 15.46-65.78 CNY ha-1 yr-1, respectively. Nevertheless, in terms of the NEEB, the benefits of OA application on crop yield and SOC sequestration were largely offset by the increased material and labor costs. Compared with AMA, AME could save 10%-27% of agricultural costs. The AME of MR at a rate of 24 Mg ha-1 yr-1 achieved the highest NEEB. The results of this study suggest that a strategy involving the appropriate OA, optimal application rate, and cheapest incorporation cost for a specific individual soil should be adopted to achieve a sustainable solution for promoting crop productivity, enhancing SOC sequestration, and ensuring farmer income in infertile farming regions.

Reduced nitrogen fertilization under flooded conditions cut down soil N2O and CO2 efflux: An incubation experiment.

Unreasonable water (W) and inorganic nitrogen (N) fertilization cause an intensification of soil greenhouse gas (GHGs) emissions. W-N interactions (W × N) patterns can maximise the regulation of soil GHGs efflux through the rational matching of W and N fertilization factors. However, the effects of W × N patterns on soil GHGs efflux and the underlying mechanism remain unclear. In this study, urea fertilizers were applied to paddy soils in a gradient of 100 (N100), 80 (N80), and 60 mg kg-1 (N60) concentrations. Flooding (W1) and 60% field holding capacity (W2) was set for each N fertilizer application to observe the effects of W × N patterns on soil properties and GHGs efflux through incubation experiments. The results showed that W significantly affected soil electrical conductivity and different N forms (i.e., alkali hydrolyzed N, ammonium N, nitrate N and microbial biomass N) contents. Soil organic carbon (C) content was reduced by 14.40% in W1N60 relative to W1N100, whereas microbial biomass C content was increased by 26.87%. Moreover, soil methane (CH4) fluxes were low in all treatments, with a range of 1.60-1.65 µg CH4 kg-1. Soil nitrous oxide (N2O) and carbon dioxide (CO2) fluxes were significantly influenced by W, N and W × N. Global warming potential was maintained at the lowest level in W1N60 treatment at 0.67 g CO2-eq kg-1, suggesting W1N60 as the preferred W × N pattern with high environmental impact. Our findings demonstrate that reduced N fertilization contributes to the effective mitigation of soil N2O and CO2 efflux by lowering the soil total N and organic C contents and regulating soil microbial biomass C and N.

Critical Quality Control Methods for a Novel Anticoagulant Candidate LFG-Na by HPSEC-MALLS-RID and Bioactivity Assays.

A low molecular weight fucosylated glycosaminoglycan sodium (LFG-Na) is a novel anticoagulant candidate from the sea cucumber Holothuria fuscopunctata that selectively inhibits intrinsic tenase (iXase). The molecular weight, molecular weight distribution and bioactivities are the critical quality attributes of LFG-Na. The determination of these quality attributes of such an oligosaccharides mixture drug is challenging but critical for the quality control process to ensure its safety and efficacy in clinical use. Herein, the molecular weight and molecular weight distribution of LFG-Na were successfully determined using high performance size exclusion chromatography coupled with multi angle laser light scattering and refractive index detector (HPSEC-MALLS-RID). Comparing to the conventional method, HPSEC-MALLS-RID based on the refractive index increment (dn/dc) did not require the reference substances to establish the calibration curve. The acceptance criteria of LFG-Na were established, the weight-average molecular weight (Mw) should be 4000 to 6000 Da, the polydispersity (Mw/Mn) < 1.40, and the fraction with molecular weights of 1500 to 8000 Da should be no less than 80% of the total. HPSEC-MALLS-RID was also utilized for the determination of the starting material native fucosylated glycosaminoglycan (NFG) to choose a better manufacturing process. Furthermore, APTT assay was selected and the potency of anti-iXase, referring to the parallel line assay (PLA) method, was established to clarify the consistency of its biological activities. The results suggest that HPSEC-MALLS-RID and bioactivity assays are critical quality control methods for multi-component glycosaminoglycan LFG-Na. The methods also provide a feasible strategy to control the quality of other polysaccharide medicines.

Clinical outcomes observation in stage IIB-IIIB cervical cancer treated by adjuvant surgery following concurrent chemoradiotherapy.

BACKGROUND: To explore the feasibility of adjuvant surgery following concurrent chemoradiation therapy (CCRT) in stage IIB-IIIB (according to FIGO staging of 2009) cervical cancer and analyze risk factors of recurrence after surgery. METHODS: Forty-nine patients diagnosed with stage IIB-IIIB cervical cancer were reviewed retrospectively. We investigated the risk factors of recurrence after surgery using Chi-squared Test and further analyzed multiple factors affecting postoperative recurrence using the multi-factor logistic regression. Furthermore, the correlation of surgery outcomes (including operation time, bleeding, and hospitalization date and surgery complications) with the time which carried out between CCRT and completion surgery was analyzed. RESULTS: Tumor histology and residual tumor in the cervix were significantly associated with postoperative recurrence (P = 0.014 and P = 0.040, respectively). Logistic regression analysis demonstrated that the independent risk factors of postoperative recurrence were age and residual tumor in the cervix (P = 0.017 and P = 0.030, respectively). Complications (operation time, bleeding, hospitalization date) were compared between patients with an interval with radiotherapy less than 6 weeks and patients with an interval longer than 6 weeks. There were statistical differences in the amount of bleeding and postoperative complications between the two groups (P = 0.019 and P = 0.044, respectively). CONCLUSION: CCRT combined with surgery for stage IIB-IIIB cervical cancer was feasible, reduced the rate of postoperative recurrence and surgery complications were tolerated.

ABHD15 promotes cell viability, glycolysis, and inhibits apoptosis in cardiomyocytes under hypoxia.

BACKGROUND AND AIMS: Myocardial infarction (MI) has been an important heart disease affecting human health. The aim of this study was to investigate the regulatory effect of abhydrolase domain containing 15 (ABHD15) on hypoxic cardiomyocytes. METHODS AND RESULTS: Hypoxic cardiomyocytes are commonly used as an vitro model for the study of MI. We found that cardiomyocyte viability was decreased under hypoxia, but cell glucose uptake, insulin receptor phosphorylation level and apoptosis were increased. Interestingly, ABHD15 expression was up-regulated in hypoxia-induced cardiomyocytes. Then, we identified the function of ABHD15 in hypoxic cardiomyocytes by using ABHD15 overexpression vector or short interfering RNA (siRNA) against ABHD15. The results showed that overexpression of ABHD15 promoted hypoxic cardiomyocyte viability, glucose uptake and IR phosphorylation (p-IR), and inhibited cell apoptosis. However, knockdown of ABHD15 attenuated hypoxic cardiomyocyte viability, glucose uptake and IR phosphorylation, and promoted apoptosis. Moreover, we found that ABHD15 promoted glucose transporter 4 (GLUT4) expression, translocation and enhance rate-limiting enzyme activation of glycolysis, thereby affecting glucose uptake. Furthermore, our study suggested that ABHD15 may affect the viability and apoptosis of hypoxic cardiomyocytes through IR/Ras/Raf/ERK/MEK and IR/PI3K/AKT/Bcl2/Bad/caspase9 signaling pathways, respectively. When the phosphorylation of IR, Raf or ERK was blocked by inhibitors, the protective effect of overexpressing ABHD15 on the viability of hypoxic cardiomyocytes was eliminated. Furthermore, inhibiting the phosphorylation of IR, AKT or Bcl2 abolished the inhibitory effect of overexpressing ABHD15 on hypoxic cardiomyocyte apoptosis. CONCLUSION: ABHD15 regulated myocardial cell viability, glycolysis, and apoptosis under hypoxia, providing a novel potential therapeutic strategy for MI.