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Leaf angle is an important agronomic trait and influences crop architecture and yield. Studies have demonstrated the roles of phytohormones, particularly auxin and brassinosteroids, and various factors in controlling leaf inclination. However, the underlying mechanism especially the upstream regulatory networks still need being clarified. Here we report the functional characterization of rice leaf inclination3 (LC3), a SPOC domain-containing transcription suppressor, in regulating leaf inclination through interacting with LIP1 (LC3-interacting protein 1), a HIT zinc finger domain-containing protein. LC3 deficiency results in increased leaf inclination and enhanced expressions of OsIAA12 and OsGH3.2. Being consistent, transgenic plants with OsIAA12 overexpression or deficiency of OsARF17 which interacts with OsIAA12 do present enlarged leaf inclination. LIP1 directly binds to promoter regions of OsIAA12 and OsGH3.2, and interacts with LC3 to synergistically suppress auxin signaling. Our study demonstrate the distinct effects of IAA12-ARF17 interactions in leaf inclination regulation, and provide informative clues to elucidate the functional mechanism of SPOC domain-containing transcription suppressor and fine-controlled network of lamina joint development by LC3-regulated auxin homeostasis and auxin signaling through.

In adult brain, new neurons are generated throughout adulthood in the subventricular zone and the dentate gyrus; this process is commonly known as adult neurogenesis. The regulation or modulation of adult neurogenesis includes various intrinsic pathways (signal transduction pathway and epigenetic or genetic modulation pathways) or extrinsic pathways (metabolic growth factor modulation, vascular, and immune system pathways). Altered neurogenesis has been identified in Alzheimer's disease (AD), in both human AD brains and AD rodent models. The exact mechanism of the dysregulation of adult neurogenesis in AD has not been completely elucidated. However, neuroinflammation has been demonstrated to alter adult neurogenesis. The presence of various inflammatory components, such as immune cells, cytokines, or chemokines, plays a role in regulating the survival, proliferation, and maturation of neural stem cells. Neuroinflammation has also been considered as a hallmark neuropathological feature of AD. In this review, we summarize current, state-of-the art perspectives on adult neurogenesis, neuroinflammation, and the relationship between these two phenomena in AD. Furthermore, we discuss the potential therapeutic approaches, focusing on the anti-inflammatory and proneurogenic interventions that have been reported in this field.

Background Ceftriaxone is a β-lactam antibiotic used to treat central nervous system infections. Whether the neuroprotective effects of ceftriaxone after TBI are mediated by attenuating neuroinflammation but not its antibacterial actions is not well established. Methods Anesthetized male Sprague–Dawley rats were divided into sham-operated, TBI + vehicle, and TBI + ceftriaxone groups. Ceftriaxone was intraperitoneally injected at 0, 24, and 48 h with 50 or 250 mg/kg/day after TBI. During the first 120 min after TBI, we continuously measured heart rate, arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure. The infarct volume was measured by TTC staining. Motor function was measured using the inclined plane. Glutamate transporter 1 (GLT-1), neuronal apoptosis and TNF-α expression in the perilesioned cortex were investigated using an immunofluorescence assay. Bacterial evaluation was performed by Brown and Brenn’s Gram staining. These parameters above were measured at 72 h after TBI. Results Compared with the TBI + vehicle group, the TBI + ceftriaxone 250 mg/kg group showed significantly lower ICP, improved motor dysfunction, reduced body weight loss, decreased infarct volume and neuronal apoptosis, decreased TBI-induced microglial activation and TNF-α expression in microglia, and increased GLT-1 expression in neurons and microglia. However, the grades of histopathological changes of antibacterial effects are zero. Conclusions The intraperitoneal injection of ceftriaxone with 250 mg/kg/day for three days may attenuate TBI by increasing GLT-1 expression and reducing neuroinflammation and neuronal apoptosis, thereby resulting in an improvement in functional outcomes, and this neuroprotective effect is not related to its antibacterial effects.

Background Taiwan introduced PharmaCloud, a system designed to streamline access to comprehensive medication records from various healthcare settings. Despite its potential, the impact of physician-led medication reconciliation (MR) utilizing PharmaCloud on outpatient outcomes remains unclear. This study aims to address this gap by evaluating the effectiveness of PharmaCloud-enabled MR in improving patient outcomes. Methods We collected data from outpatients with major polypharmacy (≥ 10 medications) between May 19, 2019, and April 18, 2020, comparing those who received MR with those who did not. Outcomes including total medical expenditures, ED visits, hospitalizations, mortality rate, and number of medications were compared between the two cohorts over a 12-month follow-up period. Results The study enrolled 209 patients with MR and 9,053 patients without MR. Patients who received MR were older, had lower body mass index, took more medications, and had a higher prevalence of hypertension, cerebrovascular disease, chronic kidney disease, and mental disorder. After 12 months of follow-up, patients who received MR had a higher proportion of reduced medications (adjusted odds ratio: 1.4; 95% confidence interval: 1.0 − 2.0), but also had more ED visits in the first 12 months compared to those who did not receive MR. The study did not find any significant differences in total medical expenditures, hospitalizations, and mortality rates between the two cohorts. Conclusions The model reduced medication use. Further research, including prospective designs, pharmacist involvement, and evaluations of reduced complications from fewer medications, is needed to better clarify patient outcomes.

Background The World Health Organization (WHO) proposed the concept of intrinsic capacity (comprising composite physical and mental capacity) which aligns with their concepts of healthy aging and functional ability. Consequently, the WHO promotes the Integrated Care for Older People (ICOPE) framework as guidance for geriatric care. Consequently, each government should have a screening tool corresponding to ICOPE framework to promote geriatric care. The present study examined the initial psychometric properties of the Taiwan version of ICOPE (i.e., ICOPES-TW). Methods Older people ( n  = 1235; mean age = 72.63 years; 634 females [51.3%]) were approached by well-trained interviewers for participation. A number of measures were administered including the ICOPES-TW, WHOQOL-AGE (assessing quality of life [QoL]), Clinical Frailty Scale (assessing frailty), Barthel Index (assessing basic activity of daily living [BADL]), and Lawton Instrumental Activities of Daily Living Scale (assessing instrumental activity of daily living [IADL]). Results The ICOPES-TW had a two-factor structure (body functionality [eigenvalue = 1.932] and life adaptation [eigenvalue = 1.170]) as indicated by the results of exploratory factor analysis. Internal consistency of the ICOPES-TW was low (Cronbach’s α = 0.55 [entire ICOPES-TW], 0.45 (body functionality factor), and 0.52 (life adaptation factor). ICOPES-TW scores were significantly (i) positively correlated with age ( r  = 0.321), IADL ( r  = 0.313), and frailty ( r  = 0.601), and (ii) negatively correlated with QoL ( r =–0.447), and BADL ( r =–0.447), with all p -values < 0.001. Conclusion The ICOPES-TW could be a useful screening tool for healthcare providers to quickly evaluate intrinsic capacity for Taiwanese older people given that it has moderate to strong associations with age, BADL, IADL, QoL, and frailty.

Danshen has been widely used for the treatment of central nervous system diseases. We investigated the effect of dihydroisotanshinone I (DT), a compound extracted from Danshen, as well as the corresponding mechanisms in an in vitro-based 6-OHDA-induced Parkinson’s disease (PD) model. SH-SY5Y human neuroblastoma cell lines were pretreated with 6-hydroxydopamine (6-OHDA) and challenged with DT. Subsequently, the cell viability and levels of reactive oxygen species (ROS) and caspase-3 were analyzed. The effect of DT on the 6-OHDA-treated SH-SY5Y cells and the expression of the core circadian clock genes were measured using a real-time quantitative polymerase chain reaction. Our results indicated that DT attenuated the 6-OHDA-induced cell death in the SH-SY5Y cells and suppressed ROS and caspase-3. Moreover, DT reversed both the RNA and protein levels of BMAL1 and SIRT1 in the 6-OHDA-treated SH-SY5Y cells. Additionally, the SIRT1 inhibitor attenuated the effect of DT on BMAL1 and reduced the cell viability. The DT and SIRT1 activators activated SIRT1 and BMAL1, and then reduced the death of the SH-SY5Y cells damaged by 6-OHDA. SIRT1 silencing was enhanced by DT and resulted in a BMAL1 downregulation and a reduction in cell viability. In conclusion, our investigation suggested that DT reduces cell apoptosis, including an antioxidative effect due to a reduction in ROS, and regulates the circadian genes by enhancing SIRT1 and suppressing BMAL1. DT may possess novel therapeutic potential for PD in the future, but further in vivo studies are still needed.

Objective To compare the real‐world effectiveness and tolerability of calcitonin gene‐related peptide (CGRP) monoclonal antibodies (mAbs) and onabotulinumtoxinA in chronic migraine (CM) patients. Methods This multicenter study involved retrospective analysis of prospectively collected data of CM patients treated with CGRP mAbs or onabotulinumtoxinA, including difficult‐to‐treat (DTT) patients (i.e., ≥3 preventive failures). Treatment outcomes were determined at 6 months based on prospective headache diaries and Migraine Disability Assessment (MIDAS). Results The study included 316 (55 M/261F, mean age 44.4 ± 13.5 years) and 333 (61 M/272F, mean age 47.9 ± 13.4 years) CM patients treated with CGRP mAbs or onabotulinbumtoxinA, respectively. At 6 months, CGRP mAb treatment was associated with a greater decrease in monthly migraine days (MMDs) (−13.0 vs. −8.7 days/month, p < 0.001) and a higher ≥50% responder rate (RR) (74.7% vs. 50.7%, p < 0.001) compared with onabotulinumtoxinA injections. The findings were consistent in DTT patients (−13.0 vs. −9.1 MMDs, p < 0.001; ≥50% RR: 73.9% vs. 50.3%, p < 0.001) or those with medication‐overuse headache (MOH) (−13.3 vs. −9.0 MMDs, p < 0.001; ≥50% RR: 79.0% vs. 51.6%, p < 0.001). Besides, patients receiving CGRP mAbs had greater improvement (−42.2 vs. −11.8, p < 0.001) and a higher ≥50% RR (62.0% vs. 40.0%, p = 0.001) in MIDAS scores and a lower rate of adverse events (AEs) (6.0% vs. 21.0%, p < 0.001). However, none of the patients discontinued treatment due to AEs. Conclusions In this multicenter, real‐world study, CGRP mAbs were more effective than onabotulinumtoxinA in CM patients, even in DTT or MOH patients. All of these injectables were well tolerated. Further prospective studies are needed to verify these findings.

The zinc-finger protein which regulates apoptosis and cell cycle arrest 1 (Zac1), encoded by Plagl1 gene, is a seven-zinc-finger containing transcription factor belonging to the imprinted genome and is expressed in diverse types of embryonic and adult human tissues. Zac1 is postulated to be a tumor suppressor by inducing cell cycle arrest and apoptosis through interacting and modulating transcriptional activity of p53 as it was named. Correspondingly, the reduction or loss of Zac1 expression is associated with the incidence and progression of several human tumors, including cervical cancer, breast cancer, ovarian cancer, pituitary tumors, and basal cell carcinoma, implying the rationality of utilizing Zac1 expression as novel a biomarker for the evaluation of cervical cancer prognosis. However, to date, it has not been elucidated whether Zac1 expression is related to the prognosis of patients in clinical cervical cancer tumor samples. To address the questions outlined above, we report here a comprehensive investigation of Zac1 expression in biopsies of clinical cervical carcinoma. By analyzing Zac1 expression in various gene expression profiling of cervical cancer databases, we show the association between high Zac1 expression and poor prognosis of cervical cancer. Functional enrichment analysis showed that high Zac1 expression was associated with epithelial-mesenchymal transition (EMT), which was further observed in clinical characteristics and metastatic carcinoma samples using immunohistochemical staining. Correspondingly, hypomethylation of CpG island on Zac1 promoter was observed in samples with high Zac1 expression in cervical carcinoma. Finally, overexpression of Zac1 in a variety of cervical cancer cell lines increase their mesenchymal biomarker expression and migration, strengthening the correlation between cervical cancers with high Zac1 expression and metastasis in clinical. In summary, this research firstly revealed that identifying Zac1 expression or the methylation status of CpG site on Zac1 promoter may provide us with novel indicators for the evaluation of cervical cancer metastasis.

Intrinsic capacity (IC) is a comprehensive indicator of the overall well-being of older adults, and assessing of IC can help identify early stage of disability and tailor intervention to individual needs. However, there is a lack of effective and simple IC assessment tools. This study aimed to establish predictive scoring algorithms of IC to identify older adults at high risk of impaired functional ability. We conducted a cross-sectional study in Southern Taiwan, measuring IC using 7 subitems: cognition, locomotion, vitality, vision, hearing, psychological well-being, and medication usage were measured. Functional ability outcomes included frailty, basic activities of daily living, and instrumental activities of daily living (IADL). The capability of 7 domains of IC in predicting functional ability was assessed by multivariable logistic regression. The prediction of capability of scoring algorithms was indicated by receiver operating characteristic (AUC) curves and measures of sensitivity and specificity. A total of 1,152 older adults were recruited and analyzed. Locomotion emerged as a significant predictor of IADL disability and worsening frailty. The IC-based weighted scoring algorism for predicting IADL demonstrated satisfactory capability (AUC: 0.80), as did the algorithm for predicting worsening frailty (AUC: 0.90). The optimal cutoff points for predicting IADL disability and frailty worse were estimated respectively at 13 and 16, with sensitivity/specificity values of 0.74/0.75 for the IADL prediction algorithm and 0.92/0.77 for the frailty prediction algorithm. Our 7-domain IC screening tool proves to be sensitive and practical for early identification of functional disability and frailty among community-dwelling older adults in Taiwan.