Plasma Insulin Predicts Early Amyloid-ß Pathology Changes in Alzheimer's Disease.

Background: Evidence suggests that type 2 diabetes (T2D) is an independent risk factor for Alzheimer's disease (AD), sharing similar pathophysiological traits like impaired insulin signaling. Objective: To test the association between plasma insulin and cerebrospinal fluid (CSF) AD pathology. Methods: A total of 304 participants were included in the Alzheimer's Disease Neuroimaging Initiative, assessing plasma insulin and CSF AD pathology. We explored the cross-sectional and longitudinal associations between plasma insulin and AD pathology and compared their associations across different AD clinical and pathological stages. Results: In the non-demented group, amyloid-ß (Aß)+ participants (e.g., as reflected by CSF Aß42) exhibited significantly lower plasma insulin levels compared to non-demented Aß-participants (p <  0.001). This reduction in plasma insulin was more evident in the A+T+ group (as shown by CSF Aß42 and pTau181 levels) when compared to the A-T-group within the non-dementia group (p = 0.002). Additionally, higher plasma insulin levels were consistently associated with more normal CSF Aß42 levels (p <  0.001) across all participants. This association was particularly significant in the Aß-group (p = 0.002) and among non-demented individuals (p <  0.001). Notably, baseline plasma insulin was significantly correlated with longitudinal changes in CSF Aß42 (p = 0.006), whereas baseline CSF Aß42 did not show a similar correlation with changes in plasma insulin over time. Conclusions: These findings suggest an association between plasma insulin and early Aß pathology in the early stages of AD, indicating that plasma insulin may be a potential predictor of changes in early Aß pathology.

Sex differences in the relationship between depression and Alzheimer's disease-mechanisms, genetics, and therapeutic opportunities.

Depression and Alzheimer's disease (AD) are prevalent neuropsychiatric disorders with intriguing epidemiological overlaps. Their interrelation has recently garnered widespread attention. Empirical evidence indicates that depressive disorders significantly contribute to AD risk, and approximately a quarter of AD patients have comorbid major depressive disorder, which underscores the bidirectional link between AD and depression. A growing body of evidence substantiates pervasive sex differences in both AD and depression: both conditions exhibit a higher incidence among women than among men. However, the available literature on this topic is somewhat fragmented, with no comprehensive review that delineates sex disparities in the depression-AD correlation. In this review, we bridge these gaps by summarizing recent progress in understanding sex-based differences in mechanisms, genetics, and therapeutic prospects for depression and AD. Additionally, we outline key challenges in the field, holding potential for improving treatment precision and efficacy tailored to male and female patients' distinct needs.

Identification and functional marker development of SbPLSH1 conferring purple leaf sheath in sorghum.

KEY MESSAGE: We identified a SbPLSH1gene conferring purple leaf sheath in sorghum (sorghumbicolor(L.) Moench)and developed a functional markerfor it. The purple leaf sheath of sorghum, a trait mostly related to anthocyanin deposition, is a visually distinguishable morphological marker widely used to evaluate the purity of crop hybrids. We aimed to dissect the genetic mechanism for leaf sheath color to mine the genes regulating this trait. In this study, two F2 populations were constructed by crossing a purple leaf sheath inbred line (Gaoliangzhe) with two green leaf sheath inbred lines (BTx623 and Silimei). Based on the results of bulked-segregant analysis sequencing, bulk-segregant RNA sequencing, and map-based cloning, SbPLSH1 (Sobic.006G175700), which encodes a bHLH transcription factor on chromosome 6, was identified as the candidate gene for purple leaf sheath in sorghum. Genetic analysis demonstrated that overexpression of SbPLSH1 in Arabidopsis resulted in anthocyanin deposition and purple petiole, while two single-nucleotide polymorphism (SNP) variants on the exon 6 resulted in loss of function. Further haplotype analysis revealed that there were two missense mutations and one cis-acting element mutation in SbPLSH1, which are closely associated with leaf sheath color in sorghum. Based on the variations, a functional marker (LSC4-2) for marker-assisted selection was developed, which has a broad-spectrum capability of distinguishing leaf sheath color in natural variants. In summary, this study lays a foundation for analyzing the genetic mechanism for sorghum leaf sheath color.

CAIDE Score, Alzheimer's Disease Pathology, and Cognition in Cognitively Normal Adults: The CABLE Study.

Background: Cardiovascular Risk Factors, Ageing and Dementia (CAIDE) risk score serves as a credible predictor of an individual's risk of dementia. However, studies on the link of the CAIDE score to Alzheimer's disease (AD) pathology are scarce. Objective: To explore the links of CAIDE score to cerebrospinal fluid (CSF) biomarkers of AD as well as to cognitive performance. Methods: In the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study, we recruited 600 cognitively normal participants. Correlations between the CAIDE score and CSF biomarkers of AD as well as cognitive performance were probed through multiple linear regression models. Whether the correlation between CAIDE score and cognitive performance was mediated by AD pathology was researched by means of mediation analyses. Results: Linear regression analyses illustrated that CAIDE score was positively associated with tau-related biomarkers, including pTau (p < 0.001), tTau (p < 0.001), as well as tTau/Aß42 (p = 0.008), while it was in negative association with cognitive scores, consisting of MMSE score (p < 0.001) as well as MoCA score (p < 0.001). The correlation from CAIDE score to cognitive scores was in part mediated by tau pathology, with a mediation rate varying from 3.2% to 13.2%. Conclusions: A higher CAIDE score, as demonstrated in our study, was linked to more severe tau pathology and poorer cognitive performance, and tau pathology mediated the link of CAIDE score to cognitive performance. Increased dementia risk will lead to cognitive decline through aggravating neurodegeneration.

An electrophoretic mobility shift assay using the protein isolated from host plants.

BACKGROUND: The electrophoretic mobility shift assay (EMSA) is a common technology to detect DNA-protein interactions. However, in most cases, the protein used in EMSA is obtained via prokaryotic expression, and rarely from plants. At the same time, the proteins expressed from prokaryotic systems usually cannot fold naturally and have no post translationally modification, which may affect the binding of proteins to DNA. RESULTS: Here, we develop a technique to quickly isolate proteins of interest from host plants and then analyze them using fluorescent EMSA. This technology system is called: protein from plants fluorescent EMSA method (PPF-EMSA). In PPF-EMSA, a special transient transformation method is employed to transiently deliver genes into the plant, enabling efficient synthesis the encoded proteins. Then, the target protein is isolated using immunoprecipitation, and the DNA probes were labeled with cyanine 3 (Cy3). Both fluorescent EMSA and super-shift fluorescent EMSA can be performed using the proteins from plants. Three kinds of plants, Betula platyphylla, Populus. davidiana×P. bolleana and Arabidopsis thaliana, are used in this study. The proteins isolated from plants are in a natural state, can fold naturally and are posttranslationally modified, enabling true binding to their cognate DNAs. CONCLUSION: As transient transformation can be performed quickly and not depended on whether stable transformation is available or not, we believe this method will have a wide application, enabling isolation of proteins from host plant conveniently.

A retrospective study on the correction of distal arthrogryposis with a progressive extension brace.

Purpose: Camptodactyly, clasped thumbs, and windblown hands are distinctive features of distal arthrogryposis (DA). Current therapeutic interventions often yield suboptimal effects, predisposing patients to relapses and complications. This study explicates a corrective approach involving a progressive extension brace for the management of DA and evaluates its clinical outcomes. Methods: Between 2015 and 2023, progressive extension braces were used in 32 DA patients, with an average follow-up of 4.8 years. Patients were stratified by age into four groups: 0-1, 1-3, 3-7, and above 7 years. The correction of camptodactyly was assessed based on the total active movement (TAM) of metacarpophalangeal joints (MPJ) and proximal interphalangeal joints (PIPJ), as well as the extensor lag of PIPJ. Clasped thumb correction was evaluated by measuring the thumb-to-index finger metacarpal angle (M1M2 angle) and the degree of deviation at the first MPJ (M1P1 angle). The quality of life for the children was measured using PedsQL 4.0, while parental satisfaction was gauged using the FACE questionnaire. Results: Earlier intervention with a progressive extension brace yielded superior corrective results. Infants aged 0-1 year and toddlers aged 1-3 years achieved average TAM scores of 152° and 126° after correction; however, patients older than 3 years experienced a significant decrease in TAM with the same treatment. Infants and toddlers with DA showed improvement in the average extensor lag from 46° to 6°. The M1M2 angle increased from an average of 38° to 65°, with the M1P1 angle decreasing from an average of 43° to 5°. After the treatment, average PedsQL scores of 94.7 (parent-reported) and 89.3 (child-reported) were achieved. Among the 32 parents, 24 expressed high satisfaction, 5 expressed moderate satisfaction, and 3 expressed fair satisfaction. Conclusion: The early, progressive, and consistent use of an extension brace significantly improved joint mobility and corrected camptodactyly and clasped thumbs. It can be an effective approach to addressing hand deformities in patients with DA.

Semi-supervised learning in diagnosis of infant hip dysplasia towards multisource ultrasound images.

Background: Automated diagnosis of infant hip dysplasia is heavily affected by the individual differences among infants and ultrasound machines. Methods: Hip sonographic images of 493 infants from various ultrasound machines were collected in the Department of Orthopedics in Yangzhou Maternal and Child Health Care Service Centre. Herein, we propose a semi-supervised learning method based on a feature pyramid network (FPN) and a contrastive learning scheme based on a Siamese architecture. A large amount of unlabeled data of ultrasound images was used via the Siamese network in the pre-training step, and then a small amount of annotated data for anatomical structures was adopted to train the model for landmark identification and standard plane recognition. The method was evaluated on our collected dataset. Results: The method achieved a mean Dice similarity coefficient (DSC) of 0.7873 and a mean Hausdorff distance (HD) of 5.0102 in landmark identification, compared to the model without contrastive learning, which had a mean DSC of 0.7734 and a mean HD of 6.1586. The accuracy, precision, and recall of standard plane recognition were 95.4%, 91.64%, and 94.86%, respectively. The corresponding area under the curve (AUC) was 0.982. Conclusions: This study proposes a semi-supervised deep learning method following Graf's principle, which can better utilize a large volume of ultrasound images from various devices and infants. This method can identify the landmarks of infant hips more accurately than manual operators, thereby improving the efficiency of diagnosis of infant hip dysplasia.

The key pathways for drought tolerance in Cerasus humilis were unveiled through transcriptome analysis.

Drought stress exerts a significant impact on the growth, development, and yield of fruit trees. Cerasus humilis is an endemic drought-resistant fruit tree in northern China. To elucidate the underlying mechanism of drought resistance in C. humilis, comprehensive physiological measurements and transcriptome analysis were conducted on the leaves of C. humilis subjected to 15- or 22-days of drought stress. We identified multiple GO terms and KEGG pathways associated with the drought stress response by performing GO and KEGG analysis on DEGs. Furthermore, through the prediction of transcription factors (TFs) and analysis of their expression levels, we observed differential expression patterns among most members of stress-responsive TF families as the duration of drought stress increased. WGCNA analysis was performed on the transcriptome to identify gene cluster modules that exhibited a strong correlation with the durations of drought. Subsequently, these modules underwent GO and KEGG enrichment analyses. The study revealed that the TF-mediated lignin biosynthesis pathway, along with the plant hormone signal transduction pathway, played a prominent role in responding to drought stress of C. humilis. Gene profiling analysis, qRT-PCR, and determination of phytohormone and lignin contents further supported this hypothesis. The hierarchical gene regulatory network was finally constructed based on DEGs from the aforementioned key enriched pathways to predict the gene regulatory mechanisms in response to stress for C. humilis. The findings from this study provide valuable insights into how C. humilis copes with drought stress while analyzing crucial gene pathways associated with its resistance from a TF perspective. This research is significant for the genetic breeding of economic forests.

Metabolomics for Clinical Biomarker Discovery and Therapeutic Target Identification.

As links between genotype and phenotype, small-molecule metabolites are attractive biomarkers for disease diagnosis, prognosis, classification, drug screening and treatment, insight into understanding disease pathology and identifying potential targets. Metabolomics technology is crucial for discovering targets of small-molecule metabolites involved in disease phenotype. Mass spectrometry-based metabolomics has implemented in applications in various fields including target discovery, explanation of disease mechanisms and compound screening. It is used to analyze the physiological or pathological states of the organism by investigating the changes in endogenous small-molecule metabolites and associated metabolism from complex metabolic pathways in biological samples. The present review provides a critical update of high-throughput functional metabolomics techniques and diverse applications, and recommends the use of mass spectrometry-based metabolomics for discovering small-molecule metabolite signatures that provide valuable insights into metabolic targets. We also recommend using mass spectrometry-based metabolomics as a powerful tool for identifying and understanding metabolic patterns, metabolic targets and for efficacy evaluation of herbal medicine.

Physical frailty, genetic predisposition, and incident dementia: a large prospective cohort study.

Physical frailty and genetic factors are both risk factors for increased dementia; nevertheless, the joint effect remains unclear. This study aimed to investigated the long-term relationship between physical frailty, genetic risk, and dementia incidence. A total of 274,194 participants from the UK Biobank were included. We applied Cox proportional hazards regression models to estimate the association between physical frailty and genetic and dementia risks. Among the participants (146,574 females [53.45%]; mean age, 57.24 years), 3,353 (1.22%) new-onset dementia events were recorded. Compared to non-frailty, the hazard ratio (HR) for dementia incidence in prefrailty and frailty was 1.396 (95% confidence interval [CI], 1.294-1.506, P < 0.001) and 2.304 (95% CI, 2.030-2.616, P < 0.001), respectively. Compared to non-frailty and low polygenic risk score (PRS), the HR for dementia risk was 3.908 (95% CI, 3.051-5.006, P < 0.001) for frailty and high PRS. Furthermore, among the participants, slow walking speed (HR, 1.817; 95% CI, 1.640-2.014, P < 0.001), low physical activity (HR, 1.719; 95% CI, 1.545-1.912, P < 0.001), exhaustion (HR, 1.670; 95% CI, 1.502-1.856, P < 0.001), low grip strength (HR, 1.606; 95% CI, 1.479-1.744, P < 0.001), and weight loss (HR, 1.464; 95% CI, 1.328-1.615, P < 0.001) were independently associated with dementia risk compared to non-frailty. Particularly, precise modulation for different dementia genetic risk populations can also be identified due to differences in dementia risk resulting from the constitutive pattern of frailty in different genetic risk populations. In conclusion, both physical frailty and high genetic risk are significantly associated with higher dementia risk. Early intervention to modify frailty is beneficial for achieving primary and precise prevention of dementia, especially in those at high genetic risk.

A Review of Bioactive Compound Effects from Primary Legume Protein Sources in Human and Animal Health.

The global demand for sustainable and nutritious food sources has catalyzed interest in legumes, known for their rich repertoire of health-promoting compounds. This review delves into the diverse array of bioactive peptides, protein subunits, isoflavones, antinutritional factors, and saponins found in the primary legume protein sources-soybeans, peas, chickpeas, and mung beans. The current state of research on these compounds is critically evaluated, with an emphasis on the potential health benefits, ranging from antioxidant and anticancer properties to the management of chronic diseases such as diabetes and hypertension. The extensively studied soybean is highlighted and the relatively unexplored potential of other legumes is also included, pointing to a significant, underutilized resource for developing health-enhancing foods. The review advocates for future interdisciplinary research to further unravel the mechanisms of action of these bioactive compounds and to explore their synergistic effects. The ultimate goal is to leverage the full spectrum of benefits offered by legumes, not only to advance human health but also to contribute to the sustainability of food systems. By providing a comprehensive overview of the nutraceutical potential of legumes, this manuscript sets a foundation for future investigations aimed at optimizing the use of legumes in the global pursuit of health and nutritional security.

Effect of apheresis plasma donation on plasma uric acid levels, the lipid profile, and major plasma proteins in plasma donors in China: A multicenter, prospective cohort study.

Abnormal plasma uric acid (UA) levels, the lipid profile, and plasma proteins in blood are associated with a range of adverse health outcomes. This multicenter, prospective cohort study aimed to determine the possible effects of multiple apheresis plasma donations on plasma UA levels, the lipid profile, and major proteins in plasma donors. Participants were enrolled from 1 April 2021 to 31 August 2022. When their plasma UA (men: >420 µmol/L, women: >360 µmol/L) and/or lipid levels (total cholesterol [TC]: ≥6.2 mmol/L, triglycerides [TGs]: ≥2.3 mmol/L, low-density lipoprotein cholesterol: ≥4.1 mmol/L, or high-density lipoprotein cholesterol [HDL-C]: <1.0 mmol/L) were abnormal at their first plasma donation, the enrolled participants were followed up until they had completed 10 plasma donations. A total of 11485 participants were enrolled, of whom 1861 met the inclusion criteria. During the study period, 320 donors completed 10 plasma donations. None of the participants took any corrective medicine for their abnormal index. The measured parameters were significantly different from the first to the tenth plasma donations (donors with asymptomatic hyperuricemia: UA, P < 0.001; donors with asymptomatic hyperlipidemia: HDL-C, P < 0.001; TC, P = 0.025; TGs, P < 0.001; apolipoprotein B, P = 0.025; all of the plasma donors, immunoglobulin G, P < 0.001). The levels of HDL-C, TC, and apolipoprotein B were increased, and the levels of UA, TGs, and immunoglobulin G were decreased over this time. However, immunoglobulin G levels were still in the normal range. Moreover, the changes in these parameters were closely associated with the frequency of plasma donation during the study period. Repeated apheresis plasma donations can reduce plasma UA and TG levels and increase HDL-C levels; and further evaluation of the clinical significance with a larger sample size is required.

A novel nomogram integrating body composition and inflammatory-nutritional markers for predicting postoperative complications in patients with adhesive small bowel obstruction.

Background: Postoperative complications in adhesive small bowel obstruction (ASBO) significantly escalate healthcare costs and prolong hospital stays. This study endeavors to construct a nomogram that synergizes computed tomography (CT) body composition data with inflammatory-nutritional markers to forecast postoperative complications in ASBO. Methods: The study's internal cohort consisted of 190 ASBO patients recruited from October 2017 to November 2021, subsequently partitioned into training (n = 133) and internal validation (n = 57) groups at a 7:3 ratio. An additional external cohort comprised 52 patients. Body composition assessments were conducted at the third lumbar vertebral level utilizing CT images. Baseline characteristics alongside systemic inflammatory responses were meticulously documented. Through univariable and multivariable regression analyses, risk factors pertinent to postoperative complications were identified, culminating in the creation of a predictive nomogram. The nomogram's precision was appraised using the concordance index (C-index) and the area under the receiver operating characteristic (ROC) curve. Results: Postoperative complications were observed in 65 (48.87%), 26 (45.61%), and 22 (42.31%) patients across the three cohorts, respectively. Multivariate analysis revealed that nutrition risk score (NRS), intestinal strangulation, skeletal muscle index (SMI), subcutaneous fat index (SFI), neutrophil-lymphocyte ratio (NLR), and lymphocyte-monocyte ratio (LMR) were independently predictive of postoperative complications. These preoperative indicators were integral to the nomogram's formulation. The model, amalgamating body composition and inflammatory-nutritional indices, demonstrated superior performance: the internal training set exhibited a 0.878 AUC (95% CI, 0.802-0.954), 0.755 accuracy, and 0.625 sensitivity; the internal validation set displayed a 0.831 AUC (95% CI, 0.675-0.986), 0.818 accuracy, and 0.812 sensitivity. In the external cohort, the model yielded an AUC of 0.886 (95% CI, 0.799-0.974), 0.808 accuracy, and 0.909 sensitivity. Calibration curves affirmed a strong concordance between predicted outcomes and actual events. Decision curve analysis substantiated that the model could confer benefits on patients with ASBO. Conclusion: A rigorously developed and validated nomogram that incorporates body composition and inflammatory-nutritional indices proves to be a valuable tool for anticipating postoperative complications in ASBO patients, thus facilitating enhanced clinical decision-making.

Birch WRKY transcription factor, BpWRKY32, confers salt tolerance by mediating stomatal closing, proline accumulation, and reactive oxygen species scavenging.

Plant WRKY transcription factors (TFs) play important roles in abiotic stress responses. However, how WRKY facilitate physiological changes to confer salt tolerance still needs to be studied. Here, we identified a WRKY TF from birch (Betula platyphylla Suk), BpWRKY32, which is significantly (P < 0.05) induced by salt stress. BpWRKY32 binds to W-box motif and is located in the nucleus. Under salt stress conditions, fresh weights (FW) of OE lines (BpWRKY32 overexpression lines) are increased by 66.36% than that of WT, while FW of knockout of BpWRKY32 (bpwrky32) lines are reduced by 39.49% compared with WT. BpWRKY32 regulates the expression of BpRHC1, BpNRT1, and BpMYB61 to reduce stomatal, and width-length ratio of the stomatal aperture in OE lines are reduced by 46.23% and 64.72% compared with in WT and bpwrky32 lines. BpWRKY32 induces P5CS expression, but inhibits P5CDH expression, leading to the proline content in OE lines are increased by 33.41% and 97.58% compared with WT and bpwrky32 lines. Additionally, BpWRKY32 regulates genes encoding SOD and POD family members, which correspondingly increases the activities of SOD and POD. These results suggested that BpWRKY32 regulates target genes to reduce the water loss rate, enhance the osmotic potential, and reduce the ROS accumulation, leading to improved salt tolerance.

Phosphorylation of birch BpNAC90 improves the activation of gene expression to confer drought tolerance.

The NAC transcription factors (TFs) play important roles in mediating abiotic stress tolerance; however, the mechanism is still not fully known. Here, an NAC gene (BpNAC90) from a gene regulatory network of Betula platyphylla (birch) that responded to drought was characterized. Overexpression and knockout of BpNAC90 displayed increased and reduced drought tolerance, respectively, relative to wild-type (WT) birch. BpNAC90 binds to different DNA motifs to regulate target genes in conferring drought tolerance, such as Eomes2, ABRE and Tgif2. BpNAC90 is phosphorylated by drought stress at Ser 205 by birch SNF1-related protein kinase 2 (BpSRK2A). Mutated BpNAC90 (termed S205A) with abolished phosphorylation, was transformed into birch for overexpression. The transgenic S205A plants displayed significantly reduced drought tolerance compared with plants overexpressing BpNAC90, but still showed increased drought tolerance relative to WT birch. At the same time, S205A showed a decreased capability to bind to motifs and reduced activation of target gene expression, which contributed to the reduced drought tolerance. Additionally, BpSRK2A and BpNAC90 can be induced by drought stress and form a complex to phosphorylate BpNAC90. The results together indicated that phosphorylation of BpNAC90 is necessary in conferring drought tolerance in birch.

Acetylation of transcription factor BpTCP20 by acetyltransferase BpPDCE23 modulates salt tolerance in birch.

Teosinte branched 1/Cycloidea/Proliferating cell factor (TCP) transcription factors function in abiotic stress responses. However, how TCPs confer salt tolerance is unclear. Here, we characterized a TCP transcription factor, BpTCP20, that responds to salt stress in birch (Betula platyphylla Suk). Plants overexpressing BpTCP20 displayed increased salt tolerance, and Bptcp20 knockout mutants displayed reduced salt tolerance relative to the wild-type (WT) birch. BpTCP20 conferred salt tolerance by mediating stomatal closure and reducing reactive oxygen species accumulation. Chromatin immunoprecipitation sequencing showed that BpTCP20 binds to NeuroD1, T-box, and two unknown elements (termed TBS1 and TBS2) to regulate target genes. In birch, salt stress led to acetylation of BpTCP20 acetylation at lysine 259. A mutated BpTCP20 variant (abolished for acetylation, termed BpTCP20259) was overexpressed in birch, which led to decreased salt tolerance compared with plants overexpressing BpTCP20. However, BpTCP20259-overexpressing plants still displayed increased salt tolerance relative to untransformed wild-type plants. BpTCP20259 showed reduced binding to the promoters of target genes and decreased target gene activation, leading to decreased salt tolerance. In addition, we identified dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex (BpPDCE23), an acetyltransferase that interacts with and acetylates BpTCP20 to enhance its binding to DNA motifs. Together, these results suggest that BpTCP20 is a transcriptional regulator of salt tolerance, whose activity is modulated by BpPDCE23-mediated acetylation.

Associations of Frailty with Neuropsychiatric Symptoms of Alzheimer's Disease: A Longitudinal Study.

Background: Frailty is a vulnerability state increasing the risk of many adverse health outcomes, but little is known about the effects of frailty on neuropsychiatric health. Objective: To explore the associations between frailty and the risk of neuropsychiatric symptoms (NPSs) in Alzheimer's disease (AD), especially in its different clinical stages. Methods: We included 2,155 individuals assessed using modified frailty index-11 (mFI-11), Neuropsychiatric Inventory (NPI) and Neuropsychiatric Inventory Questionnaire (NPI-Q) in the Alzheimer's Disease Neuroimaging Initiative (ADNI). The relationships between frailty and NPSs were explored with logistic regression models and Cox proportional hazard regression models. Causal mediation analyses were conducted to explore the mediation factors between frailty and NPSs. Results: Among mild cognitive impairment (MCI) participants, frailty was cross-sectionally associated with an increased risk of apathy, and longitudinally associated with increased risk of depression and apathy. Among AD participants, frailty was cross-sectionally associated with increased risk of depression and anxiety, and longitudinally associated with an increased risk of apathy. Among participants with cognitive progression, frailty was associated with increased risk of depression and apathy. In MCI participants, the influence of frailty on NPSs was partially mediated by hippocampus volume, whole brain volume, and monocytes, with mediating proportions ranging from 8.40% to 9.29%. Conclusions: Frailty was associated with NPSs such as depression, anxiety, and apathy among MCI, AD, and cognitive progression participants. Atrophy of the hippocampus and whole brain, as well as peripheral immunity may be involved in the potential mechanisms underlying the above associations.

Transcriptome-Based Identification of the SaR2R3-MYB Gene Family in Sophora alopecuroides and Function Analysis of SaR2R3-MYB15 in Salt Stress Tolerance.

As one of the most prominent gene families, R2R3-MYB transcription factors significantly regulate biochemical and physiological processes under salt stress. However, in Sophora alopecuroides, a perennial herb known for its exceptional saline alkali resistance, the comprehensive identification and characterization of SaR2R3-MYB genes and their potential functions in response to salt stress have yet to be determined. We investigated the expression profiles and biological functions of SaR2R3-MYB transcription factors in response to salt stress, utilizing a transcriptome-wide mining method. Our analysis identified 28 SaR2R3-MYB transcription factors, all sharing a highly conserved R2R3 domain, which were further divided into 28 subgroups through phylogenetic analysis. Some SaR2R3-MYB transcription factors showed induction under salt stress, with SaR2R3-MYB15 emerging as a potential regulator based on analysis of the protein-protein interaction network. Validation revealed the transcriptional activity and nuclear localization of SaR2R3-MYB15. Remarkably, overexpression of SaR2R3-MYB15 in transgenic plants could increase the activity of antioxidant enzymes and the accumulation of proline but decrease the content of malondialdehyde (MDA), compared with wild-type plants. Moreover, several salt stress-related genes showed higher expression levels in transgenic plants, implying their potential to enhance salt tolerance. Our findings shed light on the role of SaR2R3-MYB genes in salt tolerance in S. alopecuroides.

Feasibility of thoracoscopic monosubsegmentectomy for small ground-glass opacity dominant lung cancer.

BACKGROUND: Monosubsegmentectomy (MSS) involves removal of less lung parenchyma than monosegmentectomy (MS) does. However, the clinical efficacy of MSS in lung cancer treatment remains unclear, with concerns regarding insufficient surgical margins and increased complications. METHODS: Between February 2015 and December 2019, patients who underwent thoracoscopic MSS (n = 126) or MS (n = 678) for small ground-glass opacity (GGO) dominant lung cancer were examined. The primary endpoints were the procedure success rate (defined as resection with a surgical margin ≥2 cm or tumor size) and surgical margin. RESULTS: There were no significant differences in age, sex, smoking history, or comorbidities between the groups. Both groups achieved a success rate of 100%. No significant group differences were observed in the number of lymph nodes removed (p = 0.060), overall complications (p = 0.147), or major complications (p = 0.450). The MSS group had a smaller surgical margin (median, 17 vs. 21mm, p < 0.001) and longer operative time (median, 138 vs. 130 min, p = 0.005) than the MS group did. Propensity score-matched analysis of 122 pairs of patients revealed consistent results. Surgical margins were further compared based on the number of resected subsegments. The 1 subsegment group had the smallest median surgical margin, followed by the 2 and 3 subsegments groups (17, 20, and 23 mm, p < 0.001). CONCLUSIONS: Thoracoscopic MSS is an acceptable option for treating patients with small-sized GGO-dominant lung cancer. However, the close surgical margins and prolonged operative time should be considered.