Unveiling orphan receptor-like kinases in plants: novel client discovery using high-confidence library predictions in the Kinase-Client (KiC) assay.

Plants are remarkable in their ability to adapt to changing environments, with receptor-like kinases (RLKs) playing a pivotal role in perceiving and transmitting environmental cues into cellular responses. Despite extensive research on RLKs from the plant kingdom, the function and activity of many kinases, i.e., their substrates or "clients", remain uncharted. To validate a novel client prediction workflow and learn more about an important RLK, this study focuses on P2K1 (DORN1), which acts as a receptor for extracellular ATP (eATP), playing a crucial role in plant stress resistance and immunity. We designed a Kinase-Client (KiC) assay library of 225 synthetic peptides, incorporating previously identified P2K phosphorylated peptides and novel predictions from a deep-learning phosphorylation site prediction model (MUsite) and a trained hidden Markov model (HMM) based tool, HMMER. Screening the library against purified P2K1 cytosolic domain (CD), we identified 46 putative substrates, including 34 novel clients, 27 of which may be novel peptides, not previously identified experimentally. Gene Ontology (GO) analysis among phosphopeptide candidates revealed proteins associated with important biological processes in metabolism, structure development, and response to stress, as well as molecular functions of kinase activity, catalytic activity, and transferase activity. We offer selection criteria for efficient further in vivo experiments to confirm these discoveries. This approach not only expands our knowledge of P2K1's substrates and functions but also highlights effective prediction algorithms for identifying additional potential substrates. Overall, the results support use of the KiC assay as a valuable tool in unraveling the complexities of plant phosphorylation and provide a foundation for predicting the phosphorylation landscape of plant species based on peptide library results.

Exploring the Smoking-Epilepsy Nexus: a systematic review and meta-analysis of observational studies : Smoking and epilepsy.

BACKGROUND: Epilepsy, characterized by recurrent unprovoked seizures, poses significant challenges to affected individuals globally. While several established risk factors for epilepsy exist, the association with cigarette smoking remains debated. This study aims to conduct systematic review and meta-analysis to elucidate the potential association between smoking and the likelihood of epilepsy. METHODS: The search was performed on March 31st, 2023, using the Medline, Embase, Web of Science, Scopus, and ScienceDirect. We included cohort, cross-sectional, and case-control studies in our meta-analysis, conducting subgroup analyses based on smoking history, sex, and epilepsy type to yield specific insights. RESULTS: We identified 2550 studies, of which 17 studies were finally included in this study. The pooled odds ratio of epilepsy was 1.14 (0.96-1.36) in smokers compared to non-smokers. In current smokers compared to non-smokers, the odds ratio was 1.46 (1.13-1.89), while, in former smokers compared to non-smokers, the odds ratio was 1.14 (0.83-1.56). CONCLUSIONS: While the overall association between smoking and epilepsy did not reach statistical significance, a notable association was found among current smokers. The study emphasizes the importance of smoking cessation as a potential preventive measure against epilepsy, especially given the proconvulsive effects of nicotine. Future research should address limitations and explore specific clinical scenarios to enhance our understanding of the complex relationship between cigarette use and epilepsy. SYSTEMATIC REVIEW REGISTRATION: CRD42022342510.

Rice OsGATA16 is a positive regulator for chlorophyll biosynthesis and chloroplast development.

Chloroplasts are essential organelles in plants that contain chlorophylls and facilitate photosynthesis for growth and development. As photosynthetic efficiency significantly impacts crop productivity, understanding the regulatory mechanisms of chloroplast development has been crucial in increasing grain and biomass production. This study demonstrates the involvement of OsGATA16, an ortholog of Arabidopsis GATA, NITRATE INDUCIBLE, CARBON-METABOLISM INVOLVED (GNC), and GNC-LIKE/CYTOKININ-RESPONSIVE GATA FACTOR 1 (GNL/CGA1), in chlorophyll biosynthesis and chloroplast development in rice (Oryza sativa). The osgata16-1 knockdown mutants produced pale-green leaves, while OsGATA16-overexpressed plants (OsGATA16-OE1) generated dark-green leaves, compared to their parental japonica rice. Reverse transcription and quantitative PCR analysis revealed downregulation of genes related to chloroplast division, chlorophyll biosynthesis, and photosynthesis in the leaves of osgata16-1 and upregulation in those of OsGATA16-OE1. Additionally, in vivo binding assays showed that OsGATA16 directly binds to the promoter regions of OsHEMA, OsCHLH, OsPORA, OsPORB, and OsFtsZ, and upregulates their expression. These findings indicate that OsGATA16 serves as a positive regulator controlling chlorophyll biosynthesis and chloroplast development in rice.

Neighborhood and Depressive Symptoms in Older Adults Living in Rural and Urban Regions in South Korea.

Neighborhoods have a significant impact on depressive symptoms in older adults. In response to the increasing depression of older adults in Korea, this study aims to identify the relationship between perceived and objective neighborhood characteristics in depressive symptoms and find differences between rural and urban areas. We used a National survey collected in 2020 of 10,097 Korean older adults aged 65 and older. We also utilized Korean administration data for identifying the objective neighborhood characteristics. Multilevel modeling results indicated that depressive symptoms decreased when older adults perceived their housing condition (b = -0.04, p < 0.001), their interaction with neighbors (b = -0.02, p < 0.001), and overall neighborhood environment (b = -0.02, p < 0.001) positively. Among the objective neighborhood characteristics, only nursing homes (b = 0.09, p < 0.05) were related to depressive symptoms of older adults living in urban areas. For older adults living in rural areas, the number of social workers (b = -0.03, p < 0.001), the number of senior centers (b = -0.45, p < 0.001), and nursing home (b = -3.30, p < 0.001) in the neighborhood were negatively associated with depressive symptoms. This study found that rural and urban areas have different neighborhood characteristics related to older adults' depressive symptoms in South Korea. This study encourages policymakers to consider neighborhood characteristics to improve the mental health of older adults.

Computational prediction and in vitro analysis of the potential ligand binding site within the extracellular ATP receptor, P2K2.

The plant extracellular ATP (eATP) receptor, P2K2, binds eATP with strong ligand affinity through its extracellular lectin domain. Ligand binding activates the intracellular kinase domain of P2K2 resulting in a variety of intracellular responses and, ultimately, increased plant immunity to invading fungal and bacterial pathogens. Here, using a computational prediction approach, we developed a tertiary structure model of the P2K2 extracellular lectin domain. In silico target docking of ATP to the P2K2-binding site predicted interaction with several residues through hydrophobic interactions and hydrogen bonding. Our confirmation of the modeling was obtained by showing that H99, R144, and S256 are key residues essential for in vitro binding of ATP by P2K2.

Electrophoretic Molecular Communication With Piecewise Constant Electric Field.

This paper studies a novel electrophoretic molecular communication (EMC) framework utilizing a piecewise constant electric field. EMC is a particular type of molecular communication that exploits electric fields to induce the movement of charged particles to enhance communication performance. Our previous work proposed an EMC framework utilizing a time-varying electric field that exponentially changes; however, the field with such a complicated shape might be challenging to be implemented in practice. Thus, this paper proposes a new EMC approach exploiting a piecewise constant electric field that can be readily implemented via, e.g., an on/off switch method. We formulate two optimization problems to design the electric field based on different objectives: minimizing a mean squared error and minimizing a bit interval. The solutions of each, such as optimal on-off timings and corresponding strengths of the constant electric fields, are obtained through the Lagrange multiplier approach and the geometric programming, respectively. The Monte Carlo simulation results verify that the proposed piecewise constant electric field significantly reduces the bit error rate relative to the constant field benchmark while performing less well, but not significantly, than the exponential field benchmark.

Changes in the Suicide Rate of Older Adults According to Gender, Age, and Region in South Korea from 2010 to 2017.

BACKGROUND: South Korea's suicide rates are the highest among Organization for Economic Co-operation and Development (OECD) countries, making it one of the most important societal issues in South Korea. METHODS: the statistics on causes of death and resident registration central population (RRCP) provided by the National Statistical Office were used to calculate the suicide rate among older adults in Korea. We examined gender (male, female), age (young-old, old-old), and region (urban, rural) by conducting latent growth modeling to estimate changes in the overall older adult suicide rate and verify its relationship. RESULTS: over a period of 8 years, the older adult suicide rate was 104.232 on average in 2010 and it decreased by approximately 10.317 every year, and the rate of decrease gradually slowed down. The initial value of the older adult suicide rate was found to be higher among males, the old-old group, and those living in rural regions. In the quadratic function change rate, only males and the old-old group were statistically significant. CONCLUSION: in this study, the direction of and the rate of change in the older adult suicide rates and the relationship between gender, age, and region were examined. It is expected that this study will provide basic data to assist in establishing older adult suicide prevention policies, considering the gender, age, and region of the aging population.

Effects of Changes in Smoking Behavior of Older Adults' Oral Health.

While smoking is a crucial health risk, it adversely affects oral health, particularly becoming riskier for older adults who have smoked for a long time. This study identifies the patterns of smoking behavior changes in older adults aged 65 years and older and examines how the smoking behavior changes affect their oral health. Longitudinal data were derived from Korean Longitudinal Study of Aging (KLoSA) between 2006 and 2018, targeting the older adults 65 years and older in South Korea. The independent variable was the amount of smoking, and the dependent variable was oral health. For data analysis, SPSS 25.0 and M-plus 8.0 programs were utilized. As a result, the patterns of changes in smoking behavior of the older adults finally derived were 'non-smoking,' 'decreasing,' 'high-level maintenance,' and 'decreasing after increasing.' Furthermore, the relationship between the smoking behavior change pattern of the older adults and oral health was revealed. Specifically, as for the smoking behavior change pattern of the older adults, it was confirmed that the oral health was better in the 'non-smoking' pattern compared to the 'high-level maintenance' pattern. On the other hand, it was confirmed that the 'decreasing' pattern and the 'decreasing after rising' pattern did not significantly affect oral health. The findings imply that even if older adults smoked a lot in the past, if they quit smoking at some point, it can positively affect their oral health. Furthermore, it is suggested to allow public officials, medical professionals, and welfare experts to actively intervene for older adults to stop smoking for their oral health.

Genetic Variations miR-10aA>T, miR-30cA>G, miR-181aT>C, and miR-499bA>G and the Risk of Recurrent Pregnancy Loss in Korean Women

This study investigated the genetic association between recurrent pregnancy loss (RPL) and microRNA (miRNA) polymorphisms in miR-10aA>T, miR-30cA>G, miR-181aT>C, and miR-499bA>G in Korean women. Blood samples were collected from 381 RPL patients and 281 control participants, and genotyping of miR-10aA>T, miR-30cA>G, miR-181aT>C, and miR-499bA>G was carried out by TaqMan miRNA RT-Real Time polymerase chain reaction (PCR). Four polymorphisms were identified, including miR-10aA>T, miR-30cA>G, miR-181aT>C, and miR-499bA>G. MiR-10a dominant model (AA vs. AT + TT) and miR-499bGG genotypes were associated with increased RPL risk (adjusted odds ratio [AOR] = 1.520, 95% confidence interval [CI] = 1.038−2.227, p = 0.032; AOR = 2.956, 95% CI = 1.168−7.482, p = 0.022, respectively). Additionally, both miR-499 dominant (AA vs. AG + GG) and recessive (AA + AG vs. GG) models were significantly associated with increased RPL risk (AOR = 1.465, 95% CI = 1.062−2.020, p = 0.020; AOR = 2.677, 95% CI = 1.066−6.725, p = 0.036, respectively). We further propose that miR-10aA>T, miR-30cA>G, and miR-499bA>G polymorphisms effects could contribute to RPL and should be considered during RPL patient evaluation.

The Moderating Effect of Social Support between Loneliness and Depression: Differences between the Young-Old and the Old-Old.

This study aimed to investigate the moderation of social support in the association between loneliness and depression in different age groups of older adults. The sample consisted of 1532 community-dwelling adults aged 65 years or older, based on the data from the National Social Life, Health, and Aging Project (NSHAP), Wave 3 (2015-2016). Eleven items of the Center for Epidemiologic Studies Depression Scale (CES-D) were used to measure depressive symptoms. Similarly, a four-item scale was used to measure social support (each from spouse and family), and a three-item scale for loneliness. The results were as follows. Loneliness was associated with depression in both the young-old and the old-old groups. Spousal support and family support were associated with reduced depression in the young-old group, whereas only spousal support was associated with relieving depression in the old-old group. Social support had a significant moderating effect on the relationship between loneliness and depression in the old-old group, whereas it had no significant effect in the young-old group. From these results, it can be concluded that spousal support plays a significant role in seniors' mental health. The role of caregivers for a person's well-being grows later in life, so practitioners could help couples communicate with this consideration. In addition, regular contacts with family members and spousal support are recommended to prevent older old adults' depression.

Activation of the plant mevalonate pathway by extracellular ATP.

The mevalonate pathway plays a critical role in multiple cellular processes in both animals and plants. In plants, the products of this pathway impact growth and development, as well as the response to environmental stress. A forward genetic screen of Arabidopsis thaliana using Ca2+-imaging identified mevalonate kinase (MVK) as a critical component of plant purinergic signaling. MVK interacts directly with the plant extracellular ATP (eATP) receptor P2K1 and is phosphorylated by P2K1 in response to eATP. Mutation of P2K1-mediated phosphorylation sites in MVK eliminates the ATP-induced cytoplasmic calcium response, MVK enzymatic activity, and suppresses pathogen defense. The data demonstrate that the plasma membrane associated P2K1 directly impacts plant cellular metabolism by phosphorylation of MVK, a key enzyme in the mevalonate pathway. The results underline the importance of purinergic signaling in plants and the ability of eATP to influence the activity of a key metabolite pathway with global effects on plant metabolism.

Patient blood management when blood is not an option: a report of two cases.

There are many patients who refuse to receive blood transfusions for religious or other reasons. Bloodless medicine and surgery are no longer new concept, but patients who refuse blood transfusion are still transferred to the bloodless center, regardless of patients' intention, for treatment. Here, we discuss the need for patient blood management when blood is not an option to treat them. Two patients of advanced age were transferred to our bloodless center due to refusal of transfusion. They are Jehovah's Witnesses and refused to receive blood transfusion despite life-threatening anemia and severe underlying diseases. Patient blood management protocols including iron supplementation, subcutaneous erythropoietin, folic acid and vitamin B were implemented to improve hematopoiesis, and supportive care was also performed to treat underlying diseases. Levels of Hemoglobin/Hematocrit and their symptom gradually improved about a week after treatment, and their condition had gradually stabilized. They were discharged safely. We treated patients of advanced age with severe underlying diseases and life-threatening anemia using patient blood management due to refusal of a blood transfusion. The patient blood management may be a useful alternative strategy, which meet the needs of patients who refuse blood transfusions as well as the need to reduce the use of blood products due to limited supply.

Effectiveness of nasotracheal intubation in anterior cervical surgery including C3 lesions.

OBJECTIVE: Anterior approach cervical surgery is widely used for accessing C3 lesions. When operating with an anterior approach, the surgical field is obstructed by mandible. Neck extension is popular method to secure better surgical field but risk devastating neurological damage. To overcome this limited surgical field without neck extension, we adopted nasotracheal intubation and evaluated its efficiency. METHODS: We retrospectively analyzed 16 patients who underwent anterior cervical discectomy or corpectomy of C3 lesions via nasotracheal intubation. We enrolled an additional 29 patients who underwent anterior cervical discectomy or corpectomy of C3 lesions via orotracheal intubation as a control group. All patients had been diagnosed with cervical spondylotic myelopathy or ossification of the posterior longitudinal ligament. We measured the mandibular-cervical angle, which is the angle between the lower mandibular line and anterior vertebral line. RESULTS: The mandibular-cervical angle was increased by 7.3 with nasotracheal intubation compared to orotracheal intubation. CONCLUSIONS: Nasotracheal intubation is an effective surgical option for securing the surgical field without neck extension in anterior cervical surgery including C3 lesions.

Measurement Indicators of Age-Friendly Communities: Findings From the AARP Age-Friendly Community Survey.

BACKGROUND AND OBJECTIVES: Cities and counties worldwide have adopted the concept of "age-friendly communities." These communities aspire to promote older adults' well-being by providing a safe, affordable built environment and a social environment that encourages their participation. A major limitation in this field is the lack of valid and reliable measures that capture the complex dimensionality and dynamic nature of the aging-environment interface. RESEARCH DESIGN AND METHODS: This study uses data from the AARP 2016 Age-Friendly Community Surveys (N = 3,652 adults aged 65 and older). The survey includes 62 indicators of age-friendliness, for example, outdoor spaces, transportation, housing, social participation, and community and health services. We randomly split the sample into 2 equal subsamples for confirmatory factor analysis (CFA) and structural equation modeling (SEM). RESULTS: CFA results indicated that both the 5-factor model and the second-order factor model adequately fit the data. In the SEM 5-factor model, outdoor space (ß = 0.134; p = .017), social participation (ß = 0.307; p < .001), and community and health services (ß = -0.149; p = .008) were associated with self-rated health, the outcome of interest. The path coefficients of housing and transportation were not significant. In the second-order factor model, people who lived in more age-friendly communities reported better self-rated health (ß = 0.295; p < .001). DISCUSSION AND IMPLICATIONS: Our findings show that the Age-Friendly Community Survey measures demonstrate reliability and concurrent validity. To promote older adults' well-being, practitioners, policymakers, and researchers should focus on improving their built and social environments. They can use these measures for short- and long-term planning, monitoring, and evaluating age-friendly community initiatives.

Geographic proximity to neighborhood resources and depression among older adults in South Korea.

OBJECTIVES: Older adults are closely connected to their neighborhoods and they spend more time there than younger adults. Because their mobility is often impeded by diminished health and functioning, access to neighborhood health and social services is essential for their well-being. This article examines whether geographic proximity to these types of neighborhood resources is associated with depression among older adults in South Korea. METHODS: Data are from A Profile of Older Adults: 2015 which sampled 1,455 community-dwelling individuals ages 60 and older in South Korea. The Patient Health Questionnaire-9 (PHQ-9) was used to assess depression, the outcome. We measured geographic proximity to neighborhood destinations, which included the time it takes the respondent to go to the grocery store, hospital, government office, senior center, social service center, and bus stop. We conducted latent profile analyses (LPA) with a distal outcome using the BCH method to determine whether geographic proximity to neighborhood resources is associated with depression. RESULTS: The LPA identified three distinct subgroups of geographic proximity to neighborhood resources: High Access (10%), Moderate Access (41%), and Low Access (49%). Low Access (b = 3.71, p < .001) and Moderate Access (b = 3.00, p < .001) groups had higher levels of depression compared to those in the High Access group. DISCUSSION: Our findings suggest that access to essential services in one's neighborhood is associated with lower levels of depression, which supports existing evidence that age-friendly community initiatives are important to older adults' psychological well-being.

Cyclic nucleotide-gated ion channel 6 is involved in extracellular ATP signaling and plant immunity.

Extracellular ATP (eATP) is known to act as a danger signal in both plants and animals. In plants, eATP is recognized by the plasma membrane (PM)-localized receptor P2K1 (LecRK-I.9). Among the first measurable responses to eATP addition is a rapid rise in cytoplasmic free calcium levels ([Ca2+ ]cyt ), which requires P2K1. However, the specific transporter/channel proteins that mediate this rise in [Ca2+ ]cyt are unknown. Through a forward genetic screen, we identified an Arabidopsis ethylmethanesulfonate (EMS) mutant impaired in the [Ca2+ ]cyt response to eATP. Positional cloning revealed that the mutation resided in the cngc6 gene, which encodes cyclic nucleotide-gated ion channel 6 (CNGC6). Mutation of the CNGC6 gene led to a notable decrease in the PM inward Ca2+ current in response to eATP. eATP-induced mitogen-activated protein kinase activation and gene expression were also significantly lower in cngc6 mutant plants. In addition, cngc6 mutant plants were also more susceptible to the bacterial pathogen Pseudomonas syringae. Taken together, our results indicate that CNGC6 plays a crucial role in mediating eATP-induced [Ca2+ ]cyt signaling, as well as plant immunity.

Successful use of ultrasound-guided peripheral nerve block for lower limb surgery in a patient with heart failure with reduced ejection fraction: a case report.

The number of patients with heart failure with reduced ejection fraction (HFrEF) is increasing. These patients have a reduced cardiorespiratory reserve. Therefore, preoperative evaluation is essential to determine the best type of anaesthesia to use in patients with HFrEF. A 70-year-old man with HFrEF was scheduled to undergo debridement of skin necrosis due to thrombotic occlusion of the right common iliac artery. He had undergone wound dressing changes under local anaesthesia every other day for several months, and treatment for heart failure was on-going. A sciatic nerve and fascia iliaca compartment block was performed under ultrasound guidance because of the patient's cardiopulmonary function. After confirming adequate sensory blockage, surgery was performed without any haemodynamic instability or complications. Thereafter, debridement was performed twice more using the same block technique, and a skin autograft was also successfully performed. We successfully performed an ultrasound-guided sciatic nerve and fascia iliaca compartment block in a patient with HFrEF who was scheduled to undergo lower limb surgery. Peripheral nerve block is an alternative option for patients with HFrEF.

Genetic Polymorphisms in miR-604A>G, miR-938G>A, miR-1302-3C>T and the Risk of Idiopathic Recurrent Pregnancy Loss.

The purpose of this study was to investigate whether polymorphisms in five microRNAs (miRNAs), miR-604A>G, miR-608C>G, 631I/D, miR-938G>A, and miR-1302-3C>T, are associated with the risk of idiopathic recurrent pregnancy loss (RPL). Blood samples were collected from 388 patients with idiopathic RPL (at least two consecutive spontaneous abortions) and 227 control participants. We found the miR-604 AG and AG + GG genotypes of miR-604, the miR-938 GA and GA + AA genotypes of miR-938, and the miR-1302-3CT and CT + TT genotypes of miR-1302-3 are less frequent than the wild-type (WT) genotypes, miR-604AA, miR-938GG, and miR-1302-3CC, respectively, in RPL patients. Using allele-combination multifactor dimensionality reduction (MDR) analysis, we found that eight haplotypes conferred by the miR-604/miR-608/miR-631/miR-938/miR-1302-3 allele combination, A-C-I-G-T, A-C-I-A-C, G-C-I-G-C, G-C-I-G-T, G-G-I-G-C, G-G-I-G-T, G-G-I-A-C, G-G-D-G-C, three from the miR-604/miR-631/miR-938/miR-1302-3 allele combination, A-I-G-T, G-I-G-C, G-I-A-T, one from the miR-604/miR-631/miR-1302-3 allele combination, G-I-C, and two from the miR-604/miR-1302-3 allele combination, G-C and G-T, were less frequent in RPL patients, suggesting protective effects (all p < 0.05). We also identified the miR-604A>G and miR-938G>A polymorphisms within the seed sequence of the mature miRNAs and aligned the seed sequences with the 3'UTR of putative target genes, methylenetetrahydrofolate reductase (MTHFR) and gonadotropin-releasing hormone receptor (GnRHR), respectively. We further found that the binding affinities between miR-604/miR-938 and the 3'UTR of their respective target genes (MTHFR, GnRHR) were significantly different for the common (miR-604A, miR-938G) and variant alleles (miR-604G, miR-938A). These results reveal a significant association between the miR-604A>G and miR-938G>A polymorphisms and idiopathic RPL and suggest that miRNAs can affect RPL in Korean women.

3'-UTR Polymorphisms in Thymidylate Synthase with Colorectal Cancer Prevalence and Prognosis.

Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer-related mortality in Western countries. Polymorphisms in one-carbon metabolism and angiogenesis-related genes have been shown to play important roles in tumor development, progression, and metastasis for many cancers, including CRC. Moreover, recent studies have reported that polymorphisms in specific microRNA (miRNA)-binding regions, which are located in the 3'-untranslated region (UTR) of miRNA-regulated genes, are present in a variety of cancers. Here, we investigated the association between two thymidylate synthase (TYMS or TS) 3'-UTR polymorphisms, 1100T>C [rs699517] and 1170A>G [rs2790], and CRC susceptibility and progression in Korean patients. A total of 450 CRC patients and 400 healthy controls were enrolled in this study, and genotyping at the TS locus was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or TaqMan allelic discrimination assays. We found that TS 1170A>G genotypes, as well as the TS 1100T-1170G and 1100C-1170A haplotypes, are strongly associated with CRC. The TS 1100TC+CC type was associated with a poor survival (OS and RFS) rate. In addition, levels of the TS 1100C and TS 1170G allele were found to be significantly increased in CRC tissue. Our study provides the first evidence for 3'-UTR variants in TS genes as potential biomarkers of CRC prognosis and prevention.