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Organic semiconductors offer a tunable platform for photocatalysis, yet the more difficult exciton dissociation, compared to that in inorganic semiconductors, lowers their photocatalytic activities. In this work, we report that the charge carrier lifetime is dramatically prolonged by incorporating a suitable donor-acceptor (β-ketene-cyano) pair into a covalent organic framework nanosheet. These nanosheets show an apparent quantum efficiency up to 82.6% at 450 nm using platinum as co-catalyst for photocatalytic H 2 evolution. Charge carrier kinetic analysis and femtosecond transient absorption spectroscopy characterizations verify that these modified covalent organic framework nanosheets have intrinsically lower exciton binding energies and longer-lived charge carriers than the corresponding nanosheets without the donor-acceptor unit. This work provides a model for gaining insight into the nature of short-lived active species in polymeric organic photocatalysts. While organic semiconductors offer a tunable platform for photocatalysis, they often show worse performances. Here, authors examine how a donor-acceptor pair’s incorporation into a covalent organic framework boosts photocatalytic H 2 evolution performances with a platinum co-catalyst.

Previous trial evidence suggested potential risk of serious urinary tract infections (UTIs) and genital infections in type 2 diabetes patients using sodium glucose co-transporter-2 inhibitors (SGLT2) inhibitors. We conducted a systematic review and meta-analysis to assess the effects of SGLT2 inhibitors on UTIs and genital infections in patients with type 2 diabetes. In total, 77 RCTs involving 50,820 participants were eligible. The meta-analyses of randomized controlled trials (RCTs) showed no significant difference in UTIs between SGLT2 inhibitors versus control (2,526/29,086 vs. 1,278/14,940; risk ratio (RR) 1.05, 95% confidence interval (CI) 0.98 to 1.12; moderate quality evidence), but suggested increased risk of genital infections with SGLT2 inhibitors (1,521/24,017 vs. 216/12,552; RR 3.30, 95% CI 2.74 to 3.99; moderate quality evidence). Subgroup analyses by length of follow up (interaction p = 0.005), type of control (interaction p = 0.04) and individual SGLT2 inhibitors (interaction p = 0.03) also showed statistically significant differences in genital infections. The upcoming major trials may provide important additional insights on UTIs, and more efforts are needed to address comparative effects of each individual SGLT2 inhibitors on the infections.

•The strength of TI electric field distributed across non-human primate brain was simulated and directly measured using invasively implanted multiple depth electrodes.•TI amplitude in deep brain regions under safety current can reach the strength that has shown subthreshold modulation effect in tACS.•The distribution of TI electric field obtained from experimental data can fit to the predicted distribution of computational simulation.•A pilot test in clinical patients showed that the potential effect of TI stimulation to the substantia nigra can improve specific symptoms of tremor in motor disorder. Temporal interference (TI) stimulation, a novel non-invasive stimulation strategy, has recently been shown to modulate neural activity in deep brain regions of living mice. Yet, it is uncertain if this method is applicable to larger brains and whether the electric field produced under traditional safety currents can penetrate deep regions as observed in mice. Despite recent model-based simulation studies offering positive evidence at both macro- and micro-scale levels, the absence of electrophysiological data from actual brains hinders comprehensive understanding and potential application of TI. This study aims to directly measure the spatiotemporal properties of the interfered electric field in the rhesus monkey brain and to validate the effects of TI on the human brain. Two monkeys were involved in the measurement, with implantation of several stereo-electroencephalography (SEEG) depth electrodes. TI stimulation was applied to anesthetized monkeys using two pairs of surface electrodes at differing stimulation parameters. Model-based simulations were also conducted and subsequently compared with actual recordings. Additionally, TI stimulation was administered to patients with motor disorders to validate its effects on motor symptoms. Through the integration of computational electric field simulation with empirical measurements, it was determined that the temporally interfering electric fields in the deep central regions are capable of attaining a magnitude sufficient to induce a subthreshold modulation effect on neural signals. Additionally, an improvement in movement disorders was observed as a result of TI stimulation. This study is the first to systematically measure the TI electric field in living non-human primates, offering empirical evidence that TI holds promise as a more focal and precise method for modulating neural activities in deep regions of a large brain. This advancement paves the way for future applications of TI in treating neuropsychiatric disorders.

Identifying compound-protein (drug-target, DTI) interactions (CPI) accurately is a key step in drug discovery. Including virtual screening and drug reuse, it can significantly reduce the time it takes to identify drug candidates and provide patients with timely and effective treatment. Recently, more and more researchers have developed CPI’s deep learning model, including feature representation of a 2D molecular graph of a compound using a graph convolutional neural network, but this method loses much important information about the compound. In this paper, we propose a novel three-channel deep learning framework, named SSGraphCPI, for CPI prediction, which is composed of recurrent neural networks with an attentional mechanism and graph convolutional neural network. In our model, the characteristics of compounds are extracted from 1D SMILES string and 2D molecular graph. Using both the 1D SMILES string sequence and the 2D molecular graph can provide both sequential and structural features for CPI predictions. Additionally, we select the 1D CNN module to learn the hidden data patterns in the sequence to mine deeper information. Our model is much more suitable for collecting more effective information of compounds. Experimental results show that our method achieves significant performances with RMSE (Root Mean Square Error) = 2.24 and R2 (degree of linear fitting of the model) = 0.039 on the GPCR (G Protein-Coupled Receptors) dataset, and with RMSE = 2.64 and R2 = 0.018 on the GPCR dataset RMSE, which preforms better than some classical deep learning models, including RNN/GCNN-CNN, GCNNet and GATNet.

Background hsa_circ_0001727 (circZKSCAN1) has been reported to be a tumor-associated circRNA by sponging microRNAs. Intriguingly, we found that circZKSCAN1 encoded a secretory peptide (circZKSaa) in the liver. The present study aims to elucidate the potential role and molecular mechanism of circZKSaa in the regulation of hepatocellular carcinoma (HCC) progression. Methods The circRNA profiling datasets (RNA-seq data GSE143233 and GSE140202) were reanalyzed and circZKSCAN1 was selected for further study. Mass spectrometry, polysome fractionation assay, dual-luciferase reporter, and a series of experiments showed that circZKSCAN1 encodes circZKSaa. Cell proliferation, apoptosis, and tumorigenesis in nude mice were examined to investigate the functions of circZKSaa. Mechanistically, the relationship between the circZKSaa and mTOR in HCC was verified by immunoprecipitation analyses, mass spectrometry, and immunofluorescence staining analyses. Results Receiver operating characteristic (ROC) analysis demonstrated that the secretory peptide circZKSaa encoded by circZKSCAN1 might be the potential biomarker for HCC tissues. Through a series of experiments, we found that circZKSaa inhibited HCC progression and sensitize HCC cells to sorafenib. Mechanistically, we found that the sponge function of circZKSCAN1 to microRNA is weak in HCC, while overexpression of circZKSaa promoted the interaction of FBXW7 with the mammalian target of rapamycin (mTOR) to promote the ubiquitination of mTOR, thereby inhibiting the PI3K/AKT/mTOR pathway. Furthermore, we found that the high expression of cicZKSCAN1 in sorafenib-treated HCC cells was regulated by QKI-5 . Conclusions These results reveal that a novel circZKSCAN1-encoded peptide acts as a tumor suppressor on PI3K/AKT/mTOR pathway, and sensitizes HCC cells to sorafenib via ubiquitination of mTOR. These findings demonstrated that circZKSaa has the potential to serve as a therapeutic target and biomarker for HCC treatment.

The fruit and vegetable industry produces millions of tons of residues, which can cause large economic losses. Fruit and vegetable wastes and by-products contain a large number of bioactive substances with functional ingredients that have antioxidant, antibacterial, and other properties. Current technologies can utilize fruit and vegetable waste and by-products as ingredients, food bioactive compounds, and biofuels. Traditional and commercial utilization in the food industry includes such technologies as microwave-assisted extraction (MAE), supercritical fluid extraction (SFE), ultrasonic-assisted extraction (UAE), and high hydrostatic pressure technique (HHP). Biorefinery methods for converting fruit and vegetable wastes into biofuels, such as anaerobic digestion (AD), fermentation, incineration, pyrolysis and gasification, and hydrothermal carbonization, are described. This study provides strategies for the processing of fruit and vegetable wastes using eco-friendly technologies and lays a foundation for the utilization of fruit and vegetable loss/waste and by-products in a sustainable system.

To evaluate the predictive value of systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and complement 3 in the therapeutic outcomes of systemic lupus erythematosus-associated immune thrombocytopenia (SLE-ITP). Clinical data from 72 patients diagnosed with SLE-ITP and admitted to the Affiliated Central Hospital of Dalian University of Technology between January 2013 and September 2024 were collected and analyzed. Associations between therapeutic outcomes and clinical characteristics, as well as laboratory findings including SII and NLR, were evaluated systematically. The patients achieved complete remission (CR) 32 (44.4%), partial remission (PR) 19 (26.4%), and no remission (NR) 21 (29.2%). SII exhibited statistically significant differences among the three groups ( =0.027). The median SII values were 145.7 (43.7-238.7) for the CR group, 57.2 (20.5-90.2) for the PR group, and 117.8 (80.7-238.6) for the NR group. Additionally, complement 3 levels were significantly lower in the CR group compared to the PR and NR groups ( =0.010). Logistic regression analysis revealed that the NLR was positively correlated with therapeutic efficacy (OR=1.982, 95% CI: 1.18-3.33, =0.010). SII and complement 3 were significantly negatively correlated with therapeutic outcomes (SII: OR=0.991, 95% CI: 0.984-0.998, =0.011; C3: OR=0.045, 95% CI: 0.002-0.919, =0.044). ROC curve analysis demonstrated that the combined predictive model of NLR, SII, and complement 3 achieved an area under the curve (AUC) of 0.743 (95% CI: 0.620-0.866, =0.001), specificity of 76.2%, and sensitivity of 66.7%, indicating excellent predictive efficacy. The combined predictive model significantly enhances the predictive efficacy for SLE-ITP treatment outcomes compared to individual indicators.

Gut-derived bacterial lipopolysaccharide (LPS) and subsequent hepatic toll-like receptor 4 (TLR4) activation have been recognized to be involved in the onset of diet-induced nonalcoholic fatty liver disease (NAFLD), but little is known about the variation of LPS and TLR4 during the progression of NAFLD. Probiotics were able to inhibit proliferation of harmful bacteria and improve gastrointestinal barrier function. However, it’s unclear whether LPS/TLR4 is involved in the protection effect of probiotics on NAFLD. In this study, we described characteristic of gut microbiota structure in the progression of NAFLD, and we also analyzed the relationship between gut microbiota and LPS/TLR4 in this process. Furthermore, we applied probiotics intervention to investigate the effect of probiotics on gut flora structure, intestinal integrity, serum LPS, liver TLR4 and liver pathology. Our results showed that serum LPS and liver TLR4 were highly increased during progression of NAFLD, with gut flora diversity and gut mircobiological colonization resistance (B/E) declining. Furthermore, probiotics could improve gut microbiota structure and liver pathology. Probiotics could also downregulate serum LPS and liver TLR4. Our results suggested that both gut flora alteration and endotoxemia may be involved in the progression of NAFLD. Probiotics may delay the progression of NAFLD via LPS/TLR4 signaling.

Plants that are fighting microbial pathogens often divert resources that could be used for growth into the immune response. For crops, this translates into lower yield when plant immunity is activated. Wang et al. show that, in rice, reversible phosphorylation of a key transcription factor allows the plant to defend against fungal attack when needed but then, within days, reallocate resources back to growth (see the Perspective by Greene and Dong). Thus, both pathogen defense and crop yield can be sustained. Science , this issue p. 1026 ; see also p. 976 A transcription factor that builds a high-yielding rice plant also supports immune responses. Plant immunity often penalizes growth and yield. The transcription factor Ideal Plant Architecture 1 (IPA1) reduces unproductive tillers and increases grains per panicle, which results in improved rice yield. Here we report that higher IPA1 levels enhance immunity. Mechanistically, phosphorylation of IPA1 at amino acid Ser 163 within its DNA binding domain occurs in response to infection by the fungus Magnaporthe oryzae and alters the DNA binding specificity of IPA1. Phosphorylated IPA1 binds to the promoter of the pathogen defense gene WRKY45 and activates its expression, leading to enhanced disease resistance. IPA1 returns to a nonphosphorylated state within 48 hours after infection, resuming support of the growth needed for high yield. Thus, IPA1 promotes both yield and disease resistance by sustaining a balance between growth and immunity.

Electronic nematicity that spontaneously breaks rotational symmetry is a generic phenomenon in correlated quantum systems including high-temperature superconductors and the AV3Sb5 (A can be K, Rb or Cs) family of kagome superconductors. However, the underlying mechanism of nematicity in these systems is hard to identify because of its entanglement with other ordered phases. Recently, a family of titanium-based kagome superconductors ATi3Bi5 have been synthesized, where electronic nematicity occurs in the absence of charge order. It provides a platform to study nematicity in its pure form, as well as its interplay with orbital degrees of freedom. Here we reveal the band topology and orbital characters of the multiorbital RbTi3Bi5. We use polarization-dependent angle-resolved photoemission spectroscopy with density functional theory to identify the coexistence of flat bands, type-II Dirac nodal lines and non-trivial topology in this compound. Our study demonstrates the change in orbital character along the Fermi surface contributed by the kagome bands, implying a strong intrinsic interorbital coupling in the Ti-based kagome metals. Furthermore, doping-dependent measurements uncover the orbital-selective features in the kagome bands, which can be explained by d–p hybridization. Hence, interorbital coupling together with d–p hybridization is probably the origin of electronic nematicity in ATi3Bi5.The origin of nematicity in kagome superconductors has been hard to explain due to other entangled phases. Now, the role of orbital hybridization and coupling is revealed to induce electronic nematicity in the kagome superconductor RbTi3Bi5.