A low-cost machine learning framework for predicting drug-drug interactions based on fusion of multiple features and a parameter self-tuning strategy.

Poly-drug therapy is now recognized as a crucial treatment, and the analysis of drug-drug interactions (DDIs) offers substantial theoretical support and guidance for its implementation. Predicting potential DDIs using intelligent algorithms is an emerging approach in pharmacological research. However, the existing supervised models and deep learning-based techniques still have several limitations. This paper proposes a novel DDI analysis and prediction framework called the Multi-View Semi-supervised Graph-based (MVSG) framework, which provides a comprehensive judgment by integrating multiple DDI features and functions without any time-consuming training process. Unlike conventional approaches, MVSG can search for the most suitable similarity (or distance) measurement among DDI data and construct graph structures for each feature. By employing a parameter self-tuning strategy, MVSG fuses multiple graphs according to the contributions of features' information. The actual anticancer drug data are extracted from the authoritative public database for evaluating the effectiveness of our framework, including 904 drugs, 7730 DDI records and 19 types of drug interactions. Validation results indicate that the prediction is more accurate when multiple features are adopted by our framework. In comparison to conventional machine learning techniques, MVSG can achieve higher performance even with less labeled data and without a training process. Finally, MVSG is employed to narrow down the search for potential valuable combinations.

Effects of low-dose furosemide combined with aminophylline on the renal function in septic shock patients.

BACKGROUND: To investigate the effects of low-dose furosemide and aminophylline on the renal function in patients with septic shock. METHODS AND RESULTS: A total of 109 eligible septic shock patients in the intensive care unit were randomly divided into a control group (n = 55) and an intervention group (n = 54). The control group received normal saline, and the intervention group received low-dose furosemide (0.048 mg/kg.h-1) with aminophylline (0.3 mg/kg.h-1). The primary outcomes included the levels of serum creatinine (Scr), creatinine clearance rate (Ccr), blood urea nitrogen (BUN), glomerular filtration rate (GFR), and urine output on admission and on days 3, 7 and 14. The secondary outcomes were the sequential organ failure assessment (SOFA) scores, continuous renal replacement therapy (CRRT) time and intensive care unit (ICU) mortality, hospital mortality and 28-day mortality. There were no significant differences in the levels of Scr, Ccr, BUN, or GFR between the two groups, while the urine output was higher in the intervention group on days 3, 7, and 14. Compared with the control group, the SOFA scores, ICU mortality, hospital mortality and 28-day mortality were significantly lower in the intervention group on days 3, 7, and 14, the CRRT time was shorter, and the cumulative fluid balance was lower on days 3 and 7 in the intervention group. CONCLUSIONS: Although low-dose furosemide and aminophylline have fewer protective effects on the renal function in septic shock patients, they could reduce the CRRT time and improve the prognosis.

Clonal Vγ6+Vδ4+ T cells promote IL-17-mediated immunity against Staphylococcus aureus skin infection.

T cell cytokines contribute to immunity against Staphylococcus aureus, but the predominant T cell subsets involved are unclear. In an S. aureus skin infection mouse model, we found that the IL-17 response was mediated by γδ T cells, which trafficked from lymph nodes to the infected skin to induce neutrophil recruitment, proinflammatory cytokines IL-1α, IL-1ß, and TNF, and host defense peptides. RNA-seq for TRG and TRD sequences in lymph nodes and skin revealed a single clonotypic expansion of the encoded complementarity-determining region 3 amino acid sequence, which could be generated by canonical nucleotide sequences of TRGV5 or TRGV6 and TRDV4 However, only TRGV6 and TRDV4 but not TRGV5 sequences expanded. Finally, Vγ6+ T cells were a predominant γδ T cell subset that produced IL-17A as well as IL-22, TNF, and IFNγ, indicating a broad and substantial role for clonal Vγ6+Vδ4+ T cells in immunity against S. aureus skin infections.

A Novel and Fast Encryption System Based on Improved Josephus Scrambling and Chaotic Mapping.

To address the shortcomings of weak confusion and high time complexity of the existing permutation algorithms, including the traditional Josephus ring permutation (TJRP), an improved Josephus ring-based permutation (IJRBP) algorithm is developed. The proposed IJRBP replaces the remove operation used in TJRP with the position exchange operation and employs random permutation steps instead of fixed steps, which can offer a better scrambling effect and a higher permutation efficiency, compared with various scrambling methods. Then, a new encryption algorithm based on the IJRBP and chaotic system is developed. In our scheme, the plaintext feature parameter, which is related to the plaintext and a random sequence generated by a chaotic system, is used as the shift step of the circular shift operation to generate the diffusion matrix, which means that a minor change in the source image will generate a totally different encrypted image. Such a strategy strikes a balance between plaintext sensitivity and ciphertext sensitivity to obtain the ability to resist chosen-plaintext attacks (CPAs) and the high robustness of resisting noise attacks and data loss. Simulation results demonstrate that the proposed image cryptosystem has the advantages of great encryption efficiency and the ability to resist various common attacks.

Design and ARM-Based Implementation of Bitstream-Oriented Chaotic Encryption Scheme for H.264/AVC Video.

In actual application scenarios of the real-time video confidential communication, encrypted videos must meet three performance indicators: security, real-time, and format compatibility. To satisfy these requirements, an improved bitstream-oriented encryption (BOE) method based chaotic encryption for H.264/AVC video is proposed. Meanwhile, an ARM-embedded remote real-time video confidential communication system is built for experimental verification in this paper. Firstly, a 4-D self-synchronous chaotic stream cipher algorithm with cosine anti-controllers (4-D SCSCA-CAC) is designed to enhance the security. The algorithm solves the security loopholes of existing self-synchronous chaotic stream cipher algorithms applied to the actual video confidential communication, which can effectively resist the combinational effect of the chosen-ciphertext attack and the divide-and-conquer attack. Secondly, syntax elements of the H.264 bitstream are analyzed in real-time. Motion vector difference (MVD) coefficients and direct-current (DC) components in Residual syntax element are extracted through the Exponential-Golomb decoding operation and entropy decoding operation based on the context-based adaptive variable length coding (CAVLC) mode, respectively. Thirdly, the DC components and MVD coefficients are encrypted by the 4-D SCSCA-CAC, and the encrypted syntax elements are re-encoded to replace the syntax elements of the original H.264 bitstream, keeping the format compatibility. Besides, hardware codecs and multi-core multi-threading technology are employed to improve the real-time performance of the hardware system. Finally, experimental results show that the proposed scheme, with the advantage of high efficiency and flexibility, can fulfill the requirement of security, real-time, and format compatibility simultaneously.

Combined fluorescence-guided surgery and photodynamic therapy for glioblastoma multiforme using cyanine and chlorin nanocluster.

INTRODUCTION: Glioblastoma multiforme (GBM) is the most common primary intracranial malignancy; survival can be improved by maximizing the extent-of-resection. METHODS: A near-infrared fluorophore (Indocyanine-Green, ICG) was combined with a photosensitizer (Chlorin-e6, Ce6) on the surface of superparamagnetic-iron-oxide-nanoparticles (SPIONs), all FDA-approved for clinical use, yielding a nanocluster (ICS) using a microemulsion. The physical-chemical properties of the ICS were systematically evaluated. Efficacy of photodynamic therapy (PDT) was evaluated in vitro with GL261 cells and in vivo in a subtotal resection trial using a syngeneic flank tumor model. NIR imaging properties of ICS were evaluated in both a flank and an intracranial GBM model. RESULTS: ICS demonstrated high ICG and Ce6 encapsulation efficiency, high payload capacity, and chemical stability in physiologic conditions. In vitro cell studies demonstrated significant PDT-induced cytotoxicity using ICS. Preclinical animal studies demonstrated that the nanoclusters can be detected through NIR imaging in both flank and intracranial GBM tumors (ex: 745 nm, em: 800 nm; mean signal-to-background 8.5 ± 0.6). In the flank residual tumor PDT trial, subjects treated with PDT demonstrated significantly enhanced local control of recurrent neoplasm starting on postoperative day 8 (23.1 mm3 vs 150.5 mm3, p = 0.045), and the treatment effect amplified to final mean volumes of 220.4 mm3 vs 806.1 mm3 on day 23 (p = 0.0055). CONCLUSION: A multimodal theragnostic agent comprised solely of FDA-approved components was developed to couple optical imaging and PDT. The findings demonstrated evidence for the potential theragnostic benefit of ICS in surgical oncology that is conducive to clinical integration.

Injury, dysbiosis, and filaggrin deficiency drive skin inflammation through keratinocyte IL-1α release.

BACKGROUND: Atopic dermatitis (AD) is associated with epidermal barrier defects, dysbiosis, and skin injury caused by scratching. In particular, the barrier-defective epidermis in patients with AD with loss-of-function filaggrin mutations has increased IL-1α and IL-1ß levels, but the mechanisms by which IL-1α, IL-1ß, or both are induced and whether they contribute to the aberrant skin inflammation in patients with AD is unknown. OBJECTIVE: We sought to determine the mechanisms through which skin injury, dysbiosis, and increased epidermal IL-1α and IL-1ß levels contribute to development of skin inflammation in a mouse model of injury-induced skin inflammation in filaggrin-deficient mice without the matted mutation (ft/ft mice). METHODS: Skin injury of wild-type, ft/ft, and myeloid differentiation primary response gene-88-deficient ft/ft mice was performed, and ensuing skin inflammation was evaluated by using digital photography, histologic analysis, and flow cytometry. IL-1α and IL-1ß protein expression was measured by means of ELISA and visualized by using immunofluorescence and immunoelectron microscopy. Composition of the skin microbiome was determined by using 16S rDNA sequencing. RESULTS: Skin injury of ft/ft mice induced chronic skin inflammation involving dysbiosis-driven intracellular IL-1α release from keratinocytes. IL-1α was necessary and sufficient for skin inflammation in vivo and secreted from keratinocytes by various stimuli in vitro. Topical antibiotics or cohousing of ft/ft mice with unaffected wild-type mice to alter or intermix skin microbiota, respectively, resolved the skin inflammation and restored keratinocyte intracellular IL-1α localization. CONCLUSIONS: Taken together, skin injury, dysbiosis, and filaggrin deficiency triggered keratinocyte intracellular IL-1α release that was sufficient to drive chronic skin inflammation, which has implications for AD pathogenesis and potential therapeutic targets.

A Symmetric Plaintext-Related Color Image Encryption System Based on Bit Permutation.

Recently, a variety of chaos-based image encryption algorithms adopting the traditional permutation-diffusion structure have been suggested. Most of these algorithms cannot resist the powerful chosen-plaintext attack and chosen-ciphertext attack efficiently for less sensitivity to plain-image. This paper presents a symmetric color image encryption system based on plaintext-related random access bit-permutation mechanism (PRRABPM). In the proposed scheme, a new random access bit-permutation mechanism is used to shuffle 3D bit matrix transformed from an original color image, making the RGB components of the color image interact with each other. Furthermore, the key streams used in random access bit-permutation mechanism operation are extremely dependent on plain image in an ingenious way. Therefore, the encryption system is sensitive to tiny differences in key and original images, which means that it can efficiently resist chosen-plaintext attack and chosen-ciphertext attack. In the diffusion stage, the previous encrypted pixel is used to encrypt the current pixel. The simulation results show that even though the permutation-diffusion operation in our encryption scheme is performed only one time, the proposed algorithm has favorable security performance. Considering real-time applications, the encryption speed can be further improved.

A Simple Chaotic Map-Based Image Encryption System Using Both Plaintext Related Permutation and Diffusion.

Recently, to conquer most non-plain related chaos-based image cryptosystems' security flaws that cannot resist the powerful chosen/knownn plain-text attacks or differential attacks efficiently for less plaintext sensitivity, many plain related chaos-based image cryptosystems have been developed. Most cryptosystems that have adopted the traditional permutation-diffusion structure still have some drawbacks and security flaws: (1) most plaintext related image encryption schemes using only plaintext related confusion operation or only plaintext related diffusion operation relate to plaintext inadequately that cannot achieve high plaintext sensitivity; (2) in some algorithms, the generation of security key that needs to be sent to the receiver is determined by the original image, so these algorithms may not applicable to real-time image encryption; (3) most plaintext related image encryption schemes have less efficiency because more than one round permutation-diffusion operation is required to achieve high security. To obtain high security and efficiency, a simple chaotic based color image encryption system by using both plaintext related permutation and diffusion is presented in this paper. In our cryptosystem, the values of the parameters of cat map used in permutation stage are related to plain image and the parameters of cat map are also influenced by the diffusion operation. Thus, both the permutation stage and diffusion stage are related to plain images, which can obtain high key sensitivity and plaintext sensitivity to resist chosen/known plaintext attacks or differential attacks efficiently. Furthermore, only one round of plaintext related permutation and diffusion operation is performed to process the original image to obtain cipher image. Thus, the proposed scheme has high efficiency. Complete simulations are given and the simulation results prove the excellent security and efficiency of the proposed scheme.

Elucidating pH-dependent collagen triple helix formation through interstrand hydroxyproline-glutamic acid interactions.

Here, we describe systematic explorations into the molecular basis underlying hydroxyproline-mediated interstrand interactions on the triple-helical stability of collagen-mimetic peptides containing glutamic acid residues. Our studies reveal that the triple-helical stability of these peptides relies on the existence of interstrand interactions between hydroxyprolines and glutamic acid residues that are pH dependent. These unique interactions have been used to engineer collagen peptides that form triple helices on demand through pH control.

A novel approach for diabetic foot diagnosis: Deep learning-based detection of lower extremity arterial stenosis.

PURPOSE OF THE STUDY: Assessing the lower extremity arterial stenosis scores (LEASS) in patients with diabetic foot ulcer (DFU) is a challenging task that requires considerable time and efforts from physicians, and it may yield varying results. The presence of vascular wall calcification and other irrelevant tissue information surrounding the vessel can further compound the difficulties of this evaluation. Automatic detection of lower extremity arterial stenosis (LEAS) is expected to help doctors develop treatment plans for patients faster. METHODS: In this paper, we first reconstructed the 3D model of blood vessels by medical digital image processing and then utilized it as the training data for deep learning (DL) in conjunction with the non-calcified part of blood vessels in the original data. We proposed an improved model of vascular stenosis small target detection based on YOLOv5. We added Convolutional Block Attention Module (CBAM) in backbone, replaced Path Aggregation Network (PANET) with Bidirectional Feature Pyramid Network (BiFPN) and replaced C3 with GhostC3 in neck to improve the recognition of three types of stenosis targets (I: <50 %, II: 51 % - 99 %, III: completely occluded). Additionally, we utilized K-Means++ instead of K-Means for better algorithm convergence performance, and enhanced the Complete-IoU (CIoU) loss function to Alpha-Scylla-IoU (ASIoU) loss for faster reasoning and convergence. Lastly, we conducted comparisons between our approach and five other prominent models. RESULT: Our method had the best average ability to detect three types of stenosis with 85.40% mean Average Precision (mAP) and 74.60 Frames Per Second (FPS) and explored the possibility of applying DL to the detection of LEAS in diabetic foot. The code is available at github.com/wuchongxin/yolov5_LEAS.git.

Stable, Scalable, and Free-Standing Perovskite Quantum Dots Composite Reinforced by Cellulose Fibers.

Perovskite quantum dots (PQDs) have attracted emerging attention as fluorescent and light-absorbing materials for next-generation optoelectronics due to their outstanding properties and cost-efficiency. However, PQD thin film suffers significant instability due to structure and material failures, which hinders their application in flexible and reliable PQD-based advanced wearable devices. Herein, we use commercial cellulose fiber-based filter paper as a substrate to synthesize PQDs in situ and fabricate PQD-paper free-standing flexible composite film. The abundant hydroxy capping ligands of cellulose fibers and the unique dense network structure of the filter paper can facilitate confined crystallization, forming strong interactions between the PQDs and substrate, the unpackaged PQD composite film showed extraordinary stability (>30 days) in the air with high humidity (90%). Meanwhile, the strong interaction between PQDs and paper enables an ultrasimple drop-cast synthesis process with excellent process tolerance, making it customizable and easy to scale up (10 cm in diameter). Due to the uniformly dispersed PQDs on cellulose fibers of the substrate, the composite demonstrates impressive photo-responsive properties. Photodetector (PD) arrays were designed on free-standing PQD paper and flexible graphitic electrodes, and circuits were fabricated by drawing. The PD arrays can work as optical and electrical dual-mode image sensors with incredible bending robustness, enduring up to 100,000 cycles at 180°.

Optimization of lipid nanoparticles for gene editing of the liver via intraduodenal delivery.

Lipid nanoparticles (LNPs) have recently emerged as successful gene delivery platforms for a diverse array of disease treatments. Efforts to optimize their design for common administration methods such as intravenous injection, intramuscular injection, or inhalation, revolve primarily around the addition of targeting ligands or the choice of ionizable lipid. Here, we employed a multi-step screening method to optimize the type of helper lipid and component ratios in a plasmid DNA (pDNA) LNP library to efficiently deliver pDNA through intraduodenal delivery as an indicative route for oral administration. By addressing different physiological barriers in a stepwise manner, we down-selected effective LNP candidates from a library of over 1000 formulations. Beyond reporter protein expression, we assessed the efficiency in non-viral gene editing in mouse liver mediated by LNPs to knockdown PCSK9 and ANGPTL3 expression, thereby lowering low-density lipoprotein (LDL) cholesterol levels. Utilizing an all-in-one pDNA construct with Strep. pyogenes Cas9 and gRNAs, our results showcased that intraduodenal administration of selected LNPs facilitated targeted gene knockdown in the liver, resulting in a 27% reduction in the serum LDL cholesterol level. This LNP-based all-in-one pDNA-mediated gene editing strategy highlights its potential as an oral therapeutic approach for hypercholesterolemia, opening up new possibilities for DNA-based gene medicine applications.

Piezoresistivity modeling of soft tissue electrical-mechanical properties: A validation study.

In general, the electrical property of soft tissues is sensitive to the force applied to their surface. To further study the relationship between the force and the electrical property of soft tissues, this paper attempts to investigate the effect of static and higher-order stresses on electrical properties. Overall, a practical experimental platform is designed to acquire the force information and the electrical property of soft tissues during a contact procedure, which is featured different compression stimuli, such as constant pressing force, constant pressing speed, and step-force compression, etc. Furthermore, the piezoresistive characteristic is innovatively introduced to model the mechanical-electrical properties of soft tissue. Finite Element Modeling (FEM) is adopted to fit the static piezoresistivity of the soft tissue. Finally, experimental studies were performed to demonstrate the effect of stress on the electrical properties and the feasibility of the proposed piezoresistive model to describe soft tissues' mechanical and electrical properties.

TREM-1 induces pyroptosis in cardiomyocytes by activating NLRP3 inflammasome through the SMC4/NEMO pathway.

Sepsis often causes cell death via pyroptosis and hence results in septic cardiomyopathy. Triggering receptors expressed in myeloid cells-1 (TREM-1) may initiate cellular cascade pathways and, in turn, induce cell death and vital organ dysfunction in sepsis, but the evidence is limited. We set to investigate the role of TREM-1 on nucleotide-binding oligomerization domain-like receptors with pyrin domain-3 (NLRP3) inflammasome activation and cardiomyocyte pyroptosis in sepsis models using cardiac cell line (HL-1) and mice. In this study, TREM-1 was found to be significantly increased in HL-1 cells challenged with lipopolysaccharide (LPS). Pyroptosis was also significantly increased in the HL-1 cells challenged with lipopolysaccharide and an NLRP3 inflammasome activator, nigericin. The close interaction between TREM-1 and structural maintenance of chromosome 4 (SMC4) was also identified. Furthermore, inhibition of TREM-1 or SMC4 prevented the upregulation of NLRP3 and decreased Gasdermin-D, IL-1ß and caspase-1 cleavage. In mice subjected to caecal ligation and puncture, the TREM-1 inhibitor LR12 decreased the expression of NLRP3 and attenuated cardiomyocyte pyroptosis, leading to improved cardiac function and prolonged survival of septic mice. Our work demonstrates that, under septic conditions, TREM-1 plays a critical role in cardiomyocyte pyroptosis. Targeting TREM-1 and its associated molecules may therefore lead to novel therapeutic treatments for septic cardiomyopathy.

Access to quinolines through gold-catalyzed intermolecular cycloaddition of 2-aminoaryl carbonyls and internal alkynes.

A facile and general method leading to polyfunctionalized quinolines was developed. In the presence of a highly efficient combination encompassing (PPh)(3)AuCl and AgOTf, the reactions between 2-aminocarbonyls and an array of internal alkynes proceeded smoothly to afford quinoline derivatives in good to excellent yields (up to 93%).

Direct and stereoselective synthesis of 1,3-cis-3- arylsulphonaminodeoxydisaccharides and oligosaccharides.

The 3-aminoglycosides are ubiquitous in biologically important classes of glycoconjugates and naturally occurring oligosaccharides. Despite the rapid growth in the development of synthetic method of 3-amino glycosides, the current state-of-the art suffers from limited substrate scope, low yields, long reaction times, and anomeric mixtures. This work presents a novel direct method for the synthesis of 1,3-cis-3-arylsulphonaminodeoxydisaccharides and oligosaccharides via α-selective glycosylation and hydroamination of glycal in a one-pot manner. This efficient multicomponent reaction methodology provides ready access to 1,3-cis-3-arylsulphonaminodeoxydisaccharides and oligosaccharides and allows derivatization by variation of each component.

Smart handheld device with flexible wrist and electrical bioimpedance sensor for tissue inspection.

With the evolving demands of surgical intervention, there is a strong need for smaller and functionally augmented instruments to improve surgical outcomes, operational convenience, and diagnostic safety. Owing to the narrow and complicated anatomy, the probe head of the medical instrument is required to possess both good maneuverability and compact size. In addition, the development of medical instrument is moving toward patient-specialized, of which the articulation positions can be customized to reach the target position. To fulfill these requirements, this study presents the design of a smart handheld device which equips with a low cost, easy control, disposable flexible wrist, and an electrical bioimpedance sensor for medical diagnosis. Prototype of the device is made and tested. The experimental results demonstrate that the proposed device can provide accurate manipulation and effective tissue detection, showing a great potential in various medical applications.

N-Heterocyclic carbene-mediated oxidative esterification of aldehydes: ester formation and mechanistic studies.

An unexpected N-heterocyclic carbene-catalyzed esterification of α,ß-unsaturated aldehydes including aromatic aldehydes with reactive cinnamyl bromides in the presence of air oxygen or MnO(2) as an oxidant is described. In the presence of oxygen, halogenated and electron-deficient aldehydes react smoothly to furnish esters in good yields. Great efforts have been made on mechanistic studies to deduce a plausible mechanism, based on the experimental results and isotopic labeling experiment.

Acute fatty liver of pregnancy causes severe acute pancreatitis and stillborn fetus: A case report.

RATIONALE: Acutefatty liver of pregnancy (AFLP) is a potentially fatal obstetric emergency characterized by acute hepatic failure secondary to fatty infiltration. The resultant effects include coagulopathy, electrolyte abnormalities, and multisystem organ dysfunction. Pancreatitis typically develops after the onset of renal and hepatic dysfunction. Pancreatitis has been suggested as a poor prognostic indicator because it is associated with more adverse outcomes. PATIENT CONCERNS: A 29-year-old Chinese woman at 34.7 weeks pregnancy was admitted to hospital due to paroxysmal hypogastric pain and massive colporrhagia for 1 day. DIAGNOSIS: Laboratory tests revealed hepatic and renal impairment, coagulopathy. Thoracoabdominal computed tomography (CT) scanning showed pleural and peritoneal effusion, fatty liver, and pancreatitis. She was diagnosed with AFLP, severe acute pancreatitis (SAP), multiple organ dysfunction syndrome (MODS), and intrauterine fetal death. INTERVENTIONS: The patient was treated with blood component transfusions, plasma exchange combined with renal replacement therapy, antibiotic de-escalation, gastric and pancreatic secretion inhibitor, and enteral nutrition. OUTCOMES: After successful management, the patient was discharged without any complications on day 35 of admission. At 10 months follow-up, thoracoabdominal enhanced CT revealed was normal and laboratory tests revealed normal liver and kidney function. LESSONS: Once AFLP is highly suspected or confirmed, the pregnancy should be terminated in time and active symptomatic management should be given.