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Hypoxia of solid tumor compromises the therapeutic outcome of photodynamic therapy (PDT) that relies on localized O 2 molecules to produce highly cytotoxic singlet oxygen ( 1 O 2 ) species. Herein, we present a safe and versatile self-assembled PDT nanoagent, i.e., OxgeMCC-r single-atom enzyme (SAE), consisting of single-atom ruthenium as the active catalytic site anchored in a metal-organic framework Mn 3 [Co(CN) 6 ] 2 with encapsulated chlorin e6 (Ce6), which serves as a catalase-like nanozyme for oxygen generation. Coordination-driven self-assembly of organic linkers and metal ions in the presence of a biocompatible polymer generates a nanoscale network that adaptively encapsulates Ce6. The resulted OxgeMCC-r SAE possesses well-defined morphology, uniform size distribution and high loading capacity. When conducting the in situ O 2 generation through the reaction between endogenous H 2 O 2 and single-atom Ru species of OxgeMCC-r SAE, the hypoxia in tumor microenvironment is relieved. Our study demonstrates a promising self-assembled nanozyme with highly efficient single-atom catalytic sites for cancer treatment. The hypoxic microenvironment in solid tumors limits the efficacy of photodynamic therapy (PDT) since oxygen is necessary to produce high cytotoxic singlet oxygen species. Here, the authors develop an improved self-assembled single-atom nanozyme which allows oxygen generation to enhance PDT efficacy.

Small interfering RNAs (siRNAs) are essential for proper development and immunity in eukaryotes 1 . Plants produce siRNAs with lengths of 21, 22 or 24 nucleotides. The 21- and 24-nucleotide species mediate cleavage of messenger RNAs and DNA methylation 2 , 3 , respectively, but the biological functions of the 22-nucleotide siRNAs remain unknown. Here we report the identification and characterization of a group of endogenous 22-nucleotide siRNAs that are generated by the DICER-LIKE 2 (DCL2) protein in plants. When cytoplasmic RNA decay and DCL4 are deficient, the resulting massive accumulation of 22-nucleotide siRNAs causes pleiotropic growth disorders, including severe dwarfism, meristem defects and pigmentation. Notably, two genes that encode nitrate reductases— NIA1 and NIA2 —produce nearly half of the 22-nucleotide siRNAs. Production of 22-nucleotide siRNAs triggers the amplification of gene silencing and induces translational repression both gene specifically and globally. Moreover, these 22-nucleotide siRNAs preferentially accumulate upon environmental stress, especially those siRNAs derived from NIA1/2 , which act to restrain translation, inhibit plant growth and enhance stress responses. Thus, our research uncovers the unique properties of 22-nucleotide siRNAs, and reveals their importance in plant adaptation to environmental stresses. Characterization of 22-nucleotide short interfering RNAs in plants finds that they accumulate in response to environmental stress, causing translational repression, inhibition of plant growth and enhanced stress responses.

Herein, a simple one‐pot way is designed to prepare a type of multifunctional metal–organic framework (MOF)‐based hybrid nanogels by in situ hybridization of dopamine monomer in the skeleton of MnCo. The resultant hybrid nanoparticles (named as MCP) show enhanced photothermal conversion efficiency in comparison with pure polydopamine or MnCo nanoparticles (NPs) synthesized under a similar method and, therefore, show great potential for photothermal therapy (PTT) in vivo. The MCP NPs are expected to possess T 1 positive magnetic resonance imaging ability due to the high‐spin Mn‐N6 (S = 5/2) in the skeleton of MnCo. To improve the therapy efficiency as a PTT agent, the MCP NPs are further modified with functional polyethylene glycol (PEG) and thiol terminal cyclic arginine–glycine–aspartic acid peptide, respectively: the first one is to increase the stability, biocompatibility, and blood circulation time of MCP NPs in vivo; the second one is to increase the tumor accumulation of MCP‐PEG NPs and improve their therapeutic efficiency as photothermal agent. A one‐pot method to prepare multifunctional hybrid nanogels by in situ hybridization of dopamine monomer in the skeleton of MnCo is reported. After surface modification with polyethylene glycol and targeting molecules, the resultant hybrid nanoparticles with enhanced photothermal conversion efficiency demonstrate improved blood circulation time and tumor accumulation and, therefore, show great potential to kill tumor in vivo under near infrared (NIR) irradiation.

Background Neuronal apoptosis plays a critical event in the pathogenesis of early brain injury after subarachnoid hemorrhage (SAH). This study investigated the roles of Tauroursodeoxycholic acid (TUDCA) in attenuate neuronal apoptosis and underlying mechanisms after SAH. Methods Sprague–Dawley rats were subjected to model of SAH and TUDCA was administered via the internal carotid injection. Small interfering RNA (siRNA) for TGR5 were administered through intracerebroventricular injection 48 h before SAH. Neurological scores, brain water content, Western blot, TUNEL staining and immunofluorescence staining were evaluated. Results TUDCA alleviated brain water content and improved neurological scores at 24 h and 72 h after SAH. TUDCA administration prevented the reduction of SIRT3 and BCL-2 expressions, as well as the increase of BAX and cleaved caspase-3.Endogenous TGR5 expression were upregulated after SAH and treatment with TGR5 siRNA exacerbated neurological outcomes after SAH and the protective effects of TUDCA at 24 h after SAH were also abolished by TGR5 siRNA. Conclusions Our findings demonstrate that TUDCA could attenuated neuronal apoptosis and improve neurological functions through TGR5/ SIRT3 signaling pathway after SAH. TUDCA may be an attractive candidate for anti-apoptosis treatment in SAH.

It is challenging to design an efficient lossy compression scheme for complicated sources based on block codes, especially to approach the theoretical distortion-rate limit. In this paper, a lossy compression scheme is proposed for Gaussian and Laplacian sources. In this scheme, a new route using “transformation-quantization” was designed to replace the conventional “quantization-compression”. The proposed scheme utilizes neural networks for transformation and lossy protograph low-density parity-check codes for quantization. To ensure the system’s feasibility, some problems existing in the neural networks were resolved, including parameter updating and the propagation optimization. Simulation results demonstrated good distortion-rate performance.

Aging, noise, and ototoxic drug-induced hair cell (HC) loss are the major causes of sensorineural hearing loss. Aminoglycoside antibiotics are commonly used in the clinic, but these often have ototoxic side effects due to the accumulation of oxygen-free radicals and the subsequent induction of HC apoptosis. Blebbistatin is a myosin II inhibitor that regulates microtubule assembly and myosin-actin interactions, and most research has focused on its ability to modulate cardiac or urinary bladder contractility. By regulating the cytoskeletal structure and reducing the accumulation of reactive oxygen species (ROS), blebbistatin can prevent apoptosis in many different types of cells. However, there are no reports on the effect of blebbistatin in HC apoptosis. In this study, we found that the presence of blebbistatin significantly inhibited neomycin-induced apoptosis in HC-like HEI-OC-1 cells. We also found that blebbistatin treatment significantly increased the mitochondrial membrane potential (MMP), decreased ROS accumulation, and inhibited pro-apoptotic gene expression in both HC-like HEI-OC-1 cells and explant-cultured cochlear HCs after neomycin exposure. Meanwhile, blebbistatin can protect the synaptic connections between HCs and cochlear spiral ganglion neurons. This study showed that blebbistatin could maintain mitochondrial function and reduce the ROS level and thus could maintain the viability of HCs after neomycin exposure and the neural function in the inner ear, suggesting that blebbistatin has potential clinic application in protecting against ototoxic drug-induced HC loss.

The aim of this study is to investigate the correlation between soft drusen and the likelihood of mortality from all causes and specific ailments within a representative United States population. This cohort study encompassed 4497 individuals from the 2005 to 2008 National Health and Nutrition Examination Survey (NHANES) cycles, and followed for survival to December 31, 2019. Data on soft drusen were obtained from fundus images. Survey-weighted Cox regression models were utilized to evaluate the hazard of soft drusen incidence and mortality. After a median follow-up of 12.33 (11.33, 12.58) years, 1014 (22.5%) patients died from all causes. Overall, individuals with soft drusen exhibited an increased risk for all-cause mortality (HR 1.41; 95% CI 1.22 to 1.64), cardiovascular disease (CVD)-related death (HR 1.53; 95% CI 1.15 to 2.04), and mortality from other causes (HR 1.48; 95% CI 1.20 to 1.83). Further stratified analysis revealed that the mortality rates were heightened in participants who had distinct soft drusen or both types of soft drusen, as well as those with soft drusen measuring 500 μm or more in diameter. The investigation revealed that soft drusen was linked to all-cause mortality, CVD mortality, and mortality resulting from non-cardiovascular and non-cancerous conditions, indicating that soft drusen may symbolize frailty and aging processes.

A key component of the joint source-channel coding (JSCC) scheme based on double low-density parity-check (D-LDPC) codes is the introduction of a linking matrix between the source LDPC code and channel LDPC code, by which the decoding information including the source redundancy and channel state information can be transferred iteratively. However, the linking matrix is a fixed one-to-one mapping, i.e., an identity matrix in a conventional D-LDPC code system, which may not take full advantage of the decoding information. Therefore, this paper introduces a general linking matrix, i.e., a non-identity linking matrix, connecting the check nodes (CNs) of the source LDPC code and the variable nodes (VNs) of the channel LDPC code. Further, the encoding and decoding algorithms of the proposed D-LDPC coding system are generalized. A joint extrinsic information transfer (JEXIT) algorithm is derived for calculating the decoding threshold of the proposed system with a general linking matrix. In addition, several general linking matrices are optimized with the aid of the JEXIT algorithm. Finally, the simulation results demonstrate the superiority of the proposed D-LDPC coding system with general linking matrices.

Aims Patients with congestive heart failure (CHF) may also suffer from chronic kidney disease (CKD), and the two conditions may interact to increase the risk of death. The purpose of this study was to investigate the risk factors contributing to in‐hospital mortality in patients with CHF and CKD and to develop a nomogram to predict the risk of in‐hospital mortality. Methods and results This retrospective study used data from the Marketplace for Medical Information in Intensive Care (MIMIC‐IV, version 1.0). Patients diagnosed with CHF and CKD in MIMIC‐IV were included in this study. The least absolute shrinkage and selection operator (LASSO) logistic regression is used to select risk variables for the nomogram model, and bootstrap is used for internal validation. Simplified Acute Physiology Score II (SAPS II) and Logistic Organ Dysfunction Score (LODS) were compared with the nomogram model by the area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA). A total of 4638 adult patients with CHF and CKD were included in the final cohort; of them, 707 (15.2%) died and 3931 (84.8%) survived during hospitalization. Our final model included the following 13 variables: age, acute kidney injury, myocardial infarction, anaemia, heart rate ≥ 100 b.p.m., systolic blood pressure ≥ 130 mmHg, anion gap (AG) ≥ 20 mEq/L, sodium ≥ 145 mEq/L, red blood cell distribution width (RDW) ≥ 15.5%, white blood cell count ≥ 10 K/μL, continuous renal replacement therapy (CRRT), angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers, and beta‐blocker. The corrected C‐statistic of the nomogram was 0.767, and the calibration curve indicating good concordance between the predicted and observed values. The nomogram demonstrated good accuracy for predicting the in‐hospital mortality with an AUC of 0.771 (95% CI: 0.752–0.790), while the AUC for SAPS II and LODS was 0.747 (95% CI: 0.726–0.767) and 0.752 (95% CI: 0.730–0.773), respectively. DCA found that when the threshold probability was 0.05 to 0.41, the nomogram model could provide a greater net benefit than SAPS II. Conclusions In this retrospective cohort analysis of patients with CHF and CKD, we identified 13 independent variables associated with in‐hospital mortality using LASSO logistic regression. RDW, AG, and CRRT were reported to play a significant role in in‐hospital mortality among patients with CHF and CKD for the first time. Based on a simplified model including 13 variables, a nomogram was drawn to predict the risk of in‐hospital mortality. In comparison with SAPS II and LODS, the nomogram model performed well.

Covert wireless communication ensures information security by hiding the existence of the information transmission itself. Available works mainly focused on the covert throughput study of one-hop wireless communications, while the performance limit of covert throughput in important two-way two-hop scenarios remains largely unknown. As the most significant contribution, this paper, for the first time, investigates such performance limit in a system where two sources wish to covertly exchange information through a relay against the detection of a warden, i.e., a malicious node that attempts to detect the existence of communication between the two sources. As the second contribution, this paper considers various scenarios regarding the warden’s prior knowledge about the relay, the sources/relay’s prior knowledge about the warden, as well as different relaying patterns, and then proposes a covertness strategy to resist the warden’s detection for each scenario. As the last contribution, we derive the scaling law result for the covert throughput of the system for each scenario, i.e., the maximum number of bits that the two sources can exchange subject to a constraint on the detection probability of the warden. The results in this paper indicate that the covert throughput of the concerned system follows the well-known square root scaling law, which is independent of the relaying patterns, detection schemes, covertness strategies, and prior knowledges of the sources/relay and warden.