Unraveling the microbial puzzle: exploring the intricate role of gut microbiota in endometriosis pathogenesis.

Endometriosis (EMs) is a prevalent gynecological disorder characterized by the growth of uterine tissue outside the uterine cavity, causing debilitating symptoms and infertility. Despite its prevalence, the exact mechanisms behind EMs development remain incompletely understood. This article presents a comprehensive overview of the relationship between gut microbiota imbalance and EMs pathogenesis. Recent research indicates that gut microbiota plays a pivotal role in various aspects of EMs, including immune regulation, generation of inflammatory factors, angiopoietin release, hormonal regulation, and endotoxin production. Dysbiosis of gut microbiota can disrupt immune responses, leading to inflammation and impaired immune clearance of endometrial fragments, resulting in the development of endometriotic lesions. The dysregulated microbiota can contribute to the release of lipopolysaccharide (LPS), triggering chronic inflammation and promoting ectopic endometrial adhesion, invasion, and angiogenesis. Furthermore, gut microbiota involvement in estrogen metabolism affects estrogen levels, which are directly related to EMs development. The review also highlights the potential of gut microbiota as a diagnostic tool and therapeutic target for EMs. Interventions such as fecal microbiota transplantation (FMT) and the use of gut microbiota preparations have demonstrated promising effects in reducing EMs symptoms. Despite the progress made, further research is needed to unravel the intricate interactions between gut microbiota and EMs, paving the way for more effective prevention and treatment strategies for this challenging condition.

Faslpr gene dosage tunes the extent of lymphoproliferation and T cell differentiation in lupus.

Sle1 and Faslpr are two lupus susceptibility loci that lead to manifestations of systemic lupus erythematosus. To evaluate the dosage effects of Faslpr in determining cellular and serological phenotypes associated with lupus, we developed a new C57BL/6 (B6) congenic lupus strain, B6.Sle1/Sle1.Faslpr/+ (Sle1homo.lprhet) and compared it with B6.Faslpr/lpr (lprhomo), B6.Sle1/Sle1 (Sle1homo), and B6.Sle1/Sle1.Faslpr/lpr (Sle1homo.lprhomo) strains. Whereas Sle1homo.lprhomo mice exhibited profound lymphoproliferation and early mortality, Sle1homo.lprhet mice had a lifespan comparable to B6 mice, with no evidence of splenomegaly or lymphadenopathy. Compared to B6 monogenic lupus strains, Sle1homo.lprhet mice exhibited significantly elevated serum ANA antibodies and increased proteinuria. Additionally, Sle1homo.lprhet T cells had an increased propensity to differentiate into Th1 cells. Gene dose effects of Faslpr were noted in upregulating serum IL-1⍺, IL-2, and IL-27. Taken together, Sle1homo.lprhet strain is a new C57BL/6-based model of lupus, ideal for genetic studies, autoantibody repertoire investigation, and for exploring Th1 effector cell skewing without early-age lymphoproliferative autoimmunity.

Estimating elemental composition of personal PM2.5 by a modeling approach in two megacities, China.

Personal exposure to PM2.5, and the elemental composition therein, may vary greatly from ambient measurements at fixed monitoring sites. Here, we characterized the differences between personal, indoor, and outdoor concentrations of PM2.5-bound elements, and predicted personal exposures to 21 PM2.5-bound elements. Personal-indoor-outdoor PM2.5 filter samples were collected for five consecutive days across two seasons from 66 healthy non-smoking retired adults in Beijing (BJ) and Nanjing (NJ), China. Personal element-specific models were developed using liner mixed effects models and evaluated by R2 and root mean square error (RMSE). The mean (SD) concentrations of personal exposures varied by element and city, ranging from 2.5 (1.4) ng/m3 for Ni in BJ to 4271.2 (1614.8) ng/m3 for S in NJ. Personal exposures to PM2.5 and most elements were significantly correlated with both indoor and outdoor (except Ni in BJ) measurements, but frequently exceeded indoor levels and fell below outdoor levels. Indoor and outdoor PM2.5 elemental concentrations were the strongest determinants of most personal elemental exposures, with RM2 ranging from 0.074 to 0.975 for indoor and from 0.078 to 0.917 for outdoor levels, respectively. Home ventilation conditions (especially window opening behavior), time-activity patterns, meteorological factors, household characteristics, and season were also key factors influencing personal exposure levels. The final models accounted for 24.2 %-94.0 % (RMSE: 0.135-0.718) of the variance in personal PM2.5 elemental exposures. By incorporating these crucial determinants, the modeling approach used here can improve PM2.5-bound elemental exposure estimates and better associate compositionally dependent PM2.5 exposures and health risks.

Online Science Instruction Can Promote Adolescents' Autonomy Need Satisfaction: a Latent Growth Curve Analysis.

This research examined the differential motivational effects of a pre-college science enrichment program delivered in both online and in-person learning formats. Using self-determination theory as a guiding framework, we hypothesized that (a) students would exhibit growth in their perceived satisfaction of needs for autonomy, competence, and relatedness, (b) online learning would be associated with greater growth in autonomy, and (c) in-person learning would be associated with greater growth in both competence and relatedness. Using a sample of 598 adolescent participants, results of latent growth curve modeling indicated that satisfaction of the three needs grew unconditionally over the course of the program. However, format type was unrelated to growth in need satisfaction. Rather, this effect was found to be conditional upon the type of science project undertaken by students: astrophysics students exhibited significantly greater autonomy growth when receiving online instruction than did biochemistry students. Our findings suggest that online science learning can be just as effective in motivating students as in-person learning provided that the learning tasks are conducive to remote instruction.

A novel particle swarm optimization based on hybrid-learning model.

The convergence speed and the diversity of the population plays a critical role in the performance of particle swarm optimization (PSO). In order to balance the trade-off between exploration and exploitation, a novel particle swarm optimization based on the hybrid learning model (PSO-HLM) is proposed. In the early iteration stage, PSO-HLM updates the velocity of the particle based on the hybrid learning model, which can improve the convergence speed. At the end of the iteration, PSO-HLM employs a multi-pools fusion strategy to mutate the newly generated particles, which can expand the population diversity, thus avoid PSO-HLM falling into a local optima. In order to understand the strengths and weaknesses of PSO-HLM, several experiments are carried out on 30 benchmark functions. Experimental results show that the performance of PSO-HLM is better than other the-state-of-the-art algorithms.

Low-temperature electrolytes based on linear carboxylic ester co-solvents for SiO x /graphite composite anodes.

Silicon-based anode materials have been applied in lithium-ion batteries with high energy density. However, developing electrolytes that can meet the specific requirements of these batteries at low temperatures still remains a challenge. Herein, we report the effect of linear carboxylic ester ethyl propionate (EP), as the co-solvent in a carbonate-based electrolyte, on SiO x /graphite (SiOC) composite anodes. Using electrolytes with EP, the anode provides better electrochemical performance at both low temperatures and ambient temperature, showing a capacity of 680.31 mA h g-1 at -50 °C and 0.1C (63.66% retention relative to that at 25 °C), and a capacity retention of 97.02% after 100 cycles at 25 °C and 0.5C. Within the EP-containing electrolyte, SiOC‖LiCoO2 full cells also exhibit superior cycling stability at -20 °C for 200 cycles. These substantial improvements of the EP co-solvent at low temperatures are probably due to its involvement to form a solid electrolyte interphase with high integrity and facile transport kinetics in electrochemical processes.

Truncated total variation in fractional B-spline wavelet transform for micro-CT image denoising.

BACKGROUND: In medical applications, computed tomography (CT) is widely used to evaluate various sample characteristics. However, image quality of CT reconstruction can be degraded due to artifacts. OBJECTIVE: To propose and test a truncated total variation (truncation TV) model to solve the problem of large penalties for the total variation (TV) model. METHODS: In this study, a truncated TV image denoising model in the fractional B-spline wavelet domain is developed to obtain the best solution. The method is validated by the analysis of CT reconstructed images of actual biological Pigeons samples. For this purpose, several indices including the peak signal-to-noise ratio (PSNR), structural similarity index (SSIM) and mean square error (MSE) are used to evaluate the quality of images. RESULTS: Comparing to the conventional truncated TV model that yields 22.55, 0.688 and 361.17 in PSNR, SSIM and MSE, respectively, using the proposed fractional B-spline-truncated TV model, the computed values of these evaluation indices change to 24.24, 0.898 and 244.98, respectively, indicating substantial reduction of image noise with higher PSNR and SSIM, and lower MSE. CONCLUSIONS: Study results demonstrate that compared with many classic image denoising methods, the new denoising algorithm proposed in this study can more effectively suppresses the reconstructed CT image artifacts while maintaining the detailed image structure.

Association between dietary inflammatory index and risk of endometriosis: A population-based analysis.

Background and aims: Chronic inflammation plays a significant role in the etiology of endometriosis, which might be affected by dietary intake. This study aimed to investigate the association between dietary inflammatory index (DII) and the risk of endometriosis. Methods: A cross-sectional analysis using data from the National Health and Nutrition Examination Survey (1999-2006) was conducted on 3,410 American participants, among whom 265 reported a diagnosis of endometriosis. DII scores were calculated based on the dietary questionnaire. The association of DII scores with endometriosis was evaluated by adjusted multivariate logistic regression analyzes, which were further investigated in the subgroups. Results: In the fully adjusted models, the odds ratio (OR) for endometriosis participants in the highest and middle tertiles of DII scores were 1.57 [95% confidence interval (CI): 1.14-2.17] and 1.18 (95% CI: 0.84-1.65), compared to the lowest tertile (P trend = 0.007). In subgroup analyzes, the significant positive association between DII scores and the endometriosis risk was also observed in non-obese women (ORtertile3vs1: 1.69, 95% CI: 1.12-2.55; P trend = 0.012), women without diabetes (ORtertile3vs1: 1.62, 95% CI: 1.16-2.27; P trend = 0.005), women with hypertension (ORtertile3vs1: 2.25, 95% CI: 1.31-3.87; P trend = 0.003), parous women (ORtertile3vs1: 1.55, 95% CI: 1.11-2.17; P trend = 0.011), and women using oral contraceptives (ORtertile3vs1: 1.63, 95% CI: 1.15-2.30; P trend = 0.006). Conclusion: This nationally representative study found that increased intake of the pro-inflammatory diet, as a higher DII score, was positively associated with endometriosis risk among American adults. Our results suggested anti-inflammatory dietary interventions may be promising in the prevention of endometriosis. Further prospective studies are necessary to confirm these findings.

Over 18.1% Efficiency of Layer-by-Layer Polymer Solar Cells by Enhancing Exciton Utilization near the ITO Electrode.

In this work, layer-by-layer (LbL) polymer solar cells (PSCs) are constructed without/with the incorporation of a dissociation strengthening layer (DSL) on the basis of the wide-bandgap donor D18-Cl, as well as the narrow-bandgap nonfullerene acceptor Y6. The efficiency of LbL PSCs is enhanced from 17.62 to 18.15% through introducing a DSL, originating from the enhanced dissociation of D18-Cl excitons near the ITO electrode. Meanwhile, the interfacial energy between D18-Cl and Y6 layers is decreased by incorporating a DSL, which should facilitate molecular interdiffusion for more adequate exciton dissociation in LbL active layers. This work offers a simple and resultful way for realizing power conversion efficiency (PCE) improvement of LbL PSCs with maximized exciton utilization in LbL active layers. The universality of the DSL incorporation strategy on performance improvement can be further confirmed with a boosted PCE from 17.39 to 18.03% or from 17.13 to 17.61% for D18-Cl/L8-BO- or D18-Cl/N3-based LbL PSCs by incorporating a DSL.

Risk stratification and molecular heterogeneity of endometrial cancer and expression profile of TIM-3: A retrospective cohort study.

OBJECTIVE: The present study aimed to implement ProMisE classification and risk grouping on a retrospective cohort of 628 patients with endometrial cancer (EC) and determine the molecular heterogeneity across subtypes and subgroups, as well as to investigate the potential beneficiary for TIM-3 checkpoint inhibition in ECs. METHODS: Protein expressions of p53, MMR, TIM-3 and CD8 were measured by immunohistochemistry, and massively parallel sequencing was conducted for 128 cancer-related genes. Patients were categorized into four ProMisE subtypes: MMR-deficient (MMRd), POLE-ultramutated (POLEmut), p53-wild type (p53wt), and p53-abnormal (p53abn), and were subjected to risk classification. RESULTS: 43 (6.9%) patients belonged to POLEmut, 118 (18.8%) to MMRd, 69 (11%) to p53abn, and 398 (63.3%) to p53wt. Compared to the 2016 stratification system, the 2021 ESGO/ESTRO/ESP risk stratification integrated with molecular classification revealed that 11 patients (11/628, 1.8%) were upgraded due to the p53abn signature, whereas 23 patients (23/628, 3.7%) were downgraded due to the POLEmut signature. JAK1 and RAD50 mutations showed higher frequencies in patients with aggressive phenotypes. RAD51B mutation was significantly related to poor RFS of the p53wt subtype but not of the other three molecular subgroups. TIM-3 expression was detected in 30.9% immune cells (ICs) and 29.0% tumor cells (TCs) in ECs, respectively. It was frequently expressed in POLEmut and MMRd ECs as compared to that in the other two molecular subtypes in TCs and ICs. CONCLUSIONS: Our study revealed the molecular heterogeneity across subtypes and subgroups. The new risk stratification system changed the risk grouping of some patients due to the integration of molecular features. RAD51B mutation can further stratify the recurrence risk in the p53wt subtype. Patients with MMRd or POLEmut may benefit most from immunotherapy against TIM-3.

Personal exposure to PM2.5 in different microenvironments and activities for retired adults in two megacities, China.

Microenvironmental concentrations and time-activity patterns influence personal exposure to fine particulate matter (PM2.5). However, the variations and contributions of PM2.5 exposures from various microenvironments (MEs) and activities remain unclear. In this study, gravimetrically corrected real-time personal PM2.5 measurements were collected during routine activities in different MEs from 66 non-smoking retired adults. Exposure data were collected for five consecutive days over two seasons in Nanjing (NJ) and Beijing (BJ), China. Measured PM2.5 concentrations varied substantially both between and within different MEs and activities. The highest average concentrations were observed in restaurants (NJ: mean 192 µg/m3, SD 242 µg/m3; BJ: mean 91 µg/m3, SD 79 µg/m3) and were associated with sources such as passive smoking and cooking emissions. Overall, PM2.5 concentrations in different MEs and activities were moderately to highly correlated with outdoor PM2.5 concentrations (Spearman's r = 0.51-0.97) except in restaurants and during passive smoking. The at-home ME contributed approximately 85 % of the total PM2.5 exposure, corresponding to the participants spending about 87 % of their time there. The majority of household exposures occurred during sleeping, cooking, and other home-based activities. Transportation accounted for <5 % of total exposure. Our results indicate that improving indoor air quality, especially residential indoors, is important to reduce personal exposure to PM2.5.

Single-cell CRISPR immune screens reveal immunological roles of tumor intrinsic factors.

Genetic screens are widely exploited to develop novel therapeutic approaches for cancer treatment. With recent advances in single-cell technology, single-cell CRISPR screen (scCRISPR) platforms provide opportunities for target validation and mechanistic studies in a high-throughput manner. Here, we aim to establish scCRISPR platforms which are suitable for immune-related screens involving multiple cell types. We integrated two scCRISPR platforms, namely Perturb-seq and CROP-seq, with both in vitro and in vivo immune screens. By leveraging previously generated resources, we optimized experimental conditions and data analysis pipelines to achieve better consistency between results from high-throughput and individual validations. Furthermore, we evaluated the performance of scCRISPR immune screens in determining underlying mechanisms of tumor intrinsic immune regulation. Our results showed that scCRISPR platforms can simultaneously characterize gene expression profiles and perturbation effects present in individual cells in different immune screen conditions. Results from scCRISPR immune screens also predict transcriptional phenotype associated with clinical responses to cancer immunotherapy. More importantly, scCRISPR screen platforms reveal the interactive relationship between targeting tumor intrinsic factors and T cell-mediated antitumor immune response which cannot be easily assessed by bulk RNA-seq. Collectively, scCRISPR immune screens provide scalable and reliable platforms to elucidate molecular determinants of tumor immune resistance.

Slightly Elevated Progesterone on HCG Trigger Day Has an Impact on Pregnancy Outcomes of Fresh Single Blastocyst Transfer Cycles Under an Early Follicular Phase Prolonged Protocol Cycle.

Background: The effect of premature progesterone elevation on assisted reproductive technology has been debated. In different ovarian stimulation protocols, ovarian responses, and embryos transferred, conflicting results reside regarding the impact of elevated progesterone on pregnancy outcomes, according to previous studies. In addition, most studies have focused on significantly elevated progesterone levels, eg, above 1.5ng/mL, 1.75ng/mL, 2ng/mL. However, studies focusing on levels that are just slightly elevated are lacking, and some have concluded that such levels have no adverse effects on pregnancy outcomes. Methods: Clinical data of patients who underwent early follicular phase prolonged protocol cycle in vitro fertilization/intracytoplasmic sperm injection treatment were collected. Patients were divided into two groups according to progesterone level on the trigger day of human chorionic gonadotropin (HCG): Group 1: < 1.0ng/mL and Group 2: 1.0-1.5ng/mL. Differences in baseline characteristics, ovulation promotion, and embryo culture, along with clinical pregnancy outcomes, were compared between the two cohorts. Results: A total of 743 participants were included in this study, of which 587 were included in Group 1 and 156 were included in Group 2. In terms of pregnancy outcomes, Group 2 had a significantly lower clinical pregnancy rate and live birth rate per cycle than Group 1 (64.1% vs 75.7%, p < 0.05; 63.5% vs 72.7%, p < 0.05). After correction for maternal age, maternal body mass index, infertility duration, basal follicle-stimulating hormone, anti-Müllerian hormone, antral follicle count, total dose of gonadotropin, days of stimulation, and estradiol level on HCG trigger day, slightly elevated progesterone levels (P > 1.0ng/mL) remained a risk factor for pregnancy failure in fresh single D5 blastocyst transfer under an early follicular phase prolonged protocol cycle. Conclusion: Slightly elevated progesterone levels on HCG trigger day may negatively affect pregnancy outcomes in early follicular phase prolonged protocol cycles.

Influences of piezoelectric positive-negative junction on the multi-field coupled waves propagation in the piezoelectric semiconductor.

The influences of the piezoelectric positive-negative junction (PN junction) between two semiconductors with different doping types on the multi-field coupled wave propagation are studied in the present work. The layered structures of semiconductors are often used in intelligent devices, and the PN junction plays an important role for performance improvement. Due to the migration and diffusion of carriers, the electric potential and concentration of the carrier are graded distribution in the PN junction. This inhomogeneity results in the reflection and transmission of coupled waves, which are the complex of multiple physical fields including the mechanical, electric, and carrier fields. The state transfer equation method is used to obtain the transfer matrix of the PN junction, and the reflection and transmission waves under the plane strain situation are evaluated numerically. The energy fluxes of the reflection and transmission waves are estimated and used to validate the numerical results by the check of energy conservation. It is found that PN junction effects hinder the wave propagation and drastically enhance the reflection ability of the interface, especially, on the coupled carrier waves, and thus are very important and cannot be ignored for the wave propagation problem. The influences of external applied stress and bias electric field are also discussed.

Ferroptosis induced by iron overload promotes fibrosis in ovarian endometriosis and is related to subpopulations of endometrial stromal cells.

Endometriosis (EMs) is defined as the presence of tissue somewhat resembling endometrial glands and stroma outside the uterus; the retrograded endometrium grows in the peritoneal cavity and elicits fibrosis. Ferroptosis is a recently discovered form of programmed cell death, which is iron-dependent. The induction of ferroptosis has been found to participate in fibrosis. However, the relationship between EMs fibrosis and ferroptosis remains unknown. In this study, we confirmed that the iron content in ectopic stromal tissue in ovarian EMs is significantly increased. We explored the role of iron-induced ferroptosis in the pathogenesis of ovarian EMs fibrosis for the first time. We found that ferroptosis in ectopic tissues was significantly enhanced than that in eutopic tissues. Furthermore, we performed in vivo drug screening and found that ferroptosis induced by ferric ammonium citrate (FAC) could aggravate fibrosis. To clarify the mechanism of this process, the stromal composition of human uterine endometrium and endometrial tissue was characterized. Fibroblast-specific protein-1 was used for fibroblasts, smooth muscle actin alpha for myofibroblasts, and platelet-derived growth factor receptor beta (CD140b) for mesenchymal stromal cells (MSCs). The results demonstrated that the percentage of myofibroblasts was higher and the portion of MSCs was lower in ectopic endometrial stroma than those in eutopic endometrium. Moreover, the proportion of MSCs decreased significantly and the percentage of myofibroblasts increased considerably after FAC treatment in vitro. However, disruption of intracellular iron levels or ferroptosis via chelation of intracellular iron deferoxamine mesylate or ferroptosis inhibitor ferrostatin-1 could reverse this process, indicating that iron-induced ferroptosis plays a vital role in ovarian EMs fibrosis. Considering that iron accumulation can feed the Fenton reaction to generate unquenchable amounts of free radicals, causing ferroptosis and tissue damage and thereby contributing to fibrosis, we validated the underlying mechanism that excess iron can facilitate fibrotic responses. Collectively, these data provide evidence that supernumerary iron is a key regulator in promoting MSCs ferroptosis and inducing ovarian EMs fibrosis.

Air Pollution Health Impact Monitoring and Health Risk Assessment Technology and Its Application - China, 2006-2019.

Air pollution is a significant risk factor contributing to the burden of disease in China. Health risk assessment and management are important to reduce the impact of air pollution on public health. To help formulate standardized health risk assessment techniques, a series of studies were conducted from 2006 to 2019. Through systematic review, study of molecular mechanisms, epidemiological investigation, and health effect monitoring, the overall project established a monitoring and evaluation indicator system, a comprehensive information platform, software for automatic data cleaning, and standardized health risk assessment techniques. Technical specifications have been issued by the National Health Commission for promoting health risk assessments across China. This paper introduces the project, the research approach, its main research accomplishments, innovations, and public health significance, and describes directions for further research.

Analysis of the immune checkpoint lymphocyte activation gene-3 (LAG-3) in endometrial cancer: An emerging target for immunotherapy.

BACKGROUND: Lymphocyte activation gene-3 (LAG-3) is a novel molecule that participates in the immune escape of tumor cells and is a target for immunotherapy. However, the expression of LAG-3 in patients with endometrial cancer (EC) has not been comprehensively characterized. OBJECTIVES: We elucidated the expression of LAG-3 and investigated its correlation with clinicopathological parameters, ProMisE subtypes, CD8+ T-cell infiltration and relapse-free survival (RFS) in a retrospective cohort of 421 patients with endometrial cancer. METHODS: Next-generation sequencing of the polymerase epsilon (POLE) and immunohistochemistry of mismatch repair (MMR)-related protein (MLH1, PMS2, MSH2, and MSH6), p53, CD8 and LAG-3 protein in whole sections were performed. RESULTS: Positive LAG-3 was detected in tumor cells (TCs) and immune cells (ICs) in 31.6% (133/421) and 24.0% (101/421) of the patients, respectively. LAG-3 positivity in ICs was more common in high-grade, high-intermediate risk, high-risk, and advanced/metastatic subgroups and was relevant to lymphovascular space invasion, while that in TCs was more common in older individuals (≥54 years). LAG-3 expression was more prevalent in POLE ultramutated (POLEmut) and MMR-deficient (MMRd) EC than in p53-abnormal (p53abn) and p53-wild (p53wt) EC in TCs (34.4 % and 66.3% in POLEmut and MMRd versus 28.6% and 19.5% in p53abn and p53wt, P < 0.001) and ICs (78.1 % and 65.1% in POLEmut and MMRd versus 2.9% and 5.2% in p53abn and p53wt, P < 0.001). Positive expression of LAG-3 in TCs and ICs was associated with high levels of tumor-associated CD8+ T-cell immune infiltration. Additionally, LAG-3 positivity in TCs was related to improved RFS. CONCLUSIONS: This study suggests that immunotherapy targeting LAG-3 may play a role in EC patients with POLEmut or MMRd molecular markers. Positive LAG-3 expression in TCs may be a predictor of improved RFS.

Boosted Efficiency Over 18.1% of Polymer Solar Cells by Employing Large Extinction Coefficients Material as the Third Component.

A series of binary and ternary polymer solar cells (PSCs) is successfully fabricated. The optimal ternary PSCs achieve a power conversion efficiency (PCE) of 18.14%, benefiting from the increased short circuit current density (JSC ) of 26.53 mA cm-2 and fill factor (FF) of 78.51% in comparison with the JSC s (25.05 mA cm-2 and 25.65 mA cm-2 ) and the FFs (77.13% and 76.55%) of the corresponding binary PSCs. The photon harvesting ability of ternary active layers can be enhanced, which can be confirmed from the EQE spectral difference of the optimized ternary and binary PSCs, especially in the wavelength range from 680 nm to 800 nm. The refractive index and extinction coefficients of binary and ternary blend films are measured, which can well support the enhanced photon harvesting ability in different wavelength ranges. Photogenerated exciton distribution in active layers is simulated by the transmission matrix method based on the Beer-Lambert law. The photogenerated exciton density can be enhanced in the middle of the active layers by incorporating a third component in acceptors, which is conducive to charge collection by individual electrodes, resulting in the simultaneously enhanced JSC and FF of the optimal ternary PSCs.

Clinically translatable cytokine delivery platform for eradication of intraperitoneal tumors.

Proinflammatory cytokines have been approved by the Food and Drug Administration for the treatment of metastatic melanoma and renal carcinoma. However, effective cytokine therapy requires high-dose infusions that can result in antidrug antibodies and/or systemic side effects that limit long-term benefits. To overcome these limitations, we developed a clinically translatable cytokine delivery platform composed of polymer-encapsulated human ARPE-19 (RPE) cells that produce natural cytokines. Tumor-adjacent administration of these capsules demonstrated predictable dose modulation with spatial and temporal control and enabled peritoneal cancer immunotherapy without systemic toxicities. Interleukin-2 (IL2)-producing cytokine factory treatment eradicated peritoneal tumors in ovarian and colorectal mouse models. Furthermore, computational pharmacokinetic modeling predicts clinical translatability to humans. Notably, this platform elicited T cell responses in NHPs, consistent with reported biomarkers of treatment efficacy without toxicity. Combined, our findings demonstrate the safety and efficacy of IL2 cytokine factories in preclinical animal models and provide rationale for future clinical testing in humans.

Inhibiting Type I Arginine Methyltransferase Activity Promotes T Cell-Mediated Antitumor Immune Responses.

Protein arginine methyltransferases (PRMT) are a widely expressed class of enzymes responsible for catalyzing arginine methylation on numerous protein substrates. Among them, type I PRMTs are responsible for generating asymmetric dimethylarginine. By controlling multiple basic cellular processes, such as DNA damage responses, transcriptional regulation, and mRNA splicing, type I PRMTs contribute to cancer initiation and progression. A type I PRMT inhibitor, GSK3368715, has been developed and has entered clinical trials for solid and hematologic malignancies. Although type I PRMTs have been reported to play roles in modulating immune cell function, the immunologic role of tumor-intrinsic pathways controlled by type I PRMTs remains uncharacterized. Here, our The Cancer Genome Atlas dataset analysis revealed that expression of type I PRMTs associated with poor clinical response and decreased immune infiltration in patients with melanoma. In cancer cell lines, inhibition of type I PRMTs induced an IFN gene signature, amplified responses to IFN and innate immune signaling, and decreased expression of the immunosuppressive cytokine VEGF. In immunocompetent mouse tumor models, including a model of T-cell exclusion that represents a common mechanism of anti-programmed cell death protein 1 (PD-1) resistance in humans, type I PRMT inhibition increased T-cell infiltration, produced durable responses dependent on CD8+ T cells, and enhanced efficacy of anti-PD-1 therapy. These data indicate that type I PRMT inhibition exhibits immunomodulatory properties and synergizes with immune checkpoint blockade (ICB) to induce durable antitumor responses in a T cell-dependent manner, suggesting that type I PRMT inhibition can potentiate an antitumor immunity in refractory settings.