RESUMEN

Eu isotopes are promising tracers across various scientific domains such as planetary, earth, and marine science, yet their high-precision analysis has been challenging due to the similar geochemical properties of rare earth elements (REEs). In this study, a novel two-column chromatographic approach was developed utilizing AG50W-X12 and TODGA resins to separate Eu effectively from matrix and interfering elements like Ba, Nd, Sm, and Gd, while ensuring high Eu yields (99.4 ± 0.4%, n = 19) and low blanks (<20 pg). The robustness of this method is evidenced by various rock types and different Eu loading masses. The efficient purification of Eu facilitated the establishment of a high-precision calibration technique with standard-sample bracketing (SSB) and internal normalization (Nd). When a Nu Plasma 1700 multicollector-inductively coupled plasma-mass spectrometry (MC-ICP-MS) instrument was employed, repeated purification and analysis of various Geological Reference Materials (GRMs) confirmed that the long-term external precision of δ153/151Eu is better than 0.04‰ (2 standard deviation (2SD)), which represents a 2-5-fold increase in precision compared to previously reported methods. Additionally, the high-precision Eu isotopic compositions of five GRMs, including basalts, andesite, syenite, and marine sediment, were measured. The high-precision Eu isotope techniques presented herein open up new avenues for Eu isotope geochemistry.

RESUMEN

Mammalian milk exosomal miRNAs play an important role in maintaining intestinal immune homeostasis and protecting epithelial barrier function, but the specific miRNAs and whether miRNA-mediated mechanisms are responsible for these benefits remain a matter of investigation. This study isolated sheep milk-derived exosomes (sheep MDEs), identifying the enriched miRNAs in sheep MDEs, oar-miR-148a, and oar-let-7b as key components targeting TLR4 and TRAF1, which was validated by a dual-luciferase reporter assay. In dextran sulfate sodium-induced colitis mice, administration of sheep MDEs alleviated colitis symptoms, reduced colonic inflammation, and systemic oxidative stress, as well as significantly increased colonic oar-miR-148a and oar-let-7b while reducing toll-like receptor 4 (TLR4) and TNF-receptor-associated factor 1 (TRAF1) level. Further characterization in TNF-α-challenged Caco-2 cells showed that overexpression of these miRNAs suppressed the TLR4/TRAF1-IκBα-p65 pathway and reduced IL-6 and IL-12 production. These findings indicate that sheep MDEs exert gastrointestinal anti-inflammatory effects through the miRNA-mediated modulation of TLR4 and TRAF1, highlighting their potential in managing colitis.

RESUMEN

In this paper, we concentrate on updating the clinical research on sodium-glucose cotransporter inhibitors (SGLTis) for patients with type 2 diabetes who have heart failure with a preserved injection fraction, acute heart failure, atrial fibrillation, primary prevention of atherosclerotic cardiovascular disease/cardiovascular disease, and acute myocardial infarction. We searched the data of randomized controlled trials and meta-analyses of SGLTis in patients with diabetes from PubMed between January 1, 2020 and April 6, 2024 for our review. According to our review, certain SGLTis (empagliflozin, dapagliflozin, canagliflozin, and tofogliflozin), but not sodium-glucose cotransporter 1 inhibitor (SGLT1i), exhibit relatively superior clinical safety and effectiveness for treating the abovementioned diseases. Proper utilization of SGLTis in these patients can foster clinical improvement and offer an alternative medication option. However, clinical trials involving SGLTis for certain diseases have relatively small sample sizes, brief intervention durations, and conclusions based on weak evidence, necessitating additional data. These findings are significant and valuable for providing a more comprehensive reference and new possibilities for the clinical utilization and scientific exploration of SGLTis.

RESUMEN

The goal of this study was to assess the impacts or benefits of sludge in situ reduction (SIR) within wastewater treatment processes with relation to global warming potential in wastewater treatment plants, with a comprehensive consideration of wastewater and sludge treatment. The anaerobic side-stream reactor (ASSR) and the sludge process reduction activated sludge (SPRAS), two typical SIR technologies, were used to compare the carbon footprint analysis results with the conventional anaerobic - anoxic - oxic (AAO) process. Compared to the AAO, the ASSR with a typical sludge reduction efficiency (SRE) of 30 % increased greenhouse gas (GHG) emissions by 1.1 - 1.7 %, while the SPRAS with a SRE of 74 % reduced GHG emissions by 12.3 - 17.6 %. Electricity consumption (0.025 - 0.027 kg CO2-eq/m3), CO2 emissions (0.016 - 0.059 kg CO2-eq/m3), and N2O emissions (0.009 - 0.023 kg CO2-eq/m3) for the removal of secondary substrates released from sludge decay in the SIR processes were the major contributor to the increased GHG emissions from the wastewater treatment system. By lowering sludge production and the organic matter content in the sludge, the SIR processes significantly decreased the carbon footprints associated with sludge treatment and disposal. The threshold SREs of the ASSR for GHG reduction were 27.7 % and 34.6 % for the advanced dewatering - sanitary landfill and conventional dewatering - drying-incinerating routes, respectively. Overall, the SPRAS process could be considered as a cost-effective and sustainable low-carbon SIR technology for wastewater treatment.

RESUMEN

Dravet syndrome (DS) is a devastating early-onset refractory epilepsy syndrome caused by variants in the SCN1A gene. A disturbed GABAergic interneuron function is implicated in the progression to DS but the underlying developmental and pathophysiological mechanisms remain elusive, in particularly at the chromatin level. Induced pluripotent stem cells (iPSCs) derived from DS cases and healthy donors were used to model disease-associated epigenetic abnormalities of GABAergic development. Chromatin accessibility was assessed at multiple time points (Day 0, Day 19, Day 35, and Day 65) of GABAergic differentiation. Additionally, the effects of the commonly used anti-seizure drug valproic acid (VPA) on chromatin accessibility were elucidated in GABAergic cells. The distinct dynamics in the chromatin profile of DS iPSC predicted accelerated early GABAergic development, evident at D19, and diverged further from the pattern in control iPSC with continued differentiation, indicating a disrupted GABAergic maturation. Exposure to VPA at D65 reshaped the chromatin landscape at a variable extent in different iPSC-lines and rescued the observed dysfunctional development of some DS iPSC-GABA. The comprehensive investigation on the chromatin landscape of GABAergic differentiation in DS-patient iPSC offers valuable insights into the epigenetic dysregulations associated with interneuronal dysfunction in DS. Moreover, the detailed analysis of the chromatin changes induced by VPA in iPSC-GABA holds the potential to improve the development of personalized and targeted anti-epileptic therapies.

Asunto(s)

Diferenciación Celular , Epigénesis Genética , Epilepsias Mioclónicas , Neuronas GABAérgicas , Células Madre Pluripotentes Inducidas , Ácido Valproico , Células Madre Pluripotentes Inducidas/metabolismo , Humanos , Epilepsias Mioclónicas/genética , Epilepsias Mioclónicas/tratamiento farmacológico , Epilepsias Mioclónicas/metabolismo , Ácido Valproico/farmacología , Diferenciación Celular/efectos de los fármacos , Neuronas GABAérgicas/metabolismo , Neuronas GABAérgicas/efectos de los fármacos , Cromatina/metabolismo , Canal de Sodio Activado por Voltaje NAV1.1/genética , Canal de Sodio Activado por Voltaje NAV1.1/metabolismo , Anticonvulsivantes/farmacología

RESUMEN

Wastewater treatment plants produce large amounts of sludge requiring stabilization before safe disposal. Traditional biological stabilization approaches are cost-effective but generally require either an extended retention time (10-40 days), or elevated temperatures (40-80 °C) for effective pathogens inactivation. This study overcomes these limitations via a novel acidic aerobic digestion process, leveraging an acid-tolerant ammonia-oxidizing bacterium (AOB) Candidatus Nitrosoglobus. To retain this novel but slowly growing AOB, we proposed the first-ever application of a classical wastewater configuration-moving bed biofilm reactor (MBBR)-for sludge treatment. The AOB in biofilm maintains acidic pH and high nitrite levels in sludge, generating free nitrous acid in situ to expedite sludge stabilization. This process was tested in two laboratory-scale aerobic digesters processing full-scale anaerobically digested sludge. At an ambient temperature of 20 °C, pathogens were reduced to levels well below the threshold specified for the highest stabilization level (Class A), within a retention time of 3.5 days. A high volatile solids reduction of 27.4 ± 5.2% was achieved. Through drastically accelerating stabilization and enhancing reduction, this process substantially saves capital and operational costs for sludge disposal.

RESUMEN

BACKGROUND: Ulcerative colitis (UC), a chronic idiopathic inflammatory bowel disease (IBD), presents with limited current drug treatment options. Consequently, the search for safe and effective drug for UC prevention and treatment is imperative. Our prior studies have demonstrated that the phenolic compound p-Hydroxybenzaldehyde (HD) from Nostoc commune, effectively mitigates intestinal inflammation. However, the mechanisms underlying HD's anti-inflammatory effects remain unclear. PURPOSE: This study delved into the pharmacodynamics of HD and its underlying anti-inflammation mechanisms. METHODS: For in vivo experiments, dextran sodium sulfate (DSS)-induced colitis mouse model was established. In vitro inflammation model was established using lipopolysaccharide (LPS)-induced RAW264.7 and bone marrow-derived macrophages (BMDMs). The protective effect of HD against colitis was determined by monitoring clinical symptoms and histological morphology in mice. The levels of inflammatory factors and oxidative stress markers were subsequently analyzed with enzyme-linked immunosorbent assay (ELISA) and biochemical kits. Furthermore, western blotting (WB), immunofluorescence (IF), luciferase reporter gene, drug affinity reaction target stability (DARTS) assay, molecular docking, and molecular dynamics (MD) simulation were used to determine the potential target and molecular mechanism of HD. RESULTS: Our findings indicate that HD significantly alleviated the clinical symptoms and histological morphology of colitis in mice, and curtailed the production of pro-inflammatory cytokines, including TNF-α, IL-6, IFN-γ, COX-2, and iNOS. Furthermore, HD stimulated the production of SOD, CAT, and GSH-px, enhanced total antioxidant capacity (T-AOC), and reduced MDA levels. Mechanically, HD augmented the expression of Nrf2, HO-1, and NQO-1, while concurrently downregulating the phosphorylation of p65, IκBα, c-Jun, and c-Fos. ML385 and siNrf2 largely attenuated the protective effect of HD in enteritis mice and RAW 264.7 cells, as well as the promotion of HO-1 expression levels. ZnPP-mediated HO-1 knockdown reversed HD-induced inhibition of colonic inflammation. Luciferase reporter assay and IF assay confirmed the transcriptional activation of Nrf2 by HD. DARTS analysis, molecular docking, and MD results showed high binding strength, interaction efficiency and remarkable stability between Nrf2 and HD. CONCLUSION: These outcomes extend our previous research results that HD can combat oxidative stress through the Nrf2/HO-1/NQO-1/NF-κB/AP-1 pathways, effectively alleviating colitis, and propose new targets for HD to protect against intestinal barrier damage.

Asunto(s)

Benzaldehídos , Sulfato de Dextran , Factor 2 Relacionado con NF-E2 , FN-kappa B , Estrés Oxidativo , Factor de Transcripción AP-1 , Animales , Factor 2 Relacionado con NF-E2/metabolismo , Ratones , Benzaldehídos/farmacología , Estrés Oxidativo/efectos de los fármacos , FN-kappa B/metabolismo , Células RAW 264.7 , Factor de Transcripción AP-1/metabolismo , Masculino , Antiinflamatorios/farmacología , Ratones Endogámicos C57BL , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , Colitis/tratamiento farmacológico , Colitis/inducido químicamente , Modelos Animales de Enfermedad , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/inducido químicamente , Transducción de Señal/efectos de los fármacos , Hemo-Oxigenasa 1/metabolismo , Lipopolisacáridos , Hemo Oxigenasa (Desciclizante)/metabolismo , Proteínas de la Membrana/metabolismo

RESUMEN

Universal and equitable access to affordable safely managed drinking water (SMDW) is a significant challenge and is highlighted by the United Nations' Sustainable Development Goals-6.1. However, SMDW coverage by 2030 is estimated to reach only 81% of the global population. Solar water evaporation (SWE) represents one potential method to ensure decentralized water purification, but its potential for addressing the global SMDW challenge remains unclear. We use a condensation-enhanced strategy and develop a physics-guided machine learning model for assessing the global potential of SWE technology to meet SMDW demand for unserved populations without external electricity input. We find that a condensation-enhanced SWE device (1 m2) can supply enough drinking water (2.5 L day-1) to 95.8% of the population lacking SMDW. SWE can help fulfill universal SMDW coverage by 2030 with an annual cost of 10.4 billion U.S. dollars, saving 66.7% of the current investment and fulfilling the SDG-6.1 goal.

RESUMEN

In the pursuit of carbon neutrality, China's 2060 targets have been largely anchored in reducing greenhouse gas emissions, with less emphasis on the consequential benefits for air quality and public health. This study pivots to this critical nexus, exploring how China's carbon neutrality aligns with the World Health Organization's air quality guidelines (WHO AQG) regarding fine particulate matter (PM2.5) exposure. Coupling a technology-rich integrated assessment model, an emission-concentration response surface model, and exposure and health assessment, we find that decarbonization reduces sulfur dioxide (SO2), nitrogen oxides (NOx), and PM2.5 emissions by more than 90%; reduces nonmethane volatile organic compounds (NMVOCs) by more than 50%; and simultaneously reduces the disparities across regions. Critically, our analysis reveals that further targeted reductions in air pollutants, notably NH3 and non-energy-related NMVOCs, could bring most Chinese cities into attainment of WHO AQG for PM2.5 5 to 10 years earlier than the pathway focused solely on carbon neutrality. Thus, the integration of air pollution control measures into carbon neutrality strategies will present a significant opportunity for China to attain health and environmental equality.

RESUMEN

C(sp3) centers adjacent to (hetero)aryl groups are widely present in physiologically active molecules. Metal-hydride-catalyzed hydroalkylation of alkenes represents an efficient means of forging C(sp3)-C(sp3) bonds, boasting advantages as a wide source of substrates, mild reaction conditions, and facile selectivity manipulation. Nevertheless, the hydroalkylation of vinylarenes encounters constraints in terms of substrate scope, necessitating the employment of activated alkyl halides or alkenes containing chelating groups, remains a challenge. In this context, we report a general nickel-hydride-catalyzed hydroalkylation protocol for vinylarenes. Remarkably, this system enables α-selective hydroalkylation of both aryl and heteroaryl alkenes under an extra ligand-free condition, demonstrating excellent coupling efficiency and selectivity. Furthermore, through the incorporation of chiral bisoxazoline ligands, we have achieved regio- and enantioselective hydroalkylation of vinylpyrroles, thereby facilitating the synthesis of α-branched alkylated pyrrole derivatives.

RESUMEN

The inactivated quadrivalent influenza vaccine (IIV4) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23) have been administered for years and could be administered concomitantly if necessary. However, the immunogenicity and safety of the concomitant administration of these two vaccines have not been well documented, especially in the Chinese population. In this study, 480 participants aged 60 years and older were randomly assigned to the concomitant administration group (C group) or the separate administration group (S group) to receive IIV4 and PPSV23 either concomitantly or separately. Blood samples were collected before and 28 days after each vaccination. The antibodies against four influenza virus strains and twenty-three pneumococcus serotypes were tested. The results showed that the geometric mean titer (GMT) ratios (C group to S group) for the four influenza strains ranged from 0.72 to 0.95, with the lower limits of the 95% confidence intervals (CIs) ranging from 0.51 to 0.75, and the geometric mean concentration (GMC) ratios for the 23 pneumococcal serotypes ranged from 0.80 to 1.00, with the lower limits of 95% CIs ranging from 0.67 to 0.86. All values met the predefined criteria for non-inferiority. The incidence of adverse events was 0.63% in the C group and 1.56% in the S group. No serious adverse events were observed. In conclusion, the immunogenicity of the concomitant administration of IIV4 and PPSV23 was non-inferior to that of the separate administration, and the safety profile was favorable in adults aged 60 years and older in China.

RESUMEN

A visible-light-initiated energy-transfer enabled radical cyclization for the divergent synthesis of polycyclic γ-sultine derivatives has been developed. The reaction provides an alternative and expeditious access to benzofused γ-sultine frameworks, the analogues of γ-lactones and γ-sultones, and features good functional group compatibility, mild reaction conditions and excellent diastereoselectivity. The robustness and application potential of this method have also been successfully displayed by two gram-scale reactions and the synthesis of polycyclic sultones. Mechanistic studies indicated the transformations through a possible energy-transfer enabled intramolecular radical homolytic substitution or hydrogen atom transfer process mainly.

RESUMEN

Obesity shapes anti-tumor immunity through lipid metabolism; however, the mechanisms underlying how colorectal cancer (CRC) cells utilize lipids to suppress anti-tumor immunity remain unclear. Here, we show that tumor cell-intrinsic ATP6V0A1 drives exogenous cholesterol-induced immunosuppression in CRC. ATP6V0A1 facilitates cholesterol absorption in CRC cells through RAB guanine nucleotide exchange factor 1 (RABGEF1)-dependent endosome maturation, leading to cholesterol accumulation within the endoplasmic reticulum and elevated production of 24-hydroxycholesterol (24-OHC). ATP6V0A1-induced 24-OHC upregulates TGF-ß1 by activating the liver X receptor (LXR) signaling. Subsequently, the release of TGF-ß1 into the tumor microenvironment by CRC cells activates the SMAD3 pathway in memory CD8+ T cells, ultimately suppressing their anti-tumor activities. Moreover, we identify daclatasvir, a clinically used anti-hepatitis C virus (HCV) drug, as an ATP6V0A1 inhibitor that can effectively enhance the memory CD8+ T cell activity and suppress tumor growth in CRC. These findings shed light on the potential for ATP6V0A1-targeted immunotherapy in CRC.

Asunto(s)

Linfocitos T CD8-positivos , Colesterol , Neoplasias Colorrectales , Transducción de Señal , Factor de Crecimiento Transformador beta1 , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Humanos , Animales , Colesterol/metabolismo , Ratones , Línea Celular Tumoral , Factor de Crecimiento Transformador beta1/metabolismo , Memoria Inmunológica , ATPasas de Translocación de Protón Vacuolares/metabolismo , Microambiente Tumoral/inmunología , Receptores X del Hígado/metabolismo , Hidroxicolesteroles/metabolismo , Hidroxicolesteroles/farmacología , Pirrolidinas/farmacología , Proteína smad3/metabolismo , Ratones Endogámicos C57BL , Carbamatos/farmacología

RESUMEN

Helicobacter pylori (H. pylori) is currently recognized as the primary carcinogenic pathogen associated with gastric tumorigenesis, and its high prevalence and resistance make it difficult to tackle. A graph neural network-based deep learning model, employing different training sets of 13,638 molecules for pre-training and fine-tuning, was aided in predicting and exploring novel molecules against H. pylori. A positively predicted novel berberine derivative 8 with 3,13-disubstituted alkene exhibited a potency against all tested drug-susceptible and resistant H. pylori strains with minimum inhibitory concentrations (MICs) of 0.25-0.5 µg/mL. Pharmacokinetic studies demonstrated an ideal gastric retention of 8, with the stomach concentration significantly higher than its MIC at 24 h post dose. Oral administration of 8 and omeprazole (OPZ) showed a comparable gastric bacterial reduction (2.2-log reduction) to the triple-therapy, namely OPZ + amoxicillin (AMX) + clarithromycin (CLA) without obvious disturbance on the intestinal flora. A combination of OPZ, AMX, CLA, and 8 could further decrease the bacteria load (2.8-log reduction). More importantly, the mono-therapy of 8 exhibited comparable eradication to both triple-therapy (OPZ + AMX + CLA) and quadruple-therapy (OPZ + AMX + CLA + bismuth citrate) groups. SecA and BamD, playing a major role in outer membrane protein (OMP) transport and assembling, were identified and verified as the direct targets of 8 by employing the chemoproteomics technique. In summary, by targeting the relatively conserved OMPs transport and assembling system, 8 has the potential to be developed as a novel anti-H. pylori candidate, especially for the eradication of drug-resistant strains.

Asunto(s)

Antibacterianos , Berberina , Aprendizaje Profundo , Helicobacter pylori , Helicobacter pylori/efectos de los fármacos , Berberina/farmacología , Berberina/química , Berberina/farmacocinética , Antibacterianos/farmacología , Antibacterianos/química , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Pruebas de Sensibilidad Microbiana , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple/genética , Animales , Omeprazol/farmacología , Claritromicina/farmacología , Amoxicilina/farmacología

RESUMEN

The blue whistling thrush (Myophonus caeruleus) is a bird belonging to the order Passeriformes and family Muscicapidae. M. caeruleus is widely distributed in China, Pakistan, India, and Myanmar and is a resident bird in the southern part of the Yangtze River in China and summer migratory bird in the northern part of the Yangtze River. At present, there are some controversies about the classification of M. caeruleus. We use complete mitochondrial genomes to provide insights into the phylogenetic position of M. caeruleus and its relationships among Muscicapidae. The mitochondrial genome (GenBank: MN564936) is 16,815 bp long and contains 13 protein-coding genes (PCGs), 2 rRNA genes, 22 tRNA genes, and a non-coding control region (D-loop). The thirteen PCGs started with GTG and ATG and ended with five types of stop codons. The nucleotide composition of T was 23.71%, that of C was 31.45%, that of A was 30.06%, and that of G was 14.78%. The secondary structures of 22 tRNAs were predicted, all of which could form typical cloverleaf structures. There were 24 mismatches, mainly G-U mismatches. Through phylogenetic tree reconstruction, it was found that Saxicola, Monticola, Oenanthe, and Phoenicurus were clustered into one clade, together with the sister group of Myophonus.

Asunto(s)

Genoma Mitocondrial , Filogenia , ARN de Transferencia , Animales , ARN de Transferencia/genética , Pájaros Cantores/genética , Pájaros Cantores/clasificación , ARN Ribosómico/genética , Composición de Base/genética , China

RESUMEN

BACKGROUND: Postoperative pain management and cognitive function preservation are crucial for patients undergoing thoracoscopic surgery for lung cancer (LC). This is achieved using either a thoracic paravertebral block (TPVB) or sufentanil (SUF)-based multimodal analgesia. However, the efficacy and impact of their combined use on postoperative pain and postoperative cognitive dysfunction (POCD) remain unclear. AIM: To explore the analgesic effect and the influence on POCD of TPVB combined with SUF-based multimodal analgesia in patients undergoing thoracoscopic radical resection for LC to help optimize postoperative pain management and improve patient outcomes. METHODS: This retrospective analysis included 107 patients undergoing thoracoscopic radical resection for LC at The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital between May 2021 and January 2023. Patients receiving SUF-based multimodal analgesia (n = 50) and patients receiving TPVB + SUF-based multimodal analgesia (n = 57) were assigned to the control group and TPVB group, respectively. We compared the Ramsay Sedation Scale and visual analog scale (VAS) scores at rest and with cough between the two groups at 2, 12, and 24 h after surgery. Serum levels of epinephrine (E), angio-tensin II (Ang II), norepinephrine (NE), superoxide dismutase (SOD), vascular endothelial growth factor (VEGF), transforming growth factor-ß1 (TGF-ß1), tumor necrosis factor-α (TNF-α), and S-100 calcium-binding protein ß (S-100ß) were measured before and 24 h after surgery. The Mini-Mental State Examination (MMSE) was administered 1 day before surgery and at 3 and 5 days after surgery, and the occurrence of POCD was monitored for 5 days after surgery. Adverse reactions were also recorded. RESULTS: There were no significant time point, between-group, and interaction effects in Ramsay sedation scores between the two groups (P > 0.05). Significantly, there were notable time point effects, between-group differences, and interaction effects observed in VAS scores both at rest and with cough (P < 0.05). The VAS scores at rest and with cough at 12 and 24 h after surgery were lower than those at 2 h after surgery and gradually decreased as postoperative time increased (P < 0.05). The TPVB group had lower VAS scores than the control group at 2, 12, and 24 h after surgery (P < 0.05). The MMSE scores at postoperative days 1 and 3 were markedly higher in the TPVB group than in the control group (P < 0.05). The incidence of POCD was significantly lower in the TPVB group than in the control group within 5 days after surgery (P < 0.05). Both groups had elevated serum E, Ang II, and NE and decreased serum SOD levels at 24 h after surgery compared with the preoperative levels, with better indices in the TPVB group (P < 0.05). Marked elevations in serum levels of VEGF, TGF-ß1, TNF-α, and S-100ß were observed in both groups at 24 h after surgery, with lower levels in the TPVB group than in the control group (P < 0.05). CONCLUSION: TPVB combined with SUF-based multimodal analgesia further relieves pain in patients undergoing thoracoscopic radical surgery for LC, enhances analgesic effects, reduces postoperative stress response, and inhibits postoperative increases in serum VEGF, TGF-ß1, TNF-α, and S-100ß levels. This scheme also reduced POCD and had a high safety profile.

RESUMEN

Cytokines have attracted sustained attention due to their multi-functional cellular response in immunotherapy. However, their application was limited to their short half-time, narrow therapeutic window, and undesired side effects. To address this issue, we developed a portable smart blue-light controlled (PSLC) device based on optogenetic technology. By combining this PSLC device with blue-light controlled gene modules, we successfully achieved the targeted regulation of cytokine expression within the tumor microenvironment. To alter the tumor microenvironment of solid tumors, pro-inflammatory cytokines were selected as blue-light controlled molecules. The results show that blue-light effectively regulates the expression of pro-inflammatory cytokines both in vitro and in vivo. This strategy leads to enhanced and activated tumor-infiltrating immune cells, which facilitated to overcome the immunosuppressive microenvironment, resulting in significant tumor shrinkage in tumor-bearing mice. Hence, our study offers a unique strategy for cytokine therapy and a convenient device for animal studies in optogenetic immunotherapy.

Asunto(s)

Citocinas , Luz , Optogenética , Microambiente Tumoral , Animales , Citocinas/metabolismo , Ratones , Optogenética/métodos , Optogenética/instrumentación , Humanos , Línea Celular Tumoral , Inmunoterapia/métodos , Femenino , Regulación Neoplásica de la Expresión Génica , Neoplasias/terapia , Neoplasias/inmunología , Neoplasias/metabolismo

RESUMEN

Disrupted gut microbiota homeostasis is an important cause of inflammatory colitis. Studies have shown that effective supplementation with probiotics can maintain microbial homeostasis and alleviate colitis. Here, to increase the viability of probiotics in the harsh gastrointestinal environments and enable targeted delivery, a redox-sensitive selenium hyaluronic acid (HA-Se) hydrogel encapsulating probiotics was developed. HA was modified with selenocystamine dihydrochloride and crosslinked by an amide reaction to generate a redox-sensitive hydrogel with stable mechanical properties, a low hemolysis rate and satisfactory biocompatibility. The HA-Se hydrogel exhibited suitable sensitivity to 10 mM GSH or 100 µM H2O2. The encapsulation of Limosilactobacillus reuteri (LR) in the HA-Se hydrogel (HA-Se-LR) significantly increased the survival rate of the probiotics in simulated gastric and intestinal fluid. HA-Se-LR administration increased the survival rate of mice with dextran sulfate sodium (DSS)-induced colitis, significantly alleviated oxidative stress and inflammation, and increased the effect of LR on microbiota α diversity. These results indicate that the HA-Se hydrogel constructed in this study can be used as a delivery platform to treat colitis, expanding the targeted applications of the natural polymer HA in disease treatment and the administration of probiotics as drugs to alleviate disease symptoms.

Asunto(s)

Colitis , Cistamina , Sulfato de Dextran , Modelos Animales de Enfermedad , Ácido Hialurónico , Hidrogeles , Limosilactobacillus reuteri , Oxidación-Reducción , Probióticos , Animales , Ácido Hialurónico/química , Hidrogeles/química , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Ratones , Cistamina/química , Compuestos de Organoselenio/farmacología , Compuestos de Organoselenio/química , Estrés Oxidativo/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Cistina/análogos & derivados

RESUMEN

Minimizing sludge generation in activated sludge systems is critical to reducing the operational cost of wastewater treatment plants (WWTPs), particularly for small plants where bioenergy is not recovered. This study introduces a novel acidic activated sludge technology for in situ sludge yield reduction, leveraging acid-tolerant ammonia-oxidizing bacteria (Candidatus Nitrosoglobus). The observed sludge yield (Yobs) was calculated based on the cumulative sludge generation and COD removal during 400 d long-term operation. The acidic process achieved a low Yobs of 0.106 ± 0.004 gMLSS/gCOD at pH 4.6 to 4.8 and in situ free nitrous acid (FNA) of 1 to 3 mg/L, reducing sludge production by 58 % compared to the conventional neutral-pH system (Yobs of 0.250 ± 0.003 gMLSS/gCOD). The acidic system also maintained effective sludge settling and organic matter removal over long-term operation. Mechanism studies revealed that the acidic sludge displayed higher endogenous respiration, sludge hydrolysis rates, and higher soluble microbial products and loosely-bounded extracellular polymer substances, compared to the neutral sludge. It also selectively enriched several hydrolytic genera (e.g., Chryseobacterium, Acidovorax, and Ottowia). Those results indicate that the acidic pH and in situ FNA enhanced sludge disintegration, hydrolysis, and cryptic growth. Besides, a lower intracellular ATP content was observed for acidic sludge than neutral sludge, suggesting potential decoupling of catabolism and anabolism in the acidic sludge. These findings collectively demonstrate that the acidic activated sludge technology could significantly reduce sludge yield, contributing to more cost- and space-effective wastewater management.

Asunto(s)

Aguas del Alcantarillado , Eliminación de Residuos Líquidos , Aguas del Alcantarillado/microbiología , Eliminación de Residuos Líquidos/métodos , Concentración de Iones de Hidrógeno , Reactores Biológicos , Amoníaco/metabolismo