Living-Skin Detection based on Spatio-Temporal Analysis of Structured Light Pattern.

Living-skin detection is an important step for imaging photoplethysmography and biometric anti-spoofing. In this paper, we propose a new approach that exploits spatio-temporal characteristics of structured light patterns projected on the skin surface for living-skin detection. We observed that due to the interactions between laser photons and tissues inside a multi-layer skin structure, the frequency-domain sharpness feature of laser spots on skin and non-skin surfaces exhibits clear difference. Additionally, the subtle physiological motion of living-skin causes laser interference, leading to brightness fluctuations of laser spots projected on the skin surface. Based on these two observations, we designed a new living-skin detection algorithm to distinguish skin from non-skin using spatio-temporal features of structured laser spots. Experiments in the dark chamber and Neonatal Intensive Care Unit (NICU) demonstrated that the proposed setup and method performed well, achieving a precision of 85.32%, recall of 83.87%, and F1-score of 83.03% averaged over these two scenes. Compared to the approach that only leverages the property of multilayer skin structure, the hybrid approach obtains an averaged improvement of 8.18% in precision, 3.93% in recall, and 8.64% in F1-score. These results validate the efficacy of using frequency domain sharpness and brightness fluctuations to augment the features of living-skin tissues irradiated by structured light, providing a solid basis for structured light based physiological imaging. Our code is available at: https://github.com/contactless-healthcare/Structured-light-based-Living-skin-Detection.

Application of acid-activated near-infrared viscosity fluorescent probe targeting lysosomes in cancer visualization.

The higher viscosity and lower pH in lysosomes of cancer cells highlight their potential as biomarkers for cancer. Therefore, the development of acid-activated viscosity fluorescent probes is significant for the early diagnosis and treatment of cancer. Based on this, we have designed and synthesized a near-infrared fluorescent probe based on the 2-(2-hydroxyphenyl)benzothiazole (HBT) group, namely HBTH, to monitor the viscosity changes within lysosomes. It has been demonstrated that HBTH was extremely sensitive to viscosity, with a strong linear relationship between fluorescence intensity and log(viscosity) within the range of (logη) = 0-3.06 (a correlation coefficient of 0.98), proving its capability for quantitative viscosity measurement. In particular, the most obvious fluorescence enhancement of HBTH was only efficiently triggered by the combined effect of low pH and high viscosity. Furthermore, HBTH can rapidly localize to lysosomes by wash-free procedure at a low concentration (100 nM) and achieve high-fidelity imaging within 20 s. It can also monitor the dynamic processes of lysosomes in cells, viscosity changes under drug stimuli, and lysosomal behavior during mitophagy. Importantly, HBTH is capable of identifying tumors in tumor-bearing nude mice through in vivo imaging. These features make HBTH a powerful tool for the early diagnosis and treatment of cancer.

Tanshinone I improves TNBC chemosensitivity by suppressing late-phase autophagy through AKT/p38 MAPK signaling pathway.

The inhibition of autophagy is a potential therapeutic strategy to improve the chemosensitivity of triple-negative breast cancer (TNBC). In this study, we demonstrated that a natural terpenoid tanshinone I (TAN) enhanced the effectiveness of paclitaxel (PTX), at least in part, through an autophagy-dependent mechanism against TNBC. In vitro validation demonstrated that the combined therapy resulted in a synergistic decrease in the growth of TNBC cells. The chemosensitizing impact of TAN might be attributed to its inhibition of PTX-induced autophagy in the late phase by obstructing the fusion of autophagosomes and lysosomes, rather than by inhibiting lysosomal function. The findings from KEGG pathway analysis and molecular docking suggested that TAN might impact breast cancer chemoresistance primarily through the PI3K-Akt and MAPK signaling pathways. The non-canonical AKT/p38 MAPK signaling was further validated as the primary mechanism responsible for the inhibition of autophagy by TAN. In vivo study showed that the combined administration of TAN and PTX demonstrated a more significant suppression of tumor growth and autophagic activity compared to PTX monotherapy in the MDA-MB-231 xenograft nude mouse model. The safety evaluation of TAN in a zebrafish model, along with in vitro and in vivo validation, provided experimental and pre-clinical data supporting its potential as a natural adjunctive therapy in TNBC. Overall, this study suggests that the combination of TAN with PTX could provide an effective treatment option for advanced breast cancer, and targeting the AKT/p38 MAPK/late-autophagy signaling axis may be a promising approach for developing therapeutic interventions against TNBC.

Single-cell sequencing and multiple machine learning algorithms to identify key T-cell differentiation gene for progression of NAFLD cirrhosis to hepatocellular carcinoma.

Introduction: Hepatocellular carcinoma (HCC), which is closely associated with chronicinflammation, is the most common liver cancer and primarily involves dysregulated immune responses in the precancerous microenvironment. Currently, most studies have been limited to HCC incidence. However, the immunopathogenic mechanisms underlying precancerous lesions remain unknown. Methods: We obtained single-cell sequencing data (GSE136103) from two nonalcoholic fatty liver disease (NAFLD) cirrhosis samples and five healthy samples. Using pseudo-time analysis, we systematically identified five different T-cell differentiation states. Ten machine-learning algorithms were used in 81 combinations to integrate the frameworks and establish the best T-cell differentiation-related prognostic signature in a multi-cohort bulk transcriptome analysis. Results: LDHA was considered a core gene, and the results were validated using multiple external datasets. In addition, we validated LDHA expression using immunohistochemistry and flow cytometry. Conclusion: LDHA is a crucial marker gene in T cells for the progression of NAFLD cirrhosis to HCC.

Brozopine ameliorates cognitive impairment via upregulating Nrf2, antioxidation and anti-inflammation activities.

Oxidative stress and inflammation are crucial factors contributing to the occurrence and development of vascular dementia (VD). In a previous study, we demonstrated that brozopine (BZP) is an anti-ischemic drug. In this study, a model of VD in rats with modified permanent bilateral common carotid artery occlusion (2-VO) was established in vivo, a model of cellular excitotoxicity/oxidative stress was established via L-glutamate-induced PC12 cell injury, a model of neuroinflammation was established in LPS-induced BV2 cells in vitro, and the ameliorative effect of BZP on cognitive impairment was assessed. BZP treatment improved memory deficit in VD rats through inhibiting Ca2+overload and the levels of oxidative stress, ferroptosis, and inflammatory markers (IL-1ß, IL-6, and COX-2) in different brain regions. Additionally, we found that the levels of inflammatory markers in the plasma were also reduced in the VD rats. BZP was further found to have antioxidative stress, antiferroptosis (ferroptosis markers: GPX4, P53, and ACSL4), and antineuroinflammatory effects in PC12 and BV2 cells. Its mechanisms of action were found to be related to the activation of the Nrf2/TLR4/NF-κB pathway; the protective effect of BZP was partially inhibited after using Nrf2-specific inhibitors. Thus, BZP has therapeutic properties for the potential mitigation of cognitive impairment.

Baohuoside I chemosensitises breast cancer to paclitaxel by suppressing extracellular vesicle/CXCL1 signal released from apoptotic cells.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and chemotherapy is the cornerstone treatment for TNBC. Regrettably, emerging findings suggest that chemotherapy facilitates pro-metastatic changes in the tumour microenvironment. Extracellular vesicles (EVs) have been highly implicated in cancer drug resistance and metastasis. However, the effects of the EVs released from dying cancer cells on TNBC prognosis and corresponding therapeutic strategies have been poorly investigated. This study demonstrated that paclitaxel chemotherapy elicited CXCL1-enriched EVs from apoptotic TNBC cells (EV-Apo). EV-Apo promoted the chemoresistance and invasion of co-cultured TNBC cells by polarizing M2 macrophages through activating PD-L1 signalling. However, baohuoside I (BHS) remarkably sensitized the co-cultured TNBC cells to paclitaxel chemotherapy via modulating EV-Apo signalling. Mechanistically, BHS remarkably decreased C-X-C motif chemokine ligand 1 (CXCL1) cargo within EV-Apo and therefore attenuated macrophage M2 polarization by suppressing PD-L1 activation. Additionally, BHS decreased EV-Apo release by diminishing the biogenesis of intraluminal vesicles (ILVs) within multivesicular bodies (MVBs) of TNBC cells. Furthermore, BHS bound to the LEU104 residue of flotillin 2 (FLOT2) and interrupted its interaction with RAS oncogene family member 31 (RAB31), leading to the blockage of RAB31-FLOT2 complex-driven ILV biogenesis. Importantly, BHS remarkably chemosensitised paclitaxel to inhibit TNBC metastasis in vivo by suppressing EV-ApoCXCL1-induced PD-L1 activation and M2 polarization of tumour-associated macrophages (TAMs). This pioneering study sheds light on EV-ApoCXCL1 as a novel therapeutic target to chemosensitise TNBC, and presents BHS as a promising chemotherapy adjuvant to improve TNBC chemosensitivity and prognosis by disturbing EV-ApoCXCL1 biogenesis.

Acidity-activatable dynamic hybrid nanoplatforms derived from extracellular vesicles of M1 macrophages enhance cancer immunotherapy through synergistic triple immunotherapy.

Immunotherapy exhibits considerable promise for sustained tumor reduction. However, current cancer immunotherapy methods elicit limited responses due to the inadequate immunogenicity exhibited by cancer cells. This obstacle may be addressed using nanoplatforms that can activate synergistic therapies (photodynamic therapy and ferroptosis) in response to the acidic pH of the tumor microenvironment. We previously developed an amphiphilic photosensitizer, SR780, which displays satisfactory photodynamic effects. This photosensitizer is inactivated when bound to Fe3+ (SR780Fe) but is activated upon release in mildly acidic conditions. In this study, M1 macrophage-derived extracellular vesicles (EVs) were fused with REV and SR780Fe-loaded liposomes (REV@SR780Fe@Lip) to form REV@SR780Fe@LEV hybrid nanovesicles. Further modification with the RS17 peptide for tumor targeting enabled a combination of photodynamic therapy, ferroptosis, and cGAS-STING pathway activation, resulting in enhanced antitumor efficacy through a synergistic effect. Upon laser irradiation, REV@SR780Fe@LEV-RS17 demonstrated antitumor effects in 4T1 breast cancer models, including the inhibition of lung and liver metastasis, as well as prevention of tumor recurrence.

Multifunctional lipid droplet probes for observing the polarity change of ferroptosis, inflammation, fatty liver and evaluating the efficacy of drugs.

BACKGROUND: Lipid droplets (LDs) polarity is intricately linked to diverse biological processes and diseases. The visualization of LDs-polarity is of vital importance but challenging due to the lack of high-specificity, high-sensitivity and large-Stokes shift probes for real-time tracking LDs-polarity in biological systems. RESULTS: Four D-π-A based fluorescent probes (TPA-TCF1-TPA-TCF4) have been developed by combining tricyanofuran (an electron acceptor, A) and triphenylamine (an electron donor, D) derivatives with different terminal groups. Among them, TPA-TCF1 and TPA-TCF4 exhibit excellent polar sensitivity, large Stokes shift (≥182 nm in H2O), and efficient LDs targeting ability. In particular, TPA-TCF4 is capable of monitoring the change of LDs-polarity during ferroptosis, inflammation, apoptosis of cancer cell, and fatty liver. SIGNIFICANCE: All these features render TPA-TCF4 a versatile tool for pharmacodynamic evaluation of anti-cancer drugs, in-depth understanding of the biological effect of LDs on ferroptosis, and medical diagnosis of LDs-polarity related diseases.

Lipid Nanoparticular Codelivery System for Enhanced Antitumor Effects by Ferroptosis-Apoptosis Synergistic with Programmed Cell Death-Ligand 1 Downregulation.

Intrinsic or acquired resistance to chemical drugs severely limits their therapeutic efficacy in cancer treatment. Various intracellular antioxidant molecules, particularly glutathione (GSH), play a crucial role in maintaining intracellular redox homeostasis by mitigating the overproduced reactive oxygen species (ROS) due to rapid cell proliferation. Notably, these antioxidants also eliminate chemical-drug-induced ROS, eventually diminishing their cytotoxicity and rendering them less effective. In this study, we combined erastin, a GSH biosynthesis inhibitor, with 2'-deoxy-5-fluorouridine 5'-monophosphate sodium salt (FdUMP), an ROS-based drug, to effectively disrupt intracellular redox homeostasis and reverse chemotherapy resistance. Therefore, efficient ferroptosis and apoptosis were simultaneously induced for enhanced antitumor effects. Additionally, we employed small interfering RNA targeting PD-L1 (siPD-L1) as a third agent to block immune-checkpoint recognition by CD8+ T cells. The highly immunogenic cell peroxidates or damage-associated molecular patterns (DAMPs) induced by erastin acted synergistically with downregulated PD-L1 to enhance the antitumor effects. To codeliver these three drugs simultaneously and efficiently, we designed GE11 peptide-modified lipid nanoparticles (LNPs) containing calcium phosphate cores to achieve high encapsulation efficiencies. In vitro studies verified its enhanced cytotoxicity, efficient intracellular ROS induction and GSH/GPX4 downregulation, substantial lipid peroxidation product accumulation, and mitochondrial depolarization. In vivo, this formulation effectively accumulated at tumor sites and achieved significant tumor inhibition in subcutaneous colon cancer (CRC) mouse models with a maximum tumor inhibition rate of 83.89% at a relatively low dose. Overall, a strategy to overcome clinical drug resistance was verified in this study by depleting GSH and activating adaptive immunity.

Fu-Zheng-Yi-Liu Formula inhibits the stem cells and metastasis of prostate cancer via tumor-associated macrophages/C-C motif chemokine ligand 5 pathway in tumor microenvironment.

Prostate cancer (PCa) is the second most common malignancy among men globally. The Fu-Zheng-Yi-Liu (FZYL) Formula has been widely utilized in the treatment of PCa. This study investigates whether the FZYL Formula can inhibit PCa by targeting the TAMs/CCL5 pathway. We conducted in vitro co-cultures and in vivo co-injections of PCa cells and TAMs to mimic their interaction. Results showed that the FZYL Formula significantly reduced the proliferation, colony formation, subpopulations of PCSCs, and sphere-formation efficacy of PCa cells, even in the presence of TAM co-culture. Additionally, the Formula markedly decreased the migration, invasion, and epithelial-mesenchymal transition (EMT) of PCa cells induced by TAMs. The FZYL Formula also reversed M2 phenotype polarization in TAMs and dose-dependently reduced their CCL5 expression and secretion, with minimal cytotoxicity observed. Mechanistic studies confirmed that the TAMs/CCL5 axis is a critical target of the FZYL Formula, as the addition of exogenous CCL5 partially reversed the formula's inhibitory effects on PCSCs self-renewal in the co-culture system. Importantly, the Formula also significantly inhibited the growth of PCa xenografts, bone metastasis, and PCSCs activity in vivo by targeting the TAMs/CCL5 pathway. Overall, this study not only elucidates the immunomodulatory mechanism of the FZYL Formula in PCa therapy but also highlights the TAMs/CCL5 axis as a promising therapeutic target.

Molecular Dynamics Simulation of the Rejuvenation Performance of Waste Cooking Oil with High Acid Value on Aged Asphalt.

Waste cooking oil's (WCO's) potential as a rejuvenator of aged asphalt has received attention in recent years, with the acid value of WCO affecting its rejuvenation effect. This study explored the rejuvenation effect of WCO with a high acid value on aged asphalt by using molecular dynamics simulation. First, the representative molecules of WCO with a high acid value and asphalt were determined. The rejuvenation effect of WCO on aged asphalt was analyzed by adding different contents of WCO to an aged asphalt model. The effect of WCO on the thermodynamic properties of the aged asphalt was analyzed. The results show that WCO can restore the thermodynamic properties of aged asphalt binder to a certain extent. Regarding the microstructure of rejuvenated asphalt, WCO molecules dispersed around asphaltenes weakened the latter's aggregation and improved the colloidal structure of the aged asphalt. In terms of interface adhesion properties, WCO can improve the adhesion properties between asphalt binder and SiO2, but it has limited influence on water sensitivity. The results allowed us to comprehensively evaluate the rejuvenation effect of WCO with a high acid value on aged asphalt and to explore its rejuvenation mechanism.

Methyl methacrylate-modified polystyrene microspheres: an effective strategy to enhance the fluorescence of Eu-complexes.

The in vitro detection applications of europium complex-doped microspheres mainly rely on strong fluorescence intensity and a well-defined morphology. In this work, using methyl methacrylate-modified polystyrene microspheres has been proven an effective strategy to enhance the fluorescence and morphology of Eu-complexes. The experimental results showed that the modification resulted in the formation of a porous structure within the polystyrene microspheres, enhancing the doping uniformity and facilitating a more significant accumulation of fluorescent molecules. Furthermore, because of their encapsulation ability, microspheres efficiently confine the fluorescent molecules within them. In addition, the nano-scale porous structure endowed the microspheres with enhanced properties without compromising solvent swelling capability, thereby significantly boosting the fluorescence performance of porous PSMMA. In lateral flow immunoassays (LFIAs), PSMMA-Eu microspheres were effectively utilized to detect fentanyl with exceptional sensitivity by capitalizing on these benefits, capable of detecting concentrations as low as 0.10 ng mL-1. This technology has significant potential for rapid point-of-care screening and clinical applications.

Modulatory Effects of XIAOPI Formula on CXCL1 and Selected Outcomes in Triple-Negative Breast Cancer: A Randomized Controlled Clinical Trial.

Background: Triple-negative breast cancer (TNBC) is the most aggressive malignancy. Psychological distress and elevated CXCL1 level have been reported to be closely associated with the poor prognosis and quality of life of patients with TNBC. In preclinical studies using xenograft mouse models, XIAOPI formula, a nationally approved drug prescribed to patients at high risk for breast cancer, inhibited CXCL1 expression and improved survival. Traditional Chinese medicine has unique advantages in improving patients' emotional disorders and quality of life. However, the impact of XIAOPI formula on the serum level of CXCL1, psychological distress, and quality of life among patients with TNBC is currently unknown. Methods: In this study, we designed a randomized, double-blind, placebo-controlled trial. Patients with TNBC were randomly assigned to receive either the XIAOPI formula or a placebo for three months. The primary outcomes include serum CXCL1 expression, Self-Rating Anxiety Scale (SAS), and the Self-Rating Depression Scale (SDS). Secondary outcomes included the Pittsburgh Sleep Quality Index (PSQI) and the Functional Assessment of Cancer Therapy-Breast (FACT-B). Results: A total of 60 patients with TNBC were enrolled in the investigation. The results showed that the XIAOPI formula significantly decreased CXCL1 expression compared with the control group. Moreover, in comparison to the placebo, the XIAOPI formula increased FACT-B scores while decreasing SDS, SAS, and PSQI scores. Conclusion: In patients with TNBC, XIAOPI formula may be effective in reducing CXCL1 levels, enhancing psychological well-being, and quality of life. While our research offers a natural alternative therapy that may enhance the prognosis of TNBC, future validation of its therapeutic effects will require large-scale, long-term clinical trials. Clinical Registration Number: Registration website: www.chictr.org.cn, Registration date: 2018-1-19, Registration number: ChiCTR1800014535.

Cell Membrane Hybrid Lipid Nanovesicles Enhance Innate Immunity for Synergistic Immunotherapy by Promoting Immunogenic Cell Death and cGAS Activation.

Immunotherapy shows great therapeutic potential for long-term protection against tumor relapse and metastasis. Innate immune sensors, such as cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING), dissolve DNA and induce type I interferon. Through activation of the cGAS/STING pathway, chemotherapy drugs and reversine (REV) may provide synergetic anti-tumor effects. Here, we prepared drug-loaded cell membrane hybrid lipid nanovesicles (LEVs) (designated LEV@DOX@REV) by fusion of cell membranes, phospholipids, doxorubicin (DOX), and REV, to realize accurate delivery to tumors and chemo-immunotherapy. The cell membranes of LEVs confer "homing" abilities. DOX can induce immunogenic cell death as a result of its specific immunomodulatory effects, which promotes the maturation of immune cells and improves the microenvironment of the immune system. REV is proven to efficiently activate cGAS/STING signaling, thereby enhancing the immune system. The antitumor efficacy of LEV@DOX@REV was evaluated in a 4T1 subcutaneous tumor xenograft model, a distant metastatic tumor model, and a liver metastatic tumor model. LEV@DOX@REV facilitated the infiltration of cytotoxic T lymphocytes within tumors, increased the secretion of proinflammatory cytokines, and modified the tumor microenvironment. In conclusion, LEV@DOX@REV displayed favorable antitumor effects and extended the survival of tumor-bearing mice. We therefore successfully developed nanoparticles capable of enhancing immune activation that have potential therapeutic applications for cancer immunotherapy.

Distinguishing optimal candidates for primary tumor resection in patients with metastatic lung adenocarcinoma: A predictive model based on propensity score matching.

Background: Primary tumor resection is associated with survival benefits in patients with metastatic lung adenocarcinoma (mLUAD). However, there are no established methods to determine which individuals would benefit from surgery. Therefore, we developed a model to predict the patients who are likely to benefit from surgery in terms of survival. Methods: Data on patients with mLUAD were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Depending on whether surgery was performed on the primary tumor, patients were categorized into two groups: cancer-directed surgery (CDS) and no-cancer-directed surgery (No-CDS). Propensity Score Matching (PSM) was utilized to address bias between the CDS and No-CDS groups. The prognostic impact of CDS was assessed using Kaplan-Meier analysis and Cox proportional hazard models. Subsequently, we constructed a nomogram to predict the potential for surgical benefits based on multivariable logistic regression analysis using preoperative factors. Results: A total of 89,039 eligible patients were identified, including 6.4% (5705) who underwent surgery. Following PSM, the CDS group demonstrated a significantly longer median overall survival (mOS) compared with the No-CDS group (23 [21-25] vs. 7 [7-8] months; P < 0.001). The nomogram showed robust performance in both the training and validation sets (area under the curve [AUC]: 0.698 and 0.717, respectively), and the calibration curves exhibited high consistency. The nomogram proved clinically valuable according to decision curve analysis (DCA). According to this nomogram, surgical patients were categorized into two groups: no-benefit candidates and benefit candidates groups. Compared with the no-benefit candidate group, the benefit candidate group was associated with longer survival (mOS: 25 vs. 6 months, P < 0.001). Furthermore, no difference in survival was observed between the no-benefit candidates and the no-surgery groups (mOS: 6 vs. 7 months, P = 0.9). Conclusions: A practical nomogram was developed to identify optimal CDS candidates among patients with mLUAD.

Efficient Green Spin Light-Emitting Diodes Enabled by Ultrafast Energy- and Spin-Funneling in Chiral Perovskites.

Introducing molecular chirality into perovskite crystal structures has enabled the control of carrier spin states, giving rise to circularly polarized luminescence (CPL) in thin films and circularly polarized electroluminescence (CPEL) in LEDs. Spin-LEDs can be fabricated either through a spin-filtering layer enabled by chiral-induced spin selectivity or a chiral emissive layer. The former requires a high degree of spin polarization and a compatible spinterface for efficient spin injection, which might not be easily integrated into LEDs. Alternatively, a chiral emissive layer can also generate circularly polarized electroluminescence, but the efficiency remains low and the fundamental mechanism is elusive. In this work, we report an efficient green LED based on quasi-two-dimensional (quasi-2D) chiral perovskites as the emitting layer (EML), where CPEL is directly produced without separate carrier spin injection. The optimized chiral perovskite thin films exhibited strong CPL at 535 nm with a photoluminescence quantum yield (PLQY) of 91% and a photoluminescence dissymmetry factor (glum) of 8.6 × 10-2. Efficient green spin-LEDs were successfully demonstrated, with a large EL dissymmetry factor (gEL) of 7.8 × 10-2 and a maximum external quantum efficiency (EQE) of 13.5% at room temperature. Ultrafast transient absorption (TA) spectroscopic study shows that the CPEL is generated from a rapid energy transfer accompanied by spin transfer from 2D to 3D perovskites. Our study not only demonstrates a reliable approach to achieve high performance spin-LEDs but also reveals the fundamental mechanism of CPEL with an emissive layer of chiral perovskites.

Revealing the impact of thermal annealing on the perovskite/organic bulk heterojunction interface in photovoltaic devices.

Perovskite/organic bulk heterojunction (BHJ) integrated solar cells have tremendous development potential to exceed the Shockley-Queisser limit efficiency of single-junction photovoltaics, due to the merits of spectra response extension. However, the presence of energy level barriers and severe non-radiative recombination at the interface between perovskite and BHJ greatly hindered the transport and collection of charge carriers, usually leading to large Voc and photocurrent loss, as well as the stability degradation of integrated devices. Therefore, investigating the interface properties of perovskite/BHJ is crucial for understanding the charge transport process and enhancing device performance. In this study, we effectively regulated the interface properties and charge transport in perovskite/BHJ integrated devices using a thermal annealing process. Using Kelvin probe microscopy, photoluminescence, and transient absorption spectroscopy, we revealed that moderate annealing treatment would contribute to forming close interface contact and provide more channels or pathways for charge transfer, which is advantageous for the interface charge collection and device performance. In addition, the lone pair electrons of acyl, thiophene and pyrrole function groups in polymer PDPP3T and PCBM can act as the Lewis base and provide electrons to the under-coordinated lead atoms or clusters in the perovskite, effectively passivating traps on the surface and grain boundaries of the perovskite through Lewis acid-base coordination. Finally, we improved the photovoltaic conversion efficiency of the device to 21.57% with enhanced stability using an optimized thermal annealing process. This study provides a comprehensive understanding of the integrated perovskite/BHJ interface properties, which could be extended to other optoelectronic devices based on a similar integrated structure.

Genome-wide evolutionary analysis of TKL_CTR1-DRK-2 gene family and functional characterization reveals that TaCTR1 positively regulates flowering time in wheat.

BACKGROUND: Flowering time has an important effect on regional adaptation and yields for crops. The tyrosine kinase-like (TKL) gene family is widely existed and participates in many biological processes in plants. Furthermore, only few TKLs have been characterized functions in controlling flowering time in wheat. RESULTS: Here, we report that TaCTR1, a tyrosine kinase-like (TKL) gene, regulates flowering time in wheat. Based on identification and evolutionary analysis of TKL_CTR1-DRK-2 subfamily in 15 plants, we proposed an evolutionary model for TaCTR1, suggesting that occurrence of some exon fusion events during evolution. The overexpression of TaCTR1 caused early flowering time in transgenic lines. Transcriptomics analysis enabled identification of mass differential expression genes including plant hormone (ET, ABA, IAA, BR) signaling, flavonoid biosynthesis, phenolamides and antioxidant, and flowering-related genes in TaCTR1 overexpression transgenic lines compared with WT plants. qRT-PCR results showed that the expression levels of ethylene (ET) signal-related genes (ETR, EIN, ERF) and flowering-related genes (FT, PPD1, CO, PRR, PHY) were altered in TaCTR1-overexpressing wheat compared with WT plants. Metabonomics analysis showed that flavonoid contents were altered. CONCLUSIONS: Thus, the results show that TaCTR1 plays a positive role in controlling flowering time by activating various signaling pathways and regulating flowering-related genes, and will provide new insights on the mechanisms of wheat flowering regulation.

Anti-PD-L1 antibody TQB2450 combined with tyrosine kinase receptor inhibitor AL2846 for immunotherapy-refractory advanced hepatocellular carcinoma and esophageal squamous cell carcinoma: A prospective phase 1b cohort study.

BACKGROUND: Effective systemic therapy remains limited for advanced esophageal squamous cell carcinoma (ESCC) and hepatocellular carcinoma (HCC), particularly after prior failed treatment with immune checkpoint inhibitors (ICIs). Theoretically, a combination of tyrosine kinase inhibitors (TKIs) with ICIs may restore immunotherapy sensitivity. METHODS: In this phase 1b study, patients received AL2846, an antiangiogenic TKI with multiple targets (c-MET, VEGFR1, c-KIT, Axl, RET, KDR, and VEGFR3), in combination with an anti-PD-L1 antibody (TQB2450) until disease progression, intolerable toxicity, death, or discontinuation for any cause. The primary end points included overall response rate (ORR) and safety, with secondary end points encompassing progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and duration of response. RESULTS: Between November 2021 and September 2022, 18 patients with ESCC and 15 patients with HCC, whose ORR was 11.1% (95% confidence interval [CI], 3.1%-32.8%) and 0%, respectively, were enrolled. Adverse events (AEs) of any grade and treatment-related AEs were documented in 32 patients (97.0%) and 31 patients (93.9%), respectively. Grade 3 or higher AEs were observed in 10 patients (30.3%), with vomiting (6.1%) and infectious pneumonia (9.1%) being the most prevalent. Median PFS and OS values were 3.22 months (95% CI, 1.35-5.68 months) and 5.98 months (95% CI, 3.71-8.87 months), respectively, in patients with ESCC, and 5.55 months (95% CI, 2.66 months to not evaluable [NE]) and 16.72 months (95% CI, 4.86 months to NE), respectively, in patients with HCC. The DCRs were 66.7% (95% CI, 43.75%-83.72%) in patients with ESCC and 73.3% (95% CI, 48.05%-89.10%) in patients with HCC. CONCLUSIONS: Combined TQB2450 and AL2846 therapy exhibited a favorable safety profile in immunotherapy-refractory patients with advanced ESCC and HCC.

Plasma proteome profiling reveals dynamic of cholesterol marker after dual blocker therapy.

Dual blocker therapy (DBT) has the enhanced antitumor benefits than the monotherapy. Yet, few effective biomarkers are developed to monitor the therapy response. Herein, we investigate the DBT longitudinal plasma proteome profiling including 113 longitudinal samples from 22 patients who received anti-PD1 and anti-CTLA4 DBT therapy. The results show the immune response and cholesterol metabolism are upregulated after the first DBT cycle. Notably, the cholesterol metabolism is activated in the disease non-progressive group (DNP) during the therapy. Correspondingly, the clinical indicator prealbumin (PA), free triiodothyronine (FT3) and triiodothyronine (T3) show significantly positive association with the cholesterol metabolism. Furthermore, by integrating proteome and radiology approach, we observe the high-density lipoprotein partial remodeling are activated in DNP group and identify a candidate biomarker APOC3 that can reflect DBT response. Above, we establish a machine learning model to predict the DBT response and the model performance is validated by an independent cohort with balanced accuracy is 0.96. Thus, the plasma proteome profiling strategy evaluates the alteration of cholesterol metabolism and identifies a panel of biomarkers in DBT.