A retrospective study of adjuvant albumin-bound paclitaxel plus S-1 after D2 gastrectomy versus oxaliplatin plus S-1 in gastric cancer.

Adjuvant oxaliplatin plus S-1 (SOX) chemotherapy for gastric cancer (GC) after D2 gastrectomy has been proven effective. There has yet to be a study that evaluates adjuvant nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus S-1. In this single-center, retrospective study, GC patients after D2 gastrectomy received either nab-paclitaxel plus S-1 (AS group) or SOX group were recruited between January 2018 and December 2020 in The First Affiliated Hospital of Zhejiang University. Intravenous nab-paclitaxel 120 mg/m2 or 260 mg/m2 and oxaliplatin 130 mg/m2 were administered as eight 3 week cycle, especially in the AS and SOX group. Patients received S-1 twice daily with a dose of 40 mg/m2 in the two groups on days 1-14 of each cycle. The end points were disease-free survival (DFS) rate at 3 years and adverse events (AEs). There were 56 eligible patients, 28 in the AS group and 35 in the SOX group. The 3 year DFS rate was 78.0% in AS group versus 70.7% in SOX group (p = 0.46). Subgroup analysis showed that the patients with signet-ring positive in the AS group had a prolonged DFS compared with the SOX group (40.0 vs. 13.8 m, p = 0.02). The diffuse-type GC or low differentiation in the AS group was associated with numerically prolonged DFS compared with the SOX group, but the association was not statistically significant (p = 0.27 and p = 0.15 especially). Leukopenia (14.3%) were the most prevalent AEs in the AS group, while thrombocytopenia (28.5%) in the SOX group. Neutropenia (7.1% in AS group) and thrombocytopenia (22.8% in SOX group) were the most common grade 3 or 4 AEs. In this study analyzing past data, a tendency towards a greater 3 year DFS was observed when using AS regimen in signet-ring positive patients. AS group had fewer thrombocytopenia compared to SOX group. More studies should be conducted with larger sample sizes.

Tunlametinib (HL-085) plus vemurafenib in patients with advanced BRAF V600-mutant solid tumors: an open-label, single-arm, multicenter, phase I study.

BACKGROUND: Tunlametinib (HL-085) is a novel, highly selective MEK inhibitor with substantial clinical activities in patients with NRAS-mutant melanoma. This phase I study evaluated the safety and preliminary efficacy of tunlametinib plus vemurafenib in patients with advanced BRAF V600-mutant solid tumors. METHODS: Patients with confirmed advanced BRAF V600-mutant solid tumors who had progressed on or shown intolerance or no available standard therapies were enrolled and received tunlametinib plus vemurafenib. This study consisted of a dose-escalation phase and a dose-expansion phase. Primary end points of this study were safety, the recommended phase II dose (RP2D), and preliminary efficacy. RESULTS: From August 17, 2018 to April 19, 2022, 72 patients were enrolled. No dose-limiting toxicities occurred, and the maximum tolerated dose was not reached. The RP2D for BRAF V600-mutant non-small cell lung cancer (NSCLC) patients was tunlametinib 9 mg plus vemurafenib 720 mg, twice daily (BID, bis in die). Until the data cut-off date of December 15, 2023, of 33 NSCLC patients with evaluable disease, the objective response rate (ORR) was 60.6% (20/33; 95% confidence interval [CI], 42.1-77.1), the median progression free survival (PFS) was 10.5 months (95%CI, 5.6-14.5) and median duration of response (DoR) was 11.3 months (95%CI, 6.8-NE). At the RP2D, ORR was 60.0% (9/15; 95% CI, 32.3-83.7), the median PFS was 10.5 months (95%CI, 5.6 -NE) and median DoR was 11.3 months (95%CI, 3.9-NE). Of 24 colorectal cancer patients with evaluable disease, the ORR was 25.0% (6/24; 95% CI, 5.6-NE). All 72 patients had treatment-related adverse events (TRAEs), and the most common grade 3-4 TRAEs were anemia (n = 13, 18.1%) and blood creatine phosphokinase increased (n = 10, 13.9%). Tunlametinib was absorbed rapidly with Tmax of 0.5-1 h. Vemurafeinib did not influence the system exposure of tunlametinib and vice versa, indicating no drug-drug interaction for this combination. CONCLUSIONS: Tunlametinib (HL-085) plus vemurafenib had a favorable safety profile and showed promising antitumor activity in patients with BRAF V600-mutant solid tumors. The RP2D for NSCLC was tunlametinib 9 mg BID plus vemurafeinib 720 mg BID. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03781219.

Finotonlimab with chemotherapy in recurrent or metastatic head and neck cancer: a randomized phase 3 trial.

Immunotherapy combined with chemotherapy regimen has been shown to be effective in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). However, due to the small number of patients, its efficacy remains controversial in Asian populations, particularly in mainland China. Here a randomized, double-blind phase 3 trial evaluated the efficacy and safety of finotonlimab (SCT-I10A), a programmed cell death 1 (PD-1) monoclonal antibody, combined with cisplatin plus 5-fluorouracil (C5F) for the first-line treatment of R/M HNSCC. Eligible patients (n = 370) were randomly 2:1 assigned to receive finotonlimab plus C5F (n = 247) or placebo plus C5F (n = 123). The primary endpoint was overall survival (OS). In the finotonlimab plus C5F group, OS was 14.1 months (95% confidence interval (CI) 11.1-16.4), compared with 10.5 months (95% CI 8.1-11.8) in the placebo plus C5F group. The hazard ratio was 0.73 (95% CI 0.57-0.95, P = 0.0165), meeting the predefined superiority criteria for the primary endpoint. Finotonlimab plus C5F showed significant OS superiority compared with C5F alone and acceptable safety profile with R/M HNSCC, supporting its use as a first-line treatment option for R/M HNSCC. These results validate the efficacy and safety of the combination of finotonlimab and C5F in Asian patients with R/M HNSCC. ClinicalTrials.gov identifier: NCT04146402 .

Ligand-Enabled C6-Selective C-H Arylation of Pyrrolo[2,3-d] Pyrimidine Derivatives with Pd Catalysts: An Approach to the Synthesis of EGFR Inhibitor AEE-788.

Herein, we report the Pd(II)-catalyzed direct C-H arylation of pyrrolo[2,3-d]pyrimidine derivatives with aryl iodides, which is enabled by bidentate pyridine-pyridine ligands. A range of aryl iodides proved to be suitable coupling partners affording the desired products in good yields with high levels of C6 selectivity. This protocol features good tolerance of reactive functional groups, mild reaction conditions, and a simple reaction system, which provides an expeditious route to an essential class of 6-arylpyrrolo[2,3-d]pyrimidines frequently found in bioactive compounds, and provides a step-economical access to the second-generation EGFR inhibitor AEE-788.

Effects of Dried Tea Residues of Different Processing Techniques on the Nutritional Parameters, Fermentation Quality, and Bacterial Structure of Silaged Alfalfa.

The effects of dried tea residues on the nutritional parameters and fermentation quality, microbial community, and in vitro digestibility of alfalfa silage were investigated. In this study, dried tea residues generated from five different processing techniques (green tea, G; black tea, B; white tea, W; Pu'er raw tea, Z; Pu'er ripe tea, D) were added at two addition levels (5% and 10% fresh weight (FW)) to alfalfa and fermented for 90 days. The results showed that the tea residues increased the crude protein (CP) content (Z10: 23.85%), true protein nitrogen (TPN) content, DPPH, and ABST radical scavenging capacity, total antioxidant capacity (T-AOC), and in vitro dry matter digestibility (IVDMD) of the alfalfa silage. Moreover, the pH, ammonia-N (NH3-N) content, and acetic acid (AA) content decreased (p < 0.05). The effects of tea residues were promoted on these indicators with increasing tea residue addition. In addition, this study revealed that the influence of dried tea residues on the nutritional quality of alfalfa silage was greater than that on fermentation quality. Based on the nutrient composition, the addition of B or G to alfalfa silage can improve its silage quality, and these tea byproducts have the potential to be used as silage additives.

Female labour participation and infant mortality in Nigeria: implication for the sustainable development goal 3.

Over the time, link between female labour participation and infant mortality has become a subject of debate among scholars and policymakers in developing countries. This subject becomes more critical for a country like Nigeria where there is a persistent challenge to attain minimal global infant mortality rates by 2030, and where over 47% of female working population is unemployed. Against this background, this study utilizes fully modified ordinary least squares to estimate the relationship between female labour participation and infant mortality in Nigeria. The results show that at least 98 children per 1,000 births died in Nigeria between 1990 and 2020. Similarly, over 47% of female working population is currently unemployed in Nigeria. Female labour participation and infant mortality possess a significant negative relationship. Consequently, participation of women in the labour market has a significant effect in reducing infant mortality in Nigeria. In the same vein, female employment contributed to the reduction of infant mortality, though not substantial in nature. As such, the Nigerian policymakers should create a conducive environment that will facilitate participation of more women in the Nigerian labour market so that there will be further reduction of infant mortality in order to achieve the SDG 3.

Au fil du temps, le lien entre la participation des femmes au travail et la mortalité infantile est devenu un sujet de débat parmi les universitaires et les décideurs politiques des pays en développement. Ce sujet devient plus critique pour un pays comme le Nigeria, où il est toujours difficile d'atteindre des taux de mortalité infantile mondiaux minimaux d'ici 2030 et où plus de 47 % de la population active féminine est au chômage. Dans ce contexte, cette étude utilise les moindres carrés ordinaires entièrement modifiés pour estimer la relation entre la participation des femmes au travail et la mortalité infantile au Nigéria. Les résultats montrent qu'au moins 98 enfants pour 1 000 naissances sont morts au Nigeria entre 1990 et 2020. De même, plus de 47 % de la population active féminine est actuellement au chômage au Nigeria. La participation des femmes au travail et la mortalité infantile entretiennent une relation négative significative. Par conséquent, la participation des femmes au marché du travail a un effet significatif sur la réduction de la mortalité infantile au Nigéria. Dans le même ordre d'idées, l'emploi des femmes a contribué à la réduction de la mortalité infantile, même si elle n'est pas substantielle. En tant que tel, les décideurs politiques nigérians devraient créer un environnement propice qui facilitera la participation d'un plus grand nombre de femmes au marché du travail nigérian afin de réduire davantage la mortalité infantile afin d'atteindre l'ODD 3.

A phase IV study to evaluate the safety of fruquintinib in Chinese patients in real-world clinical practice.

INTRODUCTION: Fruquintinib is approved in China for patients with metastatic colorectal cancer (CRC) who progressed after 2 lines of chemotherapy. This postmarketing study was conducted to evaluate the safety of fruquintinib in the Chinese population, including previously treated patients with advanced CRC and other solid tumors. METHODS: Patients in the first cycle of fruquintinib or expected to start fruquintinib within a week were enrolled. Fruquintinib was administrated according to the label or per physicians' discretion. Patient characteristics and safety information were collected at baseline, 1 month, and 6 months after consent (or 30 days after the last dose). RESULTS: Overall, 3005 patients enrolled between April 24, 2019 and September 27, 2022. All enrolled patients received at least one dose of fruquintinib. Most patients had metastases at baseline. The median age was 60 years. More than half (64.0%) of the patients started fruquintinib at 5 mg, and the median treatment exposure was 2.7 months. Nearly one-third (32.5%) of patients with CRC received fruquintinib with concomitant antineoplastic agents. Treatment-emergent adverse events (TEAEs) leading to dose modification were reported in 626 (20.8%) patients, and 469 (15.6%) patients experienced TEAEs leading to treatment discontinuation. The most common grade ≥ 3 TEAEs were hypertension (6.6%), palmar-plantar erythrodysesthesia syndrome (2.2%), and platelet count decreased (1.0%). Combination therapy did not lead to excessive toxicities. CONCLUSIONS: The safety profile of fruquintinib in the real world was generally consistent with that in clinical studies, and the incidence of TEAEs was numerically lower than known VEGF/VEGFR inhibitor-related AEs. Fruquintinib exhibited manageable safety and tolerability in Chinese patients in the real-world setting.

Unveiling Multiquantum Excitonic Correlations in Push-Pull Polymer Semiconductors.

Bound and unbound Frenkel-exciton pairs are essential transient precursors for a variety of photophysical and biochemical processes. In this work, we identify bound and unbound Frenkel-exciton complexes in an electron push-pull polymer semiconductor using coherent two-dimensional spectroscopy. We find that the dominant A0-1 peak of the absorption vibronic progression is accompanied by a subpeak, each dressed by distinct vibrational modes. By considering the Liouville pathways within a two-exciton model, the imbalanced cross-peaks in one-quantum rephasing and nonrephasing spectra can be accounted for by the presence of pure biexcitons. The two-quantum nonrephasing spectra provide direct evidence for unbound exciton pairs and biexcitons with dominantly attractive force. In addition, the spectral features of unbound exciton pairs show mixed absorptive and dispersive character, implying many-body interactions within the correlated Frenkel-exciton pairs. Our work offers novel perspectives on the Frenkel-exciton complexes in semiconductor polymers.

Guiding the Formation of Metal-Organic Structures of 1,4-Diaminoanthraquinone through Surface-Based Cu Atoms.

The gradual guidance of the formation of metal-organic structures through surface-based Cu atoms for 1,4-diaminoanthraquinones (DAQs) has been studied by scanning tunneling microscopy (STM) at room temperature. On the Ag(110) surface, the transition from a hydrogen-bond network structure to metal-organic coordination structures of DAQs can be induced by introducing foreign copper atoms. Due to the weak interaction between DAQs and Ag(110), thermal treatment easily leads to the desorption of DAQs from the surface. To address this challenge, Cu(111) is selected as the substrate. Under thermal driving and in the presence of copper adatoms, the hydrogen-bond network structure of DAQs on the surface gradually undergoes a transition into a metal-coordinated structure, eventually leading to the formation of metal-organic complexes through amino dehydrogenation. It is demonstrated that the construction of a metal-organic coordination structure on metal surfaces is a result of the competition among factors such as metal atoms, functional groups of molecules, surface chemical activity, and temperature.

Phase 1b/2 study of penpulimab (AK105), an antiprogrammed cell death-1 immunoglobulin G1 antibody, in advanced or metastatic solid tumors (AK105-204).

BACKGROUND: Penpulimab, a new-generation antiprogrammed cell death-1 immunoglobulin G1 monoclonal antibody, was engineered to optimize receptor occupancy and eliminate fragment crystallizable γ-mediated effector function. In this multicenter, phase 1b/2, multicohort study, the objective was to investigate the efficacy, safety, and immunogenicity of penpulimab in advanced solid tumors. METHODS: Patients who had unresectable, advanced solid tumors were enrolled from six centers and received 200 mg penpulimab on day 1 every 2 weeks for up to 24 months. The primary end point was the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors, version criteria 1.1. RESULTS: Between September 2, 2019, and January 1, 2020, 65 patients were enrolled and received penpulimab. At the time of data cutoff (May 11, 2022), the median follow-up was 12.6 months (range, 1.1-28.6 months). The ORR was 12.3 (95% confidence interval [CI], 5.5%-22.8%), with three (4.6%) complete responses and five (7.7%) partial responses. Twelve patients (18.5%) achieved stable disease, resulting in a disease control rate of 30.8% (95% CI, 19.9%-43.4%). The median duration of response was not reached (95% CI, 6.70 months to not estimable). In all cohorts, the median progression-free survival was 1.74 months (95% CI, 1.41-2.69 months), and the median overall survival was 16.59 months (95% CI, 7.82-22.18 months). Grade 3 or greater treatment-related adverse events and immune-related adverse events occurred in 9.2% and 27.7% of patients, respectively. Positive antidrug antibody responses to penpulimab were observed in one patient (1.8%). CONCLUSIONS: Penpulimab showed promising antitumor activity with an acceptable safety profile, offering a potential new treatment approach for solid tumors. These findings supported the evaluation of penpulimab's durable activity and safety, as monotherapy or in combination therapy, in specific malignancies.

Exciton Bimolecular Annihilation Dynamics in Push-Pull Semiconductor Polymers.

Exciton-exciton annihilation is a ubiquitous nonlinear dynamic phenomenon in materials hosting Frenkel excitons. In this work, we investigate the nonlinear exciton dynamics of an electron push-pull conjugated polymer by fluence-dependent transient absorption and excitation-correlation photoluminescence spectroscopy, where we can quantitatively show the latter to be a more selective probe of the nonlinear dynamics. Simulations based on a time-independent exciton annihilation model show a decreasing trend for the extracted annihilation rates with excitation fluence. Further investigation of the fluence-dependent transients suggests that the exciton-exciton annihilation bimolecular rates are not constant in time, displaying a t-1/2 time dependence, which we rationalize as reflective of one-dimensional exciton diffusion, with a diffusion length estimated to be 9 ± 2 nm. In addition, exciton annihilation gives rise to a long-lived species that recombines on a nanosecond time scale. Our conclusions shed broad light onto nonlinear exciton dynamics in push-pull conjugated polymers.

Synergistic effects of ferulic acid esterase-producing lactic acid bacteria, cellulase and xylanase on the fermentation characteristics, fibre and nitrogen components and microbial community structure of Broussonetia papyrifera during ensiling.

BACKGROUND: The high fibre content of whole plants of Broussonetia papyrifera limits its efficient utilization. Ferulic acid esterase (FAE), in combination with xylanase, can effectively cleave the lignin-carbohydrate complex, promoting the function of cellulase. However, little is known about the impact of these additives on silage. To effectively utilize natural woody plant resources, FAE-producing Lactiplantibacillus plantarum RO395, xylanase (XY) and cellulase (CE) were used to investigate the dynamic fermentation characteristics, fibre and nitrogen components and microbial community structure during B. papyrifera ensiling. RESULTS: Broussonetia papyrifera was either not treated (CK) or treated with FAE-producing lactic acid bacteria (LP), CE, XY, LP + CE, LP + XY or LP + CE + XY for 3, 7, 15, 30 or 60 days, respectively. In comparison with those in the CK treatment, the L. plantarum and enzyme treatments (LP + CE, LP + XY and LP + XY + CE), especially the LP + XY + CE treatment, significantly increased the lactic acid concentration and decreased the pH and the contents of acid detergent insoluble protein and NH3 -N (P < 0.05). Enzyme addition improved the degradation efficiency of lignocellulose, and a synergistic effect was observed after enzyme treatment in combination with LP; in addition, the lowest acid detergent fibre, neutral detergent fibre, hemicellulose and cellulose contents were detected after the LP + CE + XY treatment (P < 0.05). Moreover, CE, XY and LP additions significantly improved the microbial community structure, increased the relative abundance of Lactiplantibacillus and Firmicutes, and effectively inhibited undesirable bacterial (Enterobacter) growth during ensiling. CONCLUSION: FAE-producing L. plantarum and the two tested enzymes exhibited synergistic effects on improving the quality of silage, which indicates that this combination can serve as an efficient method for improved B. papyrifera silage utilization. © 2023 Society of Chemical Industry.

Chain Conformation and Exciton Delocalization in a Push-Pull Conjugated Polymer.

Linear and nonlinear optical line shapes reveal details of excitonic structure in polymer semiconductors. We implement absorption, photoluminescence, and transient absorption spectroscopies in DPP-DTT, an electron push-pull copolymer, to explore the relationship between their spectral line shapes and chain conformation, deduced from resonance Raman spectroscopy and from ab initio calculations. The viscosity of precursor polymer solutions before film casting displays a transition that suggests gel formation above a critical concentration. Upon crossing this viscosity deflection concentration, the line shape analysis of the absorption spectra within a photophysical aggregate model reveals a gradual increase in interchain excitonic coupling. We also observe a red-shifted and line-narrowed steady-state photoluminescence spectrum along with increasing resonance Raman intensity in the stretching and torsional modes of the dithienothiophene unit, which suggests a longer exciton coherence length along the polymer-chain backbone. Furthermore, we observe a change of line shape in the photoinduced absorption component of the transient absorption spectrum. The derivative-like line shape may originate from two possibilities: a new excited-state absorption or Stark effect, both of which are consistent with the emergence of a high-energy shoulder as seen in both photoluminescence and absorption spectra. Therefore, we conclude that the exciton is more dispersed along the polymer chain backbone with increasing concentrations, leading to the hypothesis that polymer chain order is enhanced when the push-pull polymers are processed at higher concentrations. Thus, tuning the microscopic chain conformation by concentration would be another factor of interest when considering the polymer assembly pathways for pursuing large-area and high-performance organic optoelectronic devices.

The Memorial Sloan Kettering Prognostic Score: Correlation with survival in patients with advanced gastric cancer.

BACKGROUND: Notwithstanding that the past decade has witnessed unprecedented medical progress, gastric cancer (GC) remains a leading cause of cancer death, highlighting the need for effective prognostic markers. The Memorial Sloan Kettering Prognostic Score (MPS) has been validated as a valuable prognostic tool for patients with metastatic pancreatic adenocarcinoma (mPDAC). This study aimed to assess the prognostic value of the MPS in advanced GC. METHODS: Data from 367 patients were analyzed in the present study. The MPS for each patient was calculated based on the sum of scores based on the neutrophil-to-lymphocyte ratio and serum albumin levels. Multivariate analyses were performed to identify the independent clinicopathological parameters associated with overall survival (OS). Further subgroup analyses based on clinicopathological features were conducted. RESULTS: Patients with MPS 0 (n = 161), MPS 1 (n = 158), and MPS 2 (n = 48) exhibited significantly different OS, with a median survival duration of 20.7 (95%CI: 12.2-29.2), 14.9 (95%CI: 12.5-17.3), and 12.7 (95%CI: 9.3-16.0) months, respectively (p < 0.001). Significant differences in survival were observed among different groups of patients receiving chemotherapy (18.5 months vs. 14.7 months vs. 11.0 months, p = 0.03) or the subgroup receiving chemotherapy plus immunotherapy as first-line treatment (32.6 months vs. 17.7 months vs. 12.7 months, p = 0.02). The MPS was identified as an independent prognostic factor in multivariate analysis. During subgroup analyses, MPS-low (MPS 0) was consistently associated with a better prognosis than MPS-high (MPS 1 or 2). CONCLUSIONS: MPS is a practical, simple, and useful prognostic tool for patients with advanced GC. Further studies are warranted to validate its prognostic value in advanced GC.

Insights into the Rearrangement of the Molecular Assembly Structure of 6-Aminonicotinic Acid in Its Hydrated Environment.

Water, as a ubiquitous and essential component of life, is known to have a significant impact on the structure and function of organic molecules. In this study, we investigate the role of water in the phase transition of organic molecular assembly structures by scanning tunneling microscopy at room temperature. The results show that the -O-H···O hydrogen induced by water molecules can lead to a significant structural transition in the molecular assembly, specifically through selective weakening of -C-H···O between 6-aminonicotinic acid and the formation of new -O-H···O bonds between 6-aminonicotinic acid and water molecules. Subsequent thermal treatment of these molecular assembly structures reveals that the formation of -N-H···O hydrogen bonds induced by water molecules has created a different pathway for the phase transition of the molecular assembly structure. This knowledge has important implications for the design of organic molecules with specific nanostructures that can be controlled through hydration.

Resolving Nonlinear Recombination Dynamics in Semiconductors via Ultrafast Excitation Correlation Spectroscopy: Photoluminescence versus Photocurrent Detection.

We explore the application of excitation correlation spectroscopy to detect nonlinear photophysical dynamics in two distinct semiconductor classes through time-integrated photoluminescence and photocurrent measurements. In this experiment, two variably delayed femtosecond pulses excite the semiconductor, and the time-integrated photoluminescence or photocurrent component arising from the nonlinear dynamics of the populations induced by each pulse is measured as a function of inter-pulse delay by phase-sensitive detection with a lock-in amplifier. We focus on two limiting materials systems with contrasting optical properties: a prototypical lead-halide perovskite (LHP) solar cell, in which primary photoexcitations are charge photocarriers, and a single-component organic-semiconductor diode, which features Frenkel excitons as primary photoexcitations. The photoexcitation dynamics perceived by the two detection schemes in these contrasting systems are distinct. Nonlinear-dynamic contributions in the photoluminescence detection scheme arise from contributions to radiative recombination in both materials systems, while photocurrent arises directly in the LHP but indirectly following exciton dissociation in the organic system. Consequently, the basic photophysics of the two systems are reflected differently when comparing measurements with the two detection schemes. Our results indicate that photoluminescence detection in the LHP system provides valuable information about trap-assisted and Auger recombination processes, but that these processes are convoluted in a nontrivial way in the photocurrent response and are therefore difficult to differentiate. In contrast, the organic-semiconductor system exhibits more directly correlated responses in the nonlinear photoluminescence and photocurrent measurements, as charge carriers are secondary excitations only generated through exciton dissociation processes. We propose that bimolecular annihilation pathways mainly contribute to the generation of charge carriers in single-component organic semiconductor devices. Overall, our work highlights the utility of excitation correlation spectroscopy in modern semiconductor materials research, particularly in the analysis of nonlinear photophysical processes, which are deterministic for their electronic and optical properties.

Cryptotanshinone Reverses Corticosteroid Insensitivity by Inhibition of Phosphoinositide-3-Kinase-δ in Chronic Obstructive Pulmonary Disease.

Purpose: Corticosteroid insensitivity has become a major barrier in the treatment of chronic obstructive pulmonary disease (COPD). It is known that oxidative stress reduces the expression and activity of histone deacetylase (HDAC)-2 by activating phosphoinositide-3-kinase-δ(PI3Kδ)/Akt pathway, which is a common mechanism. The aim of this study was to investigate whether cryptotanshinone (CPT) can improve corticosteroid sensitivity and to investigate the molecular mechanisms by which this occurs. Patients and Methods: Corticosteroid sensitivity in peripheral blood mononuclear cells (PBMCs) collected from COPD patients, or in human monocytic U937 monocytic cells exposed to cigarette smoke extract (CSE), was quantified as the dexamethasone concentration required to achieve 30% inhibition of tumor necrosis factor-α (TNFα)-induced interleukin 8 (IL-8) production in the presence or absence of cryptotanshinone. PI3K/Akt activity (measured as the relative ratio of phosphorylated Akt at Ser-473 to total Akt) and HDAC2 expression levels were determined by western blotting. HDAC activity was evaluated by a Fluo-Lys HDAC activity assay kit in U937 monocytic cells. Results: Both PBMCs in patients with COPD and U937 cells exposed to CSE were found to be insensitive to dexamethasone, accompanied by increased phosphorylated Akt (pAkt) and decreased HDAC2 protein expression. The pretreatment of cryptotanshinone restored their sensitivity to dexamethasone, and simultaneously downregulated the level of phosphorylated Akt and upregulated the level of HDAC2 protein. Pretreatment with cryptotanshinone or IC87114 reversed the decrease in HDAC activity in CSE-stimulated U937 cells. Conclusion: Cryptotanshinone restores corticosteroid sensitivity induced by oxidative stress via inhibition of PI3Kδ and is a potential treatment for corticosteroid-insensitive diseases such as COPD.

Association between adult food insecurity and self-reported asthma in the United States: NHANES 2003-2018.

OBJECTIVE: Asthma is a chronic disease of the lungs. The development of asthma is related to various risk factors. Food insecurity is a critical social determinant of health, although there is little information on the association between adult food insecurity and asthma. The purpose of this study is to explore the potential correlation in US adults. METHODS: The study population data were extracted from NHANES 2003-2018. Food insecurity was measured using the USDA FSSM and categorized as full, marginal, low, or very low food security. The assessment of self-reported asthma was determined by self-report questionnaires. The self-reported positive outcomes were that participants had asthma and a history of asthma attacks and asthma-related ER visits in the past year. We developed two multivariate logistic regression models. Stratified analyses were performed by gender and age. RESULTS: A total of 38,077 participants were considered in our final analysis. Compared to participants with FFS, the ORs (95% CIs) for asthma were 1.16 (1.00-1.33), 1.42 (1.23-1.64), and 1.56 (1.34-1.80) for participants with MFS, LFS, and VLFS, respectively (Model II). Additionally, after full adjustment, individuals with VLFS had 49% greater risks of asthma attacks (OR = 1.49; 95% CI 1.13-1.97). The ORs (95% CIs) for asthma-related ER visits were 1.59 (1.14-2.23) and 1.98 (1.36-2.87) for participants with LFS and VLFS, respectively (Model II). The positive correlations remained robust when stratified by gender and age. CONCLUSION: Our research showed that food insecurity among US adults was associated with asthma, asthma attacks, and asthma-related ER visits.

Standardized Sanguisorba officinalis L. Extract Inhibits Adipogenesis and Promotes Thermogenesis via Reducing Oxidative Stress.

Obesity produces many health problems, including systemic oxidative stress. This study comprehensively investigated the effects of Sanguisorba officinalis L. extract (SO) as an antioxidant on abnormal lipid accumulation and oxidative stress in 3T3-L1 adipocytes and high-fat diet (HFD)-induced obese mice (n = 48). We evaluated the anti-adipogenic and antioxidant effects of SO on 3T3-L1 by cell viability, Oil red O staining, and NBT assays. The ameliorative effects of SO in HFD-induced C57BL/6J mice were investigated by measuring body weight, serum lipids, adipocyte size, hepatic steatosis, AMPK pathway-related proteins, and thermogenic factors. In addition, the effect of SO on oxidative stress in obese mice was evaluated by the activity of antioxidant enzymes and the production of lipid peroxidation products and ROS production in adipose tissue. We found that SO dose-dependently decreased lipid accumulation and ROS production in 3T3-L1 adipocytes. In C57BL/6J obese mice, SO (above 200 mg/kg) attenuated the HFD-induced gain in body weight and white adipose tissue (WAT) weight without affecting appetite. SO also decreased serum glucose, lipid, and leptin levels and attenuated adipocyte hypertrophy and hepatic steatosis. Furthermore, SO increased the expression of SOD1 and SOD2 in WAT, decreased ROS and lipid peroxides, and activated the AMPK pathway and thermogenic factors. In summary, SO reduces oxidative stress in adipose tissue by increasing antioxidant enzyme activity and improves obesity symptoms through AMPK-pathway-regulated energy metabolism and mitochondrial respiratory thermogenesis.

Efficacy and safety of KL-A167 in previously treated recurrent or metastatic nasopharyngeal carcinoma: a multicenter, single-arm, phase 2 study.

Background: KL-A167 is a fully humanized monoclonal antibody targeting programmed cell death-ligand 1. This phase 2 study aimed to evaluate the efficacy and safety of KL-A167 in Chinese patients with previously treated recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC). Methods: This was a multicentre, single-arm, phase 2 study of KL-A167 in R/M NPC (KL167-2-05-CTP) (NCT03848286), conducted at 42 hospitals across the People's Republic of China. Eligible patients had histologically confirmed non-keratinising R/M NPC, and had failed at least two lines of chemotherapy. Patients received KL-A167 900mg intravenously once every 2 weeks until confirmed disease progression, intolerable toxicity, or withdrawal of informed consent. The primary endpoint was objective response rate (ORR) assessed by the independent review committee (IRC) according to RECIST v1.1. Findings: Between Feb 26th, 2019 and Jan 13th, 2021, 153 patients were treated. Totally, 132 patients entered full analysis set (FAS) and were evaluated for the efficacy. As of data cutoff date on Jul 13th, 2021, the median follow-up time was 21.7 months (95%CI 19.8-22.5). For FAS population, the IRC-assessed ORR was 26.5% (95%CI 19.2-34.9%), and disease control rate (DCR) was 56.8% (95%CI 47.9-65.4%). Median progression-free survival (PFS) was 2.8 months (95%CI 1.5-4.1) . Median duration of response was 12.4 months (95%CI 6.8-16.5), and median overall survival (OS) was 16.2 months (95%CI 13.4-21.3). When using the cutoff of 1000 copies/ml, 5000 copies/ml and 10,000 copies/ml for plasma EBV DNA titer, baseline low plasma EBV DNA was consistently related with better DCR, PFS and OS. Dynamic change of plasma EBV DNA was significantly associated with ORR and PFS. Among 153 patients, treatment related-adverse events (TRAEs) occurred in 73.2% of patients, and grade ≥3 TRAEs were in 15.0% of patients. No TRAE leading to death was reported. Conclusion: In this study, KL-A167 showed promising efficacy and an acceptable safety profile in patients with previously treated R/M NPC. Baseline plasma EBV DNA copy number might be a potentially useful prognostic biomarker for KL-A167 treatment, and post-treatment EBV DNA decrease might be correlated with better response to KL-A167. Funding: Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd., China National Major Project for New Drug Innovation (2017ZX09304015).