Understanding the structure of measles virus and its implications for novel drug discovery.

Introduction: Despite having a stably effectively vaccine for decades, the Measles virus (MV) still causes periodic outbreaks given its highly contagious nature and a consistent decline in immunization coverage, which was further exacerbated during the COVID-19 pandemic, leading to reduced immunization rates. Equally concerning, there are also no approved treatments for measles.

Areas Covered: Herein, the authors explore the current challenges of MV therapy discovery.

Thermoresponsive hydrogelation of N-acetyl chitohexaose: Gelation mechanism and application in controlled protein release.

Chitin is a polysaccharide composed of N-acetylglucosamine units that form highly crystalline structures in biological systems; however, the precise mechanism underlying its self-assembly in aqueous environments remains unclear. In this study, we demonstrated that N-acetyl chitohexaose (GN6), a chitin oligosaccharide with a degree of polymerization of six, uniquely undergoes thermally induced self-assembly into crystalline nanofibers and forms reversible hydrogels in water. Among chitin oligosaccharides ranging from monomer to hexamer, only GN6 exhibited gelation upon heating, which is attributed to its optimal molecular length and balanced hydrophilic-hydrophobic characteristics.

Structural basis of the hepatitis B virus X protein in complex with DDB1.

A cure for chronic hepatitis B requires eliminating or permanently silencing covalently closed circular DNA (cccDNA). A pivotal target of this approach is the hepatitis B virus (HBV) X protein (HBx), which is a key factor that promotes transcription from cccDNA. However, the HBx structure remains unsolved.

Effect of wider step-width gait on hip joint contact force.

Hip joint contact force (HJCF) overloading is a primary mechanical cause of hip osteoarthritis. Hip adduction moment (HAM) is a surrogate measure for estimating HJCF. Gait modification, especially wider step-width (SW), can significantly decrease the peaks and impulses of HAM, suggesting a possible strategy for preventing joint overloading.

ARNAX is an ideal adjuvant for COVID-19 vaccines to enhance antigen-specific CD4 and CD8 T-cell responses and neutralizing antibody induction.

Unlabelled: ARNAX is a synthetic nucleotide-based Toll-like receptor 3 (TLR3) ligand that specifically stimulates the TLR3/TIR domain-containing adaptor molecule 1 (TICAM-1) pathway without activating inflammatory responses. ARNAX activates cellular immunity via cross-presentation; hence, its practical application has been demonstrated in cancer immunotherapy. Given the importance of cellular immunity in virus infections, ARNAX is expected to be a more effective vaccine adjuvant for virus infections than alum, an adjuvant approved for human use that mainly enhances humoral immunity.

Structural and virological identification of neutralizing antibody footprint provides insights into therapeutic antibody design against SARS-CoV-2 variants.

Medical treatments using potent neutralizing SARS-CoV-2 antibodies have achieved remarkable improvements in clinical symptoms, changing the situation for the severity of COVID-19 patients. We previously reported an antibody, NT-108 with potent neutralizing activity. However, the structural and functional basis for the neutralizing activity of NT-108 has not yet been understood.

Structural analysis reveals how tetrameric tyrosine-phosphorylated STAT1 is targeted by the rabies virus P-protein.

Signal transducer and activator of transcription (STAT) family members mediate signaling in the Janus kinase (JAK)-STAT pathway and are activated by phosphorylation at a conserved tyrosine residue, resulting in dimerization through reciprocal interactions between the phosphotyrosine and a Src homology 2 (SH2) domain. Tyrosine-phosphorylated STAT (pY-STAT) then translocates to the nucleus to induce the expression of genes encoding antiviral proteins. Although the active and functional forms of STATs are conventionally considered to be dimers, STATs can undergo higher-order oligomerization, which is implicated in regulating transcriptional activity.

The effect of orthosis management on joint instability in knee joint disease: A systematic review.

Introduction: Joint instability is a common finding of clinical importance in patients with knee disease. This literature review aimed to examine the evidence regarding the effect of orthosis management on joint instability in knee joint disease.

Methods: The detailed protocol for this study was published in the International Prospective Register of Systematic Reviews in the field of health and social welfare (CRD 42022335360).

A powered simple walking model explains the decline in propulsive force and hip flexion torque compensation in human gait.

Excessive hip flexion torque to prioritize leg swings in the elderly is likely to be a factor that reduces their propulsive force and gait stability, but the mechanism is not clear. To understand the mechanism, we investigated how propulsive force, hip flexion torque, and margin of stability (MoS) change when only the hip spring stiffness is increased without changing the walking speed in the simple walking model, and verified whether the relationship holds in human walking. The results showed that at walking speeds between 0.

Biomechanical effects of medial meniscus radial tears on the knee joint during gait: A concurrent finite element musculoskeletal framework investigation.

The biomechanical variation in the knee during walking that accompanies medial meniscal radial tears stemming from knee osteoarthritis (OA) has not been explored. This study introduced a finite element musculoskeletal model using concurrent lower limb musculoskeletal dynamics and knee joint finite element analysis in a single framework and expanded the models to include knees with medial meniscal radial tears and total medial meniscectomy. The radial tears involved three locations: anterior horn, midbody, and posterior horn with grades of 33%, 50%, and 83% of the meniscus width.

Structure of the human galanin receptor 2 bound to galanin and Gq reveals the basis of ligand specificity and how binding affects the G-protein interface.

Galanin is a neuropeptide expressed in the central and peripheral nervous systems, where it regulates various processes including neuroendocrine release, cognition, and nerve regeneration. Three G-protein coupled receptors (GPCRs) for galanin have been discovered, which is the focus of efforts to treat diseases including Alzheimer's disease, anxiety, and addiction. To understand the basis of the ligand preferences of the receptors and to assist structure-based drug design, we used cryo-electron microscopy (cryo-EM) to solve the molecular structure of GALR2 bound to galanin and a cognate heterotrimeric G-protein, providing a molecular view of the neuropeptide binding site.

Association between foot posture and tibiofemoral contact forces during barefoot walking in patients with knee osteoarthritis.

Background: Accumulating evidence indicates that abnormal foot posture are risk factors for knee osteoarthritis (OA). However, the relationship between foot posture and tibiofemoral contact force (CF) during habitual weight-bearing activities remains unclear. This study aimed to determine the association between tibiofemoral CF and foot posture while walking.

Effects of flat-flexible shoes on lower limb joint kinetics and kinematics in gait.

Flat-flexible shoes with unique characteristics, such as low pitch and flexibility, can increase the efficiency of ankle energy and running performance. If flat-flexible shoes have the same effect during walking, they could be used for gait training. This study aimed to investigate the effects of flat-flexible shoes on the kinematics and kinetics of the lower limb.

A SARS-CoV-2 antibody broadly neutralizes SARS-related coronaviruses and variants by coordinated recognition of a virus-vulnerable site.

Potent neutralizing SARS-CoV-2 antibodies often target the spike protein receptor-binding site (RBS), but the variability of RBS epitopes hampers broad neutralization of multiple sarbecoviruses and drifted viruses. Here, using humanized mice, we identified an RBS antibody with a germline V gene that potently neutralized SARS-related coronaviruses, including SARS-CoV and SARS-CoV-2 variants. X-ray crystallography revealed coordinated recognition by the heavy chain of non-RBS conserved sites and the light chain of RBS with a binding angle mimicking the angiotensin-converting enzyme 2 (ACE2) receptor.

The effects of trunk endurance training on running kinematics and its variability in novice female runners.

The functional importance of trunk muscle strength for running movement is widely recognised, but the kinematic effects of undertaking specific training are unclear. This study investigated the change in joint angle and its variability during running following trunk muscle training. Eighteen young female and novice runners participated.

Structure, solubility, and permeability relationships in a diverse middle molecule library.

To develop methodology to predict the potential druggability of middle molecules, we examined the structure, solubility, and permeability relationships of a diverse library (HKDL ver.1) consisting of 510 molecules (359 natural product derivatives, 76 non-natural products, 46 natural products, and 29 non-natural product derivatives). The library included peptides, depsipeptides, macrolides, and lignans, and 476 of the 510 compounds had a molecular weight in the range of 500-2000 Da.