AtSNU13 modulates pre-mRNA splicing of RBOHD and ALD1 to regulate plant immunity.

Pre-mRNA splicing is a significant step for post-transcriptional modifications and functions in a wide range of physiological processes in plants. Human NHP2L binds to U4 snRNA during spliceosome assembly; it is involved in RNA splicing and mediates the development of human tumors. However, no ortholog has yet been identified in plants. Therefore, we report At4g12600 encoding the ortholog NHP2L protein, and AtSNU13 associates with the component of the spliceosome complex; the atsnu13 mutant showed compromised resistance in disease resistance, indicating that AtSNU13 is a positive regulator of plant immunity. Compared to wild-type plants, the atsnu13 mutation resulted in altered splicing patterns for defense-related genes and decreased expression of defense-related genes, such as RBOHD and ALD1. Further investigation shows that AtSNU13 promotes the interaction between U4/U6.U5 tri-snRNP-specific 27 K and the motif in target mRNAs to regulate the RNA splicing. Our study highlights the role of AtSNU13 in regulating plant immunity by affecting the pre-mRNA splicing of defense-related genes.

The clade III subfamily of OsSWEETs directly suppresses rice immunity by interacting with OsHMGB1 and OsHsp20L.

The clade III subfamily of OsSWEETs includes transmembrane proteins necessary for susceptibility to bacterial blight (BB). These genes are targeted by the specific transcription activator-like effector (TALE) of Xanthomonas oryzae pv. oryzae and mediate sucrose efflux for bacterial proliferation. However, the mechanism through which OsSWEETs regulate rice immunity has not been fully elucidated. Here, we demonstrated that the cytosolic carboxyl terminus of OsSWEET11a/Xa13 is required for complementing susceptibility to PXO99 in IRBB13 (xa13/xa13). Interestingly, the C-terminus of ZmXa13, the maize homologue of OsSWEET11a/Xa13, could perfectly substitute for the C-terminus of OsSWEET11a/Xa13. Furthermore, OsSWEET11a/Xa13 interacted with the high-mobility group B1 (OsHMGB1) protein and the small heat shock-like protein OsHsp20L through the same regions in the C-terminus. Consistent with the physical interactions, knockdown or knockout of either OsHMGB1 or OsHsp20L caused an enhanced PXO99-resistant phenotype similar to that of OsSWEET11a/OsXa13. Surprisingly, the plants in which OsHMGB1 or OsHsp20L was repressed developed increased resistance to PXO86, PXO61 and YN24, which carry TALEs targeting OsSWEET14/Xa41 or OsSWEET11a/Xa13. Additionally, OsHsp20L can interact with all six members of clade III OsSWEETs, whereas OsHMGB1 can interact with five other members in addition to OsSWEET12. Overall, we revealed that OsHMGB1 and OsHsp20L mediate conserved BB susceptibility by interacting with clade III OsSWEETs, which are candidates for breeding broad-spectrum disease-resistant rice.

Ame-miR-1-3p of bee venom reduced cell viability through the AZIN1/OAZ1-ODC1-polyamines pathway and enhanced the defense ability of honeybee (Apis mellifera L.).

Bee venom serves as an essential defensive weapon for bees and also finds application as a medicinal drug. MicroRNAs (miRNAs) serve as critical regulators and have been demonstrated to perform a variety of biological functions. However, the presence of miRNAs in bee venom needs to be confirmed. Therefore, we conducted small RNA sequencing and identified 158 known miRNAs, 15 conserved miRNAs and 4 novel miRNAs. It is noteworthy that ame-miR-1-3p, the most abundant among them, accounted for over a quarter of all miRNA reads. To validate the function of ame-miR-1-3p, we screened 28 candidate target genes using transcriptome sequencing and three target gene prediction software (miRanda, PITA and TargetScan) for ame-miR-1-3p. Subsequently, we employed real-time quantitative reverse transcription PCR (qRT-PCR), Western blot and other technologies to confirm that ame-miR-1-3p inhibits the relative expression of antizyme inhibitor 1 (AZIN1) by targeting the 3' untranslated region (UTR) of AZIN1. This, in turn, caused ODC antizyme 1 (OAZ1) to bind to ornithine decarboxylase 1 (ODC1) and mark ODC1 for proteolytic destruction. The reduction in functional ODC1 ultimately resulted in a decrease in polyamine biosynthesis. Furthermore, we determined that ame-miR-1-3p accelerates cell death through the AZIN1/OAZ1-ODC1-polyamines pathway. Our studies demonstrate that ame-miR-1-3p diminishes cell viability and it may collaborate with sPLA2 to enhance the defence capabilities of honeybees (Apis mellifera L.). Collectively, these data further elucidate the defence mechanism of bee venom and expand the potential applications of bee venom in medical treatment.

The functions of laccase gene GhLAC15 in fiber colouration and development in brown-colored cotton.

The monotonicity of color type in naturally colored cottons (NCCs) has become the main limiting factor to their widespread use, simultaneously coexisting with poor fiber quality. The synchronous improvement of fiber quality and color become more urgent and crucial as the demand for sustainable development increases. The homologous gene of wild cotton Gossypium stocksii LAC15 in G. hirsutum, GhLAC15, was also dominantly expressed in the developing fibers of brown cotton XC20 from 5 DPA (day post anthesis) to 25 DPA, especially at the secondary cell wall thickening stage (20 DPA and 25 DPA). In XC20 plants with downregulated GhLAC15 (GhLAC15i), a remarkable reduction in proanthocyanidins (PAs) and lignin contents was observed. Some of the key genes in the phenylpropane and flavonoid biosynthesis pathway were down-regulated in GhLAC15i plants. Notably, the fiber length of GhLAC15i plants showed an obvious increase and the fiber color was lightened. Moreover, we found that the thickness of cotton fiber cell wall was decreased in GhLAC15i plants and the fiber surface became smoother compared to that of WT. Taken together, this study revealed that GhLAC15 played an important role in PAs and lignin biosynthesis in naturally colored cotton fibers. It might mediate fiber color and fiber quality by catalyzing PAs oxidation and lignin polymerization, ultimately regulating fiber colouration and development.

Prioritizing Non-Carbon Dioxide Removal Mitigation Strategies Could Reduce the Negative Impacts Associated with Large-Scale Reliance on Negative Emissions.

Carbon dioxide removal (CDR) is necessary for reaching net zero emissions, with studies showing potential deployment at multi-GtCO2 scale by 2050. However, excessive reliance on future CDR entails serious risks, including delayed emissions cuts, lock-in of fossil infrastructure, and threats to sustainability from increased resource competition. This study highlights an alternative pathway─prioritizing near-term non-CDR mitigation and minimizing CDR dependence. We impose a 1 GtCO2 limit on global novel CDR deployment by 2050, forcing aggressive early emissions reductions compared to 8-22 GtCO2 in higher CDR scenarios. Our results reveal that this low CDR pathway significantly decreases fossil fuel use, greenhouse gas (GHG) emissions, and air pollutants compared to higher CDR pathways. Driving rapid energy transitions eases pressures on land (including food cropland), water, and fertilizer resources required for energy and negative emissions. However, these sustainability gains come with higher mitigation costs from greater near-term low/zero-carbon technology deployment for decarbonization. Overall, this work provides strong evidence for maximizing non-CDR strategies such as renewables, electrification, carbon neutral/negative fuels, and efficiency now rather than betting on uncertain future CDR scaling. Ambitious near-term mitigation in this decade is essential to prevent lock-in and offer the best chance of successful deep decarbonization. Our constrained CDR scenario offers a robust pathway to achieving net zero emissions with limited sustainability impacts.

A forecasting model for suitable dental implantation in canine mandibular premolar region based on finite element analysis.

In recent years, dental implants have become a trend in the treatment of human patients with missing teeth, which may also be an acceptable method for companion animal dentistry. However, there is a gap challenge in determining appropriate implant sizes for different dog breeds and human. In this study, we utilized skull computed tomography data to create three-dimensional models of the mandibles of dogs in different sizes. Subsequently, implants of various sizes were designed and subjected to biomechanical finite element analysis to determine the optimal implant size. Regression models were developed, exploring the relationship between the average weight of dogs and the size of premolar implants. Our results illustrated that the regression equations for mean body weight (x, kg) and second premolar (PM2), third premolar (PM3), and fourth premolar (PM4) implant length (y, mm) in dogs were: y = 0.2785x + 7.8209, y = 0.2544x + 8.9285, and y = 0.2668x + 10.652, respectively; the premolar implant diameter (mm) y = 0.0454x + 3.3506, which may provide a reference for determine suitable clinical implant sizes for dogs.

Trends in the incidence and survival of cancer in individuals aged 55 years and older in the United States, 1975-2019.

BACKGROUND: In ageing societies such as the United States, evaluating the incidence and survival rates of cancer in older adults is essential. This study aimed to analyse the incidence and survival rates of cancer in individuals aged 55 years or older in the United States. METHODS: This retrospective study (1975-2019) was conducted using combined registry data from the Surveillance, Epidemiology, and End Results database. Data from the 9, 12, and 17 Registries (Nov 2021 Sub) datasets were used. RESULTS: In 2019, the incidence of cancer in individuals older than 55 years and the overall population was 1322.8 and 382.1 per 100,000 population, respectively. From 2000 to 2019, the incidence of cancer in individuals older than 55 years showed a decreasing trend, whereas their five-year survival rates showed an increasing trend. The incidence of cancer in the 75-79 and 80-84 year age groups was the highest among all age groups. CONCLUSIONS: The incidence of colon cancer declined significantly, whereas that of intrahepatic bile duct cancer increased considerably. These trends may be due to increased screening for cancers with high incidence rates and improved control of the risk factors for cancer. Rapid development of targeted therapy and immunotherapy combined with early tumour detection may be an important reason for the improved survival rates.

Evaluation of disease severity and prediction of severe cases in children hospitalized with influenza A (H1N1) infection during the post-COVID-19 era: a multicenter retrospective study.

BACKGROUND: The rebound of influenza A (H1N1) infection in post-COVID-19 era recently attracted enormous attention due the rapidly increased number of pediatric hospitalizations and the changed characteristics compared to classical H1N1 infection in pre-COVID-19 era. This study aimed to evaluate the clinical characteristics and severity of children hospitalized with H1N1 infection during post-COVID-19 period, and to construct a novel prediction model for severe H1N1 infection. METHODS: A total of 757 pediatric H1N1 inpatients from nine tertiary public hospitals in Yunnan and Shanghai, China, were retrospectively included, of which 431 patients diagnosed between February 2023 and July 2023 were divided into post-COVID-19 group, while the remaining 326 patients diagnosed between November 2018 and April 2019 were divided into pre-COVID-19 group. A 1:1 propensity-score matching (PSM) was adopted to balance demographic differences between pre- and post-COVID-19 groups, and then compared the severity across these two groups based on clinical and laboratory indicators. Additionally, a subgroup analysis in the original post-COVID-19 group (without PSM) was performed to investigate the independent risk factors for severe H1N1 infection in post-COIVD-19 era. Specifically, Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to select candidate predictors, and logistic regression was used to further identify independent risk factors, thus establishing a prediction model. Receiver operating characteristic (ROC) curve and calibration curve were utilized to assess discriminative capability and accuracy of the model, while decision curve analysis (DCA) was used to determine the clinical usefulness of the model. RESULTS: After PSM, the post-COVID-19 group showed longer fever duration, higher fever peak, more frequent cough and seizures, as well as higher levels of C-reactive protein (CRP), interleukin 6 (IL-6), IL-10, creatine kinase-MB (CK-MB) and fibrinogen, higher mechanical ventilation rate, longer length of hospital stay (LOS), as well as higher proportion of severe H1N1 infection (all P < 0.05), compared to the pre-COVID-19 group. Moreover, age, BMI, fever duration, leucocyte count, lymphocyte proportion, proportion of CD3+ T cells, tumor necrosis factor α (TNF-α), and IL-10 were confirmed to be independently associated with severe H1N1 infection in post-COVID-19 era. A prediction model integrating these above eight variables was established, and this model had good discrimination, accuracy, and clinical practicability. CONCLUSIONS: Pediatric H1N1 infection during post-COVID-19 era showed a higher overall disease severity than the classical H1N1 infection in pre-COVID-19 period. Meanwhile, cough and seizures were more prominent in children with H1N1 infection during post-COVID-19 era. Clinicians should be aware of these changes in such patients in clinical work. Furthermore, a simple and practical prediction model was constructed and internally validated here, which showed a good performance for predicting severe H1N1 infection in post-COVID-19 era.

Successful Conservative Treatment of Necrotizing Pneumonia in Pediatric Patients: Two Case Reports.

Objective: Necrotizing pneumonia is a rare and serious complication in pediatric patients, and its treatment often involves the complexity of choosing between surgical intervention and medical management. The disease is difficult to treat because of its devastating characteristics and high mortality rate, especially when considering the risks associated with surgery. The purpose of this report is to present two cases of necrotizing pneumonia in pediatric patients and demonstrate successful conservative management to provide additional insights for clinical decision-making. Case Report: We report two pediatric patients, aged 3 years 7 months and 7 years respectively, who presented with varying degrees of clinical symptoms, including persistent high fever, shortness of breath, and were confirmed to have necrotizing pneumonia after thorough diagnosis and underwent a period of intensive care. Weeks of treatment. Both patients received long-term antibiotic therapy, ventilator support, and analgesia. Conservative management including type of antibiotics, duration of treatment, specific parameters of respiratory support, and analgesic medications is detailed. Conclusion: Our case report highlights that necrotizing pneumonia can be successfully treated with conservative treatment, thus obviating the need for early surgical intervention. These findings are potentially important for guiding clinical practice, suggesting that conservative management can be an effective treatment strategy for necrotizing pneumonia in certain circumstances.

Molecular mechanism of selenium against lead-induced apoptosis in chicken brainstem relating to heat shock protein, selenoproteins, and inflammatory cytokines.

Extensive application of lead (Pb) brought about environmental pollution and toxic reactions of organisms. Selenium (Se) has the effect of antagonizing Pb poisoning in humans and animals. However, it is still unclear how Pb causes brainstem toxicity. In the present study, we wanted to investigate whether Se can alleviate Pb toxicity in chicken brainstems by reducing apoptosis. One hundred and eighty chickens were randomly divided into four groups, namely the control group, the Se group, the Pb group, and the Se/Pb group. Morphological examination, ultrastructural observation, relative mRNA expressions of genes on heat shock proteins (HSPs); selenoproteins; inflammatory cytokines; and apoptosis-related factors were investigated. The results showed that Pb exposure led to tissue damage and apoptosis in chicken brainstems. Furthermore, an atypical expression of HSPs (HSP27, HSP40, HSP60, HSP70, and HSP90); selenoprotein family glutathione peroxidase (GPx) 1, GPx2, GPx3, and GPx4), thioredoxin reductases (Txnrd) (Txnrd1, Txnrd2, and Txnrd3), dio selenoprotein famliy (diodothyronine deiodinases (Dio)1, Dio2, and Dio3), as well as other selenoproteins (selenoprotein (Sel)T, SelK, SelS, SelH, SelM, SelU, SelI, SelO, Selpb, selenoprotein n1 (Sepn1), Sepp1, Sepx1, Sepw1, 15-kDa selenoprotein (Sep15), and selenophosphate synthetases 2 (SPS2)); inflammatory cytokines (Interleukin 2 (IL-2), IL-4, IL-6, IL-12ß, IL-17, and Interferon-γ (IFN-γ)); and apoptosis-related genes (B-cell lymphoma-2 (Bcl-2), tumor protein 53 (p53), Bcl-2 Associated X (Bax), Cytochrome c (Cyt c), and Caspase-3) were identified. An inflammatory reaction and apoptosis were induced in chicken brainstems after exposure to Pb. Se alleviated the abnormal expression of HSPs, selenoproteins, inflammatory cytokines, and apoptosis in brainstem tissues of chickens treated with Pb. The results indicated that HSPs, selenoproteins, inflammatory, and apoptosis were involved in Se-resisted Pb poisoning. Overall, Se had resistance effect against Pb poisoning, and can be act as an antidote for Pb poisoning in animals.

Modified Suture-Button Latarjet Procedure With Coracoacromial Ligament and Pectoralis Minor Preservation Achieves Good Clinical Outcomes at 2-Year Follow-Up: Case Series of Latarjet Technique.

PURPOSE: To evaluate whether the modified suture-button Latarjet procedure with coracoacromial ligament (CAL) and pectoralis minor (PM) preservation could achieve excellent outcomes at the 2-year follow-up. METHODS: During January 2019 to January 2021, the data of patients who underwent modified suture-button Latarjet with CAL and PM preservation in our department were collected. The glenoid bone loss of these patients was greater than 20% or greater than 10% with high demands for exercise. Partial coracoid osteotomy was based on the results of a preoperative 3-dimensional computed tomography evaluation of the glenoid defect area and corresponding coracoid process morphology. The preoperative and postoperative clinical results were assessed. The minimal clinically important difference (MCID) was used to compare improvement in clinical outcomes. Graft-glenoid union and remodeling were assessed using postoperative 3-dimensional computed tomography, and magnetic resonance imaging was performed to confirm the integrity of the CAL and PM postoperatively. RESULTS: In total, 35 patients were included in this study; the mean follow-up time was 26.9 ± 1.9 months. No case of recurrent dislocation or sublaxity. Significant improvements were observed in mean visual analog scale (VAS) scores for pain during motion, American Shoulder and Elbow Surgeons (ASES) score, Rowe score, and Walch-Duplay score (P < .001). The percentage of patients achieving at least an MCID improvement in clinical outcomes was VAS 85.71%, ASES 97.14%, Rowe 100%, and Walch-Duplay 97.14%. Thirty-three patients (94.3% of all cases) were able to return to their preoperative sport levels, 34 grafts (97.1%) achieved bone union (1 soft union) in 6.3 ± 2.2 months, and the coracoid grafts restored 97.1 ± 4.0% of the perfect-fitting circle at the last follow-up. Postoperative computed tomography scan showed that 31 grafts (88.6%) were placed ideally in vertical view. In the axial view, 25 grafts (82.9%) were flushed to the glenoid, whereas 1 and 5 grafts were fixed medially and laterally, respectively. The CAL and PM were visualized postoperatively. No arthropathy was observed in any patient at the last follow-up. CONCLUSIONS: The modified suture-button Latarjet procedure with CAL and PM preservation obtained good clinical and radiological results without recurrence or complications. A substantial number of patients (>85%) achieved the MCID for the VAS, ASES, Rowe, and Walch-Duplay scores. In addition, the malpositioned graft (17.1%) did not cause arthropathy of the joints at 2-year follow-up. LEVEL OF EVIDENCE: Level IV, retrospective case series.

[High-value utilization technology and approach of Chinese medicinal residues under background of "Dual Carbon"].

In recent years, the traditional Chinese medicine(TCM)industry has experienced rapid development, resulting in a significant amount of Chinese medicinal residues generated during the industrial manufacturing process. Currently, the main methods of handling Chinese medicinal residues include stacking, landfilling, and incineration, which lead to substantial resource waste and potential environmental pollution. With "carbon peak" and "carbon neutrality"( "Dual Carbon")becoming national strategic goals, the TCM industry is ushering in a new wave of "low-carbon" trends, and the high-value utilization of Chinese medicinal residues has become a breakthrough for implementing a low-carbon economy in the TCM sector. From the perspective of a low-carbon economy, this article reviewed literature in China and abroad to summarize the microbial transformation technology, enzymatic conversion technology, biomass pyrolysis, gasification, hydrothermal liquefaction, and other high-value utilization technologies for Chinese medicinal residues. It also overviewed the applications of Chinese medicinal residue in feed additives, organic fertilizers, edible mushroom cultivation substrates, preparation of activated carbon for wastewater treatment, and new energy batteries. Considering the current status of resource utilization of Chinese medicinal residues, feasible strategies and suggestions for resource development and utilization were proposed to improve the quality and efficiency of the Chinese medicinal resource industry chain and promote green development, thereby providing research ideas and theoretical basis for achieving carbon peak and carbon neutrality goals.

Portal venous blood flow velocity is a factor associated with portal venous thrombosis after partial splenic artery embolization in hepatic cirrhosis patients.

Objective: To investigate risk factors for portal venous thrombosis (PVT) after partial splenic artery embolization (PSE) in hepatic cirrhosis patients. Methods: The authors retrospectively analyzed 151 hepatic cirrhosis patients with hypersplenism who underwent partial splenic artery embolization between January 2020 and December 2021. The patients were divided into a PVT group and a non-PVT group according to whether they had PVT after PSE. Univariate analyses were performed to select risk factors for PVT after PSE, and multivariate analysis was used to analyze variates with a value of P less than 0.1 in univariate analysis. Results: There were 151 patients enroled in the study, with 22 patients in the PVT group and 129 patients in the non-PVT group. There was no significant difference in terms of age, sex, smoking, hypertension, diabetes, Child-Pugh between two groups. White blood cell (WBC) and platelet counts after PSE were significantly higher than those before PSE in both the PVT group and non-PVT group. Univariate analysis showed that portal venous blood flow velocity, ligation of oesophageal varices and WBC after PSE were found to have a P value less than 0.1. Multivariate analysis showed that portal venous blood flow velocity was a factor associated with PVT after PSE. Conclusion: Portal venous blood flow velocity was a factor associated with PVT after PSE. Portal venous blood flow velocity should be considered before patients undergo PSE.

Exploring SDHI fungicide resistance in Botrytis cinerea through genetic transformation system and AlphaFold model-based molecular docking.

BACKGROUND: Gray mold caused by Botrytis cinerea is one of the most serious diseases affecting strawberry. Succinate dehydrogenase inhibitor (SDHI) fungicides have been used for more than a decade to control the disease. Monitoring resistance and improving in-depth understanding of resistance mechanisms are essential for the control of B. cinerea. RESULTS: In this study, resistance monitoring of a SDHI fungicide boscalid was conducted on B. cinerea isolated from strawberries in Korea during 2020 and 2021, with resistance rates of 76.92% and 72.25%, respectively. In resistant strains, mutations P225F/H and H272R were found in SdhB, with P225F representing the dominant mutation type. Simultaneous mutations G85A, I93V, M158V, and V168I in SdhC were detected in 54.84% of sensitive strains. Sensitivity profiles of different Sdh genotypes of B. cinerea strains to six SDHIs were determined in vitro and in vivo. In addition, the mutation(s) were genetically validated through in situ SdhB (SdhC) expression. Docking assays between SDHIs and AlphaFold model-based Sdh complexes revealed generally consistent patterns with their in vitro phenotypes. CONCLUSION: Resistance of B. cinerea to SDHI fungicide on strawberry was systematically investigated in this study. Deciphering of SDHI resistance through the genetic transformation system and AlphaFold model-based molecular docking will provide valuable insights into other target site-based fungicide resistance in fungal pathogens. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Combustion Enhancement of Gel Propellant Containing High Concentration Aluminum Particles Based on Carbon Synergistic Effect.

The addition of aluminum particles to gel propellants can improve combustion performance. However, the agglomeration of aluminum during the combustion process can result in a series of negative effects. In this paper, the aluminum agglomeration inhibition method of gel propellant based on carbon synergistic effect is proposed. Carbon particles exhibit excellent combustion properties, and the gaseous product CO2 generated during combustion can mitigate the agglomeration of aluminum. The research demonstrates that incorporating carbon particles into aluminum-containing gel effectively reduces the incomplete combustion of aluminum particles and increases the volumetric calorific value of the gel. When the mass fraction of carbon is 5 wt%, the volume calorific value of the gel reaches the highest. Meanwhile, the rheological experiments show that the addition of carbon particles can improve the shear-thinning properties of the gel, which is beneficial to the atomization and combustion processes of the gel.

Role of Embinin in the reabsorption of nucleus pulposus in lumbar disc herniation: Promotion of nucleus pulposus neovascularization and apoptosis of nucleus pulposus cells.

Reabsorption of the nucleus pulposus (NP) in lumbar disc herniation (LDH) refers to the natural absorption or even complete disappearance of LDH. In order to better treat LDH, it is necessary to further study its mechanism and develop new therapeutic drugs. Clematidis Radix Et Rhizoma is a ranunculus family plant which has multiple biological activities, and Embinin is one of its bioactive ingredients. However, its effects on LDH were unclear. In this study, the role of Embinin was investigated in LDH rat models. LDH model was established by lumbar epidural insertion of tail disc. Our results showed that Embinin promoted lumbar disc neovascularization, induced apoptosis of NP cells in LDH rats, and promoted lumbar disc resorption. Furthermore, mechanistic study showed that Embinin activated the cAMP pathway in the rat models. In conclusion, Embinin has the potential to serve as a drug for the treatment of LDH.

Prognostic nomogram model for selecting between transarterial chemoembolization plus lenvatinib, with and without PD-1 inhibitor in unresectable hepatocellular carcinoma.

OBJECTIVES: To establish and verify a prognostic nomogram model for selecting in unresectable hepatocellular carcinoma (uHCC) treated by transarterial chemoembolization plus lenvatinib (TACE-L) with or without PD-1 inhibitor. METHODS: Data of 241 uHCC patients who underwent TACE-L (n = 128) and TACE-L plus PD-1 inhibitor (TACE-L-P, n = 113) were retrospectively reviewed. The differences in tumour responses, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) between two groups were compared, and a prognostic nomogram model was established based on independent clinical-radiologic factors and confirmed by Cox regression analysis for predicting PFS and OS. The treatment selection for uHCC patients was stratified by the nomogram score. RESULTS: Compared to TACE-L, TACE-L-P presented prolonged PFS (14.0 vs. 9.0 months, P < .001), longer OS (24.0 vs. 15.0 months, P < .001), and a better overall objective response rate (54.0% vs. 32.8%, P = .001). There was no significant difference between the rate of AEs in the TACE-L-P and the TACE-L (56.64% vs. 46.09%, P = .102) and the rate of grade ≥ 3 AEs (11.50% vs. 9.38%, P = .588), respectively. The nomogram model presented good discrimination, with a C-index of 0.790 for predicting PFS and 0.749 for predicting OS. Patients who underwent TACE-L and obtained a nomogram score >9 demonstrated improved 2-year PFS when transferred to TACE-L-P, and those with a nomogram ≤25 had better 2-year OS when transferred to TACE-L-P. CONCLUSIONS: TACE-L-P showed significant improvements in efficiency and safety for uHCC patients compared with TACE-L. The nomogram was useful for stratifying treatment decisions and selecting a suitable population for uHCC patients. ADVANCES IN KNOWLEDGE: Prognostic nomogram model is of great value in predicting individualized survival benefits for uHCC patients after TACE-L or/and TACE-L-P. And the nomogram was helpful for selection between TACE-L-P and TACE-L among uHCC patients.

miRNA-seq analysis of liver tissue from largemouth bass (Micropterus salmoides) in response to oxytetracycline and enzyme-treated soy protein.

The specific miRNA regulation triggered by enzyme-treated soybean protein in response to well-known stressors, such as the prophylactic use of the antimicrobial oxytetracycline, remains unknown. Hence, this study aimed to evaluate the regulatory changes of hepatic miRNAs induced by oxytetracycline and enzyme-treated soybean protein in largemouth bass dietary formulations. The experiment was designed with three groups: the normal control (NC), the oxytetracycline exposure treatment group (OTC), and the pre-treatment with enzyme-treated soybean protein before oxytetracycline exposure group (ETSP). miRNA sequencing was employed to characterize the differences between these groups. In conclusion, the NC group exhibited up-regulation of 13 host miRNAs and down-regulation of 1 miRNA compared to the OTC group, whereas the ETSP group showed an increasing trend of 36 host miRNAs and a decreasing trend of 13 host miRNAs compared to the OTC group. Nine miRNAs were identified as prudential targets for enzyme-treated soy protein, protecting the largemouth bass liver from oxytetracycline. Furthermore, gene ontology analysis revealed nine key miRNAs that mediate signaling pathways with significant differences. The cellular lipid metabolic process was identified as the most important biological process, and the propanoate metabolism pathway was highlighted as significant. These results will facilitate further exploration of the mechanism by which enzyme-treated soy protein alleviates the effects of oxytetracycline on largemouth bass in water environments.

Episodic memory network characteristics in patients with amnestic mild cognitive impairment accompanied by executive function impairment.

OBJECTIVE: To explore the functional connectivity (FC) characteristics of the episodic memory network (EMN) in amnestic mild cognitive impairment (aMCI) patients with different levels of executive function (EF). METHODS: This study included 76 participants from the Alzheimer's Disease Neuroimaging Initiative database, comprising 23 healthy controls (HCs) and 53 aMCI patients. Based on EF levels, aMCI patients were categorized into aMCI-highEF and aMCI-lowEF groups. Cognitive function scores, pathological markers (cerebrospinal fluid ß-amyloid, total tau protein, phosphorylated tau protein, AV45-PET, and FDG-PET), and functional magnetic resonance imaging were collected and compared among the three groups. Seed-based FC analysis was used to examine differences in the EMN among the groups, and partial correlation analysis was employed to investigate the relationship between changes in FC and cognitive function scores as well as pathological markers. RESULTS: Compared to the aMCI-highEF group, the aMCI-lowEF group exhibited more severe cognitive impairment, decreased cerebral glucose metabolism, and elevated AV45 levels. Significant FC differences in the left superior temporal gyrus (STG) of the EMN were observed among the three groups. Post hoc analysis revealed that the aMCI-lowEF group had increased FC in the left STG compared to the HCs and aMCI-highEF groups, with statistically significant differences. Correlation analysis showed a significant negative correlation between the differences in FC in the left STG of aMCI-highEF and aMCI-lowEF groups and Rey Auditory Verbal Learning Test forgetting scores. Receiver operator characteristic curve analysis indicated an area under the curve of 0.741 for distinguishing between aMCI-highEF and aMCI-lowEF groups based on FC of left STG, with a sensitivity of 0.808 and a specificity of 0.667. CONCLUSION: aMCI-lowEF exhibits characteristic changes in FC within the EMN, providing theoretical support for the role of EF in mediating EMN alterations and, consequently, impacting episodic memory function.

Multifunctional tannic acid-based nanocomposite methacrylated silk fibroin hydrogel with the ability to scavenge reactive oxygen species and reduce inflammation for bone regeneration.

The microenvironment of bone defect site is vital for bone regeneration. Severe bone defect is often accompanied with severe inflammation and elevated generation of reactive oxygen species (ROS) during bone repair. In recent years, the unfriendly local microenvironment has been paid more and more attention. Some bioactive materials with the ability to regulate the microenvironment to promote bone regeneration urgently need to be developed. Here, we develop a multifunctional composite hydrogel composed of photo-responsive methacrylate silk fibroin (SFMA), laponite (LAP) nanocomposite and tannic acid (TA), aiming to endow hydrogel with antioxidant, anti-inflammatory and osteogenic induction ability. Characterization results confirmed that the SFMA-LAP@TA hydrogel could significantly improve the mechanical properties of hydrogel. The ROS-Scavenging ability of the hydrogel enabled bone marrow mesenchymal stem cells (BMSCs) to survive against H2O2-induced oxidative stress. In addition, the SFMA-LAP@TA hydrogel effectively decreased the expression of pro-inflammatory factors in RAW264.7. More importantly, the SFMA-LAP@TA hydrogel could enhance the expression of osteogenic markers of BMSCs under inflammatory condition and greatly promote new bone formation in a critical-sized cranial defect model. Above all, the multifunctional hydrogel could effectively promote bone regeneration in vitro and in vivo by scavenging ROS and reducing inflammation, providing a prospective strategy for bone regeneration.