PIF7-mediated epigenetic reprogramming promotes the transcriptional response to shade in Arabidopsis.

For shade-intolerant plants, changes in light quality through competition from neighbors trigger shade avoidance syndrome (SAS): a series of morphological and physiological adaptations that are ultimately detrimental to plant health and crop yield. Phytochrome-interacting factor 7 (PIF7) is a major transcriptional regulator of SAS in Arabidopsis; however, how it regulates gene expression is not fully understood. Here, we show that PIF7 directly interacts with the histone chaperone anti-silencing factor 1 (ASF1). The ASF1-deprived asf1ab mutant showed defective shade-induced hypocotyl elongation. Histone regulator homolog A (HIRA), which mediates deposition of the H3.3 variant into chromatin, is also involved in SAS. RNA/ChIP-sequencing analyses identified the role of ASF1 in the direct regulation of a subset of PIF7 target genes. Furthermore, shade-elicited gene activation is accompanied by H3.3 enrichment, which is mediated by the PIF7-ASF1-HIRA regulatory module. Collectively, our data reveal that PIF7 recruits ASF1-HIRA to increase H3.3 incorporation into chromatin to promote gene transcription, thus enabling plants to effectively respond to environmental shade.

Pharmacological inhibition of Kir4.1 evokes rapid-onset antidepressant responses.

Major depressive disorder, a prevalent and severe psychiatric condition, necessitates development of new and fast-acting antidepressants. Genetic suppression of astrocytic inwardly rectifying potassium channel 4.1 (Kir4.1) in the lateral habenula ameliorates depression-like phenotypes in mice. However, Kir4.1 remains an elusive drug target for depression. Here, we discovered a series of Kir4.1 inhibitors through high-throughput screening. Lys05, the most potent one thus far, effectively suppressed native Kir4.1 channels while displaying high selectivity against established targets for rapid-onset antidepressants. Cryogenic-electron microscopy structures combined with electrophysiological characterizations revealed Lys05 directly binds in the central cavity of Kir4.1. Notably, a single dose of Lys05 reversed the Kir4.1-driven depression-like phenotype and exerted rapid-onset (as early as 1 hour) antidepressant actions in multiple canonical depression rodent models with efficacy comparable to that of (S)-ketamine. Overall, we provided a proof of concept that Kir4.1 is a promising target for rapid-onset antidepressant effects.

Inhibition of Pck1 in intestinal epithelial cells alleviates acute pancreatitis via modulating intestinal homeostasis.

Intestinal barrier dysfunction usually occurred in acute pancreatitis (AP) but the mechanism remains unclear. In this study, RNA sequencing of ileum in L-arginine-induced AP mice demonstrated that phosphoenolpyruvate kinase 1 (Pck1) was significantly up-regulated. Increased Pck1 expression in intestinal epithelial cells (IECs) was further validated in ileum of AP mice and duodenum of AP patients. In AP mice, level of Pck1 was positively correlated with pancreatic and ileal histopathological scores, serum amylase activity, and intestinal permeability (serum diamine oxidase (DAO), D-lactate, and endotoxin). In AP patients, level of Pck1 had a positive correlation with Ranson scores, white blood cell count and C-reactive protein. Inhibition of Pck1 by 3-Mercaptopicolinic acid hydrochloride (3-MPA) alleviated pancreatic and ileal injuries in AP mice. AP + 3-MPA mice showed improved intestinal permeability, including less epithelial apoptosis, increased tight junction proteins (TJPs) expression, decreased serum DAO, D-lactate, endotoxin, and FITC-Dextran levels, and reduced bacteria translocation. Lysozyme secreted by Paneth cells and mucin2 (MUC2) secretion in goblet cells were also partly restored in AP + 3-MPA mice. Meanwhile, inhibition of Pck1 improved intestinal immune response during AP, including elevation of M2/M1 macrophages ratio and secretory immunoglobulin A (sIgA) and reduction in neutrophils infiltration. In vitro, administration of 3-MPA dramatically ameliorated inflammation and injuries of epithelial cells in enteroids treated by LPS. In conclusion, inhibition of Pck1 in IECs might alleviate AP via modulating intestinal homeostasis.

SBFI26 induces triple-negative breast cancer cells ferroptosis via lipid peroxidation.

SBFI26, an inhibitor of FABP5, has been shown to suppress the proliferation and metastasis of tumour cells. However, the underlying mechanism by which SBFI26 induces ferroptosis in breast cancer cells remains largely unknown. Three breast cancer cell lines were treated with SBFI26 and CCK-8 assessed cytotoxicity. Transcriptome was performed on the Illumina platform and verified by qPCR. Western blot evaluated protein levels. Malondialdehyde (MDA), total superoxide dismutase (T-SOD), Fe, glutathione (GSH) and oxidized glutathione (GSSG) were measured. SBFI26 induced cell death time- and dose-dependent, with a more significant inhibitory effect on MDA-MB-231 cells. Fer-1, GSH and Vitamin C attenuated the effects but not erastin. RNA-Seq analysis revealed that SBFI26 treatment significantly enriched differentially expressed genes related to ferroptosis. Furthermore, SBFI26 increased intracellular MDA, iron ion, and GSSG levels while decreasing T-SOD, total glutathione (T-GSH), and GSH levels.SBFI26 dose-dependently up-regulates the expression of HMOX1 and ALOX12 at both gene and protein levels, promoting ferroptosis. Similarly, it significantly increases the expression of SAT1, ALOX5, ALOX15, ALOXE3 and CHAC1 that, promoting ferroptosis while downregulating the NFE2L2 gene and protein that inhibit ferroptosis. SBFI26 leads to cellular accumulation of fatty acids, which triggers excess ferrous ions and subsequent lipid peroxidation for inducing ferroptosis.

Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii served as key components of fecal microbiota transplantation to alleviate colitis.

Fecal microbiota transplantation (FMT) is a promising therapy for inflammatory bowel disease (IBD) via rectifying gut microbiota. The aim of this study was to identify a mechanism of how specific bacteria-associated immune response contributes to alleviated colitis. Forty donors were divided into high (donor H) and low (donor L) groups according to the diversity and the abundance of Bacteroides and Faecalibacterium by 16S rRNA sequencing. FMT was performed on dextran sulfate sodium (DSS)-induced colitis in mice. Mice with colitis showed significant improvement in intestinal injury and immune imbalance after FMT with group donor H (P < 0.05). Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii were identified as targeted strains in donor feces by real-time PCR and droplet digital PCR. Mice with colitis were treated with mono- or dual-bacterial gavage therapy. Dual-bacterial therapy significantly ameliorated intestinal injury compared with mono-bacterial therapy (P < 0.05). Dual-bacterial therapy increased the M2/M1 macrophage polarization and improved the Th17/Treg imbalance and elevated IL-10 production by Tregs compared with the DSS group (P < 0.05). Metabolomics showed increased abundance of lecithin in the glycerophospholipid metabolism pathway. In conclusion, B. thetaiotaomicron and F. prausnitzii, as the key bacteria in donor feces, alleviate colitis in mice. The mechanism may involve increasing lecithin and regulating IL-10 production of intestinal Tregs.NEW & NOTEWORTHY We demonstrate that donors with high abundance of Bacteroides and Faecalibacterium ameliorate dextran sulfate sodium (DSS)-induced colitis in mice by fecal microbiota transplantation (FMT). The combination therapy of Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii is superior to mono-bacterial therapy in ameliorating colitis in mice, of which mechanism may involve promoting lecithin and inducing IL-10 production of intestinal Tregs.

Swine pseudorabies virus attenuated vaccine reprograms the kidney cancer tumor microenvironment and synergizes with PD-1 blockade.

The global incidence rate of kidney cancer (KC) has been steadily increasing over the past 30 years. With the aging global population, kidney cancer has become an escalating concern that necessitates vigilant surveillance. Nowadays, surgical intervention remains the optimal therapeutic approach for kidney cancer, while the availability of efficacious treatments for advanced tumors remains limited. Oncolytic viruses, an emerging form of immunotherapy, have demonstrated encouraging anti-neoplastic properties and are progressively garnering public acceptance. However, research on oncolytic viruses in kidney cancer is relatively limited. Furthermore, given the high complexity and heterogeneity of kidney cancer, it is crucial to identify an optimal oncolytic virus agent that is better suited for its treatment. The present study investigates the oncolytic activity of the Pseudorabies virus live attenuated vaccine (PRV-LAV) against KC. The findings clearly demonstrate that PRV-LAV exhibits robust oncolytic activity targeting KC cell lines. Furthermore, the therapeutic efficacy of PRV-LAV was confirmed in both a subcutaneous tumor-bearing nude mouse model and a syngeneic mouse model of KC. Combined RNA-seq analysis and flow cytometry revealed that PRV-LAV treatment substantially enhances the infiltration of a diverse range of lymphocytes, including T cells, B cells, macrophages, and NK cells. Additionally, PRV-LAV treatment enhances T cell activation and exerts antitumor effects. Importantly, the combination of PRV-LAV with anti-PD-1 antibodies, an approved drug for KC treatment, synergistically enhances the efficacy against KC. Overall, the discovery of PRV-LAV as an effective oncolytic virus holds significant importance for improving the treatment efficacy and survival rates of KC patients.

Colonic mucin-2 attenuates acute necrotizing pancreatitis in rats by modulating intestinal homeostasis.

Mucin-2 (MUC2) secreted by goblet cells participates in the intestinal barrier, but its mechanism in acute necrotizing pancreatitis (ANP) remains unclear. In acute pancreatitis (AP) patients, the functions of goblet cells (MUC2, FCGBP, CLCA1, and TFF3) decreased, and MUC2 was negatively correlated with AP severity. ANP rats treated with pilocarpine (PILO) (PILO+ANP rats) to deplete MUC2 showed more serious pancreatic and colonic injuries, goblet cell dysfunction, gut dysbiosis, and bacterial translocation than those of ANP rats. GC-MS analysis of feces showed that PILO+ANP rats had lower levels of butyric acid, isobutyric acid, isovaleric acid, and hexanoic acid than those of ANP rats. The expression of MUC2 was associated with colonic injury and gut dysbiosis. All these phenomena could be relieved, and goblet cell functions were also partially reversed by MUC2 supplementation in ANP rats. TNF-α-treated colonoids had exacerbated goblet cell dysfunction. MUC2 expression was negatively correlated with the levels of pro-inflammatory cytokines (IL-1ß and IL-6) (p < .05) and positively related to the expression of tight junction proteins (Claudin 1, Occludin, and ZO1) (p < .05). Downregulating MUC2 by siRNA increased the levels of the pro-inflammatory cytokines in colonoids. MUC2 might maintain intestinal homeostasis to alleviate ANP.

Design and synthesis of novel site-specific antibody-drug conjugates that target TROP2.

The approval of Trodelvy® validates TROP2 as a druggable but challenging target for antibody-drug conjugates (ADCs) to treat metastatic triple-negative breast cancer (mTNBC). Here, based on the TROP2-targeted antibody sacituzumab, we designed and developed several site-specific ADC candidates, which employ MMAE (monomethyl auristatin E) as the toxin, via IgG glycoengineering or affinity-directed traceless conjugation. Systematic evaluation of these site-specific ADCs in homogeneity, hydrophilicity, stability, and antitumor efficiency was conducted. The results indicate that the site-specific ADCs gsADC 3b made from one-step glycoengineering exhibit good aggregation stability and in vivo efficacy, providing a new format of ADCs that target TROP2.

Relationship between the severity of functional mitral regurgitation at admission and one-year outcomes in patients hospitalized for acute heart failure with mildly reduced ejection fraction.

BACKGROUND: The epidemiological distribution of functional mitral regurgitation (FMR) in heart failure (HF) and mildly reduced ejection fraction (HFmrEF) patients and its impact on outcomes remains unclear. We attempt to investigate the prognosis of FMR in patients with HFmrEF. METHODS: The HF center registry study is a prospective, single, observational study conducted at the Second Affiliated Hospital of Shenzhen University, where 2330 patients with acute HF (AHF) were enrolled and 890 HFmrEF patients were included in the analysis. The patients were stratified into three categories based on the severity of FMR: none/mild, moderate, and moderate-to-severe/severe groups. Subsequently, a comparison of the clinical characteristics among these groups was conducted, along with an assessment of the incidence of the primary endpoint (comprising all-cause mortality and readmission for HF) during a one-year follow-up period. RESULTS: The one-year follow-up results indicated that the primary composite endpoint occurrence rates in the three groups were 23.5%, 32.9%, and 36.5%, respectively. The all-cause mortality rates in the three groups were 9.3%, 13.7%, and 16.4% respectively. Survival analysis demonstrated a statistically significant difference in the occurrence rates of the primary composite endpoint and all-cause mortality among the three groups (P < 0.05). Multifactor Cox regression revealed that moderate FMR and moderate-to-severe/severe FMR were independent risk factors for adverse clinical prognosis in HFmrEF patients, with hazard ratios and 95% confidence intervals of 1.382 (1.020-1.872, P = 0.037) and 1.546 (1.092-2.190, P = 0.014) respectively. CONCLUSIONS: Moderate FMR and moderate-to-severe/severe FMR independently predict an unfavorable prognosis in patients with HFmrEF.

Apolipoprotein E E3/E4 genotype is associated with an increased risk of coronary atherosclerosis in patients with hypertension.

OBJECTIVE: Apolipoprotein E (APOE) gene polymorphisms were associated with coronary atherosclerosis and hypertension. However, the relationship between APOE polymorphisms and coronary atherosclerosis susceptibility in hypertensive patients is unclear. The aim of this study was to assess the relationship. METHODS: A total of 1713 patients with hypertension who were admitted to Meizhou People's Hospital from November 2019 to August 2023 were retrospectively analyzed, including 848 patients with coronary atherosclerosis and 865 patients without coronary atherosclerosis. The rs429358 and rs7412 polymorphisms of APOE were genotyped, and relationship between APOE polymorphisms and the risk of coronary atherosclerosis in hypertensive patients were analyzed. RESULTS: There were 10 (0.6%), 193 (11.3%), 30 (1.8%), 1234 (72.0%), 233 (13.6%), and 13 (0.8%) individuals with APOE ɛ2/ɛ2, ɛ2/ɛ3, ɛ2/ɛ4, ɛ3/ɛ3, ɛ3/ɛ4, and ɛ4/ɛ4 genotype, respectively. The frequency of APOE ɛ3/ɛ4 was higher (16.4% vs. 10.9%, p = 0.001) in the patients with coronary atherosclerosis than controls. Logistic analysis showed that body mass index (BMI) ≥ 24.0 kg/m2 (24.0 kg/m2 vs. 18.5-23.9 kg/m2, odds ratio (OR): 1.361, 95% confidence interval (CI): 1.112-1.666, p = 0.003), advanced age (≥ 65/<65, OR:1.303, 95% CI: 1.060-1.602, p = 0.012), history of smoking (OR: 1.830, 95% CI: 1.379-2.428, p < 0.001), diabetes mellitus (OR: 1.380, 95% CI: 1.119-1.702, p = 0.003), hyperlipidemia (OR: 1.773, 95% CI: 1.392-2.258, p < 0.001), and APOE ɛ3/ɛ4 genotype (ɛ3/ɛ4 vs. ɛ3/ɛ3, OR: 1.514, 95% CI: 1.133-2.024, p = 0.005) were associated with coronary atherosclerosis in hypertensive patients. CONCLUSIONS: Overweight (BMI ≥ 24.0 kg/m2), advanced age, history of smoking, diabetes mellitus, and APOE ɛ3/ɛ4 genotype were independent risk factors for coronary atherosclerosis in hypertensive patients.

Analysis of driving factors for potential toxic metals in major urban soils of China: a geodetetor-based quantitative study.

Potential toxic metal (PTM) is hazardous to human health, but the mechanism of spatial heterogeneity of PTM at a macro-scale remains unclear. This study conducts a meta-analysis on the data of PTM concentrations in the soil of 164 major cities in China from 2006 to 2021. It utilizes spatial analysis methods and geodetector to investigate the spatial distribution characteristics of PTMs. The geographic information systems (GIS) and geodetector were used to investigate the spatial distribution characteristics of PTMs, assess the influence of natural factors (NFs) and anthropogenic factors (AFs) on the spatial heterogeneity of PTMs in urban soils, and identified the potential pollution areas of PTMs. The results indicated that the pollution levels of PTMs in urban soils varied significantly across China, with higher pollution levels in the south than in the north. Cd and Hg were the most severely contaminated elements. The geodetector analysis showed that temperature and precipitation in NFs and land use type in AFs were considered as the main influencing factors, and that both AF and NF together led to the PTM variation. All these factors showed a mutually enhancing pattern which has important implications for urban soil management. PTM high-risk areas were identified to provide early warning of pollution risk under the condition of climate change.

[Effect and mechanism of free total rhubarb anthraquinones on pyroptosis of J774A.1 macrophages].

In this study, J774A.1 macrophages stimulated by lipopolysaccharide(LPS) and adenosine triphosphate(ATP) were used to establish an in vitro model of pyroptosis, and the intervention mechanism of free total rhubarb anthraquinones(FTRAs) on pyroptosis was investigated. J774A.1 macrophages were cultured in vitro, and the experiment was assigned to the control group and groups with different concentrations of LPS(0.25, 0.5, and 1 µg·mL~(-1)) and ATP(1.25, 2.5, and 5 mmol·L~(-1)). An in vitro model of macrophage pyroptosis was established by detecting cell viability through CCK-8, propidium iodide(PI) apoptotic cell staining, lactate dehydrogenase(LDH), interleukin(IL)-18, and tumor necrosis factor(TNF)-α release. Then, J774A.1 macrophages were randomly divided into six groups: blank control group, LPS+ATP group, high-dose FTRA group, and low, medium, and high-dose FTRA pre-protection group. The phenotypic characteristics and key indicators of pyroptosis were detected as the basis for evaluating the effect of FTRAs on pyroptosis induced by LPS and ATP. Western blot and RT-PCR were used to detect the expression levels of protein and mRNA related to the pyroptosis pathway in caspase-1/11 and elucidate the molecular mechanism of the anti-pyroptosis effect. The results showed that the stimulation condition of 0.50 µg·mL~(-1) LPS+5.00 mmol·L~(-1) ATP was the most effective in the in vitro model of macrophage pyroptosis. FTRAs pre-protected cells for 24 h and then can increase cell viability under pyroptosis conditions, alleviate cell damage, lower the positive rate of PI staining, and reduce the release of LDH, IL-18, and TNF-α. FTRAs were able to significantly inhibit the activation of GSDMD proteins and significantly down-regulate the protein expression of the pyroptosis pathway signature molecules, TLR4, NLRP3, cleaved-caspase-1, and cleaved-caspase-11, but they had no significant effect on ASC proteins. FTRAs were also able to significantly inhibit the mRNA expression of caspase-1, caspase-11, and GSDMD. These results indicate that FTRAs have an inhibitory effect on the pyroptosis model induced by LPS and ATP and play an anti-pyroptosis effect by regulating classical and non-classical pyroptosis signaling pathways and reducing the production of inflammatory cytokines.

RHOJ as a novel mechanosensitive modulator of endothelial inflammation.

Physiological high shear stress (HSS), a frictional force generated by flowing blood, is essential for endothelial homeostasis under normal physiological conditions. HSS suppresses atherosclerosis by inhibiting endothelial inflammation. However, the molecular mechanisms underlying this process have not been fully elucidated. Here, we report that HSS downregulated the mRNA and protein levels of ras homolog family member J (RHOJ) in endothelial cells (ECs). Silencing endogenous RHOJ expression decreased the mRNA and protein levels of proinflammatory vascular cell adhesion molecule 1 (VCAM-1) and intercellular cell adhesion molecule 1 (ICAM-1) in ECs, leading to a reduction in monocyte adhesion to ECs. Conversely, the overexpression of RHOJ had the opposite effect. RNA-sequencing analysis uncovered several differentially expressed genes (such as yes-associated protein 1 (YAP1),heme oxygenase-1 (HO1), and monocyte chemoattractant protein-1 (MCP1)) and pathways (such as nuclear factor-kappa B (NF-κB), fluid shear stress and atherosclerosis, and cell adhesion pathways) as RHOJ targets. Additionally, HSS was observed to alleviate endothelial inflammation by inhibiting RHOJ expression. Finally, methylated RNA immunoprecipitation sequencing (MeRIP-seq) illustrated that fluid shear stress regulates RHOJ expression in an N6-methyladenosine (m6A)-dependent manner. Mechanistically, the RNA m6A writer, methyltransferase 3 (METTL3), and the RNA m6A readers, YTH N6-methyladenosine RNA-binding protein F 3 (YTHDF3) and YTH N6-methyladenosine RNA-binding protein C 1/2 (YTHDC1/2), are involved in this process. Taken together, our data demonstrate that HSS-induced downregulation of RHOJ contributes to endothelial homeostasis by suppressing endothelial inflammation and that RHOJ inhibition in ECs is a promising therapeutic strategy for endothelial dysfunction.

Opportunities and challenges of neoadjuvant targeted therapy in nonsmall cell lung cancer.

PURPOSE OF REVIEW: The aim of this study is to summarize the completed and ongoing clinical trials of neoadjuvant targeted therapy, discuss tolerability and efficacy, and explain the role of neoadjuvant targeted therapy in patients with resectable nonsmall cell lung cancer (NSCLC). At the same time, the existing challenges are presented, including assessment methods, biomarkers, surrogate endpoints and so on. We also put forward our views on possible ways to make improvements and establish neoadjuvant therapy a standard treatment in resectable NSCLC. RECENT FINDINGS: The mortality of lung cancer has decreased in the last 10 years, which can partly be attributed to advancement of targeted therapy. Targeted therapy has become the first-line treatment for patients with advanced mutation gene positive NSCLC, achieving the effect of prolonging overall survival (OS). Compared with chemotherapy, targeted therapy is associated with good tolerability and high response rate. Neoadjuvant targeted therapy has emerged in recent years and attracted attention of researchers. Early findings proved that neoadjuvant targeted therapy alone can improve patients' disease-free survival (DFS) and the efficacy of combining with other forms of neoadjuvant therapy is also being explored by researchers. SUMMARY: Neoadjuvant targeted therapy is playing an important role in NSCLC and worth more in-depth research.

HSP90s are required for hypocotyl elongation during skotomorphogenesis and thermomorphogenesis via the COP1-ELF3-PIF4 pathway in Arabidopsis.

Light and temperature are two key environmental signals that share several molecular components that, in turn, regulate plant growth. Darkness and high ambient temperatures promote skoto- and thermomorphogenesis, including stem elongation. Heat shock proteins 90 (HSP90s) facilitate the adaptation of organisms to various adverse environmental stimuli. Here, we showed that HSP90s are required for hypocotyl elongation during both skoto- and thermomorphogenesis. When HSP90s activities are impaired by the knockdown of HSP90s expression or the application of HSP90 inhibitors, the expression levels and protein abundance of PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) markedly decreased. EARLY FLOWERING 3 (ELF3) deficiency was resistant to the inhibition of HSP90s activities. Furthermore, HSP90s interacted with and destabilized ELF3. In the CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) mutant, the changes in endogenous PIF4 and ELF3 protein levels caused by the inhibition of HSP90s activities were abolished. HSP90s enhanced the interaction between COP1 and ELF3, reduced ELF3 functional effects on PIF4 and modulated hypocotyl elongation during skoto- and thermomorphogenesis. Our results indicated that HSP90s participate in light and temperature signalling via the COP1-ELF3-PIF4 module to regulate hypocotyl growth in changing environments.

One-Pot Assembly of Dual-Site-Specific Antibody-Drug Conjugates via Glycan Remodeling and Affinity-Directed Traceless Conjugation.

The drug-to-antibody ratio (DAR) value and dual-drug combination greatly influence the therapeutic index of antibody-drug conjugates (ADCs). The reported approaches usually require multifunctional branched linkers, a combination of complicated technologies, or protein-protein ligation, which may incorporate multihydrophobic fragments or result in low coupling efficiency. Herein, we developed a facile and efficient one-pot method to assemble dual-site-specific ADCs with defined DARs at both the N-glycosylation site and K248 site, either with the same payloads or with two types of payloads. The constructed dual-site ADCs showed acceptable homogeneity, excellent buffer stability, and enhanced in vitro and in vivo efficiency.

Organic Semiconductor-Organism Interfaces for Augmenting Natural and Artificial Photosynthesis.

Carbon neutrality is increasingly broadly recognized as a vehicle for climate action and sustainable development. Photosynthesis contributes to maintaining a suitable carbon-oxygen balance for survival and plays an irreplaceable role in mitigating the greenhouse effect. However, the energy conversion efficiency of photosynthesis is only about 1%, far below the theoretical maximum. With the ecological demand of carbon neutrality, it is wise and necessary to further improve the efficiency of photosynthesis. Among methods to do so, the most direct and original one is improving the utilization of photosynthetic pigments to the weak absorption region of the spectrum and thus enhancing the solar energy utilization efficiency.This Account summarizes our group's work on constructing conjugated polymer-photosynthetic organism interfaces to augment photosynthetic efficiency. Side chain modification of ionic groups or preparation of nanoparticles makes conjugated polymers water-soluble and electrically charged, which allows them to bind to the surface of photosynthetic microorganisms through electrostatic interactions or be absorbed by plant roots. Owing to the designable and unparalleled light capture and emission capabilities, funnel-like excitation energy transfer mode, and enviable biocompatibility, organic semiconductor conjugated polymers can be used as "artificial antennas" to make up for the lack of natural antenna pigments and expand the photosynthetically active radiation (PAR) range. With this strategy, we achieved enhancement of the photosynthetic efficiency of a broad range of organisms, including oxygenic photosynthetic organisms, from organelle to prokaryotic cyanobacteria, eukaryotic lower plants, and higher plants, as well as anoxygenic photosynthetic organisms. Unlike conventional semiconductors, conjugated polymers have not only electronic conductivity but also ionic conductivity, which is the main means of bioelectrical signal transduction. Therefore, they are able to act as "electron bridges" to accelerate the electron transfer rate at the material-organism interface. On this basis, we introduced conjugated polymers into artificial photosynthesis systems, including biological photovoltaics and artificial carbon sequestration, to increase energy conversion efficiency. These studies open a new frontier for functional studies of conjugated molecules and provide inspirations for the design of photosynthesis systems in the future.

Substrate-mediated plasmon hybridization toward high-performance light trapping.

High-performance light trapping in metamaterials and metasurfaces offers prospects for the integration of multifunctional photonic components at subwavelength scales. However, constructing these nanodevices with reduced optical losses remains an open challenge in nanophotonics. Herein, we design and fabricate aluminum-shell-dielectric gratings by integrating low-loss aluminum materials with metal-dielectric-metal designs for high-performance light trapping featuring nearly perfect light absorption with broadband and large angular tuning ranges. The mechanism governing these phenomena is identified as the occurrence of substrate-mediated plasmon hybridization that allows energy trapping and redistribution in engineered substrates. Furthermore, we strive to develop an ultrasensitive nonlinear optical method, namely, plasmon-enhanced second-harmonic generation (PESHG), to quantify the energy transfer from metal to dielectric components. Our studies may provide a mechanism for expanding the potential of aluminum-based systems in practical applications.

Association of risk of incident acne and treatment with systemic Janus kinase inhibitors in atopic dermatitis: a systematic review and meta-analysis.

INTRODUCTION: The therapeutic efficacy of systemic Janus kinase (JAK) inhibitors in moderate-to-severe atopic dermatitis (AD) is well established. However, the associated risk of incident acne, which is a prevalent adverse event in AD patients treated with systemic JAK inhibitors, has yet to be systematically analyzed. METHODOLOGY: To evaluate the risk of incident acne in AD patients treated with systemic JAK inhibitors, an extensive database search (clinicaltrials.gov, PubMed) was performed to identify publications eligible for inclusion from January 2020 to October 2022. Five randomized clinical trials (RCTs) of abrocitinib, four RCTs of upadacitinib, and one RCT of baricitinib, encompassing a total of 7901 participants, were included in the analysis. The risk difference for incident acne between systemic JAK inhibitors and controls was assessed using Review Manager, version 5.3, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Meta-analysis elucidated a significant difference in the risk of incident acne between AD participants receiving 200 mg abrocitinib (Mantel-Haenszel risk difference, 3.69; 95% CI 1.60-8.48; P < 0.01), 15 mg upadacitinib (Mantel-Haenszel risk difference, 4.61; 95% CI 2.79-7.62; P < 0.00001), and 30 mg upadacitinib (Mantel-Haenszel risk difference, 6.82; 95% CI 4.59-10.13; P < 0.00001) compared with controls receiving placebo or dupilumab. In contrast, no significant difference was found in the risk of incident acne between participants receiving 100 mg abrocitinib, 2 mg baricitinib, and 4 mg baricitinib, as compared with controls. CONCLUSIONS: Based on the current evidence, there is an increased risk of acne related to systemic JAK inhibitors, particularly with abrocitinib and upadacitinib. For patients predisposed to acne, the balance between the benefits of symptomatic relief from AD and the potential risk of acne may need to be carefully considered. This study contributes to a nuanced understanding of the risk profile of systemic JAK inhibitors and has the potential to guide personalized treatment decisions for AD patients.

Dupilumab-Associated Psoriasis and Psoriasiform Manifestations: A Scoping Review.

BACKGROUND: Dupilumab is the first approved IL-4Rα inhibitor for the treatment of atopic dermatitis at present with good efficacy and safety. However, there have been several reports of psoriasis and psoriasiform manifestations occurring after dupilumab therapy in recent years, showing a new paradoxical cutaneous reaction associated with biologics. SUMMARY: This is a scoping review in order to summarize the demographics and epidemiology, clinical manifestations, diagnosis, potential pathogenesis, and promising management of dupilumab-associated psoriasis and psoriasiform manifestations.