Retinoschisin Is Required for Pineal Gland Calcification and Cellular Communication in Pinealocytes of Rats and Mice.

Retinoschisin (RS1) is a secretory protein specifically localized to the extracellular domains in both the lateral retina and the pineal gland (PG). However, the functions of RS1 in the pineal body are poorly understood. To address this knowledge gap, in this study, we undertook histochemical, ultrastructural, and Western blotting analyses of the PG in rats and RS1-knock-in transgenic. We found that RS1 plays a key role in pineal gland calcification (PGC) in mice through both extracellular and intracellular pathways. RS1 was clustered around the cell membrane or intracellularly in pinealocytes, actively participating in the exchange of calcium and thereby mediating PGC. Additionally, RS1 deposition is essential for maintaining PGC architecture in the intercellular space of the adult PG. In RS1-knock-in mice with a nonsense mutation (p.Y65X) in the Rs1-domain of RS1, the Rs1-domain is chaotically dispersed in pinealocytes and the intercellular region of the PG. This prevents RS1 from binding calcified spots and forming calcified nodules, ultimately leading to the accumulation of calcareous lamellae in microvesicles. Additionally, RS1 was observed to colocalize with connexin-36, thereby modulating intercellular communication in the PG of both rats and mice. Our study revealed for the first time that RS1 is essential for maintaining PGC architecture and that it colocalizes with connexin 36 to modulate intercellular communication in the PG. These findings provide novel insights into the function of the RS1 gene in the PG.

Structure-Based Optimization of One Neutralizing Antibody against SARS-CoV-2 Variants Bearing the L452R Mutation.

Neutralizing antibodies (nAbs) play an important role against SARS-CoV-2 infections. Previously, we have reported one potent receptor binding domain (RBD)-binding nAb Ab08 against the SARS-CoV-2 prototype and a panel of variants, but Ab08 showed much less efficacy against the variants harboring the L452R mutation. To overcome the antibody escape caused by the L452R mutation, we generated several structure-based Ab08 derivatives. One derivative, Ab08-K99E, displayed the mostly enhanced neutralizing potency against the Delta pseudovirus bearing the L452R mutation compared to the Ab08 and other derivatives. Ab08-K99E also showed improved neutralizing effects against the prototype, Omicron BA.1, and Omicron BA.4/5 pseudoviruses. In addition, compared to the original Ab08, Ab08-K99E exhibited high binding properties and affinities to the RBDs of the prototype, Delta, and Omicron BA.4/5 variants. Altogether, our findings report an optimized nAb, Ab08-K99E, against SARS-CoV-2 variants and demonstrate structure-based optimization as an effective way for antibody development against pathogens.

Establishing a nutrition calculation model for catering food according to the influencing factors of energy and nutrient content in food processing.

Objective: This study aimed to establish an accurate and efficient scientific calculation model for the nutritional composition of catering food to estimate energy and nutrient content of catering food. Methods: We constructed a scientific raw material classification database based on the Chinese food composition table by calculating the representative values of each food raw material type. Using China's common cooking methods, we cooked 150 dishes including grains, meat, poultry, fish, eggs, and vegetables and established a database showing the raw and cooked ratios of various food materials by calculating the ratio of raw to cooked and the China Total Diet Research database. The effects of various cooking methods on the nutritional composition of catering food were analyzed to determine correction factors for such methods on the nutritional components. Finally, we linked the raw material classification, raw and cooked ratio, and nutritional component correction factor databases to establish a model for calculating the nutritional components of catering food. The model was verified with nine representative Chinese dishes. Results: We have completed the construction of an accurate and efficient scientific calculation model for the nutritional composition of catering food, which improves the accuracy of nutrition composition calculation. Conclusion: The model constructed in this study was scientific, accurate, and efficient, thereby promising in facilitating the accurate calculation and correct labeling of nutritional components in catering food.

Risk factors and consequences of mental health problems in nurses: A scoping review of cohort studies.

Mental health problems in nurses are prevalent and impairing. To date, no literature has comprehensively synthesised cohort evidence on mental health among nurses. This scoping review aimed to synthesise the existing literature on the risk factors and consequences of mental health problems in nurses. A systematic search was conducted on PubMed, EMBASE, Epistemonikos database, Web of Science, CINAHL, and PsycINFO from inception to March 2023. We identified 171 cohort studies from 16 countries, mostly (95.3%) from high-income economies. This review indicated that nurses worldwide encountered significant mental health challenges, including depression, cognitive impairment, anxiety, trauma/post-traumatic stress disorder, burnout, sleep disorder, and other negative mental health problems. These problems were closely related to various modifiable risk factors such as nurses' behaviours and lifestyles, social support, workplace bullying and violence, shift work, job demands, and job resources. Moreover, nurses' mental health problems have negative effects on their physical health, behaviour and lifestyle, occupation and organisation, and intrapersonal factors. These findings provided an enhanced understanding of mental health complexities among nurses, and shed light on policy enactment to alleviate the negative impact of mental health problems on nurses. Addressing mental health among nurses should be a top priority.

A blueprint for tumor-infiltrating B cells across human cancers.

B lymphocytes are essential mediators of humoral immunity and play multiple roles in human cancer. To decode the functions of tumor-infiltrating B cells, we generated a B cell blueprint encompassing single-cell transcriptome, B cell-receptor repertoire, and chromatin accessibility data across 20 different cancer types (477 samples, 269 patients). B cells harbored extraordinary heterogeneity and comprised 15 subsets, which could be grouped into two independent developmental paths (extrafollicular versus germinal center). Tumor types grouped into the extrafollicular pathway were linked with worse clinical outcomes and resistance to immunotherapy. The dysfunctional extrafollicular program was associated with glutamine-derived metabolites through epigenetic-metabolic cross-talk, which promoted a T cell-driven immunosuppressive program. These data suggest an intratumor B cell balance between extrafollicular and germinal-center responses and suggest that humoral immunity could possibly be harnessed for B cell-targeting immunotherapy.