Expanding the Repertoire of Large Scaffolds with and Macrocyclic Metacyclophanes.

Understanding how changes in structure translate to changes in molecular shape is key to catalyst optimization and molecular design in medicinal chemistry and materials. One key contributor to the molecular shape is the relative orientation of substituents on a scaffold. Macrocyclic metacyclophanes display their two arenes in a parallel or antiparallel fashion, resulting in or conformations that lead to disparate relative orientations of the aryl substituents.

Intrinsic capacity transitions predict overall and cause-specific mortality, incident disability, and healthcare utilization.

Objectives: To develop an intrinsic capacity (IC) score and to investigate the association between IC transition with overall and cause-specific mortality, incident disability and healthcare utilization.

Design: Retrospective cohort study SETTING AND PARTICIPANTS: Data from 1852 respondents aged ≥ 65 years who completed the 1999 and 2003 surveys of the Taiwan Longitudinal Study on Aging were analyzed.

Measurements: Transitions of IC score were categorized into three groups: (1) Improved IC (IC >0), (2) Stable IC (IC = 0), (3) Worsened IC (IC <0).

Lysosomal TFEB-TRPML1 Axis in Astrocytes Modulates Depressive-like Behaviors.

Lysosomes are important cellular structures for human health as centers for recycling, signaling, metabolism and stress adaptation. However, the potential role of lysosomes in stress-related emotions has long been overlooked. Here, it is found that lysosomal morphology in astrocytes is altered in the medial prefrontal cortex (mPFC) of susceptible mice after chronic social defeat stress.

Development Trend in Composition Optimization, Microstructure Manipulation, and Strengthening Methods of Die Steels under Lightweight and Integrated Die Casting.

In the general environment of lightweight automobiles, the integrated die-casting technology proposed by Tesla has become the general mode to better achieve weight reduction in automobiles. The die-casting mold required by integrated die-casting technology has the characteristics of large scale and complexity. Hence, higher requirements are put forward for the comprehensive performance of the die steel.

Multi-integrated approach for unraveling small open reading frames potentially associated with secondary metabolism in .

Due to their small size and special chemical features, small open reading frame (smORF)-encoding peptides (SEPs) are often neglected. However, they may play critical roles in regulating gene expression, enzyme activity, and metabolite production. Studies on bacterial microproteins have mainly focused on pathogenic bacteria, which are importance to systematically investigate SEPs in streptomycetes and are rich sources of bioactive secondary metabolites.

Skeletal Editing of Dibenzolactones to Fluorenes via Ni- or Pd-Catalyzed Decarboxylation.

The skeletal editing of dibenzolactones to fluorenes by Ni- or Pd-catalyzed decarboxylation is reported. In contrast to previously reported intramolecular decarboxylative couplings, inductively electron-withdrawing substituents on the aryl carboxylate moiety and metal additives are not required. The decarboxylation reaction proceeds cleanly and can be applied to the skeletal editing of a natural product analogue.

Astrocyte dysfunction drives abnormal resting-state functional connectivity in depression.

Major depressive disorder (MDD) is a devastating mental disorder that affects up to 17% of the population worldwide. Although brain-wide network-level abnormalities in MDD patients via resting-state functional magnetic resonance imaging (rsfMRI) exist, the mechanisms underlying these network changes are unknown, despite their immense potential for depression diagnosis and management. Here, we show that the astrocytic calcium-deficient mice, inositol 1,4,5-trisphosphate-type-2 receptor knockout mice ( mice), display abnormal rsfMRI functional connectivity (rsFC) in depression-related networks, especially decreased rsFC in medial prefrontal cortex (mPFC)-related pathways.

Transitions in Frailty and 4-Year Mortality Risk in Taiwan Longitudinal Study on Aging.

Objectives: To explore the associations of (1) the frailty phenotype or frailty index transition with cause-specific mortality, and (2) different combinations of transition in frailty phenotype and frailty index with all-cause mortality.

Design: Retrospective cohort study.

Setting And Participants: Data from 3529 respondents aged >50 years who completed the 1999 and 2003 surveys of the Taiwan Longitudinal Study on Aging were analyzed.

Immunoglobulin Y Specific for SARS-CoV-2 Spike Protein Subunits Effectively Neutralizes SARS-CoV-2 Infectivity and Ameliorates Disease Manifestations In Vivo.

(Background) The coronavirus disease 2019 (COVID-19) that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) carries high infectivity and mortality. Efficient intervention strategies are urgently needed. Avian immunoglobulin Y (IgY) showed efficacy against viral infection whereas the in vivo efficacy remains unclear.

Effects of the Short-Foot Exercise on Foot Alignment and Muscle Hypertrophy in Flatfoot Individuals: A Meta-Analysis.

This study aimed to conduct a meta-analysis of randomized controlled trials to examine the effects of the short-foot exercise (SFE) compared to foot orthosis or other types of interventions. Eligibility criteria involved participants with flatfoot engaging in the SFE compared to other forms of intervention or control groups without specific intervention. Relevant studies published before the end of June 2022 were identified from databases.

Targeting CD38 to Suppress Osteoarthritis Development and Associated Pain After Joint Injury in Mice.

Objective: This study was undertaken to determine the role of CD38, which can function as an enzyme to degrade NAD , in osteoarthritis (OA) development.

Methods: Human knee cartilage from normal donors and OA donors were examined for CD38 expression. "Gain-of-function," through overexpression of CD38 via transient transfection, and "loss-of-function," through pharmacologic inhibition of CD38, approaches were used to assess the effects of CD38 on intracellular NAD :NADH ratio and catabolic activity in chondrocytes.

A booster dose of Delta × Omicron hybrid mRNA vaccine produced broadly neutralizing antibody against Omicron and other SARS-CoV-2 variants.

Background: With the continuous emergence of new SARS-CoV-2 variants that feature increased transmission and immune escape, there is an urgent demand for a better vaccine design that will provide broader neutralizing efficacy.

Methods: We report an mRNA-based vaccine using an engineered "hybrid" receptor binding domain (RBD) that contains all 16 point-mutations shown in the currently prevailing Omicron and Delta variants.

Results: A booster dose of hybrid vaccine in mice previously immunized with wild-type RBD vaccine induced high titers of broadly neutralizing antibodies against all tested SARS-CoV-2 variants of concern (VOCs).

In Vivo Validation of Diffuse Optical Imaging with a Dual-Direction Measuring Module of Parallel-Plate Architecture for Breast Tumor Detection.

We demonstrate a working prototype of an optical breast imaging system involving parallel-plate architecture and a dual-direction scanning scheme designed in combination with a mammography machine; this system was validated in a pilot study to demonstrate its application in imaging healthy and malignant breasts in a clinical environment. The components and modules of the self-developed imaging system are demonstrated and explained, including its measuring architecture, scanning mechanism, and system calibration, and the reconstruction algorithm is presented. Additionally, the evaluation of feature indices that succinctly demonstrate the corresponding transmission measurements may provide insight into the existence of malignant tissue.

Glucocorticoid Receptor-Dependent Astrocytes Mediate Stress Vulnerability.

Background: Major depressive disorder is a devastating psychiatric illness that affects approximately 17% of the population worldwide. Astrocyte dysfunction has been implicated in its pathophysiology. Traumatic experiences and stress contribute to the onset of major depressive disorder, but how astrocytes respond to stress is poorly understood.

Predicting neuropsychiatric symptoms of persons with dementia in a day care center using a facial expression recognition system.

Background: Behavioral and psychological symptoms of dementia (BPSD) affect 90% of persons with dementia (PwD), resulting in various adverse outcomes and aggravating care burdens among their caretakers. This study aimed to explore the potential of artificial intelligence-based facial expression recognition systems (FERS) in predicting BPSDs among PwD.

Methods: A hybrid of human labeling and a preconstructed deep learning model was used to differentiate basic facial expressions of individuals to predict the results of Neuropsychiatric Inventory (NPI) assessments by stepwise linear regression (LR), random forest (RF) with importance ranking, and ensemble method (EM) of equal importance, while the accuracy was determined by mean absolute error (MAE) and root-mean-square error (RMSE) methods.

Longitudinal changes of frailty in 8 years: comparisons between physical frailty and frailty index.

Background: Few studies have made longitudinal comparisons between frailty phenotype (FP) and frailty index (FI) changes. We aimed to investigate frailty status changes defined by FP and FI concurrently, and to compare the associated factors and incident disability among different combination of FI and FP trajectory groups.

Methods: Data on respondents aged over 50 who completed the 1999, 2003 and 2007 Taiwan Longitudinal Study on Aging (TLSA) surveys (n = 2807) were excerpted.

Toward instantaneous frequency of respiration to investigate the risk of internet gaming disorder.

With the development of Internet, the number of people with symptoms of Internet gaming disorder (IGD) has increased. In the past, psychologists used retrospective questionnaires to diagnose IGD. However, it is difficult to diagnose IGD symptoms instantaneously using retrospective questionnaires due to the requirement of an Internet gaming experience of greater than 6 months and the limitations of retrospective memory.

Influence of Chymosin on Physicochemical and Hydrolysis Characteristics of Casein Micelles and Individual Caseins.

The effects of chymosin on the physicochemical and hydrolysis characteristics of casein micelles and individual caseins were investigated. Adding 0.03 units of chymosin/mL led to the casein micelles in skim milk coagulating after a 3 h incubation period at 30 °C.