Hepatic arterial infusion chemotherapy plus camrelizumab and apatinib for advanced hepatocellular carcinoma.

BACKGROUND AND AIMS: There is limited information on combination of hepatic arterial infusion chemotherapy (HAIC) and systemic therapy for advanced hepatocellular carcinoma (Ad-HCC). We aim to compare the efficacy and safety of HAIC plus camrelizumab (a PD-1 inhibitor) and apatinib (an VEGFR-2 inhibitor) versus camrelizumab and apatinib for Ad-HCC. METHODS: From April 2019 to October 2022, 416 patients with Ad-HCC who received either HAIC plus camrelizumab and apatinib (TRIPLET protocol, n = 207) or camrelizumab and apatinib (C-A protocol, n = 209) were reviewed retrospectively. The propensity score matching (PSM) was used to reduce selective bias. Overall survival (OS) and progression-free survival (PFS) were compared using the Kaplan-Meier method with the log-rank test. Cox regression analyses of independent prognostic factors were evaluated. RESULTS: After PSM 1:1, 109 patients were assigned to two groups. The median OS of not reached in the TRIPLET group was significantly longer than that of 19.9 months in the C-A group (p < 0.001), while in the TRIPLET group, the median PFS of 11.5 months was significantly longer than that of 9.6 months in the C-A group (p < 0.001). Multivariate analyses showed that the factors significantly affected the OS were CTP grade, tumor number > 3, and TRIPLET treatment (p < 0.001). Grade 3/4 adverse events occurred at a rate of 82.1% vs. 71.3% in TRIPLET and C-A groups, respectively. CONCLUSION: The TRIPLET protocol has promising survival benefits in the management of patients with Ad-HCC, with acceptable safety. TRAIL REGISTRATION: The study has been retrospectively registered at Chinese Clinical Trial Registry ( https://www.chictr.org.cn/ , ChiCTR2300075828).

Fulvenallenyl Radical (C7H5·)-Mediated Gas-Phase Synthesis of Bicyclic Aromatic C10H8 Isomers: Can Fulvenallenyl Efficiently React with Closed-Shell Hydrocarbons?

To understand the reactivity of resonantly stabilized radicals, often found in relevant concentrations in gaseous environments, it is important to determine their main reaction pathways. Here, it is investigated whether the fulvenallenyl radical (C7H5·) reacts preferentially with closed-shell molecules or radicals. Electronic structure calculations on the C10H9 potential energy surface accessed by the reactions of C7H5· with methylacetylene (CH3CCH) and allene (H2CCCH2) were combined with RRKM-ME calculations of temperature- and pressure-dependent rate constants using the automated EStokTP software suite and kinetic modeling to assess the reactivity of C7H5· with closed-shell unsaturated hydrocarbons. Experimentally, the reactions were attempted in a chemical microreactor heated to 998 ± 10 K by preparing fulvenallenyl radicals via pyrolysis of trichloromethylbenzene (C7H5Cl3) and seeding the radicals in methylacetylene or allene carrier gas, with product identification by means of photoionization mass spectrometry. The measured photoionization efficiency curve of m/z = 128 was assigned to a linear combination of the reference curves of two C10H8 isomers, azulene (minor) and naphthalene (major), presumably resulting from the C7H5· plus C3H4 reactions. However, the calculations demonstrated that these reactions are too slow, and kinetic modeling of processes in the reactor allowed us to conclude that the observation of naphthalene and azulene is due to the C7H5· plus C3H3· reaction, where propargyl is produced by direct hydrogen atom abstraction by chlorine (Cl) atoms from allene or methylacetylene and Cl stem from the pyrolysis of C7H5Cl3. Modeling results under the copyrolysis conditions of toluene and methylacetylene in high-temperature shock tube experiments confirmed the prevalence of the fulvenallenyl reaction with propargyl over its reactions with C3H4 even when the concentrations of allene and methylacetylene largely exceed that of propargyl. Overall, the reactions of fulvenallenyl with both allene and methylacetylene were found to be noncompetitive in the formation of naphthalene and azulene thus attesting the inefficiency of the fulvenallenyl radical reactions with the prototype closed-shell hydrocarbon species. In the meantime, the new reaction pathways revealed, including H-assisted isomerizations between C10H8 isomers and decomposition reactions of various C10H9 isomers, emerge as relevant and are recommended for inclusion in combustion kinetic models for naphthalene formation.

Machine learning-based decision support model for selecting intra-arterial therapies for unresectable hepatocellular carcinoma: A national real-world evidence-based study.

IMPORTANCE: Intra-arterial therapies(IATs) are promising options for unresectable hepatocellular carcinoma(HCC). Stratifying the prognostic risk before administering IAT is important for clinical decision-making and for designing future clinical trials. OBJECTIVE: To develop and validate a machine learning(ML)-based decision support model(MLDSM) for recommending IAT modalities for unresectable HCC. DESIGN, SETTING, AND PARTICIPANTS: Between October 2014 and October 2022, a total of 2,959 patients with HCC who underwent initial IATs were enroled retrospectively from 13 tertiary hospitals. These patients were divided into the training cohort (n = 1700), validation cohort (n = 428), and test cohort (n = 200). MAIN OUTCOMES AND MEASURES: Thirty-two clinical variables were input, and five supervised ML algorithms, including eXtreme Gradient Boosting (XGBoost), Categorical Gradient Boosting (CatBoost), Gradient Boosting Decision Tree (GBDT), Light Gradient Boosting Machine (LGBM) and Random Forest (RF), were compared using the areas under the receiver operating characteristic curve (AUC) with the DeLong test. RESULTS: A total of 1856 patients were assigned to the IAT alone Group(I-A), and 1103 patients were assigned to the IAT combination Group(I-C). The 12-month death rates were 31.9% (352/1103) in the I-A group and 50.4% (936/1856) in the I-C group. For the test cohort, in the I-C group, the CatBoost model achieved the best discrimination when 30 variables were input, with an AUC of 0.776 (95% confidence intervals [CI], 0.833-0.868). In the I-A group, the LGBM model achieved the best discrimination when 24 variables were input, with an AUC of 0.776 (95% CI, 0.833-0.868). According to the decision trees, BCLC grade, local therapy, and diameter as top three variables were used to guide clinical decisions between IAT modalities. CONCLUSIONS AND RELEVANCE: The MLDSM can accurately stratify prognostic risk for HCC patients who received IATs, thus helping physicians to make decisions about IAT and providing guidance for surveillance strategies in clinical practice.

Comparative proteomics analysis of Shiraia bambusicola revealed a variety of regulatory systems on conidiospore formation.

Shiraia bambusicola is a typical parasitic medicinal fungus of the family Shiraiaceae. The fruiting bodies of S. bambusicola cannot be cultivated artificially, and active substances can be effectively produced via fermentation. The mechanism of conidia production is a research hotspot in the industrial utilization and growth development of S. bambusicola. This study is the first to systematically study the proteomics of conidiospore formation from S. bambusicola. Near-spherical conidia were observed and identified by internal transcribed spacer (ITS) sequence detection. A total of 2,840 proteins were identified and 1,976 proteins were quantified in the mycelia and conidia of S. bambusicola. Compared with mycelia, 445 proteins were differentially expressed in the conidia of S. bambusicola, with 165 proteins being upregulated and 280 proteins being downregulated. The Gene Ontology (GO) annotation results of differential proteomics showed that the biological process of S. bambusicola sporulation is complex. The Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway analysis showed that the differential proteins were mainly involved in starch and sucrose metabolism, biosynthesis of secondary metabolites, microbial metabolism in diverse environments, and other processes. Our in-depth speculative analysis showed that proteins related to carbohydrate metabolism were differentially expressed in conidiospore formation of S. bambusicola, suggesting the involvement of saccharides. Conidiation may increase the synthesis and release of ethanol and polysaccharide proteins such as glycoside hydrolase (GH), suppress host immunity, and facilitate S. bambusicola to infect and colonize of the host. In-depth analysis of differential proteomes will help reveal the molecular mechanism underlying the conidiospore formation of S. bambusicola, which has strong theoretical and practical significance.

Screening, characterization, and optimization of the fermentation conditions of a novel cellulase-producing microorganism from soil of Qinghai-Tibet Plateau.

Cellulases play an important role in the bioconversion of lignocellulose. Microorganisms found in extreme environments are a potentially rich source of cellulases with unique properties. Due to the uniqueness of the environment, the abundant microbial resources in the Qinghai-Tibet Plateau (QTP) are worth being explored. The aim of this study was to isolate and characterize an acidic, mesophilic cellulase-producing microorganism from QTP. Moreover, the fermentation conditions for cellulase production were optimized for future application of cellulase in the development of lignocellulose biomass. A novel cellulase-producing strain, Penicillium oxalicum XC10, was isolated from the soil of QTP. The cellulase produced by XC10 was a mesophilic cellulase that exhibited good acid resistance and some cold-adaptation properties, with maximum activity at pH 4.0 and 40°C. Cellulase activity was significantly enhanced by Na+ (p < 0.05) and inhibited by Mg2+, Ca2+, Cu2+, and Fe3+ (p < 0.05). After optimization, maximum cellulase activity (8.56 U/mL) was increased nearly 10-fold. Optimal fermentation conditions included an inoculum size of 3% (v/v) in a mixture of corn straw (40 g/L), peptone (5 g/L), and Mg2+ (4 g/L), at pH 4.0, 33°C, and shaking at 200 rpm. The specific properties of the P. oxalicum XC10 cellulase suggest the enzyme may serve as an excellent candidate for the bioconversion and utilization of lignocellulose biomass generated as agricultural and food-processing wastes.

Manganese-enriched prussian blue nanohybrids with smaller electrode potential and lower charge transfer resistance to enhance combination therapy.

Prussian blue (PB) is authenticated in clinical treatment, while it generally exhibits unfavorable chemodynamic therapy (CDT) performance. Herein, we developed manganese-doped prussian blue (PBM) nanoparticles to significantly enhance both CDT and photothermal therapy (PTT) effect. The lower redox potential of Mn3+/2+ (0.088 V) in PBM against that of Fe2+/3+ (0.192 V) in PB leads to favorable electron transfer of PBM with respect to PB. Besides, PBM has a lower charge-transfer resistance (Rct) of 2.98 Ω than 4.83 Ω of PB. Once PBM entering the tumor microenvironment (TME), Mn3+ may be readily reduced by glutathione (GSH) and therein to enhance intracellular oxidative stress. Meanwhile, the superoxide dismutase (SOD)-like activity of PBM facilitates the conversion of endogenous superoxide (O2•-) into H2O2. Mn2+ subsequently catalyzes H2O2 to generate toxic hydroxyl radicals (•OH). Notably, the PBM plus laser irradiation can effectively trigger a robust immunogenic cell death (ICD) due to the combination therapy of CDT and PTT. Additionally, the mice treated by PBM followed by laser irradiation efficiently avoided splenomegaly and lung metastasis, along with significant up-regulation of the Stimulator of Interferon Genes (STING) expression. Overall, PBM significantly inhibits tumor growth and metastasis, making it a promising multifunctional nanoplatform for cancer treatment.

Multimodal imaging-based prediction of recurrence for unresectable HCC after downstage and resection-cohort study.

BACKGROUND: Surgical resection (SR) following transarterial chemoembolization (TACE)-based downstaging is a promising treatment for unresectable hepatocellular carcinoma (uHCC), and identification of patients at high-risk of postoperative recurrence may assist individualized treatment. PURPOSE: To develop and externally validate pre- and postoperative prognostic models integrating multimodal CT and DSA features as well as clinico-therapeutic-pathological features for predicting disease-free survival (DFS) after TACE-based downstaging therapy. MATERIALS AND METHODS: From March 2008 to August 2022, 488 consecutive patients with BCLC A/B uHCC receiving TACE-based downstaging therapy and subsequent SR were included from four tertiary-care hospitals. All CT and DSA images were independently evaluated by two blinded radiologists. In the derivation cohort (n=390), the XGBoost algorithm was used for feature selection, and Cox regression analysis for developing nomograms for DFS (time from downstaging to postoperative recurrence or death). In the external testing cohort (n=98), model performances were compared with five major staging systems. RESULTS: The preoperative nomogram included over three tumors (HR, 1.42; P=0.003), intratumoral artery (HR, 1.38; P=0.006), TACE combined with tyrosine kinase inhibitor (HR, 0.46; P<0.001) and objective response to downstaging therapy (HR, 1.60; P<0.001); while the postoperative nomogram included over three tumors (HR, 1.43; P=0.013), intratumoral artery (HR, 1.38; P=0.020), TACE combined with tyrosine kinase inhibitor (HR, 0.48; P<0.001), objective response to downstaging therapy (HR, 1.69; P<0.001) and microvascular invasion (HR, 2.20; P<0.001). The testing dataset C-indexes of the pre- (0.651) and postoperative (0.687) nomograms were higher than all five staging systems (0.472-0.542; all P<0.001). Two prognostically distinct risk strata were identified according to these nomograms (all P<0.001). CONCLUSION: Based on 488 patients receiving TACE-based downstaging therapy and subsequent SR for BCLC A/B uHCCs, we developed and externally validated two nomograms for predicting DFS, with superior performances than five major staging systems and effective survival stratification.

Selective dual-mode detection of glyphosate facilitated by iron organic frameworks nanozymes.

To satisfy the public's urgent demand for food safety and protect the ecological environment, sensitive detection of glyphosate holds paramount importance. Here, we discovered that glyphosate can engage in specific interactions with iron organic frameworks (Fe-MOFs) nanozymes, enabling a selective detection of glyphosate. Based on this principle, an innovative colorimetric and fluorescent dual-mode detection approach was devised. Specifically, Fe-MOFs were synthesized at room temperature, exhibiting remarkable peroxidase-mimic activity. These nanozymes catalyze the conversion of colorless and fluorescent 3,3',5,5'-Tetramethylbenzidine (TMB) into blue oxidized and nonfluorescent TMB (oxTMB) in the presence of H2O2. However, the introduction of glyphosate disrupts this process by interacting with Fe-MOFs, significantly inhibiting the catalytic activity of Fe-MOFs through both physical (electrostatic and hydrogen bonding) and chemical interactions. This suppression further hindered the conversion of TMB to oxTMB, resulting in a reduction in absorbance and a corresponding enhancement in fluorescence. The method offers a colorimetric and fluorescence dual-mode detection capability with enhanced applicability. Notably, our approach avoids complex material modifications and is more stable and cost-effective than the traditional enzyme inhibition methods. This innovative detection technique holds immense potential for practical applications and provides a fresh perspective for the detection of pesticide residues.

Nab-paclitaxel, cisplatin, and capecitabine versus cisplatin and gemcitabine as first line chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma: randomised phase 3 clinical trial.

OBJECTIVE: To compare the effectiveness and safety of nab-paclitaxel, cisplatin, and capecitabine (nab-TPC) with gemcitabine and cisplatin as an alternative first line treatment option for recurrent or metastatic nasopharyngeal carcinoma. DESIGN: Phase 3, open label, multicentre, randomised trial. SETTING: Four hospitals located in China between September 2019 and August 2022. PARTICIPANTS: Adults (≥18 years) with recurrent or metastatic nasopharyngeal carcinoma. INTERVENTIONS: Patients were randomised in a 1:1 ratio to treatment with either nab-paclitaxel (200 g/m2 on day 1), cisplatin (60 mg/m2 on day 1), and capecitabine (1000 mg/m2 twice on days 1-14) or gemcitabine (1 g/m2 on days 1 and 8) and cisplatin (80 mg/m2 on day 1). MAIN OUTCOME MEASURES: Progression-free survival was evaluated by the independent review committee as the primary endpoint in the intention-to-treat population. RESULTS: The median follow-up was 15.8 months in the prespecified interim analysis (31 October 2022). As assessed by the independent review committee, the median progression-free survival was 11.3 (95% confidence interval 9.7 to 12.9) months in the nab-TPC cohort compared with 7.7 (6.5 to 9.0) months in the gemcitabine and cisplatin cohort. The hazard ratio was 0.43 (95% confidence interval 0.25 to 0.73; P=0.002). The objective response rate in the nab-TPC cohort was 83% (34/41) versus 63% (25/40) in the gemcitabine and cisplatin cohort (P=0.05), and the duration of response was 10.8 months in the nab-TPC cohort compared with 6.9 months in the gemcitabine and cisplatin cohort (P=0.009). Treatment related grade 3 or 4 adverse events, including leukopenia (4/41 (10%) v 13/40 (33%); P=0.02), neutropenia (6/41 (15%) v 16/40 (40%); P=0.01), and anaemia (1/41 (2%) v 8/40 (20%); P=0.01), were higher in the gemcitabine and cisplatin cohort than in the nab-TPC cohort. No deaths related to treatment occurred in either treatment group. Survival and long term toxicity are still being evaluated with longer follow-up. CONCLUSION: The nab-TPC regimen showed a superior antitumoural efficacy and favourable safety profile compared with gemcitabine and cisplatin for recurrent or metastatic nasopharyngeal carcinoma. Nab-TPC should be considered the standard first line treatment for recurrent or metastatic nasopharyngeal carcinoma. Longer follow-up is needed to confirm the benefits for overall survival. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900027112.

Association of serum AFP trajectories and hepatocellular carcinoma outcomes after hepatic arterial infusion chemotherapy: A longitudinal, multicenter study.

AIM: This study aims to investigate α-fetoprotein (AFP) trajectories for prediction of survival outcomes after hepatic arterial infusion chemotherapy (HAIC) treatment in large hepatocellular carcinoma (HCC). METHODS: From May 2014 to June 2020, 889 eligible patients with large HCC underwent HAIC were retrospectively enrolled from five hospitals. A latent class growth mixed (LCGM) model was applied to distinguish potential AFP level dynamic changing trajectories. Inverse-probability-of-treatment weighted (IPTW) analyses were performed to eliminate unmeasured confounders through marginal structural models. Multivariate Cox proportional hazard regression analyses were used to determine the overall survival (OS) in patients with large HCC. Performance of these serum markers for survival prediction was compared by areas under receiver operating characteristic analysis with the Delong test. RESULTS: The median follow-up time was 23.7 (interquartile range, 3.8-115.3). A total of 1009 patients with large HCC, who underwent HAIC with AFP repeatedly measured 3-10 times, were enrolled in the study. Three distinct trajectories of these serum AFP were identified using the LCGM model: high stable (37.0%; n = 373), low stable (15.7%; n = 159), and sharp-falling (47.3%; n = 477). Multivariate Cox proportional hazard regression analyses found that ALBI stage 2-3, BCLC-C stage and high-stable AFP trajectories were associated with OS. AFP trajectories yield the optimal predictive performance in all risk factors. CONCLUSIONS: The AFP trajectories based on longitudinal AFP change showed outstanding performance for predicting survival outcomes after HAIC treatment in large HCC, which provide a potential monitoring tool for improving clinical decision-making.

Discovery of novel RNA viruses through analysis of fungi-associated next-generation sequencing data.

BACKGROUND: Like all other species, fungi are susceptible to infection by viruses. The diversity of fungal viruses has been rapidly expanding in recent years due to the availability of advanced sequencing technologies. However, compared to other virome studies, the research on fungi-associated viruses remains limited. RESULTS: In this study, we downloaded and analyzed over 200 public datasets from approximately 40 different Bioprojects to explore potential fungal-associated viral dark matter. A total of 12 novel viral sequences were identified, all of which are RNA viruses, with lengths ranging from 1,769 to 9,516 nucleotides. The amino acid sequence identity of all these viruses with any known virus is below 70%. Through phylogenetic analysis, these RNA viruses were classified into different orders or families, such as Mitoviridae, Benyviridae, Botourmiaviridae, Deltaflexiviridae, Mymonaviridae, Bunyavirales, and Partitiviridae. It is possible that these sequences represent new taxa at the level of family, genus, or species. Furthermore, a co-evolution analysis indicated that the evolutionary history of these viruses within their groups is largely driven by cross-species transmission events. CONCLUSIONS: These findings are of significant importance for understanding the diversity, evolution, and relationships between genome structure and function of fungal viruses. However, further investigation is needed to study their interactions.

Effect of particle density on microplastics transport in artificial and natural porous media.

The occurrence and persistence of microplastics (MPs) in natural environments are of increasing concern. Along with this, the transport of MPs in sediments has been investigated mainly focusing on the effect of plastic size and shape, media size effect, and solution chemistry. Yet, the influence of particle density is only partially understood. Therefore, column experiments on the transport of variably buoyant MPs in saturated natural sediments and glass beads were conducted, and transport parameters were quantified using a two-site kinetic transport model with a depth-dependent blocking function (the amount of retained MPs does not decrease at a constant rate with increasing depth, the majority of MPs were retained near the column inlet). Neutral, sinking, and buoyant MPs within the same size range were selected, with stable water isotope applied as conservative tracer to explore water and MP movement in the tested sediments. The results showed that 95.5 ± 1.4% of sinking MPs remained in columns packed with gravel, followed by buoyant and neutral MPs, thus indicating that particle density does affect MP mobility. Similar recovered amounts of MPs were found in columns packed with glass beads, indicating that tested sediment types do not affect the deposition behavior of MPs. The breakthrough curves of MPs were accurately described by the selected model. However, the simulated retention profiles overestimated the observed MP amount in layers closest to the column inlet. The coupled experimental and modeled results suggest an enhanced retention of sinking MPs, while neutrally and buoyant MPs exhibit a higher mobility in comparison. Thus, neutral or buoyant MPs can potentially pose a higher contamination risk to subsurface porous media environments compared to sinking MPs. Discrepancies between observed and simulated retention profiles indicate that future model development is needed for advancing the MP deposition as affected by particle density.

Overexpression of Larch SCL6 Inhibits Transitions from Vegetative Meristem to Inflorescence and Flower Meristem in Arabidopsis thaliana (L.) Heynh.

SCARECROW-LIKE6 (SCL6) plays a role in the formation and maintenance of the meristem. In Larix kaempferi (Lamb.) Carr., an important afforestation tree species in China, SCL6 (LaSCL6) has two alternative splicing variants-LaSCL6-var1 and LaSCL6-var2-which are regulated by microRNA171. However, their roles are still unclear. In this study, LaSCL6-var1 and LaSCL6-var2 were transformed into the Arabidopsis thaliana (L.) Heynh. genome, and the phenotypic characteristics of transgenic A. thaliana, including the germination percentage, root length, bolting time, flower and silique formation times, inflorescence axis length, and branch and silique numbers, were analyzed to reveal their functions. It was found that LaSCL6-var1 and LaSCL6-var2 overexpression shortened the root length by 41% and 31%, respectively, and increased the inflorescence axis length. Compared with the wild type, the bolting time in transgenic plants was delayed by approximately 2-3 days, the first flower and silique formation times were delayed by approximately 3-4 days, and the last flower and silique formation times were delayed by about 5 days. Overall, the life cycle in transgenic plants was prolonged by approximately 5 days. These results show that LaSCL6 overexpression inhibited the transitions from the vegetative meristem to inflorescence meristem and from the flower meristem to meristem arrest in A. thaliana, revealing the roles of LaSCL6-var1 and LaSCL6-var2 in the fate transition and maintenance of the meristem.

Glucan polysaccharides isolated from Lactarius hatsudake Tanaka mushroom: Structural characterization and in vitro bioactivities.

Commercially available mushroom polysaccharides have found widespread use as adjuvant tumor treatments. However, the bioactivity of polysaccharides in Lactarius hatsudake Tanaka (L. hatsudake), a mushroom with both edible and medicinal uses, remains relatively unexplored. To address this gap, five L. hatsudake polysaccharides with varying molecular weights were isolated, named LHP-1 (898 kDa), LHP-2 (677 kDa), LHP-3 (385 kDa), LHP-4 (20 kDa), and LHP-5 (4.9 kDa). Gas chromatography-mass spectrometry, nuclear magnetic resonance, and atomic force microscopy, etc., were employed to determine their structural characteristics. The results confirmed that spherical aggregates with amorphous flexible fiber chains dominated the conformation of the LHP. LHP-1 and LHP-2 were identified as glucans with α-(1,4)-Glcp as the main chain; LHP-3 and LHP-4 were classified as galactans with varying molecular weights but with α-(1,6)-Galp as the main chain; LHP-5 was a glucan with ß-(1,3)-Glcp as the main chain and ß-(1,6)-Glcp connecting to the side chains. Significant differences were observed in inhibiting tumor cell cytotoxicity and the antioxidant activity of the LHPs, with LHP-5 and LHP-4 identified as the principal bioactive components. These findings provide a theoretical foundation for the valuable use of L. hatsudake and emphasize the potential application of LHPs in therapeutic tumor treatments.

Elimination of Intragrain Defect to Enhance the Performance of FAPbI3 Perovskite Solar Cells by Ionic Liquid.

Ionic liquids have been widely used to improve the efficiency and stability of perovskite solar cells (PSCs), and are generally believed to passivate defects on the grain boundaries of perovskites. However, few studies have focused on the relevant effects of ionic liquids on intragrain defects in perovskites which have been shown to be critical for the performance of PSCs. In this work, the effect of ionic liquid 1-hexyl-3-methylimidazolium iodide (HMII) on intragrain defects of formamidinium lead iodide (FAPbI3) perovskite is investigated. Abundant {111}c intragrain planar defects in pure FAPbI3 grains are found to be significantly reduced by the addition of the ionic liquid HMII, shown by using ultra-low-dose selected area electron diffraction. As a result, longer charge carrier lifetimes, higher photoluminescence quantum yield, better charge carrier transport properties, lower Urbach energy, and current-voltage hysteresis are achieved, and the champion power conversion efficiency of 24.09% is demonstrated. These observations suggest that ionic liquids significantly improve device performance resulting from the elimination of {111}c intragrain planar defects.

Unraveling the Heterogeneity of CD8+ T-Cell Subsets in Liver Cirrhosis: Implications for Disease Progression.

Background/Aims: : Liver cirrhosis involves chronic inflammation and progressive fibrosis. Among various immune cells, CD8+ T cells are considered a major contributor to hepatic inflammation and fibrosis. However, the exact molecular pathways governing CD8+ T-cell-mediated effects in cirrhosis remain unclear. Methods: : This study analyzed transcriptomic and single-cell sequencing data to elucidate CD8+ T-cell heterogeneity and implications in cirrhosis. Results: : Weighted gene co-expression analysis of bulk RNA-seq data revealed an association between cirrhosis severity and activated T-cell markers like HLA and chemokine genes. Furthermore, single-cell profiling uncovered eight CD8+ T-cell subtypes, notably, effector memory (Tem) and exhausted (Tex) T cells. Tex cells, defined by PDCD1, LAG3, and CXCL13 expression, were increased in cirrhosis, while Tem cells were decreased. Lineage tracing and differential analysis highlighted CXCL13+ Tex cells as a terminal, exhausted subtype of cells with roles in PD-1 signaling, glycolysis, and T-cell regulation. CXCL13+ Tex cells displayed T-cell exhaustion markers like PDCD1, HAVCR2, TIGIT, and TNFRSF9. Functional analysis implicated potential roles of these cells in immunosuppression. Finally, a CXCL13+ Tex-cell gene signature was found that correlated with cirrhosis severity and poorer prognosis of liver cancer. Conclusions: : In summary, this comprehensive study defines specialized CD8+ T-cell subpopulations in cirrhosis, with CXCL13+ Tex cells displaying an exhausted phenotype associated with immune dysregulation and advanced disease. Key genes and pathways regulating these cells present potential therapeutic targets.

[Research progress on pathogenic mechanism of sepsis-induced liver injury and treatment with traditional Chinese medicine and its active components].

Sepsis is a systemic inflammatory response syndrome caused by infection, with high morbidity and mortality. Sepsis-induced liver injury(SILI) is one of the manifestations of sepsis-induced multiple organ syndrome. At present, there is no recommended pharmacological intervention for the treatment of SILI. traditional Chinese medicine(TCM), based on the holism and dialectical treatment concept, shows the therapeutic characteristics of multi-target and multi-pathway and can comprehensively prevent and treat SILI by interfering with inflammatory factors, inflammatory signaling pathways, and anti-oxidative stress and inhibiting apoptosis. This article reviewed the experimental studies on the treatment of SILI with TCM to clarify its pathogenic mechanism and therapeutic characteristics, so as to provide more ideas and directions for the development or preparation of new drugs.

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.

Timescale correlation of shallow trap states increases electrochemiluminescence efficiency in carbon nitrides.

Highly efficient interconversion of different types of energy plays a crucial role in both science and technology. Among them, electrochemiluminescence, an emission of light excited by electrochemical reactions, has drawn attention as a powerful tool for bioassays. Nonetheless, the large differences in timescale among diverse charge-transfer pathways from picoseconds to seconds significantly limit the electrochemiluminescence efficiency and hamper their broad applications. Here, we report a timescale coordination strategy to improve the electrochemiluminescence efficiency of carbon nitrides by engineering shallow electron trap states via Au-N bond functionalization. Quantitative electrochemiluminescence kinetics measurements and theoretic calculations jointly disclose that Au-N bonds endow shallow electron trap states, which coordinate the timescale of the fast electron transfer in the bulk emitter and the slow redox reaction of co-reagent at diffusion layers. The shallow electron trap states ultimately accelerate the rate and kinetics of emissive electron-hole recombination, setting a new cathodic electrochemiluminescence efficiency record of carbon nitrides, and empowering a visual electrochemiluminescence sensor for nitrite ion, a typical environmental contaminant, with superior detection range and limit.

Characterization and Assessment of Native Lactic Acid Bacteria from Broiler Intestines for Potential Probiotic Properties.

Probiotics are the most promising alternative to antibiotics for improving animal production and controlling pathogenic infections, while strains derived from natural hosts are considered highly desirable due to their good adaptation to the gastrointestinal tract. The aim of this study was to screen Lactobacillus with broad-spectrum antibacterial activity from broilers fed an antibiotic-free diet and evaluate their potential as poultry probiotics. A total of 44 lactic acid bacteria (LAB) strains were isolated from the intestines of healthy broilers, among which 3 strains exhibited outstanding antimicrobial activity and were subsequently identified through 16S rRNA sequencing as Enterococcus faecium L8, Lactiplantibacillus plantarum L10, and Limosilactobacillus reuteri H11. These three isolates demonstrated potent bacteriostatic activity against Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, and Salmonella cholerae, with inhibition zones ranging from 15.67 ± 1.53 to 21.33 ± 0.58 mm. The selected LAB strains exhibited high tolerance to acid and bile salts, with L. reuteri H11 displaying the highest survival rate (ranging from 34.68% to 110.28%) after exposure to 0.3% (w/v) bile salts for 6 h or a low pH environment (pH 2, 2.5, and 3) for 3 h. Notably, L. reuteri H11 outperformed other strains in terms of hydrophobicity (84.31%), auto-aggregation (53.12%), and co-aggregation with E. coli ATCC 25922 (36.81%) and S. aureus ATCC 6538 (40.20%). In addition, the three LAB isolates were either fully or moderately susceptible to the tested antibiotics, except for strain L8, which resisted gentamycin and vancomycin. Consequently, these three LAB strains, especially L. reuteri H11, isolated from the intestines of broiler chickens, represent promising probiotic candidates that can be employed as feed additives to enhance production performance and control poultry pathogens.