Increasing The Odds Of Hit Iidentification By Screening Against Receptor Homologs

Increasing the odds of hit identification in screening is of significance for drug discovery. The odds for finding a hit are closely related either to the diversity of libraries or to the availability of focused libraries. There are no truly diverse libraries and it is difficult to design focused libraries without sufficient information. Hence it is helpful to consider alternative approaches that can enhance the odds using existing libraries. Multiple members of a protein family have been considered collectively in inhibitor design, on the basis of the correlation between protein families and ligands derived from specific compound classes. Such a correlation has been exploited in various drug discovery studies and a general receptor-homolog-based screening scheme may be devised. The feasibility of such a scheme in enhancing the odds of hit identification is discussed.Singapore-MIT Alliance (SMA

The combined therapeutic effects of \u3csup\u3e131\u3c/sup\u3eiodine-labeled multifunctional copper sulfide-loaded microspheres in treating breast cancer

Compared to conventional cancer treatment, combination therapy based on well-designed nanoscale platforms may offer an opportunity to eliminate tumors and reduce recurrence and metastasis. In this study, we prepared multifunctional microspheres loading 131I-labeled hollow copper sulfide nanoparticles and paclitaxel (131I-HCuSNPs-MS-PTX) for imaging and therapeutics of W256/B breast tumors in rats. 18F-fluordeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) imaging detected that the expansion of the tumor volume was delayed (P\u3c0.05) following intra-tumoral (i.t.) injection with 131I-HCuSNPs-MS-PTX plus near-infrared (NIR) irradiation. The immunohistochemical analysis further confirmed the anti-tumor effect. The single photon emission computed tomography (SPECT)/photoacoustic imaging mediated by 131I-HCuSNPs-MS-PTX demonstrated that microspheres were mainly distributed in the tumors with a relatively low distribution in other organs. Our results revealed that 131I-HCuSNPs-MS-PTX offered combined photothermal, chemo- and radio-therapies, eliminating tumors at a relatively low dose, as well as allowing SPECT/CT and photoacoustic imaging monitoring of distribution of the injected agents non-invasively. The copper sulfide-loaded microspheres, 131I-HCuSNPs-MS-PTX, can serve as a versatile theranostic agent in an orthotopic breast cancer model

Unraveling the link between hypertension and depression in older adults: a meta-analysis

ObjectiveTo perform a meta-analyses to understand the current status of and risk factors for depression in older adults with hypertension.MethodsEight electronic databases and two clinical trial registries were searched to identify studies examining the incidence of and risk factors for depression among older adults with hypertension. The databases were searched from inception to June 2023. The included studies were evaluated using the Newcastle–Ottawa scale and the evaluation tool recommended by the Agency for Health care Research and Quality.ResultsA total of 18 studies with 29,694 patients were included. Meta-analysis results showed that the prevalence of depression in older adults with hypertension was 29%. The risk factors for depression among this population included sex [OR value 95% confidence interval 2.24 (1.32, 3.82)], education level [OR 95% CI 1.79 (1.02, 3.14)], residence [OR 95% CI 1.37 (1.24, 1.52)], comorbidities [OR 95% CI 1.79 (1.69, 1.90)], hypertension classification [OR 95% CI 2.81 (1.79, 4.42)], marital status [OR 95% CI 1.50 (1.33, 1.69)], sleep status [OR 95% CI 2.86 (2.21, 3.69)], activity limitation [OR 95% CI 3.42 (2.84, 4.13)], drinking [OR 95% CI 2.25 (1.58, 3.19)], social support [OR 95% CI 3.26 (2.42, 4.41)], living alone [OR 95% CI 1.79 (1.57, 2.04)], stressful events [OR 95% CI 1.62 (1.39, 1.90)], and course of diseases [OR 95% CI 3.23 (2.10, 4.97)].ConclusionThe incidence of depression in older adults with hypertension is high, and there are many risk factors. Clinical health care professionals should intervene early to target the above risk factors to reduce the incidence of depression in older adults with hypertension worldwide.Systematic review registrationPROSPERO (york.ac.uk), identifier [CRD42023417106]

Neuronal Deletion of Caspase 8 Protects against Brain Injury in Mouse Models of Controlled Cortical Impact and Kainic Acid-Induced Excitotoxicity

system. mice demonstrated superior survival, reduced seizure severity, less apoptosis, and reduced caspase 3 processing. Uninjured aged knockout mice showed improved learning and memory, implicating a possible role for caspase 8 in cognitive decline with aging.Neuron-specific deletion of caspase 8 reduces brain damage and improves post-traumatic functional outcomes, suggesting an important role for this caspase in pathophysiology of acute brain trauma

Computational Method for Drug Target Search and Application in Drug Discovery

Ligand-protein inverse docking has recently been introduced as a computer method for identification of potential protein targets of a drug. A protein structure database is searched to find proteins to which a drug can bind or weakly bind. Examples of potential applications of this method in facilitating drug discovery include: (1) identification of unknown and secondary therapeutic targets of a drug, (2) prediction of potential toxicity and side effect of an investigative drug, and (3) probing molecular mechanism of bioactive herbal compounds such as those extracted from plants used in traditional medicines. This method and recent results on its applications in solving various drug discovery problems are reviewed.Singapore-MIT Alliance (SMA

PoseVocab: Learning Joint-structured Pose Embeddings for Human Avatar Modeling

Creating pose-driven human avatars is about modeling the mapping from the low-frequency driving pose to high-frequency dynamic human appearances, so an effective pose encoding method that can encode high-fidelity human details is essential to human avatar modeling. To this end, we present PoseVocab, a novel pose encoding method that encourages the network to discover the optimal pose embeddings for learning the dynamic human appearance. Given multi-view RGB videos of a character, PoseVocab constructs key poses and latent embeddings based on the training poses. To achieve pose generalization and temporal consistency, we sample key rotations in $so(3)$ of each joint rather than the global pose vectors, and assign a pose embedding to each sampled key rotation. These joint-structured pose embeddings not only encode the dynamic appearances under different key poses, but also factorize the global pose embedding into joint-structured ones to better learn the appearance variation related to the motion of each joint. To improve the representation ability of the pose embedding while maintaining memory efficiency, we introduce feature lines, a compact yet effective 3D representation, to model more fine-grained details of human appearances. Furthermore, given a query pose and a spatial position, a hierarchical query strategy is introduced to interpolate pose embeddings and acquire the conditional pose feature for dynamic human synthesis. Overall, PoseVocab effectively encodes the dynamic details of human appearance and enables realistic and generalized animation under novel poses. Experiments show that our method outperforms other state-of-the-art baselines both qualitatively and quantitatively in terms of synthesis quality. Code is available at https://github.com/lizhe00/PoseVocab.Comment: Accepted by SIGGRAPH 2023 (Conference Track), Projectpage: https://lizhe00.github.io/projects/posevocab, Code: https://github.com/lizhe00/posevoca