NCT remodeled the infiltrating level of CD4+TIL and CD8+TIL in individuals, which is important for antitumor immunity and associated with the prognosis of NCT-NSCLC. The ypTNM stage, post-chemotherapy TIL, and CD4+TIL ascend post-chemotherapy is independent prognostic factors of NCT-NSCLC. This study indicated that TIME remodeled by chemotherapy has a better prognostic value than the naïve TIME.

Tumor-associated macrophage-derived exosomes were significantly rich in integrin (ITG) αV and β3. Exosomes derived from tumor-associated macrophages are taken up by tumor cells and activate the FAK signaling pathway to enhance the migration and invasion ability of tumor cells.

The high-resolution structure of GPR21-Gαs complexes was resolved. GPR21 ECL2 exhibited highly stable conformation and is inserted deeply into the orthosteric ligand-binding pocket of GPR21. The immersed region of ECL2 was constrained in position via an intra-loop salt bridge (K170^ECL2 and D176^ECL2). The new structure data reveal a novel signaling cascade of GPR21 mediated by ECL2.

• Cas13d-crRNAs inhibit both ancestral and mutated SARS-CoV-2 replication.
• Cas13d-crRNAs inhibit both ancestral and mutated SARS-CoV-2 replication including Delta.
• Cas13d-crRNAs could inhibit Omicron and other SARS family strains and are a potential pan-SARS inhibition strategy.

SOX2-positive retinal stem cells (RSCs) are identified in adult human pars plicata. Using the specific surface markers aquaporin 1 and tetraspanin 12, the RSCs were isolated and proved to have proliferation and differentiation abilities.

Schematic diagram of signaling pathways mediating PAX7 expression induced by CRY2 deletion. CRY2 deletion led to the activation of JNK1/2 and ERK1/2 signaling pathways, activating ETS1 to promote the transcription of PAX7 and the activation of satellite cells.

• Tissue concentrations were much higher than plasma concentration.
• Inhalation administration could enhance tetrandrine exposure in lungs.
• Unbound tetrandrine in human lungs may achieve unbound EC₉₀ according to human pharmacokinetics in literature and K_p,lung.

Cancer is a complex disease associated with a combination of abnormal physiological processes affecting multiple systems. The single nanocarriers are not satisfy complex cancer diseases. However, multifunctional nanoparticles are upgraded versions of the original function and involve a sophisticated system with a proper backbone. Here, the construction strategies and application advances of multifunctional nanoparticles are systemically summarized.

Accurate DNA replication is modulated by multiple replication-associated proteins, which is fundamental to preserve genome stability. Abundant replication proteins are involved in tumorigenesis and development, implying these proteins act as therapeutic targets in clinical. Replication-target cancer therapy emerges as the times require. Furthermore, the novel posttranslational modification of replication proteins in response to replication stress, which seems to be a promising strategy to eliminate diseases.

Design and discovery pipeline of 3D bioprinting technology for biomedical applications.

After administration, NSC-EVs can be internalized by various brain cells and vascular endothelial cells to exert their therapeutic effects. After being internalized by different types of brain cells, NSC-EVs promote the regenerative potential of endogenous NSCs, inhibit the excessive activation and neurotrophin production of astrocytes, rescue neuronal and synaptic damage from oxidative stress, promote remyelination capacity of oligodendrocytes, modulate inflammatory responses of resident microglia, and stimulate endothelial cell vascular regeneration, therefore ameliorating neurological disorders and accelerating post-disease recovery.

The human aldehyde dehydrogenase (ALDH) superfamily comprises 19 isozymes and can be divided into 11 distinct families. ALDHs are a group of nicotinamide adenine dinucleotide phosphate (NADP+)-dependent enzymes that could catalyze the reversible oxidation of endogenous and exogenous aldehydes to their corresponding carboxylic acids. However, ALDHs are frequently dysregulated and associated with various diseases like Alzheimer's disease, Parkinson's disease, and especially solid tumors. Different ALDH isoenzymes are believed to be potential biomarkers or therapeutic targets in different diseases.

Solid tumors gradually form a hypoxic malignant microenvironment during growth, which promotes tumor proliferation and metastasis by affecting metabolism, angiogenesis, and immune escape, and finally leads to therapeutic resistance. In recent years, hypoxia-inducible factor inhibitors, direct targeting of hypoxic cells, and respiratory hyperoxia have been widely used to improve the hypoxic microenvironment of tumors and enhance the sensitivity of tumor therapy.

The research process for analyzing nutrition and cardiometabolic health is shown in a bottom–up manner. Phase 1: identification of essential nutrients and healthy foods, such as vegetables and fruits, whole grains, and plant-based oils (tier 4). Phase 2: establishment and development of different types of dietary patterns, such as vegetarian diets, Mediterranean diets, ketogenic diets, calorie restriction, and intermittent fasting (tier 3). Phase 3: exploration of the molecular mechanisms of dietary interventions, including nutrient response pathways, immune regulation, the role of gut microbiota and metabolites, and circadian rhythms (tier 2). Phase 4: providing personalized dietary strategies to cardiometabolic disease patients based on diet–genetic interactions (tier 1).

Vascular calcification is caused by the imbalance of vascular microenvironment. The pro-calcific factors include chronic inflammation, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, iron homeostasis, programed cell death, and other cellular metabolic dynamics. However, the pharmacological and nutritional modulations, such as CCBs, ACEI/ARB, and vitamins, may provide potential therapeutic strategies on vascular calcification.

The number of dermal mDCs (CD11c⁺ cells) was increased with itch intensity (r = 0.886, p = 0.003) using immunofluorescence (IF). On IF, CD11c⁺ mDCs expressed IL-31 in lesional PN skin. Fluorescence in situ hybridization combined with IF also confirmed IL-31 mRNA expression by mDCs in PN lesion. Higher population of colocalization of CD11c⁺ mDCs expressing IL-31 mRNA were more than CD68⁺ macrophages and CD3⁺ T cells in consecutive sections of PN skin lesion. HC, healthy control; PN, prurigo nodularis; SPN, PN with severe pruritus (itch NRS score ≥7 points); MPN, PN with mild pruritus (itch NRS score <3 points); NRS, Numeric Rating Scale; AD, atopic dermatitis; mDC, myeloid dendritic cell.

In this study, we evaluated the effectiveness and safety of bisoprolol, metoprolol, carvedilol, and nebivolol in the treatment of chronic heart failure. The results demonstrated that bisoprolol improved the prognosis of chronic heart failure in comparison with carvedilol, and carvedilol exerted similar effects as metoprolol succinate and nebivolol and better effect than metoprolol tartrate (evidence levels: bisoprolol > carvedilol = metoprolol succinate = nebivolol > metoprolol tartrate; “ > ” means “prior to”).