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Background: Numerous studies have demonstrated that brain metastases patients may benefit from intracranial radiotherapy combined with immune checkpoint inhibitors (ICIs). However, it is unclear whether this treatment is effective for patients with small cell lung cancer brain metastases (SCLC‐BMs). Methods: We conducted a retrospective study by analyzing medical records of patients with SCLC‐BMs from January 1, 2017 to June 1, 2022. Data related to median overall survival (mOS), median progression‐free survival (mPFS), and intracranial progression‐free survival (iPFS) were analyzed. Results: A total of 109 patients were enrolled, of which 60 received WBRT and 49 received WBRT‐ICI. Compared to the WBRT alone cohort, the WBRT‐ICI cohort showed longer mOS (20.4 months vs. 29.3 months, p = 0.021), mPFS (7.9 months vs. 15.1 months, p < 0.001), and iPFS (8.3 months vs. 16.5 months, p < 0.001). Furthermore, WBRT‐ICI cohort had a better response rate for both BMs. (p = 0.035) and extracranial diseases (p < 0.001) compared to those receiving WBRT alone. Notably, the use of WBRT before ICI was associated with longer mOS compared to the use of WBRT after ICI (23.3 months for the ICI‐WBRT group vs. 34.8 months for the WBRT‐ICI group, p = 0.020). Conclusion: Our results indicated that WBRT combined with immunotherapy improved survival in SCLC‐BMs patients compared to WBRT monotherapy. Administering WBRT prior to ICI treatment is associated with improved survival outcomes compared to WBRT following ICI treatment, for patients with SCLC‐BMs. These findings highlight the significance of conducting further prospective researches on combination strategies of intracranial radiotherapy and ICI in SCLC‐BMs patients. [ABSTRACT FROM AUTHOR]

Background: Evaluation of vestibular graviceptive pathway (VGP) in patients with unilateral peripheral vestibular dysfunction (UPVD) has received increasing attention from researchers. The study aimed to investigate the value of VGP evaluation in the diagnosis of UPVD. Methods: Ninety‐five UPVD patients were divided into attack and remission phase groups. VGP evaluation‐related indicators, including subjective visual vertical (SVV), subjective visual horizontal (SVH), head tilt, ocular torsion (OT), and skew deviation (SD), were measured, and their correlations with cochleovestibular function test results were analyzed. The possible etiologies of contralesional VGP (c‐VGP) were analyzed. Results: Positive rates of SVV, SVH, OT, and SD were significantly higher, and the degrees of SVV, SVH, and OT were significantly greater in the attack phase group than the remission phase group. The sides with abnormal VGP evaluation results were correlated with the sides with hearing loss, abnormal caloric, and video head impulse test (vHIT) results. A total of 14 patients showed c‐VGP, and possible etiologies included contralateral benign paroxysmal positional vertigo (n = 4), bilateral hearing loss (n = 8), bilateral vHIT gain reduction (n = 1), autoimmune diseases (n = 6), vascular risk factors (n = 6), lacunar infarction (n = 3), and endolymphatic hydrops (n = 3). Conclusions: Alterations in SVV, SVH, OT, and SD were noted in UPVD patients in different phases, which are presumed to be related to dynamic vestibular compensation; correlations between VGP evaluation results and cochleovestibular function test results indicate that VGP evaluation may be helpful for the diagnosis of the side affected in UPVD; the presence of c‐VGP may be related to bilateral labyrinth lesions or endolymphatic hydrops on the affected side; and the involvement of autoimmune mechanisms also deserves attention. [ABSTRACT FROM AUTHOR]

Summary: Wheat fixes CO2 by photosynthesis into kernels to nourish humankind. Improving the photosynthesis rate is a major driving force in assimilating atmospheric CO2 and guaranteeing food supply for human beings. Strategies for achieving the above goal need to be improved. Here, we report the cloning and mechanism of CO2ASSIMILATION RATE AND KERNEL‐ENHANCED 1 (CAKE1) from durum wheat (Triticum turgidum L. var. durum). The cake1 mutant displayed a lower photosynthesis rate with smaller grains. Genetic studies identified CAKE1 as HSP90.2‐B, encoding cytosolic molecular chaperone folding nascent preproteins. The disturbance of HSP90.2 decreased leaf photosynthesis rate, kernel weight (KW) and yield. Nevertheless, HSP90.2 over‐expression increased KW. HSP90.2 recruited and was essential for the chloroplast localization of nuclear‐encoded photosynthesis units, for example PsbO. Actin microfilaments docked on the chloroplast surface interacted with HSP90.2 as a subcellular track towards chloroplasts. A natural variation in the hexaploid wheat HSP90.2‐B promoter increased its transcription activity, enhanced photosynthesis rate and improved KW and yield. Our study illustrated an HSP90.2–Actin complex sorting client preproteins towards chloroplasts to promote CO2 assimilation and crop production. The beneficial haplotype of Hsp90.2 is rare in modern varieties and could be an excellent molecular switch promoting photosynthesis rate to increase yield in future elite wheat varieties. [ABSTRACT FROM AUTHOR]

Objectives: Oogonial stem cells (OSCs) are germ cells that can sustain neo‐oogenesis to replenish the pool of primary follicles in adult ovaries. In lower vertebrates, fresh oocytes are produced by numerous OSCs through mitosis and meiosis during each reproduction cycle, but the OSCs in adult mammals are rare. The birds have retained many conserved features and developed unique features of ovarian physiology during evolution, and the presence of OSCs within avian species remain unknown. Materials and Methods: In this study, we investigated the existence and function of OSCs in adult chickens. The chicken OSCs were isolated and expanded in culture. We then used cell transplantation system to evaluate their potential for migration and differentiation in vivo. Results: DDX4/SSEA1‐positive OSCs were identified in both the cortex and medulla of the adult chicken ovary. These putative OSCs undergo meiosis in the reproductively active ovary. Furthermore, the isolated OSCs were expanded in vitro for months and found to express germline markers similar to those of primordial germ cells. When transplanted into the bloodstream of recipient embryos, these OSCs efficiently migrated into developing gonads, initiated meiosis, and then derived oocytes in postnatal ovaries. Conclusions: This study has confirmed the presence of functional OSCs in birds for the first time. The identification of chicken OSCs has great potential for improving egg laying and preserving endangered species. [ABSTRACT FROM AUTHOR]

A differentiation switch of bone marrow mesenchymal stem/stromal cells (BMSCs) from osteoblasts to adipocytes contributes to age‐ and menopause‐associated bone loss and marrow adiposity. Here it is found that osteocytes, the most abundant bone cells, promote adipogenesis and inhibit osteogenesis of BMSCs by secreting neuropeptide Y (NPY), whose expression increases with aging and osteoporosis. Deletion of NPY in osteocytes generates a high bone mass phenotype, and attenuates aging‐ and ovariectomy (OVX)‐induced bone‐fat imbalance in mice. Osteocyte NPY production is under the control of autonomic nervous system (ANS) and osteocyte NPY deletion blocks the ANS‐induced regulation of BMSC fate and bone‐fat balance. γ‐Oryzanol, a clinically used ANS regulator, significantly increases bone formation and reverses aging‐ and OVX‐induced osteocyte NPY overproduction and marrow adiposity in control mice, but not in mice lacking osteocyte NPY. The study suggests a new mode of neuronal control of bone metabolism through the ANS‐induced regulation of osteocyte NPY. [ABSTRACT FROM AUTHOR]

Sepsis and sepsis-induced skeletal muscle atrophy are common in patients in intensive care units with high mortality, while the mechanisms are controversial and complicated. In the present study, the atrophy of skeletal muscle was evaluated in sepsis mouse model as well as the apoptosis of muscle fibres. Sepsis induced atrophy of skeletal muscle and apoptosis of myofibres in vivo and in vitro. In cell-based in vitro experiments, lipopolysaccharide (LPS) stimulation also inhibited the proliferation of myoblasts. At the molecular level, the expression of polo-like kinase 1 (PLK1) and phosphorylated protein kinase B (p-AKT) was decreased. Overexpression of PLK1 partly rescued LPS-induced apoptosis, proliferation suppression and atrophy in C2C12 cells. Furthermore, inhibiting the AKT pathway deteriorated LPS-induced atrophy in PLK1-overexpressing C2C12 myotubes. PLK1 was found to participate in regulating apoptosis and E3 ubiquitin ligase activity in C2C12 cells. Taken together, these results indicate that sepsis induces skeletal muscle atrophy by promoting apoptosis of muscle fibres and inhibiting proliferation of myoblasts via regulation of the PLK1-AKT pathway. These findings enhance understanding of the mechanism of sepsis-induced skeletal muscle atrophy. [ABSTRACT FROM AUTHOR]