Accelerating discovery of bioactive ligands with pharmacophore-informed generative models.

Deep generative models have advanced drug discovery but often generate compounds with limited structural novelty, providing constrained inspiration for medicinal chemists. To address this, we develop TransPharmer, a generative model that integrates ligand-based interpretable pharmacophore fingerprints with a generative pre-training transformer (GPT)-based framework for de novo molecule generation. TransPharmer excels in unconditioned distribution learning, de novo generation, and scaffold elaboration under pharmacophoric constraints.

One-step engineered mesenchymal stem cell-derived exosomes against hepatic ischemia-reperfusion injury.

Hepatic ischemia-reperfusion injury (IRI) is an important factor affecting the prognosis of patients undergoing surgery. Exosomes derived from mesenchymal stem cells (MSC-EXOs) are widely used and play a therapeutic role in hepatic IRI. However, natural exosomes lack liver-targeting ability and have low bioavailability.

Methylene Blue Has Strong Extracellular Virucidal Activity Against a SARS-CoV-2-Related Pangolin Coronavirus with No Intracellular or In Vivo Efficacy.

Studies have demonstrated that methylene blue exhibits significant antiviral activity against SARS-CoV-2 or related coronaviruses at the cellular level, suggesting its potential as an anti-SARS-CoV-2 drug. Herein, we report that methylene blue does not exhibit noticeable antiviral activity in a lethal model involving SARS-CoV-2-related pangolin coronavirus GX_P2V (short_3UTR) infection in CAG-hACE2 transgenic mice. We employed plaque reduction assays and cell infection experiments to compare the extracellular virucidal activity of the compound and its ability to inhibit viral replication in cells to those of nirmatrelvir.

Self-gating stochastic-resonance-based autoencoder for unsupervised learning.

Incorporating additive noise components to an ensemble of McCulloch-Pitts neurons can enhance the information representation of the input, asymptotically approaching the average firing probability for large enough ensembles. We further multiply the input by the average firing probability to control the higher probability of self-gating, thereby forming a unified noise-boosted activation model with learnable noise-related hyperparameters. This gating strategy plays a crucial role in improving the performance of neural networks, as evidenced by the optimization of the autoencoder loss at nonzero optimal-noise-scaling hyperparameters, a phenomenon termed self-gating stochastic resonance.

Intriguing steroid glycosides for cancer therapy by suppressing the DNA damage response and mTOR/S6K signaling pathways.

Two rare 8-hydroxysteroid glycosides (6-7), and their downstream metabolites (1-5) with an unprecedented 6/6/5/5/5-pentacyclic scaffold, together with seven known analogues (8-14) were isolated from the twigs and leaves of Strophanthus divaricatus. Their structures were fully assigned by analysis of the spectroscopic and ECD data, NMR calculations, X-ray crystallographic study, and chemical methods. In addition, the inhibitory effects of 1-14 on liver and lung cancer cell lines were evaluated, and preliminary structure-activity relationship was discussed.

Dynamic immune status analysis of peripheral blood mononuclear cells in patients with bloodstream infection sepsis using single-cell RNA sequencing.

Background: is a common Gram-negative bacterium. Blood infection caused by is one of the most common causes of human sepsis, which seriously threatens the life of patients. The immune status of peripheral blood mononuclear cells (PBMCs) based on single-cell RNA sequencing (scRNA-seq) in acute stage and recovery stage of sepsis caused by bloodstream infection has not been studied.

Nonlinear Photon Generations from Subwavelength Whispering-Gallery-Mode Resonator.

The strong light localization and long photon lifetimes in whispering gallery mode (WGM) microresonators, benefiting from a high-quality () factor and a small mode volume (), could significantly enhance light-matter interactions, enabling efficient nonlinear photon generation and paving the way for exploring novel on-chip optical functionalities. However, the leakage of energy from bending losses severely limits the improvement of the factor for subwavelength WGM microresonators. Here, we demonstrated an integrated self-suspended WGM microresonator that combines external rings and bridges with a microdisk on a platform of silicon on insulator, achieving about one-hundred-fold enhancement in the factor and an ultrasmall mode volume of 2.

Anti-Inflammatory Salicin Derivatives from the Barks of .

The genus L. is traditionally used in folk medicine to alleviate pain caused by various kinds of inflammation. In the present study, 10 undescribed salicin derivatives along with 5 known congeners were isolated from the barks of , and their structures were elucidated by spectroscopic analyses, single-crystal X-ray diffraction, electronic circular dichroism (ECD) calculations, and chemical conversions.

Monoterpenoid indole alkaloids from Alstonia scholaris and their Toxoplasma gondii inhibitory activity.

Nine previously unreported various types of monoterpenoid indole alkaloids, together with seven known analogues were isolated from the stem barks of Alstonia scholaris through a silica gel free methodology. The structures of 1-9 were elucidated by spectroscopic data analysis, electronic circular dichroism calculations, and single-crystal X-ray diffraction. Compound 1 is a modified echitamine-type alkaloid with a novel 6/5/5/7/6/6 hetero hexacyclic bridged ring system, and 8 and 9 exist as a zwitterion and trifluoroacetate salt, respectively.

Nobachelins, new siderophores from protecting from infection.

The biosynthetic potential of actinobacteria to produce novel natural products is still regarded as immense. In this paper, we correlated a cryptic biosynthetic gene cluster to chemical molecules by genome mining and chemical analyses, leading to the discovery of a new group of catecholate-hydroxamate siderophores, nobachelins, from DSM 44845. Nobachelin biosynthesis genes are conserved in several bacteria from the family .

Clinical evaluation of metagenomic next-generation sequencing in unbiased pathogen diagnosis of urinary tract infection.

Background: Early availability of pathogen identification in urinary tract infections (UTIs) has critical importance in disease management. Metagenomic next-generation sequencing (mNGS) has the potential to transform how acute and serious infections are diagnosed by offering unbiased and culture-free pathogen detection. However, clinical experience with application of the mNGS test is relatively limited.

Diagnosis of septic shock by serum measurement of human neutrophil lipocalin by a rapid homogeneous assay.

Background: Human neutrophil lipocalin (HNL) is a marker of neutrophil activation and has a high efficacy in diagnosing bacterial infections. In this study, we applied the AlphaLISA technique to measure the serum level of HNL, evaluate HNL's efficacy in diagnosing septic shock, and identify any association between HNL level and septic patients' prognosis.

Methods: We collected 146 serum samples from the Fifth Medical Center of Chinese PLA General Hospital.

An automated detection of epileptic seizures EEG using CNN classifier based on feature fusion with high accuracy.

Background: Epilepsy is a neurological disorder that is usually detected by electroencephalogram (EEG) signals. Since manual examination of epilepsy seizures is a laborious and time-consuming process, lots of automatic epilepsy detection algorithms have been proposed. However, most of the available classification algorithms for epilepsy EEG signals adopted a single feature extraction, in turn to result in low classification accuracy.

Fpr2 exacerbates -induced streptococcal toxic shock-like syndrome attenuation of neutrophil recruitment.

The life-threatening disease streptococcal toxic shock-like syndrome (STSLS), caused by the bacterial pathogen (). Proinflammatory markers, bacterial load, granulocyte recruitment, and neutrophil extracellular traps (NETs) levels were monitored in wild-type (WT) and Fpr2 mice suffering from STSLS. LXA4 and AnxA1, anti-inflammatory mediators related to Fpr2, were used to identity a potential role of the Fpr2 in STSLS development.

Low-threshold nanolasers based on miniaturized bound states in the continuum.

The pursuit of compact lasers with low thresholds has imposed strict requirements on tight light confinements with minimized radiation losses. Bound states in the continuum (BICs) have been recently demonstrated as an effective mechanism to trap light. However, most reported BIC lasers are still bulky due to the absence of in-plane light confinement.

Manipulating cavity photon dynamics by topologically curved space.

Asymmetric microcavities supporting Whispering-gallery modes (WGMs) are of great significance for on-chip optical information processing. We establish asymmetric microcavities on topologically curved surfaces, where the geodesic light trajectories completely reconstruct the cavity mode features. The curvature-mediated photon-lifetime engineering enables the enhancement of the quality factors of periodic island modes by up to 200 times.

ROS-cleavable diselenide nanomedicine for NIR-controlled drug release and on-demand synergistic chemo-photodynamic therapy.

Many chemotherapeutic drugs and photosensitizers suffer from poor solubility, unspecific delivery and uncontrollable release, which severely impede their biomedical applications. Herein, we designed a type of ROS-cleavable hydrophilic diselenide nanoparticles through self-assembling of PEG-modified camptothecin (CPT, a hydrophobic drug) and meso‑tetra (4-carboxyphenyl) porphine (TCPP, a hydrophobic photosensitizer). The TCPP@SeSe-CPT nanomedicine (particle size: 116.

Comparison Analysis of Different DNA Extraction Methods on Suitability for Long-Read Metagenomic Nanopore Sequencing.

Metagenomic next-generation sequencing (mNGS) is a novel useful strategy that is increasingly used for pathogens detection in clinic. Some emerging mNGS technologies with long-read ability are useful to decrease sequencing time and increase diagnosed accuracy, which is of great significance in rapid pathogen diagnosis. Reliable DNA extraction is considered critical for the success of sequencing; hence, there is thus an urgent need of gentle DNA extraction method to get unbiased and more integrate DNA from all kinds of pathogens.

Suilyin Disrupts the Blood-Brain Barrier by Activating Group III Secretory Phospholipase A2.

Serious diseases caused by serotype 2 ( 2) include septicaemia and meningitis, which are associated with high morbidity and mortality. Proliferation in the blood can result in a breach of the blood-brain barrier (BBB) and provide entry into the cerebrospinal fluid (CSF), where bacteria cause inflammation of the meningeal membranes resulting in meningitis. The molecular mechanisms of how this pathogen crosses the BBB remain unclear.

Rapid Detection of Bacterial Pathogens and Antimicrobial Resistance Genes in Clinical Urine Samples With Urinary Tract Infection by Metagenomic Nanopore Sequencing.

Urinary tract infections (UTIs) are among the most common acquired bacterial infections in humans. The current gold standard method for identification of uropathogens in clinical laboratories is cultivation. However, culture-based assays have substantial drawbacks, including long turnaround time and limited culturability of many potential pathogens.

Highly efficient nonlinear optical emission from a subwavelength crystalline silicon cuboid mediated by supercavity mode.

The low quantum efficiency of silicon (Si) has been a long-standing challenge for scientists. Although improvement of quantum efficiency has been achieved in porous Si or Si quantum dots, highly efficient Si-based light sources prepared by using the current fabrication technooloy of Si chips are still being pursued. Here, we proposed a strategy, which exploits the intrinsic excitation of carriers at high temperatures, to modify the carrier dynamics in Si nanoparticles.