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N 6-methyladenosine (m6A) RNA methylation has been shown to play a crucial role in plant development and floral transition. Two recent studies have identified FIONA1 as an m6A methyltransferase that regulates the floral transition in Arabidopsis through influencing the stability of CONSTANS (CO), SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1), and FLOWERING LOCUS C (FLC). In this study, we confirmed that FIONA1 is an m6A methyltransferase that installs m6A marks in a small group of mRNAs. Furthermore, we show that, in addition to its role in influencing the stability of CO, SOC1, and FLC, FIONA1-mediated m6A methylation influences the splicing of FLC, a key floral repressor, and the stability of SQUAMOSA PROMOTER-BINDING PROTEIN-LIKE 3 (SPL3) and SEPALLATA3 (SEP3), floral activators, which together play a vital role in floral transition in Arabidopsis. Our study confirms the function of FIONA1 as an m6A methyltransferase and suggests a close molecular link between FIONA1-mediated m6A methylation and the splicing of FLC and the destabilization of SPL3 and SEP3 in flowering time control.

Recently, a low-fluence picosecond (ps) laser is an emerging option for removing pigmented lesions.We aimed to evaluate the efficacy and safety of a 1,064-nm ps Nd:YAG laser as compared to a 1,064-nm Qs Nd:YAG laser for melasma treatment in an Asian.Twenty Korean patients with facial melasma were enrolled and randomly treated with a 1,064-nm ps Nd:YAG laser on one side of the face and 1,064-nm Qs Nd:YAG on the other side at 2-week intervals for five sessions. At each visit, the modified Melasma Area Severity Index (mMASI), patient satisfaction scores, visual analogue scale (VAS) scores, and adverse events were assessed.Both groups showed significant clinical improvement and decreased mMASI scores compared to the baseline. No statistically significant difference was observed in the mMASI score between the two treatment techniques at any time point. The melanin index showed no statistically significant improvement in both groups, and no significant differences were observed in patient satisfaction scores and VAS scores between both modalities.A 1,064 nm ps Nd:YAG laser is as effective and safe as a conventional 1,064 nm Qs Nd:YAG laser in the treatment of melasma in Asian skin, but no superior outcome was observed.

The transition to kindergarten is considered as one of the most significant developmental milestones in childhood. Although the significance of parental caregiving for child school readiness is well documented, it remains relatively unknown how dynamic interplay of maternal and paternal caregiving unfolds over time to promote school readiness, mediated by child characteristics. The present study used observed parent-child interactions to examine how maternal and paternal insensitivity across 24 to 36 months were similarly or differentially manifested in shaping school readiness in language and self-regulation skills among children from low-income families. Further, we tested whether children's adaptive engagement mediated the relations between parental insensitivity and school readiness. To these ends, this study used extant data from the Early Head Start Research and Evaluation Study (N = 453 families of mothers, fathers, and children; 51% girls). Latent difference score model revealed commonality in the similar effects of mothers and fathers on child early language, linking both maternal and paternal insensitivity at 24 months to poorer vocabulary skills in children at age 5. Additional findings showed specificity in the differential effects of maternal and paternal insensitivity on child functioning, such that maternal insensitivity predicted deficits in children's vocabulary and self-regulation skills indirectly through poorer child engagement, whereas paternal insensitivity directly predicted children's poorer self-regulation skills. The findings highlight the longitudinal processes of early maternal and paternal insensitivity with common and differential implications for school readiness.

Background The protein kinase A (PKA)/cAMP response element-binding protein (CREB) has been suggested to be related to the inhibition of the proliferation of non-small cell lung cancer (NSCLC) cells. This study aimed to investigate the efficacy of a novel diarylcyclohexanone derivative, MHY4571, in regulating the PKA-CREB pathway and to study its anti-tumor role in squamous NSCLC. Methods We designed MHY4571 as a novel PKA inhibitor with acceptable in silico ADME properties and tested it in vitro in lung cancer cell lines and in vivo in xenograft and orthotopic mouse models of squamous cell lung carcinoma. Results MHY4571 inhibited PKA activity (> 70% inhibition) and suppressed the expression of p-PKA and p-CREB dose-dependently. MHY4571 treatment reduced lung cancer cell viability and promoted caspase 3-dependent apoptotic cell death. Orally administered MHY4571 significantly suppressed lung tumor growth in xenograft and orthotopic mouse models. PKA catalytic subunit alpha-silencing by siRNA (siPKA) strongly attenuated CREB phosphorylation; siCREB did not alter PKA protein levels or its phosphorylation, suggesting that PKA is an upstream regulator of CREB activity. MHY4571 acted synergistically with cisplatin (on co-treatment) to induce apoptotic cell death in lung cancer cells. Conclusions Our results imply that MHY4571 may be a potential drug candidate for squamous cell lung cancer treatment.

N 6-methyladenosine (m 6A) RNA methylation has been shown to play a crucial role in plant development and floral transition. Two recent studies have identified FIONA1 as an m 6A methyltransferase that regulates the floral transition via influencing the stability of CONSTANS (CO), SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1), and FLOWERING LOCUS C (FLC) in Arabidopsis. In this study, we confirmed that FIONA1 is an m 6A methyltransferase that installs m 6A marks in a small group of mRNAs. Furthermore, in addition to its role in influencing the stability of CO, SOC1, and FLC, we show that FIONA1-mediated m 6A methylation influences the splicing of FLC, a key floral repressor, and the stability of SQUAMOSA PROMOTER-BINDING PROTEIN-LIKE 3 (SPL3) and SEPALLATA3 (SEP3), floral activators, which plays a vital role in the floral transition in Arabidopsis. Our study confirms FIONA1 as an m 6A methyltransferase and suggests a close molecular link between FIONA1-mediated m 6A methylation and the splicing of FLC and the destabilization of SPL3 and SEP3 in flowering time control.

Neurofibromatosis Type II (NF2) is an autosomal dominant cancer predisposition syndrome in which germline haploinsufficiency at the NF2 gene confers a greatly increased propensity for tumor development arising from tissues of neural crest derived origin. NF2 encodes the tumor suppressor, Merlin, and its biochemical function is incompletely understood. One well-established function of Merlin is as a negative regulator of group A serine/threonine p21-activated kinases (PAKs). In these studies we explore the role of PAK1 and its closely related paralog, PAK2, both pharmacologically and genetically, in Merlin-deficient Schwann cells and in a genetically engineered mouse model (GEMM) that develops spontaneous vestibular and spinal schwannomas. We demonstrate that PAK1 and PAK2 are both hyper activated in Merlin-deficient murine schwannomas. In preclinical trials, a pan Group A PAK inhibitor, FRAX-1036, transiently reduced PAK1 and PAK2 phosphorylation in vitro, but had insignificant efficacy in vivo. NVS-PAK1-1, a PAK1 selective inhibitor, had a greater but still minimal effect on our GEMM phenotype. However, genetic ablation of Pak1 but not Pak2 reduced tumor formation in our NF2 GEMM. Moreover, germline genetic deletion of Pak1 was well tolerated, while conditional deletion of Pak2 in Schwann cells resulted in significant morbidity and mortality. These data support the further development of PAK1-specific small molecule inhibitors and the therapeutic targeting of PAK1 in vestibular schwannomas and argue against PAK1 and PAK2 existing as functionally redundant protein isoforms in Schwann cells.

Mumps is the second-most reported infectious disease in South Korea; however, due to the low pathogen confirmation rate in laboratory diagnoses, we proposed a method for reevaluating the high incidence rate via the laboratory verification of other viral diseases. In 2021, 63 cases of pharyngeal or cheek mucosal swabs of suspected mumps cases in Gwangju, South Korea, were assessed for causative pathogens using massive simultaneous pathogen testing (TaqManTM Array Cards). More than one respiratory virus was detected in 60 cases (95.2%), 44 (73.3%) of which were co-detected. Human rhinovirus was detected in 47 cases, followed by human herpesvirus (HHV)6 in 30; HHV4 (17), human bocavirus (17), HHV5 (10), and human parainfluenza virus 3 (6) were also detected. Our findings suggest the need for further investigations on the pathogenesis of diseases mimicking mumps, which are considered to aid with appropriate public health responses, treatment, and the prevention of infectious disease outbreaks.

Exosomes are nano-sized extracellular vesicles released by the majority of the cell types. Exosomes play a major role in intercellular communication via transferring cargoes between cells and altering specific functions of the target cells. The interest in the biological activities of exosomes has been increasing and their therapeutic role has already been demonstrated in various diseases. Recently, there is growing evidence that stem cell-derived exosomes (including mesenchymal stem cell, umbilical cord-derived mesenchymal cell, adipose-derived stem cell, and pluripotent stem cell) can also be used in a variety of skin conditions due to their regenerative and anti-inflammatory capacity. In this paper, we will provide a brief overview of recent studies on practical applications of exosomes in several dermatologic conditions and their potential mechanisms. By elucidating the different mechanisms and therapeutic roles of exosomes in various disease conditions, we hope dermatologists and other clinicians to establish better strategies for disease treatment with further research.

Background: The etiology of small for gestational age (SGA) is multifactorial and includes maternal/uterine-placental factors, fetal epigenetics, and genetic abnormalities. We evaluated the genetic causes and diagnostic effectiveness of targeted-panel sequencing (TES) or whole-exome sequencing (WES) in SGA infants without a known cause. Methods: A prospective study was conducted on newborn infants born with a birth weight of less than the 10th percentile for gestational age between January 2019 and December 2020 at the Pusan National University Hospital. We excluded infants with known causes of SGA, including maternal causes or major congenital anomalies or infections. SGA infants without a known etiology underwent genetic evaluation, including karyotyping, chromosomal microarray (CMA), and TES/WES. Results: During the study period, 82 SGA infants were born at our hospital. Among them, 61 patients were excluded. A total of 21 patients underwent karyotyping and chromosomal CMA, and aberrations were detected in two patients, including one chromosomal anomaly and one copy number variation. Nineteen patients with normal karyotype and CMA findings underwent TES or WES, which identified three pathogenic or likely pathogenic single-gene mutations, namely LHX3, TLK2, and MED13L. Conclusions: In SGA infants without known risk factors, the prevalence of genetic causes was 22% (5/21). The diagnostic yield of TES or WES in SGA infants with normal karyotype and CMA was 15.7% (3/19). TES or WES was quite helpful in identifying the etiology in SGA infants without a known cause.

RNA helicases (RHs) are cellular proteins that help in the regulation of post-transcriptional mRNA metabolism, which is vital for the response of crops to abiotic stresses. In this study, we determined the functional role of a cabbage (Brassica rapa) DEAD-box RH, BrRH37, in abiotic stress and abscisic acid (ABA) responses using transgenic Arabidopsis plants. Although BrRH37 contains a putative chloroplast transit peptide and a potential nuclear localization signal, confocal analysis of the expression of the BrRH37-GFP protein in tobacco leaves revealed that BrRH37 is localized in the nucleus. The transcript levels of BrRH37 in cabbage were increased upon drought, cold, or ABA application, whereas its level was decreased by heat or UV stress. The transgenic Arabidopsis plants that constitutively express BrRH37 showed enhanced seedling and root growth or survival rate under drought stress or upon ABA application, whereas their growth and survival were decreased under cold or UV stress. Notably, transcript levels of ABA biosynthesis-related genes, including ABA1 and ABA3, were significantly increased in the transgenic plants compared with that in the wild type. Importantly, BrRH37 was found to recover the growth of the RNA chaperone-deficient Escherichia coli mutant at low temperature and had the ability to break up base pairs in RNA, suggesting that BrRH37 possesses RNA chaperone activity. Altogether, our results indicate that BrRH37 plays diverse functions in plant response to abiotic stress and ABA possibly via its RNA chaperone activity.

Introduction Burn injuries are common afflictions; however, conservative wound care frequently leads to poor treatment compliance and physical disability in deep burn patients. Therefore, regenerative biologic materials, which are more effective for tissue repair, are required, particularly for deep second-degree burns. A novel spray formulation of basic fibroblast growth factors (bFGF) was produced by synthesizing fibroblast growth factor proteins. In this post-marketing surveillance (PMS) study, we assessed the safety and efficacy of bFGF and indirectly compared this formulation with cultured epidermal autografts (CEAs) for treating deep second-degree burns. Materials and methods A total of 3173 patients treated at 15 hospitals were used for PMS of bFGF in South Korea for six years. In total, 1635 patients with deep second–degree burns were selected for assessing adverse events (AEs) of bFGF treatments. Efficacy was evaluated according to time periods until re-epithelialization, and clinical usefulness of bFGF was indirectly compared with that of CEAs. Results AEs occurred in 37 patients (2.3%) and included application site pain (1.7%) and contact dermatitis (0.6%). All AEs were mild and were evaluated as probably unrelated with bFGF. The average time for re-epithelialization was 8 days; this time span was significantly longer after major burns (9.7 days) than after minor (7.8 days) or moderate burns (7.9 days). Most treated burn wounds (99.8%) were assessed as improved. The indirect comparison included 534 patients using the same inclusion criteria for CEA patients (n = 35). The bFGF treatment demonstrated superior efficacy compared to CEAs by significantly reducing the average post-burn day of application time (5.4 vs. 8.8 days) and re-epithelialization time (7.1 vs. 13.7 days). Conclusion Our study demonstrated that bFGF is a compelling regenerative therapy with competitive clinical efficacy and safety for deep second–degree burns and reduced treatment time, which is expected to reduce medical costs, particularly for deep second–degree burn patients.

Hyaluronic acid fillers are widely used for the augmentation of facial soft tissues. Hyaluronic acid fillers can be monophasic or biphasic and have different characteristics, especially regarding volumetric effects and maintenance potential. However, there is paucity of long-term quantitative and objective data on clinical outcomes following hyaluronic acid injection. In this study, the authors evaluated volumetric changes over 2 years and the maintenance potentials of both types of fillers on the anteromedial cheek using objective three-dimensional measurements. This comparative split-face study enrolled participants aged 30 to 50 years who received a midfacial injection of the test filler (Belotero Volume) on one side and a random control filler (Juvéderm, Restylane SubQ, or Yvoire Contour) on the contralateral side. The authors conducted three-dimensional scanning assessments at baseline and after 30 minutes; 3 days; 2, 4, 12, and 24 weeks; and 2 years. The volume augmentation effects for the anteromedial cheek of two monophasic fillers (Belotero Volume and Juvéderm Voluma) were maintained for at least 2 years (81 percent and 66 percent, respectively, compared to the volume at 4 weeks). Two biphasic fillers (Yvoire Contour and Restylane SubQ) maintained over 50 percent volume compared to the volume 4 weeks after injection. Monophasic fillers showed better outcomes than biphasic fillers; however, both types of hyaluronic acid fillers demonstrated superior efficacy, safety, and durability for volumetric augmentation in the anteromedial cheek. Objective data obtained using three-dimensional imaging analysis will enable dermatologists to better demonstrate the results of the procedure to patients, through the provision of visual aids.Therapeutic, II.

Background and objectives Autologous or allogeneic bone marrow-derived mesenchymal stem cells (BMSCs) have been applied in clinical trials to treat liver disease. However, only a few studies are comparing the characteristics of autologous MSCs from patients and allogeneic MSCs from normal subjects. Methods and results We compared the characteristics of BMSCs (BCs and BPs, respectively) isolated from six healthy volunteers and six patients with cirrhosis. In passage 3 (P3), senescent population and expression of p53 and p21 were slightly higher in BPs, but the average population doubling time for P3-P5 in BPs was approximately 65.3±11.1 h, which is 18.4 h shorter than that in BCs (83.7±9.2 h). No difference was observed in the expression of CD73, CD90, or CD105 between BCs and BPs. Adipogenic differentiation slightly increased in BCs, but the expression levels of leptin, peroxisome proliferator-activated receptor γ, and CCAAT-enhancer-binding protein α did not vary between differentiated BCs and BPs. While ATP and reactive oxygen species levels were slightly lower in BPs, mitochondrial membrane potential, oxygen consumption rate, and expression of mitochondria-related genes such as cytochrome c oxidase 1 were not significantly different between BCs and BPs. Conclusions Taken together, there are marginal differences in the proliferation, differentiation, and mitochondrial activities of BCs and BPs, but both BMSCs from patients with cirrhosis and healthy volunteers show comparable characteristics.

La-related proteins (LaRPs) are RNA-binding proteins (RBPs) that contain a La-type helix-turn-helix (HTH) domain and are found in all eukaryotes, including plants, animals, and yeasts. Although the functions of a few LaRPs have been determined during plant growth and development, the roles of most LaRPs in plants remain unknown. Here, the function of an Arabidopsis thaliana LaRP6a (At5g46250) harboring a La-type HTH domain and an RNA-recognition motif was determined in the growth and development of Arabidopsis. Confocal analysis of subcellular localization of the LaRP6a–GFP fusion protein revealed that LaRP6a protein is localized to both the nucleus and plasma membrane. Overexpression of LaRP6a resulted in delayed flowering and increased plant height and seed yield. The transcript level of the floral repressor FLC was markedly increased in LaRP6a-overexpressing transgenic plants. LaRP6a protein bound to the 3ʹUTR of the FLC transcript and possessed RNA chaperone activity. Collectively, these results suggest that LaRP6a plays a role in the control of flowering time by regulating FLC transcript levels.

Background Due to the ever-increasing demands for the personalized care, people seek for the tailored management according to the accurate identification of their skin type. The Baumann Skin Type Indicator, which was proposed by Leslie Baumann, is composed of four parameters: oily or dry, resistant or sensitive, pigmented or nonpigmented, and wrinkled or tight. Among these, oily sensitive skin experiences significant discomfort and resists ordinary treatment. Aims In this article, we will review the clinical manifestations, underlying pathogenesis and recommendations on treatment options that may be utilized to help patients with oily sensitive skin. Patients/methods Literature search was conducted using PubMed. The literature concerning Baumann Skin Type Indicator and oily sensitive skin type were considered. Results Oily sensitive (OS)-type skin is a complex of oily and sensitive skin that causes significant discomfort and undergoes stubborn resistance to treatments. Sebum dysfunction and hypersensitivity may play a key role in the development of sensitive skin. Considering the pathogenesis of OS-type skin, treatment should focus on both seborrhea and hypersensitivity. Conclusion Clinicians can effectively treat the oily sensitive skin by understanding underlying pathogenesis of it. Further investigations are necessary to reach a consensus on the basic pathophysiology and optimal management guidelines for oily sensitive skin.

Although many treatment options are available, the treatment of melasma remains challenging. To investigate the efficacy and safety of combined treatment for melasma with a quality (Q)-switched 1064-nm neodymium: yttrium-aluminum-garnet (Nd:YAG) laser and a topical mixture of tranexamic acid, niacinamide, and kojic acid. Twenty-five patients with melasma were enrolled. One side of the face was treated with low-fluence Q-switched 1064-nm Nd:YAG laser alone, while the other side was treated with a combination of laser treatment and a topical mixture of tranexamic acid, niacinamide, and kojic acid. Each treatment consisted of five sessions at 2-week intervals, and patients were followed up 4 weeks after the last treatment. Overall improvement was assessed using the hemi Melasma Area and Severity Index (MASI) score. A specialized imaging system (Markview®, PSIPLAUS Inc., Suwon, Korea) was used to record images of the patients' faces, and photographic assessment was performed by two independent evaluators at 2, 4, 6, 8, and 12 weeks using a five-point grading scale. Although both sides of the face showed clinical improvement, combination treatment demonstrated a greater improvement in the mean hemi MASI score compared to laser treatment alone. Improvement in melasma at 12 weeks, according to the evaluation of patient images by two independent evaluators, was greater with combination treatment. This study demonstrated that the combination of treatment with a low-fluence Q-switched 1064-nm Nd:YAG laser and a topical mixture of tranexamic acid, niacinamide, and kojic acid would be a good option for melasma treatment.

Background: nosocomial sepsis remains a significant source of morbidity and mortality in extremely low birth weight (ELBW) infants. Early and accurate diagnosis is very important, but it is difficult due to the similarities in clinical manifestation between the causative microorganisms. We tried to identify the differences between causative microorganisms in clinical and laboratory findings and to help choose antibiotics, when sepsis was suspected in ELBW infants. Methods: a retrospective study was conducted on preterm infants, born at less than 28 weeks of gestation, with a birth weight of less than 1000 g between January 2009 and December 2019. Clinical and laboratory findings of suspected sepsis, after the first 72 h of life, were assessed. We classified them into four groups according to blood culture results (gram positive, gram negative, fungal, and negative culture groups) and compared them. Results: a total of 158 patients were included after using the exclusion criteria, with 45 (29%) in the gram positive group, 35 (22%) in the gram negative group, 27 (17%) in the fungal group, and 51 (32%) in the negative culture group. There were no significant differences in mean gestational age, birth weight, and neonatal morbidities, except for the age of onset, which was earlier in the fungal group than other groups. White blood cell (WBC) counts were the highest in the gram negative group and the lowest in the fungal group. The mean platelet counts were the lowest in the fungal group. C-reactive protein (CRP) levels were the highest in the gram negative group, while glucose was the highest in the fungal group. Conclusions: in conclusion, we showed that there are some differences in laboratory findings, according to causative microorganisms in the nosocomial sepsis of ELBW infants. Increased WBC and CRP were associated with gram negative infection, while decreased platelet and glucose level were associated with fungal infection. These data may be helpful for choosing empirical antibiotics when sepsis is suspected.

With the increasing demand for body contouring, botulinum toxin (BTX) injection is being widely used off-label for muscular hypertrophy. However, to the best of our knowledge, no study has investigated the clinical efficacy of BTX type A (BTX-A) in deltoid muscle hypertrophy. This study was conducted to evaluate the efficacy and safety of intramuscular injection of BTX in reducing deltoid muscle hypertrophy. Overall, 10 patients with bilateral deltoid muscle hypertrophy were treated with an intramuscular injection of prabotulinum toxin A, with a total of 50 units [U] administered per patient. As measured by ultrasonography, the thickness of the deltoid muscles was significantly decreased at weeks 2 and 12. In addition, the clinical assessment score by blinded investigators was improved after the treatment; however, patients' satisfaction scores were relatively low. No major complications were reported. Therefore, intramuscular injection of BTX-A seems to be a candidate for novel treatment option for deltoid muscle hypertrophy. Further larger clinical studies are warranted to confirm the efficacy of BTX-A.

Background No data on the clinical results and safety profiles of the polycaprolactone (PCL) -based dermal filler for crow's feet correction have been published. Aims This study was designed to compare the efficacy and safety of a novel PCL-based dermal filler, DLMR01, with that of RJR, a purified polynucleotide dermal filler. Patients/methods A total of 30 subjects with symmetric crow's feet of 2-4 points on the Crow's Feet Grading Scale (CFGS) were enrolled in this randomized, patient/evaluator-blinded, split-face study. Each subject was randomized to receive injections of DLMR01 or RJR in their right or left crow's feet. At 4 and 12 weeks, all participants were evaluated via CFGS, Global Aesthetic Improvement Scale (GAIS), and PRIMOS software system. Results No significant difference in CFGS, GAIS, and Ra value was detected between DLMR01 side and RJR at 12 weeks (improvement rate in CFGS from baseline at week 12-DLMR01: 48.28% [14/29], RJR: 41.38% [12/29]). Conclusion The novel PCL-based dermal filler DLMR01 shows suitable efficacy and safety, widening the selection possibilities for clinicians and patients in the treatment crow's feet.

The pentatricopeptide repeat proteins PPR4 and EMB2654 have been shown to be required for the trans-splicing of plastid rps12 transcripts in Zea mays (maize) and Arabidopsis, respectively, but their roles in this process are not well understood. We investigated the functions of the Arabidopsis and Oryza sativa (rice) orthologs of PPR4, designated AtPPR4 (At5g04810) and OsPPR4 (Os4g58780). Arabidopsis atppr4 and rice osppr4 mutants are embryo-lethal and seedling-lethal 3 weeks after germination, respectively, showing that PPR4 is essential in the development of both dicot and monocot plants. Artificial microRNA-mediated mutants of AtPPR4 displayed a specific defect in rps12 trans-splicing, with pale-green, yellowish or albino phenotypes, according to the degree of knock-down of AtPPR4 expression. Comparison of RNA footprints in atppr4 and emb2654 mutants showed a similar concordant loss of extensive footprints at the 3' end of intron 1a and at the 5' end of intron 1b in both cases. EMB2654 is known to bind within the footprint region in intron 1a and we show that AtPPR4 binds to the footprint region in intron 1b, via its PPR motifs. Binding of both PPR4 and EMB2654 is essential to juxtapose the two intron halves and to maintain the RNAs in a splicing-competent structure for the efficient trans-splicing of rps12 intron 1, which is crucial for chloroplast biogenesis and plant development. The similarity of EMB2654 and PPR4 orthologs and their respective binding sites across land plant phylogeny indicates that their coordinate function in rps12 trans-splicing has probably been conserved for 500 million years.

Background and objectives The selective electrothermolysis of the sebaceous glands was suggested as a novel therapeutic option for facial acne. However, there has been no randomized controlled trial to evaluate the effectiveness and safety of the monopolar radiofrequency (RF) device using single microneedle with proximal insulation. The objective of the study was to evaluate the efficacy and tolerability of intralesional electrothermolysis using monopolar RF device and proximally-insulated single microneedle in acne patients. Study design/materials and methods The prospective randomized controlled clinical trial was performed to treat moderate-to-severe facial acne. Subjects randomized to the treatment group received three treatments at 4-week intervals with an RF device, whereas the control group received micro-needling and extraction. For efficacy evaluation, reduction rate of acne lesions were evaluated by two independent physicians. Results Sixty-three patients completed the study and the results showed statistically significant improvement of inflammatory acne at 12 weeks. The number of inflammatory lesions was significantly reduced at 12 weeks (20.86 vs. -5.13; P = 0.03) compared with controls. Conclusions Selective sebaceous gland electrothermolysis can be a safe and effective method of achieving consistent improvement in acne. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Although the importance of chloroplast RNA splicing and ribosome maturation (CRM) domain-containing proteins has been established for chloroplast RNA metabolism and plant development, the functional role of CRM proteins in mitochondria remains largely unknown. Here, we investigated the role of a mitochondria-targeted CRM protein (At3g27550), named CFM9, in Arabidopsis thaliana. Confocal analysis revealed that CFM9 is localized in mitochondria. The cfm9 mutant exhibited delayed seed germination, retarded growth and shorter height compared with the wild type under normal conditions. The growth-defect phenotypes were more manifested upon high salinity, dehydration or ABA application. Complementation lines expressing CFM9 in the mutant background fully recovered the wild-type phenotypes. Notably, the mutant had abnormal mitochondria, increased hydrogen peroxide and reduced respiration activity, implying that CFM9 is indispensable for normal mitochondrial function. More important, the splicing of many intron-containing genes in mitochondria was defective in the mutant, suggesting that CFM9 plays a crucial role in the splicing of mitochondrial introns. Collectively, our results provide clear evidence emphasizing that CFM9 is an essential factor in the splicing of mitochondrial introns, which is crucial for mitochondrial biogenesis and function and the growth and development of Arabidopsis.

As the most abundant internal modification of mRNA, N

Ribosomal RNA (rRNA) methylation is a pivotal process in the assembly and activity of ribosomes, which in turn play vital roles in the growth, development and stress responses of plants. Although few methyltransferases responsible for rRNA methylation have been identified in plant chloroplasts, the nature and function of these enzymes in chloroplasts remain largely unknown. In this study, we characterized ArabidopsisRsmD (At3g28460), an ortholog of the methyltransferase responsible for N2-methylguanosine (m2G) modification of 16S rRNA in Escherichia coli. Confocal microscopic analysis of an RsmD– green fluorescent protein fusion protein revealed that RsmD is localized to chloroplasts. Primer extension analysis indicated that RsmD is responsible for m2G methylation at position 915 in the 16S rRNA of Arabidopsis chloroplasts. Under cold stress, rsmd mutant plants exhibited retarded growth, i.e. had shorter roots, lower fresh weight and pale-green leaves, compared with wild-type (WT) plants. However, these phenotypes were not detected in response to drought or salt stress. Notably, the rsmd mutant was hypersensitive to erythromycin or lincomycin and accumulated fewer chloroplast proteins compared with the WT, suggesting that RsmD influences translation in chloroplasts. Complementation lines expressing RsmD in the rsmd mutant background recovered WT phenotypes. Importantly, RsmD harbored RNA methyltransferase activity. Collectively, the findings of this study indicate that RsmD is a chloroplast 16S rRNA methyltransferase responsible for m2G915 modification that plays a role in the adaptation of Arabidopsisto cold stress.

Pulmonary hypertension (PH) is traditionally defined as a mean pulmonary arterial pressure (mPAP) ≥25 mmHg. Although various factors cause PH, the most common etiology is PH due to left heart disease (PH-LHD). The underlying LHD is characterized by heart failure (HF) with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), valvular heart disease, cardiomyopathies, or arrhythmic diseases. Regardless of its underlying cause, elevated left atrial (LA) filling pressure is a manifestation of advanced heart disease. High LA pressure then causes persistent backflow to the pulmonary veins, which increases mPAP. PH-LHD at this stage is named isolated postcapillary PH (IpcPH). Further progression of IpcPH is associated with pulmonary vasculature remodeling and hypertrophy, which consists of adding the precapillary component of PH to the pre-existing postcapillary PH. This form of PH-LHD is called combined precapillary and postcapillary PH (CpcPH). To date, therapeutic strategies for PH-LHD have been investigated in the context of HFrEF or HFpEF. Pulmonary arterial hypertension (PAH)-specific drugs have been tested in HFrEF and HFpEF populations, although encouraging results have not been demonstrated. As PAH-specific drugs target the precapillary component of PH-LHD, future studies utilizing such therapeutics in PH-LHD patients with CpcPH appear to have a more robust pathobiological basis. This article reviews the diagnosis, pathophysiology, treatment, and future direction of PH in HF.