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1.
Anticancer Drugs ; 35(7): 644-652, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38950136

RESUMEN

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.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Recurrencia Local de Neoplasia , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/terapia , Neoplasias del Cuello Uterino/patología , Femenino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia/métodos , Inmunoterapia/métodos , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/administración & dosificación
2.
Plants (Basel) ; 13(13)2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38999580

RESUMEN

Soil acidification is a significant form of agricultural soil degradation, which is accelerated by irrational fertilizer application. Sweetpotato and wheat rotation has emerged as an important rotation system and an effective strategy to optimize nutrient cycling and enhance soil fertility in hilly areas, which is also a good option to improve soil acidification and raise soil quality. Studying the effects of different fertilization regimes on soil acidification provides crucial data for managing it effectively. An eight-year field experiment explored seven fertilizer treatments: without fertilization (CK), phosphorus (P) and potassium (K) fertilization (PK), nitrogen (N) and K fertilization (NK), NP fertilization (NP), NP with K chloride fertilization (NPK1), NP with K sulfate fertilization (NPK2), and NPK combined with organic fertilization (NPKM). This study focused on the soil acidity, buffering capacity, and related indicators. After eight years of continuous fertilization in the sweetpotato-wheat rotation, all the treatments accelerated the soil acidification. Notably, N fertilization reduced the soil pH by 1.30-1.84, whereas N-deficient soil showed minimal change. Organic fertilizer addition resulted in the slowest pH reduction among the N treatments. Both N-deficient (PK) and organic fertilizer addition (NPKM) significantly increased the soil cation exchange capacity (CEC) by 8.83% and 6.55%, respectively, compared to CK. Similar trends were observed for the soil-buffering capacity (pHBC). NPK2 increased the soil K+ content more effectively than NPK1. NPKM reduced the sodium and magnesium content compared to CK, with the highest magnesium content among the treatments at 1.60 cmol·kg-1. Regression tree analysis identified the N input and soil magnesium and calcium content as the primary factors influencing the pHBC changes. Structural equation modeling showed that the soil pH is mainly influenced by the soil ammonium N content and pHBC, with coefficients of -0.28 and 0.29, respectively. Changes in the soil pH in the sweetpotato-wheat rotation were primarily associated with the pHBC and N input, where the CEC content emerged as the main factor, modulated by magnesium and calcium. Long-term organic fertilization enhances the soil pHBC and CEC, slowing the magnesium reduction and mitigating soil acidification in agricultural settings.

3.
Plant Physiol Biochem ; 214: 108872, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38964087

RESUMEN

Bletilla striata, valued for its medicinal and ornamental properties, remains largely unexplored in terms of how light intensity affects its physiology, biochemistry, and polysaccharide formation. In this 5-month study, B. striata plants were exposed to three different light intensities: low light (LL) (5-20 µmol m-2·s-1), middle light (ML) (200 µmol m-2·s-1), and high light (HL) (400 µmol m-2·s-1). The comprehensive assessment included growth, photosynthetic apparatus, chlorophyll fluorescence electron transport, and analysis of differential metabolites based on the transcriptome and metabolome data. The results indicated that ML resulted in the highest plant height and total polysaccharide content, enhanced photosynthetic apparatus performance and light energy utilization, and stimulated carbon metabolism and carbohydrate accumulation. HL reduced Chl content and photosynthetic apparatus functionality, disrupted OEC activity and electron transfer, stimulated carbon metabolism and starch and glucose accumulation, and hindered energy metabolism related to carbohydrate degradation and oxidation. In contrast, LL facilitated leaf growth and increased chlorophyll content but decreased plant height and total polysaccharide content, compromised the photosynthetic apparatus, hampered light energy utilization, stimulated energy metabolism related to carbohydrate degradation and oxidation, and inhibited carbon metabolism and carbohydrate synthesis. Numerous genes in carbon metabolism were strongly related to polysaccharide metabolites. The katE and cysK genes in carbon metabolism were strongly related not only to polysaccharide metabolites, but also to genes involved in polysaccharide biosynthesis. Our results highlight that light intensity plays a crucial role in affecting polysaccharide biosynthesis in B. striata, with carbon metabolism acting as a mediator under suitable light intensity conditions.


Asunto(s)
Carbono , Luz , Orchidaceae , Fotosíntesis , Hojas de la Planta , Polisacáridos , Orchidaceae/metabolismo , Orchidaceae/efectos de la radiación , Orchidaceae/crecimiento & desarrollo , Orchidaceae/genética , Polisacáridos/metabolismo , Polisacáridos/biosíntesis , Hojas de la Planta/metabolismo , Hojas de la Planta/efectos de la radiación , Carbono/metabolismo , Fotosíntesis/efectos de la radiación , Clorofila/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de la radiación , Multiómica
4.
Zhonghua Nan Ke Xue ; 30(1): 32-39, 2024 Jan.
Artículo en Chino | MEDLINE | ID: mdl-39046411

RESUMEN

OBJECTIVE: To establish a predictive scoring model for bladder neck contracture (BNC) after laparoscopic enucleation of the prostate with preservation of the urethra (Madigan surgery) and explore the preventive measures against this postoperative complication. METHODS: We included 362 cases of BPH treated by laparoscopic Madigan surgery from January 2019 to March 2022 (45 with and 317 without postoperative BNC) in the training group and another 120 cases treated the same way in the verification group, collected the clinical data on the patients and evaluated the results of surgery. Using the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression, we analyzed the risk factors for postoperative BNC and constructed a predictive scoring model for evaluation of the factors. RESULTS: Compared with the baseline, the IPSS, quality of life (QOL) score and postvoid residual urine volume (PVR) were significantly decreased (P < 0.05) while the maximum urinary flow rate (Qmax) remarkably increased (P < 0.05) in the BPH patients at 3 months after surgery. Eight non-zero characteristic predictors were identified by LASSO regression analysis. Multivariate logistic regression analysis showed that short clinical experience of the surgeon, concurrent prostatitis, bladder rinse solution temperature <34℃, catheter blockage, urethral balloon injection volume >40 ml and postoperative constipation were independent risk factors for postoperative BNC (P < 0.05). The best cut-off value was 2.36 points in both the training and the verification groups. The results of evaluation exhibited a high discriminability of the predictive scoring model. CONCLUSION: Laparoscopic Madigan surgery is a safe and effective method for the treatment of BPH. Short clinical experience of the surgeon, concurrent prostatitis, bladder rinse solution temperature <34℃, catheter blockage, water injected into the urethral balloon >40 ml and postoperative constipation were independent risk factors for postoperative BNC. The predictive scoring model constructed in this study has a good discriminability and is simple and feasible, contributive to the prediction of postoperative BNC in BPH patients undergoing laparoscopic Madigan surgery.


Asunto(s)
Laparoscopía , Complicaciones Posoperatorias , Hiperplasia Prostática , Humanos , Masculino , Laparoscopía/métodos , Complicaciones Posoperatorias/prevención & control , Hiperplasia Prostática/cirugía , Factores de Riesgo , Uretra/cirugía , Contractura/prevención & control , Contractura/etiología , Próstata/cirugía , Anciano , Prostatectomía/métodos , Prostatectomía/efectos adversos , Calidad de Vida , Obstrucción del Cuello de la Vejiga Urinaria/cirugía , Obstrucción del Cuello de la Vejiga Urinaria/etiología , Obstrucción del Cuello de la Vejiga Urinaria/prevención & control , Modelos Logísticos
5.
ACS Omega ; 9(24): 25610-25624, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38911759

RESUMEN

The massive burning of fossil fuels has been important for economic and social development, but the increase in the CO2 concentration has seriously affected environmental sustainability. In industrial and agricultural production, light olefins are one of the most important feedstocks. Therefore, the preparation of light olefins by CO2 hydrogenation has been intensively studied, especially for the development of efficient catalysts and for the application in industrial production. Fe-based catalysts are widely used in Fischer-Tropsch synthesis due to their high stability and activity, and they also exhibit excellent catalytic CO2 hydrogenation to light olefins. This paper systematically summarizes and analyzes the reaction mechanism of Fe-based catalysts, alkali and transition metal modifications, interactions between active sites and carriers, the synthesis process, and the effect of the byproduct H2O on catalyst performance. Meanwhile, the challenges to the development of CO2 hydrogenation for light olefin synthesis are presented, and future development opportunities are envisioned.

6.
BMC Cancer ; 24(1): 589, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38745137

RESUMEN

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.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Quimioradioterapia , Cisplatino , Paclitaxel , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/terapia , Neoplasias del Cuello Uterino/radioterapia , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patología , Femenino , Persona de Mediana Edad , Quimioradioterapia/métodos , Quimioradioterapia/efectos adversos , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Paclitaxel/efectos adversos , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/uso terapéutico , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Adulto , Anciano , Resultado del Tratamiento , Supervivencia sin Progresión
7.
Nat Commun ; 15(1): 4124, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38750026

RESUMEN

Basal progenitor cells are crucial for maintaining foregut (the esophagus and forestomach) homeostasis. When their function is dysregulated, it can promote inflammation and tumorigenesis. However, the mechanisms underlying these processes remain largely unclear. Here, we employ genetic mouse models to reveal that Jag1/2 regulate esophageal homeostasis and foregut tumorigenesis by modulating the function of basal progenitor cells. Deletion of Jag1/2 in mice disrupts esophageal and forestomach epithelial homeostasis. Mechanistically, Jag1/2 deficiency impairs activation of Notch signaling, leading to reduced squamous epithelial differentiation and expansion of basal progenitor cells. Moreover, Jag1/2 deficiency exacerbates the deoxycholic acid (DCA)-induced squamous epithelial injury and accelerates the initiation of squamous cell carcinoma (SCC) in the forestomach. Importantly, expression levels of JAG1/2 are lower in the early stages of human esophageal squamous cell carcinoma (ESCC) carcinogenesis. Collectively, our study demonstrates that Jag1/2 are important for maintaining esophageal and forestomach homeostasis and the onset of foregut SCC.


Asunto(s)
Carcinogénesis , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Esófago , Homeostasis , Proteína Jagged-1 , Proteína Jagged-2 , Células Madre , Animales , Proteína Jagged-1/metabolismo , Proteína Jagged-1/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/metabolismo , Esófago/patología , Esófago/metabolismo , Células Madre/metabolismo , Ratones , Proteína Jagged-2/metabolismo , Proteína Jagged-2/genética , Humanos , Carcinogénesis/genética , Carcinogénesis/patología , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/metabolismo , Ratones Noqueados , Transducción de Señal , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismo , Receptores Notch/metabolismo , Receptores Notch/genética , Diferenciación Celular , Masculino , Femenino
8.
BMC Plant Biol ; 24(1): 299, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38632552

RESUMEN

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.


Asunto(s)
Fertilizantes , Hosta , Nitrógeno/farmacología , Clorofila A , Sequías , Especies Reactivas de Oxígeno , Fotosíntesis , Clorofila , Complejo de Proteína del Fotosistema II , Potasio , Hojas de la Planta
9.
Int J Biol Macromol ; 267(Pt 2): 131634, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38636747

RESUMEN

Oxidative damage is an important cause of aging. The antioxidant and anti-aging activities of Longan polysaccharides, especially purified Longan polysaccharides, have not been thoroughly investigated. Therefore, this study aimed to investigate the antioxidant and anti-aging activities and mechanisms of crude polysaccharides and purified polysaccharides from Longan. A purified acidic Longan polysaccharide LP-A was separated from Longan crude polysaccharide LP. Subsequently, its structural characterization, anti-aging activity and mechanism were studied. The results showed that LP-A was an acidic heteropolysaccharide with an average molecular weight (Mw) of 4.606 × 104 Da which was composed of nine monosaccharides. The scavenging rate of ABTS free radical in vitro reached 99 %. In the nematode life experiment, 0.3 mg/mL LP group and LP-A group could prolong the average lifespan of nematodes by 9.31 % and 25.80 %, respectively. Under oxidative stress stimulation, LP-A group could prolong the survival time of nematodes by 69.57 %. In terms of mechanism, Longan polysaccharide can regulate insulin / insulin-like growth factor (IIS) signaling pathway, increase the activity of antioxidant enzymes, reduce lipid peroxidation, enhance the body's resistance to stress damage, and effectively prolong the lifespan of nematodes. In conclusion, LP-A has better anti-aging activity than crude polysaccharide LP, which has great potential for developing as an anti-aging drug.


Asunto(s)
Envejecimiento , Antioxidantes , Caenorhabditis elegans , Estrés Oxidativo , Polisacáridos , Animales , Caenorhabditis elegans/efectos de los fármacos , Polisacáridos/farmacología , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Antioxidantes/farmacología , Antioxidantes/química , Envejecimiento/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Peso Molecular , Monosacáridos/análisis , Longevidad/efectos de los fármacos
10.
Plants (Basel) ; 13(7)2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38611502

RESUMEN

In recent years, overuse of chemical fertilization has led to soil acidification and decreased rice yield productivity in southern China. Biochar and manure co-application remediation may have positive effects on rice yield and improve acid paddy soil fertility. This study was conducted to understand the effects of co-application of wood biochar and pig manure on rice yield and acid paddy soil quality (0-40 cm soil layers) in a 5-year field experiment. The experiment consisted of six treatments: no biochar and no fertilizer (CK); biochar only (BC); mineral fertilizer (N); mineral fertilizer combined with biochar (N + BC); manure (25% manure N replacing fertilizer N) combined with mineral fertilizer (MN); and manure combined with mineral fertilizer and biochar (MN + BC). Total nitrogen application for each treatment was the same at 270 kg nitrogen ha-1y-1, and 30 t ha-1 biochar was added to the soil only in the first year. After five years, compared with N treatments, N + BC, MN, and MN + BC treatments increased the rice yield rate to 2.8%, 4.3%, and 6.3%, respectively, by improving soil organic matter, total nitrogen, and available phosphate under a 0-40 cm soil layer. MN + BC had the strongest resistance to soil acidification among all the treatments. The interaction between fertilizers and biochar application was significant (p < 0.05) in rice yield, soil electrical conductivity (10-20 cm), and soil available phosphate (20-40 cm). Principal component analysis indicated that the effect of manure on soil property was stronger than that of biochar in the 0-40 cm soil layer. The overall rice yield and soil fertility decreased in the order of biochar + mineral fertilizer + manure > mineral fertilizer + manure > biochar + mineral fertilizer > mineral fertilizer > biochar > control. These results suggest that biochar and manure co-application is a long-term viable strategy for improving acid soil productivity due to its improvements in soil pH, organic carbon, nutrient retention, and availability.

11.
Sci Total Environ ; 923: 171419, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38442752

RESUMEN

The incorporation of straw with decomposing inoculants into soils has been widely recommended to sustain agricultural productivity. However, comprehensive analyses assessing the effects of straw combined with decomposing inoculants on greenhouse gas (GHG) emissions, net primary production (NPP), the net ecosystem carbon budget (NECB), and the carbon footprint (CF) in farmland ecosystems are scant. Here, we carried out a 2-year field study in a wheat cropping system with six treatments: rice straw (S), a straw-decomposing Bacillus subtilis inoculant (K), a straw-decomposing Aspergillus oryzae inoculant (Q), a combination of straw and Bacillus subtilis inoculant (SK), a combination of straw and Aspergillus oryzae inoculant (SQ), and a control with no rice straw or decomposing inoculant (Control). We found that all the treatments resulted in a positive NECB ranging between 838 and 5065 kg C ha-1. Relative to the Control, the S treatment increased CO2 emissions by 16%, while considerably enhancing the NECB by 349%. This difference might be attributed to the straw C input and an increase in plant productivity (NPP, 30%). More importantly, in comparison to that in S, the NECB in SK and SQ significantly increased by 27-35% due to the positive response of NPP to the decomposing inoculants. Although the combination of straw and decomposing inoculants yielded a 3% increase in indirect GHG emissions, it also exhibited the lowest CF (0.18 kg CO2-eq kg-1 of grain). This result was attributed to the synergistic effects of straw and decomposing inoculants, which reduced direct N2O emissions and increased wheat productivity. Overall, the findings of the present study suggested that the combined amendment of straw and decomposing inoculants is an environmentally sustainable management practice in wheat cropping systems that can generate win-win scenarios through improvements in soil C stock, crop productivity, and GHG mitigation.


Asunto(s)
Carbono , Gases de Efecto Invernadero , Huella de Carbono , Ecosistema , Triticum , Dióxido de Carbono/análisis , Óxido Nitroso/análisis , Agricultura/métodos , Suelo , China
12.
Sci Total Environ ; 926: 171993, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38547967

RESUMEN

Calcium nitrate addition is economically viable and highly efficient for the in-situ treatment of contaminated sediment and enhancement of surface water quality, particularly in rural areas. However, conventional nitrate addition technologies have disadvantages such as excessive nitrate release, sharp ammonium increase, and weakened sulfide oxidation efficiency owing to rapid nitrate injection into the sediment. To resolve these defects, we propose a piped-slow-release (PSR) calcium nitrate dosing method and investigate its treatment efficiency and underlying mechanisms. The results illustrated that PSR dosing had a longer half-life (t1/2 = 5.08 days) and a lower maximum apparent nitrate escape rate of 1.28 % than conventional nitrate injection and other dosing methods. In addition, the PSR managed the inorganic nitrogen release into the overlying water, and after the treatment, the nitrate, ammonium, and nitrite concentrations of 0 mg/L, 8.60 mg/L, and 0 mg/L on day 28 were close to those of the control group (0 mg/L, 8.76 mg/L, and 0 mg/L, respectively). Moreover, the PSR method maintained a moderate nitrate concentration of approximately 3000 mg/L in sediment interstitial water by its controlled-release design, thus greatly enhancing the sulfide oxidation efficiency by relieving the inhibitory effects of high nitrate concentrations, with 83.0 % sulfide being eradicated within 5 days. Sulfide-ferrous nitrate reduction (denitrification and dissimilatory nitrate reduction to ammonium) genera (e.g., Sulfurimonas, Thiobacillus, and Thioalkalispira) were successively enhanced and dominated the microbial community, and the related functional genes displayed high relative abundances. These results imply that the PSR dosing method for calcium nitrate, characterized by flexible operation, high efficiency, low cost, and controllable processes, is appropriate for remediating black-odorous sediment in rural areas.


Asunto(s)
Compuestos de Amonio , Compuestos de Calcio , Nitratos , Odorantes , Sulfuros , Nitrógeno , Oxidación-Reducción , Desnitrificación
13.
Proc Natl Acad Sci U S A ; 121(10): e2320559121, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38408237

RESUMEN

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.


Asunto(s)
Carcinoma de Células Escamosas , Transducción de Señal , Animales , Ratones , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Carcinoma de Células Escamosas/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Homeostasis , Transducción de Señal/genética , Células Madre/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Proteínas Señalizadoras YAP
14.
Stem Cell Res Ther ; 15(1): 41, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38355568

RESUMEN

BACKGROUND: Corneal alkali burns can lead to ulceration, perforation, and even corneal blindness due to epithelial defects and extensive cell necrosis, resulting in poor healing outcomes. Previous studies have found that chitosan-based in situ hydrogel loaded with limbal epithelium stem cells (LESCs) has a certain reparative effect on corneal alkali burns. However, the inconsistent pore sizes of the carriers and low cell loading rates have resulted in suboptimal repair outcomes. In this study, 4D bioprinting technology was used to prepare a chitosan-based thermosensitive gel carrier (4D-CTH) with uniform pore size and adjustable shape to improve the transfer capacity of LESCs. METHODS: Prepare solutions of chitosan acetate, carboxymethyl chitosan, and ß-glycerophosphate sodium at specific concentrations, and mix them in certain proportions to create a pore-size uniform scaffold using 4D bioprinting technology. Extract and culture rat LESCs (rLESCs) in vitro, perform immunofluorescence experiments to observe the positivity rate of deltaNp63 cells for cell identification. Conduct a series of experiments to validate the cell compatibility of 4D-CTH, including CCK-8 assay to assess cell toxicity, scratch assay to evaluate the effect of 4D-CTH on rLESCs migration, and Calcein-AM/PI cell staining experiment to examine the impact of 4D-CTH on rLESCs proliferation and morphology. Establish a severe alkali burn model in rat corneas, transplant rLESCs onto the injured cornea using 4D-CTH, periodically observe corneal opacity and neovascularization using a slit lamp, and evaluate epithelial healing by fluorescein sodium staining. Assess the therapeutic effect 4D-CTH-loaded rLESCs on corneal alkali burn through histological evaluation of corneal tissue paraffin sections stained with hematoxylin and eosin, as well as immunofluorescence staining of frozen sections. RESULTS: Using the 4D-CTH, rLESCs were transferred to the alkali burn wounds of rats. Compared with the traditional treatment group (chitosan in situ hydrogel encapsulating rLESCs), the 4D-CTH-rLESC group had significantly higher repair efficiency of corneal injury, such as lower corneal opacity score (1.2 ± 0.4472 vs 0.4 ± 0.5477, p < 0.05) and neovascularization score (5.5 ± 1.118 vs 2.6 ± 0.9618, p < 0.01), and significantly higher corneal epithelial wound healing rate (72.09 ± 3.568% vs 86.60 ± 5.004%, p < 0.01). CONCLUSION: In summary, the corneas of the 4D-CTH-rLESC treatment group were similar to the normal corneas and had a complete corneal structure. These findings suggested that LESCs encapsulated by 4D-CTH significantly accelerated corneal wound healing after alkali burn and can be considered as a rapid and effective method for treating epithelial defects.


Asunto(s)
Quemaduras Químicas , Quitosano , Lesiones de la Cornea , Opacidad de la Córnea , Ratas , Animales , Quemaduras Químicas/tratamiento farmacológico , Quemaduras Químicas/patología , Quitosano/química , Álcalis/farmacología , Álcalis/uso terapéutico , Cicatrización de Heridas , Córnea , Lesiones de la Cornea/terapia , Opacidad de la Córnea/patología , Células Madre/patología , Hidrogeles/farmacología
15.
Nat Cell Biol ; 26(1): 124-137, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38168770

RESUMEN

The gut microbiota play a pivotal role in human health. Emerging evidence indicates that gut microbes participate in the progression of tumorigenesis through the generation of carcinogenic metabolites. However, the underlying molecular mechanism is largely unknown. In the present study we show that a tryptophan metabolite derived from Peptostreptococcus anaerobius, trans-3-indoleacrylic acid (IDA), facilitates colorectal carcinogenesis. Mechanistically, IDA acts as an endogenous ligand of an aryl hydrocarbon receptor (AHR) to transcriptionally upregulate the expression of ALDH1A3 (aldehyde dehydrogenase 1 family member A3), which utilizes retinal as a substrate to generate NADH, essential for ferroptosis-suppressor protein 1(FSP1)-mediated synthesis of reduced coenzyme Q10. Loss of AHR or ALDH1A3 largely abrogates IDA-promoted tumour development both in vitro and in vivo. It is interesting that P. anaerobius is significantly enriched in patients with colorectal cancer (CRC). IDA treatment or implantation of P. anaerobius promotes CRC progression in both xenograft model and ApcMin/+ mice. Together, our findings demonstrate that targeting the IDA-AHR-ALDH1A3 axis should be promising for ferroptosis-related CRC treatment.


Asunto(s)
Neoplasias Colorrectales , Ferroptosis , Microbioma Gastrointestinal , Humanos , Animales , Ratones , Ferroptosis/genética , Carcinogénesis/genética , Transformación Celular Neoplásica , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología
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