DASNet a dual branch multi level attention sheep counting network.

Grassland sheep counting is essential for both animal husbandry and ecological balance. Accurate population statistics help optimize livestock management and sustain grassland ecosystems. However, traditional counting methods are time-consuming and costly, especially for dense sheep herds.

Recent advances and future perspectives of long-acting ophthalmic preparations (LAOPs) in clinical applications.

The intricate structure of ocular barriers significantly impedes drug penetration, leading to suboptimal efficacy of conventional ophthalmic formulations. Sustained/controlled-release long-acting ophthalmic preparations (LAOPs) address these limitations by prolonging drug retention, reducing dosing frequency, and enhancing therapeutic precision. This review categorizes clinically validated LAOPs by administration route, highlighting both market-approved products and investigational candidates in ongoing clinical trials.

Plasma Protein Binding as an Optimizable Parameter for In Vivo Efficacy.

Plasma protein binding is crucial for understanding pharmacokinetics, pharmacodynamics, and safety. However, it is often not considered to be a primary parameter for optimization in drug design. This study challenges that perspective by revisiting established pharmacokinetic models and analyzing rat pharmacokinetic data of 3357 compounds.

Pharmacokinetics, Pharmacodynamics, and Bioequivalence of Test Insulin Glargine Versus Reference Preparation (Lantus) in Healthy Male Volunteers-By Euglycemic Clamp Technique.

The aim of this study was to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and safety of two insulin glargine preparations in healthy Chinese male subjects. Forty healthy Chinese male subjects were enrolled in this randomized, open, two-sequence, four-period, single-dose, crossover study and were randomly divided into RTRT or TRTR (first-period injection of test preparation, second-period injection of reference preparation, third-period injection of test preparation, fourth-period injection of reference preparation) groups. A 24 h euglycemic clamp test measured GIR.

ROOT INITIATION DEFECTIVE 1 regulates seed germination through transcription rather than alternative splicing in a temperature-dependent manner.

Timely seed germination is a crucial process for plant survival and subsequent propagation, which is significantly impacted by high temperatures. ROOT INITIATION DEFECTIVE 1 (RID1), an Arabidopsis DEAH/RHA RNA helicase, has been previously reported to modulate the cellular specification of mature female gametophyte and callus initiation from hypocotyl explants through proper alternative splicing. However, the role of RID1 in the regulation of seed germination remains largely unexplored.

Exosomal circ_0001583 Drives Glioblastoma Cell Advancement Through the miR-647/CKAP2L Pathway.

Our study aimed to explore the involvement of circ_0001583 in the progression of glioblastoma (GBM). The expression levels of CircRNA in GBM were examined using the GEO database, and quantification of circ_0001583 levels was performed through qRT-PCR in both GBM tissues and cell lines. Survival analysis was conducted using Kaplan-Meier plots.

[Pollution and Carbon Emission Reduction and Synergistic Pathways in the Operation Phase of Sponge City Source Control Facilities].

China is currently at a crucial stage of systematically advancing the construction of sponge cities and completely implementing the "synergetic enhancement of pollution and carbon emission reduction." The pollution and carbon emission reduction benefits during the operational phase of sponge source control facilities, as well as the synergistic path must be crucially understood scientifically. Taking 30 sponge city construction projects in Wuxi, Jiangsu Province as examples, we analyzed the pollution and carbon emission reduction benefits, construction costs, and determined the synergistic relationship among them during the operational phase.

Three Decades of Photodynamic Therapy for Glioblastoma: A Comprehensive Scientometric Analysis.

Background: Photodynamic therapy (PDT) has emerged as a promising adjunctive treatment for glioblastoma (GBM), yet a comprehensive bibliometric analysis of this field is lacking. This study explores research trends, major contributors, and hotspots in PDT for GBM to provide an integrated overview of its development.

Methods: Literature from 1993 to 2024 was retrieved from the Web of Science Core Collection.

LeScore: a scoring function incorporating hydrogen bonding penalty for protein-ligand docking.

Context: Molecular docking is vital for structure-based virtual screening and heavily depends on accurate and robust scoring functions. Scoring functions often inadequately account for the breakage of solvent hydrogen bonds, hindering the accuracy of predicting binding energy. Here, we introduce LeScore, a novel scoring function that specifically incorporates the hydrogen bonding penalty (HBP) in an aqueous environment, aiming to penalize unfavorable polar interactions when hydrogen bonds with water are broken but the energy loss is not fully compensated by newly formed protein-ligand interactions.

Development and evaluation of a 3D ensemble framework for automatic diagnosis of early osteonecrosis of the femoral head based on MRI: a multicenter diagnostic study.

Background: Efficient and reliable diagnosis of early osteonecrosis of the femoral head (ONFH) based on MRI is crucial for the formulation of clinical treatment plans. This study aimed to apply artificial intelligence (AI) to achieve automatic diagnosis and visualization of early ONFH, thereby improving the success rate of hip-preserving treatments.

Method: This retrospective study constructed a multicenter dataset using MRI data of 381 femoral heads from 209 patients with ONFH collected from four institutions (including 239 early ONFH cases and 142 non-ONFH cases).

AI-Augmented R-Group Exploration in Medicinal Chemistry.

Efficient R-group exploration in the vast chemical space, enabled by increasingly available building blocks or generative AI, remains an open challenge. Here, we developed an enhanced Free-Wilson QSAR model embedding R-groups by atom-centric pharmacophoric features. Regioisomers of R-groups can be distinguished by explicitly accounting for the atomic positions.

Turning attention to tumor-host interface and focus on the peritumoral heterogeneity of glioblastoma.

Approximately 90% of glioblastoma recurrences occur in the peritumoral brain zone (PBZ), while the spatial heterogeneity of the PBZ is not well studied. In this study, two PBZ tissues and one tumor tissue sample are obtained from each patient via preoperative imaging. We assess the microenvironment and the characteristics of infiltrating immune/tumor cells using various techniques.

New chapter in reform and development of organ donation and transplantation in China: Embracing past, grounding in national conditions, upholding steadfast belief, and looking forward to future.

The reform stems from honesty and determination. Since 2005, organ donation and transplantation in China has undergone thorough reform, which complies with legislation requirements and ethical principles established by the World Health Organization (WHO). Reform in China has demonstrated the unwavering confidence and utmost determination of the Chinese government and the Chinese transplantation community.

Divergent roles of landscape and young streamflow fraction in stream water quality over seven catchments.

Landscape patterns and water age are considered to play similar roles in influencing water quality, as human-caused landscape fragmentation usually leads to complex hydrological pathways and older water ages. The young streamflow fraction (F), which can significantly alter water age, is believed to disproportionately impact water quality. Landscape and F thus may play different roles in streamwater quality, but this assumption has not been examined.

Delirium in the ICU: how much do we know? A narrative review.

Delirium in critical ill patients is a complex and common neurological syndrome in the intensive care unit (ICU) that is caused by a range of structural or functional abnormalities. ICU Delirium is associated with reduced compliance, prolonged hospital stays, greater use or delayed withdrawal of sedatives, higher rates and durations of mechanical ventilation, and higher rates of mortality. The aetiology and pathogenesis of ICU delirium are unclear, and the lack of better prediction, prevention, and treatment measures leads to a non-standardized control of delirium.

Inhibition of circular JUN prevents the proliferation and invasion of glioblastoma via miR-3064-IGFBP5 axis.

Glioblastoma (GBM) remains one of the most aggressive and lethal brain tumours, characterized by rapid progression and limited treatment options. This study investigated the regulatory roles of circular RNA circJUN, and its functional interaction with microRNA miR-3064 in GBM pathogenesis. We employed bioinformatic analyses and clinical sample validation to identify circJUN as a potential target in GBM.

Multiomics and machine learning-based analysis of pancancer pseudouridine modifications.

Pseudouridine widely affects the stability and function of RNA. However, our knowledge of pseudouridine properties in tumors is incomplete. We systematically analyzed pseudouridine synthases (PUSs) expression, genomic aberrations, and prognostic features in 10907 samples from 33 tumors.

Bioinformatics Identification and Experimental Validation of a Prognostic Model for the Survival of Lung Squamous Cell Carcinoma Patients.

Lung squamous cell carcinoma (LUSC) kills more than four million people yearly. Creating more trustworthy tumor molecular markers for LUSC early detection, diagnosis, prognosis, and customized treatment is essential. Cuproptosis, a novel form of cell death, opened up a new field of study for searching for trustworthy tumor indicators.

MiR-1976/NCAPH/P65 axis inhibits the malignant phenotypes of lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is a malignancy with an abysmal survival rate. High metastasis is the leading cause of the low survival rate of LUAD. NCAPH, an oncogene, is involved in the carcinogenesis of LUAD.

Structural Basis of Conformational Dynamics in the PROTAC-Induced Protein Degradation.

Pronounced conformational dynamics is unveiled upon analyzing multiple crystal structures of the same proteins recruited to the same E3 ligases by PROTACs, and yet, is largely permissive for targeted protein degradation due to the intrinsic mobility of E3 assemblies creating a large ubiquitylation zone. Mathematical modelling of ternary dynamics on ubiquitylation probability confirms the experimental finding that ternary complex rigidification need not correlate with enhanced protein degradation. Salt bridges are found to prevail in the PROTAC-induced ternary complexes, and may contribute to a positive cooperativity and prolonged half-life.

The Science and Art of Structure-Based Virtual Screening.

Structure-based virtual screening has gained momentum again as the high attrition rate at every stage of drug discovery drives the need to explore a greater chemical space. From the Bayesian perspective, its shortcomings as a viable strategy for sustainable hit discovery are discussed, with regard to the prior hit rates of screening libraries and the performance of computational methods. Lessons are shared in selecting virtual hits for experimental validation learned from a series of eight successful campaigns, one of which impacted the discovery of a drug candidate currently in clinical trials.

Integration of Single-Cell and Bulk RNA-seq Data to Identify the Cancer-Associated Fibroblast Subtypes and Risk Model in Glioma.

Cancer-associated fibroblasts (CAFs) are an important component of the stroma. Studies showed that CAFs were pivotally in glioma progression which have long been considered a promising therapeutic target. Therefore, the identification of prognostic CAF markers might facilitate the development of novel diagnostic and therapeutic approaches.

Characterization of road-deposited sediment wash-off and accurate splitting of initial runoff pollution in heterogeneous urban spaces.

Particulate materials arising from road-deposited sediments (RDS) are an essential target for the control and management of surface runoff pollution. However, the heterogeneity of urban spaces hinders the identification and quantification of particulate pollution, which is challenging when formulating precise control measures. To elucidate the factors that drive particulate pollution in heterogeneous urban spaces, the accumulation of RDS on dry days and the total suspended solids during six natural rainfall events were investigated across three urban-rural spatial units (central urban, central suburban, and remote suburban).

Kinetic Modeling of PROTAC-Induced Protein Degradation.

Kinetics of the PROTAC-induced protein degradation were modelled using the equilibrium approximation, accounting for the protein recovery rate with a time lag. The simulated kinetic curves resemble what is experimentally observed, and the physical formulas of the half-maximal degradation concentration (DC ) were derived from them. The equations reveal that DC is proportional to the dissociation constant of the ternary complex (K ) and inversely proportional to the expression level of the E3 ligase and the effective ubiquitylation rate (k ).