Factors Affecting the Effectiveness and Safety of Polymyxin B in the Treatment of Gram-negative Bacterial Infections: A Meta-Analysis of 96 Articles.

PURPOSE: Polymyxin B, with its unique structure and mechanism of action, has emerged as a key therapeutic agent against Gram-negative bacteria. The study aims to explore potential factors to influence its effectiveness and safety. METHODS: A Model-Based Meta-Analysis (MBMA) of 96 articles was conducted, focusing on factors like dosage, bacterial species, and combined antibiotic therapy. The analysis evaluated mortality rates and incidence rate of renal dysfunction, also employing parametric survival models to assess 30-day survival rates. RESULTS: In the study involving 96 articles and 9,716 patients, polymyxin B's daily dose showed minimal effect on overall mortality, with high-dose group mortality at 33.57% (95% CI: 29.15-38.00) compared to the low-dose group at 35.44% (95% CI: 28.99-41.88), p=0.64. Mortality significantly varied by bacterial species, with Pseudomonas aeruginosa infections at 58.50% (95% CI: 55.42-63.58). Monotherapy exhibited the highest mortality at 40.25% (95% CI: 34.75-45.76), p<0.01. Renal dysfunction was more common in high-dose patients at 29.75% (95% CI: 28.52-30.98), with no significant difference across antibiotic regimens, p=0.54. The 30-day Overall Survival rate for monotherapy therapy was 63.6% (95% CI: 59.3-67.5) and 70.2% (95% CI: 64.4-76.2) for association therapy with ß-lactam drugs. CONCLUSIONS: The dosage of Polymyxin B doesn't significantly change death rates, but its effectiveness varies based on the bacterial infection. Certain bacteria like Pseudomonas aeruginosa are associated with higher mortality. Combining Polymyxin B with other antibiotics, especially ß-lactam drugs, improves survival rates. Side effects depend on the dose, with lower doses being safer. These findings emphasize the importance of customizing treatment to balance effectiveness and safety.

Dirichlet Flow Matching with Applications to DNA Sequence Design.

Discrete diffusion or flow models could enable faster and more controllable sequence generation than autoregressive models. We show that na\"ive linear flow matching on the simplex is insufficient toward this goal since it suffers from discontinuities in the training target and further pathologies. To overcome this, we develop Dirichlet flow matching on the simplex based on mixtures of Dirichlet distributions as probability paths. In this framework, we derive a connection between the mixtures' scores and the flow's vector field that allows for classifier and classifier-free guidance. Further, we provide distilled Dirichlet flow matching, which enables one-step sequence generation with minimal performance hits, resulting in $O(L)$ speedups compared to autoregressive models. On complex DNA sequence generation tasks, we demonstrate superior performance compared to all baselines in distributional metrics and in achieving desired design targets for generated sequences. Finally, we show that our classifier-free guidance approach improves unconditional generation and is effective for generating DNA that satisfies design targets. Code is available at https://github.com/HannesStark/dirichlet-flow-matching.

Spatiotemporally selective astrocytic ATP dynamics encode injury information sensed by microglia following brain injury in mice.

Injuries to the brain result in tunable cell responses paired with stimulus properties, suggesting the existence of intrinsic processes that encode and transmit injury information; however, the molecular mechanism of injury information encoding is unclear. Here, using ATP fluorescent indicators, we identify injury-evoked spatiotemporally selective ATP dynamics, Inflares, in adult mice of both sexes. Inflares are actively released from astrocytes and act as the internal representations of injury. Inflares encode injury intensity and position at their population level through frequency changes and are further decoded by microglia, driving changes in their activation state. Mismatches between Inflares and injury severity lead to microglia dysfunction and worsening of injury outcome. Blocking Inflares in ischemic stroke in mice reduces secondary damage and improves recovery of function. Our results suggest that astrocytic ATP dynamics encode injury information and are sensed by microglia.

Remdesivir for Treatment of COVID-19 Requiring Oxygen Support: A Cross-Study Comparison from Two Large, Open-Label Studies.

BACKGROUND: Remdesivir, an RNA-polymerase prodrug inhibitor approved for treatment of COVID-19, shortens recovery time and improves clinical outcomes. This prespecified analysis compared remdesivir plus standard-of-care (SOC) with SOC alone in adults hospitalized with COVID-19 requiring oxygen support in the early stage of the pandemic. METHODS: Data for 10-day remdesivir treatment plus SOC from the extension phase of an open-label study (NCT04292899) were compared with real-world, retrospective data on SOC alone (EUPAS34303). Both studies included patients aged ≥18 years hospitalized with SARS-CoV-2 up to 30 May 2020, with oxygen saturation ≤94%, on room air or supplemental oxygen (all forms), and with pulmonary infiltrates. Propensity score weighting was used to balance patient demographics and clinical characteristics across treatment groups. The primary endpoint was time to all-cause mortality or end of study (day 28). Time-to-discharge, with a 10-day landmark to account for duration of remdesivir treatment, was a secondary endpoint. RESULTS: 1974 patients treated with remdesivir plus SOC, and 1426 with SOC alone, were included after weighting. Remdesivir significantly reduced mortality versus SOC (hazard ratio [HR]: 0.46, 95% confidence interval: 0.39-0.54). This association was observed at each oxygen support level, with the lowest HR for patients on low-flow oxygen. Remdesivir significantly increased the likelihood of discharge at day 28 versus SOC in the 10-day landmark analysis (HR: 1.64; 95% confidence interval: 1.43-1.87). CONCLUSIONS: Remdesivir plus early-2020 SOC was associated with a 54% lower mortality risk and shorter hospital stays compared with SOC alone in patients hospitalized with COVID-19 requiring oxygen support. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT04292899 and EUPAS34303.

The roles of nuclear orphan receptor NR2F6 in anti-viral innate immunity.

Proper transcription regulation by key transcription factors, such as IRF3, is critical for anti-viral defense. Dynamics of enhancer activity play important roles in many biological processes, and epigenomic analysis is used to determine the involved enhancers and transcription factors. To determine new transcription factors in anti-DNA-virus response, we have performed H3K27ac ChIP-Seq and identified three transcription factors, NR2F6, MEF2D and MAFF, in promoting HSV-1 replication. NR2F6 promotes HSV-1 replication and gene expression in vitro and in vivo, but not dependent on cGAS/STING pathway. NR2F6 binds to the promoter of MAP3K5 and activates AP-1/c-Jun pathway, which is critical for DNA virus replication. On the other hand, NR2F6 is transcriptionally repressed by c-Jun and forms a negative feedback loop. Meanwhile, cGAS/STING innate immunity signaling represses NR2F6 through STAT3. Taken together, we have identified new transcription factors and revealed the underlying mechanisms involved in the network between DNA viruses and host cells.

Diagnosis and Vulnerability Risk Assessment of Atherosclerotic Plaques Using an Amino Acid-Assembled Near-Infrared Ratiometric Nanoprobe.

To reduce the risk of atherosclerotic disease, it is necessary to not only diagnose the presence of atherosclerotic plaques but also assess the vulnerability risk of plaques. Accurate detection of the reactive oxygen species (ROS) level at plaque sites represents a reliable way to assess the plaque vulnerability. Herein, through a simple one-pot reaction, two near-infrared (NIR) fluorescent dyes, one is ROS responsive and the other is inert to ROS, are coassembled in an amphiphilic amino acid-assembled nanoparticle. In the prepared NIR fluorescent amino acid nanoparticle (named FANP), the fluorescent properties and ROS-responsive behaviors of the two fluorescent dyes are well maintained. Surface camouflage through red blood cell membrane (RBCM) encapsulation endows the finally obtained FANP@RBCM nanoprobe with not only further reduced cytotoxicity and improved biocompatibility but also increased immune escape capability, prolonged blood circulation time, and thus enhanced accumulation at atherosclerotic plaque sites. In vitro and in vivo experiments demonstrate that FANP@RBCM not only works well in probing the occurrence of atherosclerotic plaques but also enables plaque vulnerability assessment through the accurate detection of the ROS level at plaque sites in a reliable ratiometric mode, thereby holding great promise as a versatile tool for the diagnosis and risk assessment of atherosclerotic disease.

Electropositive Citric Acid-Polyethyleneimine Carbon Dots Carrying the PINK1 Gene Regulate ATP-Related Metabolic Dysfunction in APP/PS1-N2a Cells.

(1) Background: Alzheimer's disease (AD) is characterized by ß-amyloid (Aß) peptide accumulation and mitochondrial dysfunction during the early stage of disease. PINK1 regulates the balance between mitochondrial homeostasis and bioenergy supply and demand via the PINK1/Parkin pathway, Na+/Ca2+ exchange, and other pathways. (2) Methods: In this study, we synthesized positively charged carbon dots (CA-PEI CDs) using citric acid (CA) and polyethyleneimine (PEI) and used them as vectors to express PINK1 genes in the APP/PS1-N2a cell line to determine mitochondrial function, electron transport chain (ETC) activity, and ATP-related metabolomics. (3) Results: Our findings showed that the CA-PEI CDs exhibit the characteristics of photoluminescence, low toxicity, and concentrated DNA. They are ideal biological carriers for gene delivery. PINK1 overexpression significantly increased the mitochondrial membrane potential in APP/PS1-N2a cells and reduced reactive-oxygen-species generation and Aß1-40 and Aß1-42 levels. An increase in the activity of NADH ubiquinone oxidoreductase (complex I, CI) and cytochrome C oxidase (complex IV, CIV) induces the oxidative phosphorylation of mitochondria, increasing ATP generation. (4) Conclusions: These findings indicate that the PINK gene can alleviate AD by increasing bioenergetic metabolism, reducing Aß1-40 and Aß1-42, and increasing ATP production.

Anthropogenic processes drive spatiotemporal variability of sulfate in groundwater from a multi-aquifer system: Dilution caused by mine drainage.

The water quality evolution of surface and groundwater caused by mining activities and mine drainage is a grave public concern worldwide. To explore the effect of mine drainage on sulfate evolution, a multi-aquifer system in a typical coal mine in Northwest China was investigated using multi-isotopes (δ34SSO4, δ18OSO4, δD, and δ18Owater) and Positive Matrix Factorization (PMF) model. Before mining, the Jurassic aquifer was dominated by gypsum dissolution, accompanied by cation exchange and bacterial sulfate reduction, and the phreatic aquifers and surface water were dominated by carbonate dissolution. Significant increase in sulfate in phreatic aquifers due to mine drainage during the early stages of coal mining. However, in contrast to common mining activities that result in sulfate contamination from pyrite oxidation, mine drainage in this mining area resulted in accelerated groundwater flow and enhanced hydraulic connections between the phreatic and confined aquifers. Dilution caused by the altered groundwater flow system controlled the evolution of sulphate, leading to different degrees of sulfate decrease in all aquifers and surface water. As the hydrogeochemical characteristic of Jurassic aquifer evolved toward phreatic aquifer, this factor should be considered to avoid misjudgment in determining the source of mine water intrusion. The study reveals the hydrogeochemical evolution induced by mine drainage, which could benefit to the management of groundwater resources in mining areas.

circRNA6448-14/miR-455-3p/OTUB2 axis stimulates glycolysis and stemness of esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a gastrointestinal malignancy with high incidence. This study aimed to reveal the complete circRNA-miRNA-mRNA regulatory network in ESCC and validate its function mechanism. METHOD: Expression of OTU Domain-Containing Ubiquitin Aldehyde-Binding Protein 2 (OTUB2) in ESCC was analyzed by bioinformatics to find the binding sites between circRNA6448-14 and miR-455-3p, as well as miR-455-3p and OTUB2. The binding relationships were verified by RNA Immunoprecipitation (RIP) and dual-luciferase assay. The expressions of circRNA6448-14, miR-455-3p, and OTUB2 were detected by quantitative real-time polymerase chain reaction (qRT-PCR). MTT assay measured cell viability, and the spheroid formation assay assessed the ability of stem cell sphere formation. Western blot (WB) determined the expression of marker proteins of stem cell surface and rate-limiting enzyme of glycolysis. The Seahorse XFe96 extracellular flux analyzer measured the rate of extracellular acidification rate and cellular oxygen consumption. Corresponding assay kits assessed cellular glucose consumption, lactate production, and adenosine triphosphate (ATP) generation. RESULTS: In ESCC, circRNA6448-14 and OTUB2 were highly expressed in contrast to miR-455-3p. Knocking down circRNA6448-14 could prevent the glycolysis and stemness of ESCC cells. Additionally, circRNA6448-14 enhanced the expression of OTUB2 by sponging miR-455-3p. Overexpression of OTUB2 or silencing miR-455-3p reversed the inhibitory effect of knockdown of circRNA6448-14 on ESCC glycolysis and stemness. CONCLUSION: This research demonstrated that the circRNA6448-14/miR-455-3p/OTUB2 axis induced the glycolysis and stemness of ESCC cells. Our study revealed a novel function of circRNA6448-14, which may serve as a potential therapeutic target for ESCC.

Exploring Caffeic Acid and Lignosulfonate as Key Phenolic Ligands for Metal-Phenolic Network Assembly.

Films formed by metals and phenols through a coordinative interaction have been extensively studied in previous years. We report the successful formation of MPN films from the phenolic compounds caffeic acid and lignosulfonate using Fe3+ ions for complexation. The likewise examined p-coumaryl alcohol showed some MPN film formation tendency, while for coniferyl alcohol and sinapyl alcohol, no successful film buildup could be observed. These newly formed films were compared to tannic acid-Fe3+ films as a reference. Film growth and degradation were tracked by using UV-vis absorption spectroscopy. The films were degradable under different conditions such as alkaline environments or in the presence of a strong chelator. Small hollow capsules with a diameter of 3 µm and thicknesses in the nanometer range were produced. Additionally, the prepared films showed varying colors and levels of wettability. By utilizing the films' coating properties, we successfully dyed human hair in various colors.

Effects of fermented sweet potato residue on nutrient digestibility, meat quality, and intestinal microbes in broilers.

This study aimed to investigate the effects of different proportions of dietary fermented sweet potato residue (FSPR) supplementation as a substitute for corn on the nutrient digestibility, meat quality, and intestinal microbes of yellow-feathered broilers. Experiment 1 (force-feeding) evaluated the nutrient composition and digestibility of mixtures with different proportions of sweet potato residue (70%, 80%, 90%, and 100%) before and after fermentation. In Experiment 2 (metabolic growth), a total of 420 one-day-old yellow-feathered broilers were randomly allocated to 4 groups and fed corn-soybean meal-based diets with 0, 5%, 8%, and 10% FSPR as a substitute for corn. The force-feeding and metabolic growth experiments were performed for 9 and 70 d, respectively. The treatment of 70% sweet potato residue (after fermentation) had the highest levels of crude protein, ether extract, and crude fiber and improved the digestibility of crude protein and amino acids (P < 0.05). Although dietary FSPR supplementation at different levels had no significant effect on growth performance and intestinal morphology, it improved slaughter rate, half-chamber rate, full clearance rate, and meat color, as well as reduced cooking loss in the breast and thigh muscles (P < 0.05). Dietary supplementation with 8% and 10% FSPR increased the serum immunoglobulin M and immunoglobulin G levels in broilers (P < 0.05). Furthermore, 10% FSPR increased the Shannon index and Ruminococcaceae_UCG-014, Ruminococcaceae_UCG-010 and Romboutsia abundances and decreased Sutterella and Megamonas abundances (P < 0.05). Spearman's correlation analysis showed that meat color was positively correlated with Ruminococcaceae_UCG-014 (P < 0.05) and negatively correlated with Megamonas (P < 0.05). Collectively, 70% sweet potato residue (after fermentation) had the best nutritional value and nutrient digestibility. Dietary supplementation with 8% to 10% FSPR as a substitute for corn can improve the slaughter performance, meat quality, and intestinal microbe profiles of broilers. Our findings suggest that FSPR has the potential to be used as a substitute for corn-soybean meals to improve the meat quality and intestinal health of broilers.

A review on fermented vegetables: Microbial community and potential upgrading strategy via inoculated fermentation.

Fermentation is a traditional method utilized for vegetable preservation, with microorganisms playing a crucial role in the process. Nowadays, traditional spontaneous fermentation methods are widely employed, which excessively depend on the microorganisms attached to the surface of raw materials, resulting in great difficulties in ideal control over the fermentation process. To achieve standardized production and improve product quality, it is essential to promote inoculated fermentation. In this way, starter cultures can dominate the fermentation processes successfully. Unfortunately, inoculated fermentation has not been thoroughly studied and applied. Therefore, this paper provides a systematic review of the potential upgrading strategy of vegetable fermentation technology. First, we disclose the microbial community structures and succession rules in some typical spontaneously fermented vegetables to comprehend the microbial fermentation processes well. Then, internal and external factors affecting microorganisms are explored to provide references for the selection of fermented materials and conditions. Besides, we widely summarize the potential starter candidates with various characteristics isolated from spontaneously fermented products. Subsequently, we exhibited the inoculated fermentation strategies with those isolations. To optimize the product quality, not only lactic acid bacteria that lead the fermentation, but also yeasts that contribute to aroma formation should be combined for inoculation. The inoculation order of the starter cultures also affects the microbial fermentation. It is equally important to choose a proper processing method to guarantee the activity and convenience of starter cultures. Only in this way can we achieve the transition from traditional spontaneous fermentation to modern inoculated fermentation.

Gene association analysis to determine the causal relationship between immune-mediated inflammatory diseases and frozen shoulder.

Multiple studies have indicated a potential correlation between immune-mediated inflammatory diseases (IMIDs) and Frozen shoulder (FS). To explore the genetic causal relationship between IMIDs and FS using 2-sample Mendelian randomization (MR) analysis. Genome-wide association study (GWAS) summary data for FS were obtained from Green's study, while data for 10 IMIDs were sourced from the FinnGen Consortium. The MR analysis was performed using inverse variance weighting, MR Egger, and weighted median methods. IVW, as the primary MR analysis technique, was complemented with other sensitivity analyses to validate the robustness of the results. Additionally, reverse MR analysis was further conducted to investigate the presence of reverse causal relationships. In the forward MR analysis, genetically determined 4 IMIDs are causally associated with FS: rheumatoid arthritis (odds ratio [OR] (95% confidence interval [95% CI]) = 1.05 [1.02-1.09], P < .01); type 1 diabetes (OR [95% CI] = 1.06 [1.03-1.09], P < .01); hypothyroidism (OR [95% CI] = 1.07 [1.01-1.14], P = .02); and Celiac disease (OR [95% CI] = 1.02 [1.01-1.04], P = .01). However, no causal relationship was found between 6 IMIDs (autoimmune hyperthyroidism, Crohn disease, ulcerative colitis, psoriasis, sicca syndrome and systemic lupus erythematosus) and FS. Sensitivity analyses did not detect any heterogeneity or horizontal pleiotropy. In the reverse MR analysis, no causal relationship was observed between FS and IMIDs. In conclusion, this MR study suggests a potential causal relationship between rheumatoid arthritis, type 1 diabetes, hypothyroidism, and Celiac disease in the onset and development of FS. Nevertheless, more basic and clinical research will be needed in the future to support our findings.

Low-intensity repetitive transcranial magnetic stimulation is safe and well tolerated by people living with MS - outcomes of the phase I randomised controlled trial (TAURUS).

Background: Low-intensity repetitive transcranial magnetic stimulation (rTMS), delivered as a daily intermittent theta burst stimulation (iTBS) for four consecutive weeks, increased the number of new oligodendrocytes in the adult mouse brain. Therefore, rTMS holds potential as a remyelinating intervention for people with multiple sclerosis (MS). Objective: Primarily to determine the safety and tolerability of our rTMS protocol in people with MS. Secondary objectives include feasibility, blinding and an exploration of changes in magnetic resonance imaging (MRI) metrics, patient-reported outcome measures (PROMs) and cognitive or motor performance. Methods: A randomised (2:1), placebo controlled, single blind, parallel group, phase 1 trial of 20 rTMS sessions (600 iTBS pulses per hemisphere; 25% maximum stimulator output), delivered over 4-5 weeks. Twenty participants were randomly assigned to 'sham' (n = 7) or active rTMS (n = 13), with the coil positioned at 90° or 0°, respectively. Results: Five adverse events (AEs) including one serious AE reported. None were related to treatment. Protocol compliance was high (85%) and blinding successful. Within participant MRI metrics, PROMs and cognitive or motor performance were unchanged over time. Conclusion: Twenty sessions of rTMS is safe and well tolerated in a small group of people with MS. The study protocol and procedures are feasible. Improvement of sham is warranted before further investigating safety and efficacy.

Improving multiple sclerosis lesion segmentation across clinical sites: A federated learning approach with noise-resilient training.

Accurately measuring the evolution of Multiple Sclerosis (MS) with magnetic resonance imaging (MRI) critically informs understanding of disease progression and helps to direct therapeutic strategy. Deep learning models have shown promise for automatically segmenting MS lesions, but the scarcity of accurately annotated data hinders progress in this area. Obtaining sufficient data from a single clinical site is challenging and does not address the heterogeneous need for model robustness. Conversely, the collection of data from multiple sites introduces data privacy concerns and potential label noise due to varying annotation standards. To address this dilemma, we explore the use of the federated learning framework while considering label noise. Our approach enables collaboration among multiple clinical sites without compromising data privacy under a federated learning paradigm that incorporates a noise-robust training strategy based on label correction. Specifically, we introduce a Decoupled Hard Label Correction (DHLC) strategy that considers the imbalanced distribution and fuzzy boundaries of MS lesions, enabling the correction of false annotations based on prediction confidence. We also introduce a Centrally Enhanced Label Correction (CELC) strategy, which leverages the aggregated central model as a correction teacher for all sites, enhancing the reliability of the correction process. Extensive experiments conducted on two multi-site datasets demonstrate the effectiveness and robustness of our proposed methods, indicating their potential for clinical applications in multi-site collaborations to train better deep learning models with lower cost in data collection and annotation.

Integrated anatomical structure, physiological, and transcriptomic analyses to identify differential cold tolerance responses of Ziziphus jujuba mill. 'Yueguang' and its autotetraploid 'Hongguang'.

Cold stress is a limiting stress factor that limits plant distribution and development; however, polyploid plants have specific characteristics such as higher resistance to abiotic stress, especially cold stress, that allow them to overcome this challenge. The cultivated cultivar Ziziphus jujuba Mill. 'Yueguang' (YG) and its autotetraploid counterpart 'Hongguang' (HG) exhibit differential cold tolerance. However, the underlying molecular mechanism and methods to enhance their cold tolerance remain unknown. Anatomical structure and physiological analysis indicated YG had a higher wood bark ratio, and xylem ratio under cold treatment compared to HG. However, the half-lethal temperature (LT50), cortex ratio, and malondialdehyde (MDA) content were significantly decreased in YG than HG, which indicated YG was cold tolerant than HG. Transcriptome analysis showed that 2084, 1725, 2888, and 2934 differentially expressed genes (DEGs) were identified in HC vs YC, H20 vs Y20, Y20 vs YC, and H20 vs HC treatment, respectively. Meanwhile, KEGG enrichment analysis of DEGs showed that several metabolic pathways, primarily plant hormone signal transduction and the MAPK signaling pathway, were involved in the differential regulation of cold tolerance between YG and HG. Furthermore, exogenous abscisic acid (ABA) and brassinolide (BR) treatments could improve their cold tolerance through increased SOD and POD activities, decreased relative electrical conductivity, and MDA content. All of these findings suggested that plant hormone signal transduction, particularly ABA and BR, might have an important role in the regulation of differential cold tolerance between YG and HG, laying the foundation for further improving cold tolerance in jujube and examining the molecular mechanisms underlying differences in cold tolerance among different ploidy cultivars.

Boosting the Photocatalytic Performance of g-C3N4 through MoS2 Nanotubes with the Cavity Enhancement Effect.

The development of catalysts with high photon utilization efficiency is crucial for enhancing the catalytic performance of photocatalysts. Graphitic carbon nitride (g-C3N4) is a prominent material in the field of photocatalysis. However, it still exhibits drawbacks such as low utilization of visible light and severe recombination of photogenerated carriers. To address these issues, this study employs MoS2 nanotubes (NTs) as cocatalysts and constructs MoS2 NTs/g-C3N4. The MoS2 NTs/g-C3N4 exhibits a significant cavity enhancement effect through multiple light reflections. This results in a broad spectral absorption range and high photon utilization efficiency, while also reducing the recombination of photogenerated carriers. The photocatalyst demonstrates outstanding performance in both photocatalytic hydrogen production and photodegradation of organic pollutants. Specifically, the hydrogen production rate is 1921 µmol·g-1·h-1, which is approximately 2.4 times that of g-C3N4. Furthermore, the photodegradation rate of Rhodamine B reaches 98.6% within 30 min, which is approximately three times higher than that of g-C3N4. Free radical capture experiments confirm that holes (h+) are the primary active species in photodegradation. A plausible photocatalytic mechanism for the catalyst is proposed. This study provides valuable insights into the development of heterojunction photocatalysts with high photon utilization efficiency.

Trilaciclib dosage in Chinese patients with extensive-stage small cell lung cancer: a pooled pharmacometrics analysis.

This study aimed to analyze potential ethnic disparities in the dose-exposure-response relationships of trilaciclib, a first-in-class intravenous cyclin-dependent kinase 4/6 inhibitor for treating chemotherapy-induced myelosuppression in patients with extensive-stage small cell lung cancer (ES-SCLC). This investigation focused on characterizing these relationships in both Chinese and non-Chinese patients to further refine the dosing regimen for trilaciclib in Chinese patients with ES-SCLC. Population pharmacokinetic (PopPK) and exposure-response (E-R) analyses were conducted using pooled data from four randomized phase 2/3 trials involving Chinese and non-Chinese patients with ES-SCLC. PopPK analysis revealed that trilaciclib clearance in Chinese patients was approximately 17% higher than that in non-Chinese patients with ES-SCLC. Sex and body surface area influenced trilaciclib pharmacokinetics in both populations but did not exert a significant clinical impact. E-R analysis demonstrated that trilaciclib exposure increased with a dosage escalation from 200 to 280 mg/m2, without notable changes in myeloprotective or antitumor efficacy. However, the incidence of infusion site reactions, headaches, and phlebitis/thrombophlebitis rose with increasing trilaciclib exposure in both Chinese and non-Chinese patients with ES-SCLC. These findings suggest no substantial ethnic disparities in the dose-exposure-response relationship between Chinese and non-Chinese patients. They support the adoption of a 240-mg/m2 intravenous 3-day or 5-day dosing regimen for trilaciclib in Chinese patients with ES-SCLC.