Characterization of PANoptosis-related genes in Crohn's disease by integrated bioinformatics, machine learning and experiments.

Currently, the biological understanding of Crohn's disease (CD) remains limited. PANoptosis is a revolutionary form of cell death reported to participate in numerous diseases, including CD. In our study, we aimed to uncover the roles of PANoptosis in CD. Differentially expressed PANoptosis-related genes (DE-PRGs) were identified by overlapping PANoptosis-related genes and differentially expressed genes between CD and normal samples in a combined microarray dataset. Three machine learning algorithms were adopted to detect hub DE-PRGs. To stratify the heterogeneity within CD patients, nonnegative matrix factorization clustering was conducted. In terms of immune landscape analysis, the "ssGSEA" method was applied. qRT-PCR was performed to examine the expression levels of the hub DE-PRGs in CD patients and colitis model mice. Ten hub DE-PRGs with satisfactory diagnostic performance were identified and validated: CD44, CIDEC, NDRG1, NUMA1, PEA15, RAG1, S100A8, S100A9, TIMP1 and XBP1. These genes displayed significant associations with certain immune cell types and CD-related genes. We also constructed gene‒microRNA, gene‒transcription factor and drug‒gene interaction networks. CD samples were classified into two PANoptosis patterns according to the expression levels of the hub DE-PRGs. Our results suggest that PANoptosis plays a nonnegligible role in CD by modulating the immune system and interacting with CD-related genes.

Treating ischemic stroke by improving vascular structure and promoting angiogenesis using Taohong Siwu Decoction: an integrative pharmacology strategy.

ETHNOPHARMACOLOGICAL RELEVANCE: Neovessels represent a crucial therapeutic target and strategy for repairing ischemic tissue. Taohong Siwu Decoction (THSWD) exhibits potential in promoting angiogenesis to address ischemic stroke (IS). However, its impact on neovessel structure and function, alongside the underlying molecular mechanisms, remains elusive. AIM OF THE STUDY: Our aim is to investigate the protective effects of THSWD on neovessel structure and function, as well as the associated molecular mechanisms, utilizing an integrative pharmacological approach. MATERIALS AND METHODS: We initially employed behavioral tests, 2,3,5-triphenyltetrazolium chloride (TTC) staining, Haematoxylin-eosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), Laser Doppler flowmetry (LDF), Evans blue staining, and immunofluorescence to evaluate the protective effects of THSWD on neovascular structure and function in middle cerebral artery occlusion/reperfusion (MCAO/R) rats. Subsequently, we utilized network pharmacology, metabolomics, and experimental validation to elucidate the underlying molecular mechanisms of THSWD in enhancing neovascular structure and function. RESULT: In addition to significantly reducing neurological deficits and cerebral infarct volume, THSWD mitigated pathological damage, blood-brain barrier (BBB) leakage, and cerebral blood flow disruption. Moreover, it preserved neovascular structure and stimulated angiogenesis. THSWD demonstrated potential in ameliorating cerebral microvascular metabolic disturbances including lipoic acid metabolism, fructose and mannose metabolism, purine metabolism, and ether lipid metabolism. Consequently, it exhibited multifaceted therapeutic effects, encompassing anti-inflammatory, antioxidant, energy metabolism modulation, and antiplatelet aggregation properties. CONCLUSION: THSWD exhibited protective effects on cerebral vascular structure and function and facilitated angiogenesis by rectifying cerebral microvascular metabolic disturbances in MCAO/R rats. Furthermore, integrated pharmacology offers a promising approach for studying the intricate traditional Chinese medicine (TCM) system in IS treatment.

Lebrikizumab Provides Rapid Clinical Responses Across All Eczema Area and Severity Index Body Regions and Clinical Signs in Adolescents and Adults with Moderate-to-Severe Atopic Dermatitis.

INTRODUCTION: Atopic dermatitis (AD) affects multiple areas of the body, some of which may be more refractory to treatment. We evaluated improvements in the Eczema Area and Severity Index (EASI) by body region and clinical signs for each body region in lebrikizumab-treated patients with moderate-to-severe AD. METHODS: ADvocate 1 and ADvocate 2 compared lebrikizumab 250 mg as monotherapy every 2 weeks versus placebo for 16 weeks. Efficacy measures included EASI, which rates the extent and severity of four clinical signs (erythema, edema/papulation, excoriation, lichenification) in four body regions (head/neck, upper extremities, trunk, lower extremities). Analyses are post hoc. RESULTS: Mean baseline EASI, body region EASI subscores, and the severity of clinical signs were consistent across both studies (EASI ranging from 16.0 to 72.0). At week 16 in both studies, patients treated with lebrikizumab showed significantly greater percent improvement in EASI across all body regions versus placebo (p ≤ 0.001), with improvements as early as week 2. In ADvocate 1, all clinical signs significantly improved across all body regions at week 16 with lebrikizumab (51.4-71.6% improvement) versus placebo (23.1-43.5%, p ≤ 0.001), with significant improvements as early as week 2 for all signs. Significant improvements for all clinical signs at week 16 were also seen in ADvocate 2 for lebrikizumab (53.5-75.6%) versus placebo (28.5-41.2%, p ≤ 0.001) and as early as week 2 for all body regions and signs except head/neck erythema and lower extremity erythema, edema/papulation, and lichenification, which showed significant improvement by week 4. CONCLUSIONS: Lebrikizumab as monotherapy consistently and rapidly reduced the extent of involvement and severity of AD in all EASI clinical signs and body regions, including the head and neck region and clinical sign of lichenification, compared with placebo. TRIAL REGISTRATION: ClinicalTrials.gov identifier: ADvocate 1 (NCT04146363) and ADvocate 2 (NCT04178967).

Hyper strength, high sensitivity integrated wearable signal sensor based on non-covalent interaction of an ionic liquid and bacterial cellulose for human behavior monitoring.

Ion-sensing hydrogels exhibit electrical conductivity, softness, and mechanical and sensory properties akin to human tissue, rendering them an ideal material for mimicking human skin. In the realm of fabricating sensors for detecting human physiological activities, they present an ideal alternative to traditional rigid metal conductors. Nevertheless, achieving ionic hydrogels with outstanding tensile properties, toughness, ionic conductivity, and transport stability poses a significant challenge. This paper describes a simple method of forming a basic network by free radical polymerization of acrylamide, and then bacterial cellulose (BC) and 1-ethyl-3-methylimidazolium chloride ([EMIM]Cl) were introduced into the basic network. The polyhydrogen bonds and electrostatic interactions in the system gave the hydrogel notable tensile properties (3271 ± 37%), toughness (7.39 ± 0.13 MJ m-3), and high ultimate tensile stress (385.1 ± 7.2 kPa). In addition, the combination of BC and [EMIM]Cl collaboratively enhanced the mechanical properties and electrical conductivity. Ion sensing hydrogels have a wide operating strain range (≈1000%) and high sensitivity (gage factor (GF) = 11.85), and are therefore considered promising candidates for next-generation gel-based strain sensor platforms.

Ultra-performance liquid chromatography-quadrupole time-of-flight mass combined with UNIFI to study the mechanism of Tao Hong Si Wu Decoction in the treatment of postpartum blood stasis.

Postpartum hemorrhage can lead to a variety of maternal complications. Tao Hong Si Wu Decoction (THSWD) is a traditional Chinese medicine used for treating gynecological diseases. However, the active ingredients of THSWD and its pharmacological mechanism of treatment for postpartum blood stasis still remained unclear. In this study, 201 components were identified in THSWD ethanol extract using ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry, including 59 terpenoids and volatile oil, 61 Phenylpropanoids, 41 flavonoids, 22 alkaloids, and other 18 components. A total of 45 active compounds were identified in the blood and 33 active compounds were identified in the uterine. Taking the common components into the blood and into the uterus combined with network pharmacology. It was demonstrated that the active compounds can bind to the core target with good affinity through molecular docking. The results of this study will provide a reference for the quality control and pharmacodynamic material base research of THSWD.

Visualization of phenanthrene effect on biochar colloids transport in porous media.

Biochar colloids (BCs) can be used as adsorbent materials for remediation of phenanthrene due to their high specific surface area and other characteristics. Understanding the effects of phenanthrene on the transport of BCs contributes to facilitate the removal of phenanthrene in soil and water habitats. In this work, the influence of phenanthrene on the transport of BCs under different environmental factors (pH, ionic strength (IS), media size) in a one-dimensional sand column was firstly explored together with a real-time visualization system to explore the transport mechanism of BCs in two-dimensional sand tank. The results show that phenanthrene adsorbed on the surface of BCs, shielded its surface charge and reduced the mobility of BCs in porous media. Acidic conditions promoted the agglomeration of BCs and adsorption of phenanthrene, resulting in a 51.03 % decrease in the maximum breakthrough rate of BCs compared to alkaline conditions. The same was true for the high IS condition, where the maximum breakthrough rate of BCs was only 0.95 % at IS = 50. Additionally, there was a substantial and positive correlation between media particle size and BCs mobility. As the quartz sand particle size increased, the maximum breakthrough rates of BCs were 2.67 %, 33.28 %, and 52.27 % in the 1-D experiment, and 0, 13.88 %, and 13.10 % in the 2-D experiment, respectively. The contact area of BCs with the medium expands under the fine particle size condition, leading to a significant decrease in the mobility of BCs at low potentials influenced by phenanthrene. This finding is significant for biochar application in phenanthrene contaminated soil and groundwater remediation.

Artificial Humic Acid Mediated Carbon-Iron Coupling to Promote Carbon Sequestration.

Fe (hydr)oxides have a substantial impact on the structure and stability of soil organic carbon (SOC) pools and also drive organic carbon turnover processes via reduction-oxidation reactions. Currently, many studies have paid much attention to organic matter-Fe mineral-microbial interactions on SOC turnover, while there is few research on how exogenous carbon addition abiotically regulates the intrinsic mechanisms of Fe-mediated organic carbon conversion. The study investigated the coupling process of artificial humic acid (A-HA) and Fe(hydr)oxide, the mechanism of inner-sphere ligands, and the capacity for carbon sequestration using transmission electron microscopy, thermogravimetric, x-ray photoelectron spectroscopy, and wet-chemical disposal. Furthermore, spherical aberration-corrected scanning transmission electron microscopy-electron energy loss spectroscopy and Mössbauer spectra have been carried out to demonstrate the spatial heterogeneity of A-HA/Fe (hydr)oxides and reveal the relationship between the increase in Fe-phase crystallinity and redox sensitivity and the accumulation of organic carbon. Additionally, the dynamics of soil structures on a microscale, distribution of carbon-iron microdomains, and the cementing-gluing effect can be observed in the constructing nonliving anthropogenic soils, confirming that the formation of stable aggregates is an effective approach to achieving organic carbon indirect protection. We propose that exogenous organic carbon inputs, specifically A-HA, could exert a substantial but hitherto unexplored effect on the geochemistry of iron-carbon turnover and sequestration in anoxic water/solid soils and sediments.

Artificial humic acid coated ferrihydrite strengthens the adsorption of phosphate and increases soil phosphate retention.

Phosphorus (P) leaching loss from farmland soils is one of the main causes of water eutrophication. Thus, effective methods must be developed to maintain sustainability in agricultural soils. Herein, we design artificial humic acid (A-HA) coated ferrihydrite (Fh) particles for fixing P in soil. The experiments in water and soil are successively conducted to explore the phosphate adsorption mechanism and soil P retention performance of A-HA coated ferrihydrite particles (A-Fh). Compared with unmodified ferrihydrite (Fh), the phosphate adsorption capacity of A-Fh is increased by 15 %, the phosphate adsorption speed and selectivity are also significantly improved. The ligand exchange, electrostatic attraction and hydrogen bonding are the dominant mechanisms of phosphate adsorption by A-Fh. In soil experiments, the addition of 2 % A-Fh increases the soil P retention performance from 0.15 to 0.7 mg/kg, and A-Fh are able to convert more phosphate adsorbed by itself into soil available P to improve soil fertility. Overall, this work highlights the importance of this a highly effective amendment for improving poor soils.

Effect of humic substances on nitrogen cycling in soil-plant ecosystems: Advances, issues, and future perspectives.

Nitrogen (N) cycle is one of the most significant biogeochemical cycles driven by soil microorganisms on the earth. Exogenous humic substances (HS), which include composted-HS and artificial-HS, as a new soil additive, can improve the water retention capacity, cation exchange capacity and soil nutrient utilization, compensating for the decrease of soil HS content caused by soil overutilization. This paper systematically reviewed the contribution of three different sources of HS in the soil-plant system and explained the mechanisms of N transformation through physiological and biochemical pathways. HS convert the living space and living environment of microorganisms by changing the structure and condition of soil. Generally, HS can fix atmospheric and soil N through biotic and abiotic mechanisms, which improved the availability of N. Besides, HS transform the root structure of plants through physiological and biochemical pathways to promote the absorption of inorganic N by plants. The redox properties of HS participate in soil N transformation by altering the electron gain and loss of microorganisms. Moreover, to alleviate the energy crisis and environmental problems caused by N pollution, we also illustrated the mechanisms reducing soil N2O emissions by HS and the application prospects of artificial-HS. Eventually, a combination of indoor simulation and field test, molecular biology and stable isotope techniques are needed to systematically analyze the potential mechanisms of soil N transformation, representing an important step forward for understanding the relevance between remediation of environmental pollution and improvement of the N utilization in soil-plant system.

Effects of Fe3+ on Hydrothermal Humification of Agricultural Biomass.

Hydrothermal humification technology for the preparation of artificial humic matters provides a new strategy, greatly promoting the natural maturation process. Iron, as a common metal, is widely used in the conversion of waste biomass; however, the influence of Fe3+ on hydrothermal humification remains unknown. In this study, FeCl3 is used to catalyze the hydrothermal humification of corn straw, and the influence of Fe3+ on the hydrothermal humification is explored by a series of characterization techniques. Results show that Fe3+ as the catalyst can promote the decomposition of corn straw, shorten the reaction time from 24 h to 6 h, and increase the yield from 6.77 % to 14.08 %. However, artificial humic acid (A-HA) obtained from Fe3+ -catalysis hydrothermal humification contains more unstable carbon and low amount of aromatics, resulting in a significantly decreased stability of the artificial humic acid. These results provide theoretical guidance for regulating the structure and properties of artificial humic acid to meet various maintenance needs.

[Active components and potential mechanism of Taohong Siwu Decoction in regulating ischemic stroke based on target cell trapping combined with network pharmacology, molecular docking, and experimental validation].

The potential anti-stroke active components in Taohong Siwu Decoction(THSWD) were identified by target cell trapping coupled with ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UPLC-Q-TOF-MS). The underlying mechanism of active components in THSWD in the treatment of ischemic stroke(IS) was explored by network pharmacology, molecular docking, and experimental validation. The UPLC-Q-TOF-MS technology combined with the UNIFI data analysis platform was used to analyze the composition of the cellular fragmentation fluid after co-incubation of THSWD with target cells. The targets of potential active components and IS were collected by network pharmacology, and the common targets underwent protein-protein interaction(PPI), Gene Ontology(GO), and Kyoto Encyclopedia of Genes and Genomes(KEGG) signaling pathway enrichment analyses. The target cell trapping component-core target-signaling pathway network was constructed, and the active components were molecularly docked to the top targets in the PPI network, followed by pharmacodynamic validation in vitro. Fifteen active components were identified in the target cellular fragmentation fluid, including bicyclic monoterpenes, cyanoglycosides, flavonols, quinoid chalcones, phenylpropanoids, and tannins. As revealed by the analysis of network pharmacology, THSWD presumably regulated PI3K-AKT, FoxO, MAPK, Jak-STAT, VEGF, HIF-1, and other signaling pathways to affect inflammatory cascade reaction, angiogenesis, oxidative stress, pyroptosis, apoptosis, and other pathological processes via paeoniflorin, butylphthalide, dehydrated safflower yellow B, 3,4-dicaffeoylquinic acid, amygdalin, paeoniflorin, and ligusticolactone. Molecular docking and in vitro pharmacodynamic validation revealed that the target cell trapping active components could promote neovascularization in rat brain microvascular endothelial cells(rBMECs) in the oxygen-glucose deprivation/reoxygenation(OGD/R) model. The application of target cell trapping coupled with UPLC-Q-TOF-MS technology can rapidly screen out the potential active components in THSWD. The active components of THSWD can be predicted to intervene in the pathogenesis of IS through network pharmacology, and molecular docking combined with experimental validation can further clarify the efficacy, thus providing a theoretical basis for research ideas on the pharmacodynamic substance basis of traditional Chinese medicine compounds.

Super-stretching and high-performance ionic thermoelectric hydrogels based on carboxylated bacterial cellulose coordination for self-powered sensors.

Self-powered sensors that do not require external power sources are crucial for next-generation wearable electronics. As environment-friendly ionic thermoelectric hydrogels can continuously convert the low-grade heat of human skin into electricity, they can be used in intelligent human-computer interaction applications. However, their low thermoelectric output power, cycling stability, and sensitivity limit their practical applications. This paper reports a 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-oxidized carboxylated bacterial cellulose (TOBC) coordination double-network ionic thermoelectric hydrogel with lithium bis(trifluoromethane) sulfonimide (LiTFSI) as an ion provider for thermodiffusion, as LiTFSI exhibits excellent thermoelectric properties with a maximum power output of up to 538 nW at a temperature difference of 20 K. The interactions between the ions and the hydrogel matrix promote the selective transport of conducting ionic ions, producing a high Seebeck coefficient of 11.53 mV K-1. Hydrogen bonding within the polyacrylamide (PAAm) network and interactions within the borate ester bond within the TOBC confer excellent mechanical properties to the hydrogel such that the stress value at a tensile deformation of 3100 % is reaches 0.85 MPa. The combination of the high ionic thermovoltage and excellent mechanical properties ionic thermoelectric hydrogels provides an effective solution for the design and application of self-powered sensors based on hydrogels.

Targeting crosstalk of STAT3 between tumor-associated M2 macrophages and Tregs in colorectal cancer.

A comprehensive analysis of the molecular mechanism underlying colorectal tumor evaluated the development of colorectal cancer (CRC) and proposed targeting small molecular inhibitors. Nonetheless, the adoptive resistance of these therapies remains a challenge with respect to achieving an effective clinical response. Thus, identifying the molecular mechanisms guiding CRC growth is essential. The results of The Cancer Genome Atlas (TCGA) dataset analysis demonstrated a critical role of signal transducer and activator of transcription 3 (STAT3) pathway in tumor immune suppression via modulation of the recruitment of Treg cells and M2 type tumor-associated macrophages. The in vivo experiments elucidate that targeting STAT3 pathways markedly reduce the proportions of TAMs and Tregs by inhibiting tumor progression. These findings revealed crosstalk between Treg cells and M2 macrophages, proving a potential therapeutic strategy for CRC therapy. Combinatorial treatment with STAT3 inhibitor and programmed death 1 (PD-1) antibody therapy effectively prevents CRC tumor growth in a mouse model with high anti-tumor immunity. In summary, targeting STAT3 disrupts the interaction between Treg cells and M2 macrophages and improves the anti-tumor response in CRC, thereby offering a promising strategy to treat patients with CRC.

Efficacy and safety of lebrikizumab in moderate-to-severe atopic dermatitis: 52-week results of two randomized double-blinded placebo-controlled phase III trials.

BACKGROUND: Lebrikizumab is a novel, high-affinity monoclonal antibody that selectively binds to interleukin (IL)-13. OBJECTIVES: To evaluate the efficacy and safety of lebrikizumab monotherapy in adolescent and adult patients with moderate-to-severe atopic dermatitis (AD) over 52 weeks of treatment in ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967). METHODS: Patients who responded to lebrikizumab 250 mg every 2 weeks (Q2W) at the end of the 16-week induction period were re-randomized 2 : 2 : 1 to receive lebrikizumab Q2W, lebrikizumab 250 mg every 4 weeks (Q4W) or placebo Q2W (lebrikizumab withdrawal) for 36 additional weeks. Response at week 16 was defined as achieving a 75% reduction in Eczema Area Severity Index (EASI 75) or an Investigator's Global Assessment (IGA) of 0 or 1, with a ≥ 2-point improvement and no rescue medication use. Multiple imputation was used to handle missing data. Intermittent use of topical therapy was permitted during the maintenance period. RESULTS: After 52 weeks, an IGA of 0 or 1 with a ≥ 2 point improvement was maintained by 71.2% of patients treated with lebrikizumab Q2W, 76.9% of patients treated with lebrikizumab Q4W and 47.9% of patients in the lebrikizumab withdrawal arm. EASI 75 was maintained by 78.4% of patients treated with lebrikizumab Q2W, 81.7% of patients treated with lebrikizumab Q4W and 66.4% of patients in the lebrikizumab withdrawal arm at week 52. Across treatment arms, proportions of patients using any rescue therapy were 14.0% (ADvocate1) and 16.4% (ADvocate2). During the combined induction and maintenance periods of ADvocate1 and ADvocate2, 63.0% of lebrikizumab-treated patients reported any treatment emergent adverse event, with most events (93.1%) being mild or moderate in severity. CONCLUSIONS: After a 16-week induction period with lebrikizumab Q2W, lebrikizumab Q2W and Q4W maintained similar improvement of the signs and symptoms of moderate-to-severe AD, with a safety profile consistent with previously published data.

Two Phase 3 Trials of Lebrikizumab for Moderate-to-Severe Atopic Dermatitis.

BACKGROUND: Lebrikizumab, a high-affinity IgG4 monoclonal antibody targeting interleukin-13, prevents the formation of the interleukin-4Rα-interleukin-13Rα1 heterodimer receptor signaling complex. METHODS: We conducted two identically designed, 52-week, randomized, double-blind, placebo-controlled, phase 3 trials; both trials included a 16-week induction period and a 36-week maintenance period. Eligible patients with moderate-to-severe atopic dermatitis (adults [≥18 years of age] and adolescents [12 to <18 years of age, weighing ≥40 kg]) were randomly assigned in a 2:1 ratio to receive either lebrikizumab at a dose of 250 mg (loading dose of 500 mg at baseline and week 2) or placebo, administered subcutaneously every 2 weeks. Outcomes for the induction period were assessed up to 16 weeks and are included in this report. The primary outcome was an Investigator's Global Assessment (IGA) score of 0 or 1 (indicating clear or almost clear skin; range, 0 to 4 [severe disease]) with a reduction (indicating improvement) of at least 2 points from baseline at week 16. Secondary outcomes included a 75% improvement in the Eczema Area and Severity Index score (EASI-75 response) and assessments of itch and of itch interference with sleep. Safety was also assessed. RESULTS: In trial 1, the primary outcome was met in 43.1% of 283 patients in the lebrikizumab group and in 12.7% of 141 patients in the placebo group (P<0.001); an EASI-75 response occurred in 58.8% and 16.2%, respectively (P<0.001). In trial 2, the primary outcome was met in 33.2% of 281 patients in the lebrikizumab group and in 10.8% of 146 patients in the placebo group (P<0.001); an EASI-75 response occurred in 52.1% and 18.1%, respectively (P<0.001). Measures of itch and itch interference with sleep indicated improvement with lebrikizumab therapy. The incidence of conjunctivitis was higher among patients who received lebrikizumab than among those who received placebo. Most adverse events during the induction period were mild or moderate in severity and did not lead to trial discontinuation. CONCLUSIONS: In the induction period of two phase 3 trials, 16 weeks of treatment with lebrikizumab was effective in adolescents and adults with moderate-to-severe atopic dermatitis. (Funded by Dermira; ADvocate1 and ADvocate2 ClinicalTrials.gov numbers, NCT04146363 and NCT04178967, respectively.).

Efficacy and safety of first-line immune checkpoint inhibitors combined with chemotherapy for extensive-stage small cell lung cancer: A network meta-analysis.

The efficacy and safety of first-line immune checkpoint inhibitors plus chemotherapy in the treatment of patients with extensive-stage small cell lung cancer (ES-SCLC) remains unevaluated, and there are no reports to directly compare the efficacy and safety among different immunotherapy (especially adebrelimab and surplulimab). Suitable phase III randomized controlled trials with two or more different arms were included. Independent reviewers screened and extracted relevant data and disagreements were resolved through consensus. Fixed-effect consistency models were used to calculate the overall survival (OS), progression-free survival (PFS), objective response rate, adverse events ≥ 3, and safety outcomes in the clinically relevant subgroups. In this network meta-analysis, six randomized controlled clinical trials (CAPSTONE-1, ASTRUM-005, CASPIAN, IMpower133, KEYNOTE-604, and an ipilimumab + chemotherapy trial) with totaling 3662 patients were involved. Compared to chemotherapy, immune checkpoint inhibitors plus chemotherapy present higher possibilities to bring about better OS and PFS. Serplulimab + chemotherapy significantly showed a better survival profit in comparison with ipilimumab + chemotherapy (0.67; 0.50-0.90). Compared with chemotherapy, adebrelimab + chemotherapy (0.72; 0,58-0.90), atezolizumab + chemotherapy (0.76; 0.60-0.96) durvalumab + chemotherapy (0.75; 0.62-0.91), and serplulimab + chemotherapy (0.63;0.49-0.82) all presented significantly better overall survival. In terms of progression-free survival, serplulimab + chemotherapy showed better efficacy in comparison with adebrelimab + chemotherapy (0.72; 0,53-0.97), atezolizumab + chemotherapy (0.62; 0.46-0.84), durvalumab + chemotherapy (0.60; 0.45-0.80). Compared with chemotherapy, adebrelimab + chemotherapy (0.67; 0.54-0.83) and serplulimab + chemotherapy (0.48; 0.48-0.86) all presented significantly better PFS. Immunotherapy plus chemotherapy had similar probabilities to cause adverse events of grade ≥ 3. In comparison with chemotherapy, immune checkpoint inhibitors plus chemotherapy were likely to be more suitable for the first-line treatment of ES-SCLC. According to our analysis, serplulimab plus chemotherapy and adebrelimab plus chemotherapy present higher possibilities to show better efficacy and safety, however, the level of evidence of this type of comparison is limited.

Bifunctional collagen fiber/carbon quantum dot fluorescent adsorbent for efficient adsorption and detection of Pb2.

In this work, fluorescent adsorbents that can efficiently detect and remove Pb2+ were developed by integrating the designed amino-modified carbon quantum dots and carboxyl-modified collagen. The adsorption properties of the fluorescent adsorbent were further optimized and analyzed using a series of response surface experiments. The maximum adsorption concentration for Pb2+ was 183 mg.g-1. The adsorption isotherms fit well with the Langmuir model, and the adsorption kinetics fit with the pseudo-second-order model. The emission intensity of the fluorescent adsorbent gradually decreased with the increase of the concentration of Pb2+, and had a good linear correlation. In addition, the mechanism of detection and removal of Pb2+ by fluorescent adsorbents was further demonstrated. The novel three-dimensional structured fluorescent aerogel can be used as a promising adsorbent with good adsorption concentration and sensing ability for Pb2+, which shows great prospects in wastewater.

Effective personalized neoantigen vaccine plus anti-PD-1 in a PD-1 blockade-resistant lung cancer patient.

Background: Although significant progress has been made in immune checkpoint inhibitor (ICI) treatment of advanced squamous cell carcinoma (SqCC), most patients still experience acquired drug resistance. Methods: We used a dendritic cell-based neoantigen vaccine combined with ICIs to treat advanced SqCC in a PD-1 blockade-resistant patient. Results: The follow-up of this patient after 12 months revealed significant tumor regression. We also identified a new JAK1 ICI-resistant mutation that could become a potential universal neoantigen target for tumor vaccines. Conclusion: Individualized management of advanced SqCC through a combined neoantigen vaccine and ICI administration could yield beneficial clinical outcomes. Vaccines targeting anti-PD-1-resistant JAK1 mutations might be of particular benefit to a specific group of solid tumor patients.

Immunotherapy based on immune checkpoint inhibitors (ICIs) is very effective in lung cancer treatment. However, many patients with initial response will later develop resistance. There are not many treatment options for patients with drug resistance. Herein, we report a patient with lung cancer who became resistant to ICI, treated with personalized vaccine plus ICI. Based on the patient's own somatic mutational profile, personalized neoantigen vaccines were designed and manufactured unique to the patient. Our report indicated that personalized vaccine plus ICI was safe and might overcome ICI resistance. A new ICI resistance mutation on JAK1 as a potential universal neoantigen target for off-the-shelf vaccine was found, which is promising for the effective treatment of a specific group of patients with JAK1 mutations.

A Bayesian three-tier quantitative decision-making framework for single arm studies in early phase oncology.

In early phase oncology drug development, single arm proof-of-concept (POC) studies are increasingly being used to drive the early decisions for future development of the drug. Decision-makings based on such studies, typically involving small sample size and early surrogate efficacy endpoints, are extremely challenging. In particular, given the tremendous competition in the development of immunotherapies, expedition of the most promising programs is desired. To this end, we have proposed a Bayesian three-tier approach to facilitate the decision-making process, inheriting all the benefits of Bayesian decision-making approaches and formally allowing the option of acceleration. With pre-specified Bayesian decision criteria, three types of decisions regarding the future development of the drug can be made: (1) terminating the program, (2) further investigation, considering totality of evidence or additional POC studies, and (3) accelerating the program. We further proposed a Bayesian adaptive three-tier (BAT) design, extending the decision-making approach to incorporate adaptive thresholds and allow for continuous monitoring of the study. We compare the performance of the proposed methods with some other existing methods through simulations.