Exploring the molecular regulation of vernalization-induced flowering synchrony in Arabidopsis.

Many plant populations exhibit synchronous flowering, which can be advantageous in plant reproduction. However, molecular mechanisms underlying flowering synchrony remain poorly understood. We studied the role of known vernalization-response and flower-promoting pathways in facilitating synchronized flowering in Arabidopsis thaliana. Using the vernalization-responsive Col-FRI genotype, we experimentally varied germination dates and daylength among individuals to test flowering synchrony in field and controlled environments. We assessed the activity of flowering regulation pathways by measuring gene expression across leaves produced at different time points during development and through a mutant analysis. We observed flowering synchrony across germination cohorts in both environments and discovered a previously unknown process where flower-promoting and repressing signals are differentially regulated between leaves that developed under different environmental conditions. We hypothesized this mechanism may underlie synchronization. However, our experiments demonstrated that signals originating from sources other than leaves must also play a pivotal role in synchronizing flowering time, especially in germination cohorts with prolonged growth before vernalization. Our results suggest flowering synchrony is promoted by a plant-wide integration of flowering signals across leaves and among organs. To summarize our findings, we propose a new conceptual model of vernalization-induced flowering synchrony and provide suggestions for future research in this field.

Can Mandarin-speaking prelingual deaf adults benefit from cochlear implant?

BACKGROUND: With advances in cochlear implant (CI) technology, prelingual deaf adults may experience improved speech perception and quality of life (QoL). It is still a challenge for Mandarin-speaking CI user with tone recognition due to CI technology focused on intonation language. OBJECTIVES: To evaluate the long-term post-CI auditory performance and social-emotional benefits in prelingual deaf Mandarin-speaking adults and the difference between them and post-lingual deaf adults. MATERIAL AND METHODS: Fifty-five adult implanted ears were included (forty-six postlingual deaf group; nine prelingual deaf group). Post-CI long-term outcomes were using vowels, consonants, disyllabic words, Mandarin monosyllable words, categories of audiology performance, speech intelligibility rating, subjective social-emotional questionnaires. RESULTS: Post-CI auditory performance and speech intelligibility of prelingual deafness adults was significantly inferior to that of those with postlingual deafness. However, both groups presented improved social-emotional benefits, with no significant difference between both groups. CONCLUSIONS: Adult CI recipients who deaf before the age of 4 can experience benefits in social-emotional life functioning, regardless of their limited auditory performance and speech intelligibility. Therefore, prelingual Mandarin-speaking deaf adults, especially those using oral communication, can be considered as relative indications for cochlear implantation. SIGNIFICANCE: To clarify and validate the benefits among Mandarin-speaking prelingual deaf adult recipients.

Long-term voice outcomes of medialization thyroplasty with adjustable implant for unilateral vocal fold paralysis.

OBJECTIVES: Medialization thyroplasty (MT) using various implants has been employed as a corrective procedure for unilateral vocal fold paralysis (UVFP). A newly developed APrevent® vocal implant system (VOIS) offers an innovative solution with a finely adjustable design. This study aimed to investigate the long-term functional voice outcomes and benefits of postoperative adjustments in patients receiving MT using the VOIS-implant. METHODS: This is a prospective case series study at single tertiary medical center. Fourteen adult patients diagnosed with UVFP received MT with the VOIS implant and were followed up for more than 1 year. Implant adjustment procedure by injecting 0.9% physiological saline solution was performed both during and after the surgery to optimize glottal closure and voice quality. Objective voice outcomes and acoustic parameters were assessed preoperatively and postoperatively at various timepoints. RESULTS: Thirteen patients (93%) received intraoperative balloon adjustment, ranging from 0.05to 0.12 ml. Four patients underwent adjustments postoperatively and exhibited a positive trend towards immediately improving acoustic voice quality. Our long-term results demonstrated a notable improvement after the surgery in voice quality, with significant decreases in VHI-30 and improvements in perceptual parameters of GRBAS scale, acoustic measures such as jitter and signal-to-noise ratio (p < 0.001) and cepstral peak prominence smoothed in sustained vowel and short sentences. The voice outcomes remained stable more than 1 year follow-up. CONCLUSIONS: Overall, MT with VOIS implantation provides a favorable long-term outcomes and stability in voice quality for patients with UVFP and also an effective tool for postoperative adjustment without major revision surgeries.

Thyroglossal Duct Cyst Papillary Carcinoma With Airway Compromise.

Thyroglossal duct cysts are typically benign and usually asymptomatic. Malignant transformation is uncommon. Intralaryngeal extension is rare and results in dysphonia or dyspnea. There is no literature nowadays reporting the thyroglossal duct cyst carcinoma combining the clinical features of intralaryngeal extension. The authors present a case of progressive hoarseness and midline neck mass for 2 years. The laryngoscope and computed tomography revealed a 6-cm thyroglossal duct cyst containing ectopic thyroid tissue with intralaryngeal extension and causing airway obstruction. Complete excision with Sistrunk operation revealed papillary thyroid carcinoma. The patient resumed normal phonation after the surgery. There was no evidence of tumor recurrence and no hoarseness or dyspnea at 6 months follow up. This is the first reported case of a huge thyroglossal duct cyst carcinoma with intralaryngeal extension causing airway compromise. Complete excision of tumor is essential and vital to the symptom relief. A thyroglossal duct cyst carcinoma with endolaryngeal involvement should be considered in the differential diagnosis when the case has a massive midline neck mass with ectopic thyroid tissue and develops dyspnea or hoarseness concurrently.

Augmented detection of septal defects using advanced optical coherence tomography network-processed phonocardiogram.

Background: Cardiac auscultation is a traditional method that is most frequently used for identifying congenital heart disease (CHD). Failure to diagnose CHD may occur in patients with faint murmurs or obesity. We aimed to develop an intelligent diagnostic method of detecting heart murmurs in patients with ventricular septal defects (VSDs) and atrial septal defects (ASDs). Materials and methods: Digital recordings of heart sounds and phonocardiograms of 184 participants were obtained. All participants underwent echocardiography by pediatric cardiologists to determine the type of CHD. The phonocardiogram data were classified as normal, ASD, or VSD. Then, the phonocardiogram signal was used to extract features to construct diagnostic models for disease classification using an advanced optical coherence tomography network (AOCT-NET). Cardiologists were asked to distinguish normal heart sounds from ASD/VSD murmurs after listening to the electronic sound recordings. Comparisons of the cardiologists' assessment and AOCT-NET performance were performed. Results: Echocardiography results revealed 88 healthy participants, 50 with ASDs, and 46 with VSDs. The AOCT-NET had no advantage in detecting VSD compared with cardiologist assessment. However, AOCT-NET performance was better than that of cardiologists in detecting ASD (sensitivity, 76.4 vs. 27.8%, respectively; specificity, 90 vs. 98.5%, respectively). Conclusion: The proposed method has the potential to improve the ASD detection rate and could be an important screening tool for patients without symptoms.

Natural phenolic compounds potentiate hypoglycemia via inhibition of Dipeptidyl peptidase IV.

Dipeptidyl peptidase IV (DPP IV) is a surface glycoprotein that can degrade glucagon like pepetide-1 (GLP-1) by decreasing blood sugar. Herbal medicines for diabetic therapy are widely used with acceptable efficacy but unsatisfied in advances. DPP IV was chosen as a template to employ molecular docking via Discovery Studio to search for natural phenolic compounds whether they have the inhibitory function of DPP IV. Then, docking candidates were validated and further performed signal pathway via Caco-2, C2C12, and AR42J cells. Lastly, a diet-induced diabetes in mice were applied to examine the efficacy and toxicity of hit natural phenolic products in long-term use (in vivo). After screening, curcumin, syringic acid, and resveratrol were found in high affinity with DPP IV enzymes. In enzymatic tests, curcumin and resveratrol showed potential inhibition of DPP IV. In vitro assays, curcumin inhibited of DPP IV activity in Caco-2 cells and ERK phosphorylation in C2C12 cells. Additionally, curcumin attenuated blood sugar in S961-treated C57BL/6 mice and in diet-induced diabetic ICR mice and long-term regulate HbA1c in diabetic mice. Curcumin targeted to DPP IV for reducing blood glucose, it possesses potential and alternative substitution of synthetic clinical drugs for the medication of diabetes.

Polyalthia Clerodane Diterpene Potentiates Hypoglycemia via Inhibition of Dipeptidyl Peptidase 4.

Serine protease dipeptidyl peptidase 4 (DPP-4) is involved in self/non-self-recognition and insulin sensitivity. DPP-4 inhibitors are conventional choices for diabetic treatment; however, side effects such as headache, bronchus infection, and nasopharyngitis might affect the daily lives of diabetic patients. Notably, natural compounds are believed to have a similar efficacy with lower adverse effects. This study aimed to validate the DPP-4 inhibitory activity of clerodane diterpene 16-hydroxycleroda-3,13-dien-15,16-olide (HCD) from Polyalthia longifolia, rutin, quercetin, and berberine, previously selected through molecular docking. The inhibitory potency of natural DPP-4 candidates was further determined by enzymatic, in vitro Caco-2, and ERK/PKA activation in myocyte and pancreatic cells. The hypoglycemic efficacy of the natural compounds was consecutively analyzed by single-dose and multiple-dose administration in diet-induced obese diabetic mice. All the natural-compounds could directly inhibit DPP-4 activity in enzymatic assay and Caco-2 inhibition assay, and HCD showed the highest inhibition of the compounds. HCD down-regulated LPS-induced ERK phosphorylation in myocyte but blocked GLP-1 induced PKA expression. For in vivo tests, HCD showed hypoglycemic efficacy only in single-dose administration. After 28-days administration, HCD exhibited hypolipidemic and hepatoprotective efficacy. These results revealed that HCD performed potential antidiabetic activity via inhibition of single-dose and long-term administrations, and could be a new prospective anti-diabetic drug candidate.

TIC236 links the outer and inner membrane translocons of the chloroplast.

The two-membrane envelope is a defining feature of chloroplasts. Chloroplasts evolved from a Gram-negative cyanobacterial endosymbiont. During evolution, genes of the endosymbiont have been transferred to the host nuclear genome. Most chloroplast proteins are synthesized in the cytosol as higher-molecular-mass preproteins with an N-terminal transit peptide. Preproteins are transported into chloroplasts by the TOC and TIC (translocons at the outer- and inner-envelope membranes of chloroplasts, respectively) machineries1,2, but how TOC and TIC are assembled together is unknown. Here we report the identification of the TIC component TIC236; TIC236 is an integral inner-membrane protein that projects a 230-kDa domain into the intermembrane space, which binds directly to the outer-membrane channel TOC75. The knockout mutation of TIC236 is embryonically lethal. In TIC236-knockdown mutants, a smaller amount of the inner-membrane channel TIC20 was associated with TOC75; the amount of TOC-TIC supercomplexes was also reduced. This resulted in a reduced import rate into the stroma, though outer-membrane protein insertion was unaffected. The size and the essential nature of TIC236 indicate that-unlike in mitochondria, in which the outer- and inner-membrane translocons exist as separate complexes and a supercomplex is only transiently assembled during preprotein translocation3,4-a long and stable protein bridge in the intermembrane space is required for protein translocation into chloroplasts. Furthermore, TIC236 and TOC75 are homologues of bacterial inner-membrane TamB5 and outer-membrane BamA, respectively. Our evolutionary analyses show that, similar to TOC75, TIC236 is preserved only in plants and has co-evolved with TOC75 throughout the plant lineage. This suggests that the backbone of the chloroplast protein-import machinery evolved from the bacterial TamB-BamA protein-secretion system.

High-Mobility Group Nucleosome-Binding Protein 1 as Endogenous Ligand Induces Innate Immune Tolerance in a TLR4-Sirtuin-1 Dependent Manner in Human Blood Peripheral Mononuclear Cells.

High-mobility group nucleosome-binding protein 1 (HMGN1) functions as a non-histone chromatin-binding protein in the cell nucleus. However, extracellular HMGN1 acts as an endogenous danger-associated inflammatory mediator (also called alarmin). We demonstrated that HMGN1 not only directly stimulated cytokine production but also had the capacity to induce immune tolerance by a TLR4-dependent pathway, similar to lipopolysaccharide (LPS)-induced tolerance. HMGN1-induced tolerance was accompanied by a metabolic shift associated with the inhibition of the induction of Warburg effect (aerobic glycolysis) and histone deacetylation via Sirtuin-1. In addition, HMGN1 pre-challenge of mice also downregulated TNF production similar to LPS-induced tolerance in vivo. In conclusion, HMGN1 is an endogenous TLR4 ligand that can induce both acute stimulation of cytokine production and long-term tolerance, and thus it might play a modulatory role in sterile inflammatory processes such as those induced by infection, trauma, or ischemia.

Simultaneous acute Marchiafava-Bignami disease and central pontine myelinolysis: A case report of a challenging diagnosis.

RATIONALE: Marchiafava-Bignami disease (MBD) is a rare disease characterized by demyelination of the corpus callosum. It is most commonly seen in patients with chronic alcoholism. The clinical diagnosis of MBD can be difficult due to its nonspecific manifestation. Central pontine myelinolysis (CPM) occurs mostly as a complication of severe and prolonged hyponatremia, especially when corrected too rapidly. However, CPM can be associated with chronic alcoholism and its clinical presentation can be heterogeneous. Because both MBD and CPM can have fatal outcomes, early recognition and treatment can result in a better prognosis. We present a very rare case of simultaneous acute Marchiafava-Bignami disease and central pontine myelinolysis in a patient with chronic alcoholism who was diagnosed unexpectedly using brain magnetic resonance imaging and improved after proper treatment. PATIENT CONCERNS: We presented a case of a 39-year-old patient who visited the hospital with general weakness and an altered neurologic condition after a week of vomiting. DIAGNOSIS: The patient was diagnosed with simultaneous acute Marchiafava-Bignami disease and central pontine myelinolysis using brain magnetic resonance imaging. INTERVENTION: Administration of a high dose of thiamine. OUTCOMES: The neurologic signs improved after a week of thiamine administration. LESSONS: This case suggests that Marchiafava-Bignami disease and central pontine myelinolysis might have a common pathogenesis, and brain magnetic resonance imaging is of crucial importance in chronic alcoholic patients presenting with nonspecific neurological deterioration. The appropriate administration of thiamine may prevent poor outcomes.

Pediatric types I and VI choledochal cysts complicated with acute pancreatitis and spontaneous perforation: A case report and literature review.

RATIONALE: Choledochal cysts are a congenital disorder of the common bile duct that can cause progressive biliary obstruction and biliary cirrhosis. They were classified by Todani into five types. Of these, type VI choledochal cysts are rarely reported in the literature. PATIENT CONCERNS: A 22-month-old girl presented with intermittent epigastralgia for approximately 10 days and fever for three days. Fasting and total parenteral nutrition were administered after admission. However, sudden onset of severe epigastric pain occurred. An abdominal sonogram showed turbid ascites and peritonitis was impressed. DIAGNOSES: An emergent exploratory laparotomy was performed, and perforation of the posterior wall of types I and VI choledochal cysts was observed. INTERVENTIONS: Intraoperative cholangiography revealed concomitant types I and VI choledochal cysts with stricture of the distal common bile duct. Definite surgery for resection of the choledochal cysts and gallbladder was performed with Roux-en-Y choledochojejunostomy. OUTCOMES: The patient had no evidence of ascending cholangitis at three years after the operation. LESSONS: Type VI choledochal cysts are rarely reported in the literature. To our knowledge, this is the first reported pediatric case of concomitant types I and VI choledochal cysts complicated with acute pancreatitis and spontaneous perforation.

Highly Efficient Inverted D:A1:A2 Ternary Blend Organic Photovoltaics Combining a Ladder-type Non-Fullerene Acceptor and a Fullerene Acceptor.

A formylated benzodi(cyclopentadithiophene) (BDCPDT) ladder-type structure with forced coplanarity is coupled with two 1,1-dicyanomethylene-3-indanone (IC) moieties via olefination to form a non-fullerene acceptor, BDCPDT-IC. The BDCPDT-IC, as an acceptor (A1) with broad light-absorbing ability and excellent solution processability, is combined with a second PC71BM acceptor (A2) and a medium band gap polymer, PBDB-T, as the donor (D) to form a ternary blend with gradient HOMO/LUMO energy alignments and panchromatic absorption. The device with the inverted architecture using the D:A1:A2 ternary blend has achieved a highest efficiency of 9.79% with a superior Jsc of 16.84 mA cm-2.

Encapsulation of 16-Hydroxycleroda-3,13-Dine-16,15-Olide in Mesoporous Silica Nanoparticles as a Natural Dipeptidyl Peptidase-4 Inhibitor Potentiated Hypoglycemia in Diabetic Mice.

Natural supplements comprise good efficacy with less adverse effects as against diabetic therapy, but their advancement as anti-diabetic agents is unsatisfactory with regard to the delivery system. Dipeptidyl peptidase-4 (DPP4)/CD26) can degrade glucagon-like pepetide-1 (GLP-1) which renders a decrease of blood glucose levels. 16-hydroxycleroda-3,13-dine-16,15-olide (HCD) extracted from Polyalthia longifolia, exhibits numerous medicinal potentials including hypoglycemic potential. On consideration of HCD application, the bioavailability is affected by low solubility. Extended experiments of anti-diabetic efficacy confirmed HCD biocompatible with mesoporous silica nanoparticles (MSNs) encapsulation resulted in a sustained release property in delivering HCD for the inhibition of DPP4 via the activity and protein levels of DPP4 analysis. In the enzymatic activity assay, MSN-HCD directly changed DPP4 activity. Moreover, MSN-HCD nanoparticles were treated with Caco-2 cells and the protein levels of DPP4 determined within the cells. The results revealed that MSN-HCD caused reduction of DPP4 activity in a time- and dose-dependent fashion. Orally administered MSN-HCD in diet-induced diabetic mice alleviated blood glucose via an oral glucose tolerance test. In addition, administration of MSN-HCD for five weeks revealed that the biochemical cues such as pyruvate transaminase (GPT), glutamate oxaloacetate transaminase (GOT), triglycerides (TG), cholesterol (CHO), and glycated hemoglobin (HbA1c) in mice were commendable as further confirmation of MSN-HCD efficacy and less adverse effects in down-regulation of hyperglycemia. Furthermore, this formulation effectively controlled blood glucose and significantly decreased the body weight of mice, suggesting that MSN-HCD exerts natural DPP4 inhibitor as a potential clinical drug for the treatment of diabetes.

Side-chain modulation of dithienofluorene-based copolymers to achieve high field-effect mobilities.

A ladder-type dithieno[3,2-b:6,7-b']fluorene (DTF), where the central fluorene is fused with two outer thiophene rings at its 2,3- and 6,7-junctions, is developed. The pentacyclic DTF monomers were polymerized with dithienodiketopyrrolopyrrole (DPP) acceptors to afford three alternating donor-acceptor copolymers PDTFDPP16, PDTFDPP20, and PDTFDPP32 incorporating different aliphatic side chains (R1 group at DTF; R2 group at the DPP moieties). The side-chain variations in the polymers play a significant role in determining not only the intrinsic molecular properties but also the intermolecular packing. As evidenced by the 2-dimensional GIXS measurements, PDTFDPP16 with octyl (R1) and 2-ethylhexyl (R2) side chains tends to align in an edge-on π-stacking orientation, whereas PDTFDPP20 using 2-butyloctyl (R1) and 2-ethylhexyl (R2) adopts a predominately face-on orientation. PDTFDPP32 with the bulkiest 2-butyloctyl (R1) and 2-octyldodecyl (R2) side chains shows a less ordered amorphous character. The OFET device using PDTFDPP20 with a face-on orientation determined by GIXS measurements achieved a high hole-mobility of up to 5 cm2 V-1 s-1. The high rigidity and coplanarity of the DTF motifs play an important role in facilitating intramolecular 1-dimensional charge transport within the polymer backbones. The implementation of main-chain coplanarity and side-chain engineering strategies in this research provides in-depth insights into structure-property relationships for guiding development of high-mobility OFET polymers.

Chloroplast Hsp93 Directly Binds to Transit Peptides at an Early Stage of the Preprotein Import Process.

Three stromal chaperone ATPases, cpHsc70, Hsp90C, and Hsp93, are present in the chloroplast translocon, but none has been shown to directly bind preproteins in vivo during import, so it remains unclear whether any function as a preprotein-translocating motor and whether they have different functions during the import process. Here, using protein crosslinking followed by ionic detergent solubilization, we show that Hsp93 directly binds to the transit peptides of various preproteins undergoing active import into chloroplasts. Hsp93 also binds to the mature region of a preprotein. A time course study of import, followed by coimmunoprecipitation experiments, confirmed that Hsp93 is present in the same complexes as preproteins at an early stage when preproteins are being processed to the mature size. In contrast, cpHsc70 is present in the same complexes as preproteins at both the early stage and a later stage after the transit peptide has been removed, suggesting that cpHsc70, but not Hsp93, is important in translocating processed mature proteins across the envelope.

High density GaN/AlN quantum dots for deep UV LED with high quantum efficiency and temperature stability.

High internal efficiency and high temperature stability ultraviolet (UV) light-emitting diodes (LEDs) at 308 nm were achieved using high density (2.5 × 10(9) cm(-2)) GaN/AlN quantum dots (QDs) grown by MOVPE. Photoluminescence shows the characteristic behaviors of QDs: nearly constant linewidth and emission energy, and linear dependence of the intensity with varying excitation power. More significantly, the radiative recombination was found to dominant from 15 to 300 K, with a high internal quantum efficiency of 62% even at room temperature.

Design and synthesis of 6,7-methylenedioxy-4-substituted phenylquinolin-2(1H)-one derivatives as novel anticancer agents that induce apoptosis with cell cycle arrest at G2/M phase.

Novel 6,7-methylenedioxy-4-substituted phenylquinolin-2(1H)-one derivatives 12a-n were designed and prepared through an intramolecular cyclization reaction and evaluated for in vitro anticancer activity. Among the synthesized compounds, 6,7-methylenedioxy-4-(2,4-dimethoxyphenyl)quinolin-2(1H)-one (12e) displayed potent cytotoxicity against several different tumor cell lines at a sub-micromolar level. Furthermore, results of fluorescence-activated cell sorting (FACS) analysis suggested that 12e induced cell cycle arrest in the G2/M phase accompanied by apoptosis in HL-60 and H460 cells. This action was confirmed by Hoechst staining and caspase-3 activation. Due to their easy synthesis and remarkable biological activities, 4-phenylquinolin-2(1H)-one analogs (4-PQs) are promising new anticancer leads based on the quinoline scaffold. Accordingly, compound 12e was identified as a new lead compound that merits further optimization and development as an anticancer candidate.

An adaptive recurrent radial basis function network tracking controller for a two-dimensional piezo-positioning stage.

An adaptive recurrent radial basis function network (ARRBFN) tracking controller for a two-dimensional piezo-positioning stage is proposed in this study. First, a mathematical model that represents the dynamics of the two-dimensional piezo-positioning stage is proposed. In this model, a hysteresis friction force that describes the hysteresis behavior of one-dimensional motion is used; and a nonconstant stiffness with the cross-coupling dynamic due to the effect of bending of a lever mechanism in x and y axes also is included. Then, according to the proposed mathematical model, an ARRBFN tracking controller is proposed. In the proposed ARRBFN control system, a recurrent radial basis function network (RRBFN) with accurate approximation capability is used to approximate an unknown dynamic function. The adaptive learning algorithms that can learn the parameters of the RRBFN on line are derived using Lyapunov stability theorem. Moreover, a robust compensator is proposed to confront the uncertainties, including approximation error, optimal parameter vectors, higher-order terms in Taylor series. To relax the requirement of the value of the lumped uncertainty in the robust compensator, an adaptive law is investigated to estimate the lumped uncertainty. Using the proposed control scheme, the position tracking performance is substantially improved and the robustness to uncertainties, including hysteresis friction force and cross-coupling stiffness, can be obtained as well. The tracking performance and the robustness to external load of the proposed ARRBFN control system are illustrated by some experimental results.