The Fifth Residue of the Coat Protein of Turnip Mosaic Virus Is Responsible for Long-Distance Movement in a Local-Lesion Host and Aphid Transmissibility in a Systemic Host.

HC-Pro and coat protein (CP) genes of a potyvirus facilitate cell-to-cell movement and are involved in the systemic movement of the viruses. The interaction between HC-Pro and CP is mandatory for aphid transmission. Two turnip mosaic virus (TuMV) isolates, RC4 and YC5, were collected from calla lily plants in Taiwan. The virus derived from the infectious clone pYC5 cannot move systemically in Chenopodium quinoa plants and loses aphid transmissibility in Nicotiana benthamiana plants, like the initially isolated virus. Sequence analysis revealed that two amino acids, P5 and A206, of YC5 CP uniquely differ from RC4 and other TuMV strains. Recombination assay and site-directed mutagenesis revealed that the fifth residue of leucine (L) at the N-terminal region of the CP (TuMV-RC4), rather than proline (P) (TuMV-YC5), is critical to permit the systemic spread in C. quinoa plants. Moreover, the single substitution mutant YC5-CPP5L became aphid transmissible, similar to RC4. Fluorescence microscopy revealed that YC5-GFP was restricted in the petioles of inoculated leaves, whereas YC5-CPP5L-GFP translocated through the petioles of inoculated leaves, the main stem, and the petioles of the upper uninoculated leaves of C. quinoa plants. In addition, YC5-GUS was blocked at the basal part of the petiole connecting to the main stem of the inoculated C. quinoa plants, whereas YC5-CPP5L-GFP translocated to the upper leaves. Thus, a single amino acid, the residue L5 at the N-terminal region right before the 6DAG8 motif, is critical for the systemic translocation ability of TuMV in a local lesion host and for aphid transmissibility in a systemic host.

Genetics in neovascular age-related macular degeneration susceptibility and treatment response to anti-VEGF intravitreal injection: A case series study.

BACKGROUND: To identify genotypes associated with neovascular age-related macular degeneration (nAMD) and investigate the associations between genotype variations and anti-vascular endothelial growth factor (VEGF) treatment response. METHODS: This observational, retrospective, case series study enrolled patients diagnosed with nAMD who received anti-VEGF treatment in National Taiwan University Hospital with at least one-year follow-up between 2012 and 2020. A genome-wide association study (GWAS) was conducted on enrolled patients and controls. Correlations between the genotypes identified from GWAS and the treatment response of functional/anatomical biomarkers, including visual acuity (VA), presence of intraretinal or subretinal fluid (SRF), serous or fibrovascular pigmented epithelium detachment (PED), and disruption of the ellipsoid zone (EZ), were analysed. RESULTS: In total, 182 patients with nAMD and 1748 controls were enrolled. GWAS revealed 16 single nucleotide polymorphisms (SNPs) as risk loci for nAMD, including seven loci in CFH and ARMS2/HTRA1 and nine novel loci, including rs117517872 and rs79835234(COPB2-DT), rs7525578(RAP1A), rs2123738(LOC105376755), rs1374879(CNTN3), rs3812692(SAR1A), rs117501587(PRKCA), rs9965945(CNDP1), and rs189769231(MATK). Our study revealed rs800292(CFH), rs11200638(HTRA1), and rs2123738(LOC105376755) correlated with poor treatment response in VA (P = 0.005), SRF (P = 0.044), and fibrovascular PED (P = 0.007), respectively. Rs9965945(CNDP1) was correlated with poor response in disruption of EZ (P = 0.046) and serous PED (P = 0.049). CONCLUSIONS: Among the 16 SNPs found in the GWAS, four loci-CFH, ARMS2/HTRA1, and two novel loci-were correlated with the susceptibility of nAMD and anatomical/functional responses after anti-VEGF treatment.

Outcomes of olfaction in patients with empty nose syndrome after submucosal implantation.

BACKGROUND: Olfactory dysfunction, such as hyposmia, is a significant symptom of empty nose syndrome (ENS). The efficacy of surgical intervention in olfaction improvements for ENS has not been investigated extensively. OBJECTIVE: The aim of this study was to evaluate changes in olfaction after surgical treatment for ENS. METHODS: This prospective cohort study at a tertiary medical center enrolled patients with ENS indicated for surgical treatment between June 2015 and June 2019. The Sniffin' Sticks 12-items odor identification test (SS-12) and subjective olfaction rating were completed by patients before and after surgery to assess olfaction. RESULTS: A total of 40 patients completed the survey both before and after surgical treatment. Prior to surgery, 25% of the patients had olfactory dysfunction detected by SS-12, whereas 80% of the patients reported a reduction in olfactory function by subjective rating. The degree of olfactory dysfunction by both assessments significantly improved following surgery. The age was a significant predictor of postoperative improvement. CONCLUSION: Surgical treatment is helpful in improving olfaction in patients with ENS who commonly suffer from olfactory dysfunction. Younger patients may benefit more from surgical intervention in aspect of olfaction.

Marker-Assisted Development and Evaluation of Monogenic Lines of Rice cv. Kaohsiung 145 Carrying Blast Resistance Genes.

Rice blast is a serious threat to global rice production. Large-scale and long-term cultivation of rice varieties with a single blast resistance gene usually leads to breakdown of resistance. To effectively control rice blast in Taiwan, marker-assisted backcrossing was conducted to develop monogenic lines carrying different blast resistance genes in the genetic background of an elite japonica rice cultivar, Kaohsiung 145 (KH145). Eleven International Rice Research Institute (IRRI)-bred blast-resistant lines (IRBLs) showing broad-spectrum resistance to local Pyricularia oryzae isolates were used as resistance donors. Sequencing analysis revealed that the recurrent parent, KH145, does not carry known resistance alleles at the target Pi2/9, Pik, Pita, and Ptr loci. For each IRBL × KH145 cross, we screened 21 to 370 (average of 108) plants per generation from the BC1F1 to BC3F1/BC4F1 generation. A total of 1,499 BC3F2/BC4F2 lines carrying homozygous resistance alleles were selected and self-crossed for four to six successive generations. The derived lines were also evaluated for background genotype using genotyping by sequencing, for blast resistance under artificial inoculation and natural infection conditions, and for agronomic performance in multiple field trials. In Chiayi and Taitung blast nurseries in 2018 to 2020, Pi2, Pi9, and Ptr conferred high resistance, Pi20 and Pik-h moderate resistance, and Pi1, Pi7, Pik-p, and Pik susceptibility to leaf blast; only Pi2, Pi9, and Ptr conferred effective resistance against panicle blast. The monogenic lines showed agronomic traits, yield, and grain quality similar to those of KH145, suggesting the potential of growing a mixture of lines to achieve durable resistance in the field.

The Motor Network Reduces Multisensory Illusory Perception.

Observing mouth movements has strikingly effects on the perception of speech. Any mismatch between sound and mouth movements will result in listeners perceiving illusory consonants (McGurk effect), whereas matching mouth movements assist with the correct recognition of speech sounds. Recent neuroimaging studies have yielded evidence that the motor areas are involved in speech processing, yet their contributions to multisensory illusion remain unclear. Using functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) in an event-related design, we aimed to identify the functional roles of the motor network in the occurrence of multisensory illusion in female and male brains. fMRI showed bilateral activation of the inferior frontal gyrus (IFG) in audiovisually incongruent trials. Activity in the left IFG was negatively correlated with occurrence of the McGurk effect. The effective connectivity between the left IFG and the bilateral precentral gyri was stronger in incongruent than in congruent trials. The McGurk effect was reduced in incongruent trials by applying single-pulse TMS to motor cortex (M1) lip areas, indicating that TMS facilitates the left IFG-precentral motor network to reduce the McGurk effect. TMS of the M1 lip areas was effective in reducing the McGurk effect within the specific temporal range from 100 ms before to 200 ms after the auditory onset, and TMS of the M1 foot area did not influence the McGurk effect, suggesting topographical specificity. These results provide direct evidence that the motor network makes specific temporal and topographical contributions to the processing of multisensory integration of speech to avoid illusion.SIGNIFICANCE STATEMENT The human motor network, including the inferior frontal gyrus and primary motor cortex lip area, appears to be involved in speech perception, but the functional contribution to the McGurk effect is unknown. Functional magnetic resonance imaging revealed that activity in these areas of the motor network increased when the audiovisual stimuli were incongruent, and that the increased activity was negatively correlated with perception of the McGurk effect. Furthermore, applying transcranial magnetic stimulation to the motor areas reduced the McGurk effect. These two observations provide evidence that the motor network contributes to the avoidance of multisensory illusory perception.

Fatigue and Muscle Strength Involving Walking Speed in Parkinson's Disease: Insights for Developing Rehabilitation Strategy for PD.

Background. Problems with gait in Parkinson's disease (PD) are a challenge in neurorehabilitation, partly because the mechanisms causing the walking disability are unclear. Weakness and fatigue, which may significantly influence gait, are commonly reported by patients with PD. Hence, the aim of this study was to investigate the association between weakness and fatigue and walking ability in patients with PD. Methods. We recruited 25 patients with idiopathic PD and 25 age-matched healthy adults. The maximum voluntary contraction (MVC), twitch force, and voluntary activation levels were measured before and after a knee fatigue exercise. General fatigue, central fatigue, and peripheral fatigue were quantified by exercise-induced changes in MVC, twitch force, and activation level. In addition, subjective fatigue was measured using the Multidimensional Fatigue Inventory (MFI) and Fatigue Severity Scale (FSS). Results. The patients with PD had lower activation levels, more central fatigue, and more subjective fatigue than the healthy controls. There were no significant differences in twitch force or peripheral fatigue index between the two groups. The reduction in walking speed was related to the loss of peripheral strength and PD itself. Conclusion. Fatigue and weakness of central origin were related to PD, while peripheral strength was important for walking ability. The results suggest that rehabilitation programs for PD should focus on improving both central and peripheral components of force.

An adaptive workflow coupled with Random Forest algorithm to identify intact N-glycopeptides detected from mass spectrometry.

MOTIVATION: Despite many attempts for algorithm development in recent years, automated identification of intact glycopeptides from LC-MS(2) spectral data is still a challenge in both sensitivity and precision. RESULTS: We implemented a supervised machine learning algorithm, Random Forest, in an automated workflow to identify N-glycopeptides using spectral features derived from ion trap-based LC-MS(2) data. The workflow streamlined high-confident N-glycopeptide spectral data and enabled adaptive model optimization with respect to different sampling strategies, training sample size and feature set. A critical evaluation of the features important for glycopeptide identification further facilitated effective feature selection for model improvement. Using split sample testing method from 577 high-confident N-glycopeptide spectral data, we demonstrated that an optimal true-positive rate, precision and false-positive rate of 73, 88 and 10%, respectively, can be attained for overall N-glycopeptide identification Availability and implementation: The workflow developed in this work and the application suite, Sweet-Heart, that the workflow supports for N-glycopeptide identification are available for download at http://sweet-heart.glycoproteomics.proteome.bc.sinica.edu.tw/.

Systemic and local bactericidal potentiality in late lactation Holstein-Friesian cows following a combined antibiotics and Enterococcus faecium SF68 dry-cow treatment.

Antibiotic dry-cow treatment contributes a major part to the total use of antibiotics in dairy herds. Enterococcus faecium strain SF68 (SF68) was of human origin but has been authorized in EU as probiotic feed additive. In the present study, one of the front and rear quarters of twelve late lactation Holstein-Friesian cows were infused once with a commercial antibiotic dry-cow formula (antibiotics quarter) on the first milk-stasis day (d 1), when the contrallateral quarters were infused with 5 x 10(8)-CFU SF68 plus half-dose antibiotic dry-cow formula (SF68/antibiotics quarter) meanwhile. Gelatinase level and cellular reactive oxygen species (ROS) production capacity were measured for blood and quarter secretion. The results showed that the count of blood total leukocytes minorly decreased on d 3 only but the microscopic somatic cell count (MSCC) continuously increased up to d 7, especially in SF68/antibiotics quarters. Plasma level of gelatinase A remained similar up to d 7 but gelatinase B was not detectable in plasma throughout the study. The level of gelatinase A in quarter secretion increased up to d 7 but gelatinase B increased even more drastically, especially in SF68/antibiotics quarters. The ROS production capacity of blood leukocytes increased temporarily only on d 3, but that of milk cells continuously increased up to d 7, especially in SF68/antitiotics quarters. Overall, late lactation Holstein-Friesian cows were systemically adaptable to the combined antibiotics and SF68 dry-cow treatment, while the local bactericidal potentiality in mammary gland was actively responsive to additional SF68 intramammary treatment.

Klymollins T-X, bioactive eunicellin-based diterpenoids from the soft coral Klyxum molle.

Five new eunicellin-based diterpenoids, klymollins T-X (1-5), along with two known compounds (6 and 7) have been isolated from the soft coral Klyxum molle. The structures of these new metabolites were elucidated by extensive spectroscopic analysis and by comparison with related known compounds. Compound 5 was found to exert significant in vitro anti-inflammatory activity against LPS-stimulated RAW264.7 macrophage cells. Furthermore, compounds 4 and 7 were shown to exhibit cytotoxicity against a limited panel of human cancer cell lines.

Improvement in pH sensitivity of low-temperature polycrystalline-silicon thin-film transistor sensors using H2 sintering.

In this article, we report an improvement in the pH sensitivity of low-temperature polycrystalline-silicon (poly-Si) thin-film transistor (TFT) sensors using an H2 sintering process. The low-temperature polycrystalline-silicon (LTPS) TFT sensor with H2 sintering exhibited a high sensitivity than that without H2 sintering. This result may be due to the resulting increase in the number of Si-OH2(+) and Si-O(-) bonds due to the incorporation of H in the gate oxide to reduce the dangling silicon bonds and hence create the surface active sites and the resulting increase in the number of chemical reactions at these surface active sites. Moreover, the LTPS TFT sensor device not only offers low cost and a simple fabrication processes, but the technique also can be extended to integrate the sensor into other systems.

An Appraisal of the Preventive Effect of Statins on the Development of Graves' Ophthalmopathy: A Hospital-Based Cohort Study.

INTRODUCTION: Graves' ophthalmopathy (GO) is an autoimmune inflammatory disorder observed in a substantial proportion of patients with Graves' disease (GD), with debilitating symptoms of disfiguring, periorbital pain, dry eyes, diplopia, and even visual disturbances. Previous studies involving Western populations have noted discrepancies in risk factors for GO. Therefore, this study aimed to determine the risk factors for GO development and the protective effect of statins in newly diagnosed patients with GD in Taiwan. METHODS: This retrospective case-control study was based on a tertiary center cohort involving patients with GD diagnosed between 2010 and 2019 at the National Taiwan University Hospital (n = 11,035). Patients who were diagnosed or treated elsewhere, had been followed up for less than 6 months or were with a diagnosis of orbital tumor were excluded. Overall, 3578 patients with GD met the inclusion criteria. Univariate and multivariate logistic regression analyses were used to ascertain the odds ratio (OR) of developing GO, with adjustment for sociodemographic factors, interventions for managing GD and thyroid hormone levels, to determine protective and risk factors for GO. RESULTS: In our multivariate model, the use of statins reduced the risk of GO development (OR 0.2; 95% confidence interval [CI] 0.08-0.50; p < 0.001). Thyroid dysfunction including hyperthyroidism (OR 4.2; 95% CI 2.97-5.88; p < 0.001) and hypothyroidism (OR 4.7; 95% CI 3.02-7.19; p < 0.001) was associated with an increased risk of developing GO. Smoking status and lipid profile were not risk factors in our cohort. CONCLUSION: In newly diagnosed patients with GD, the use of statins decreased the risk of developing GO by 80%, whereas serum lipid levels were not considered risk factors. Further nationwide population-based studies may help clarify the differences in risk factors between various ethnic groups. TRAIL REGISTRATION: This trial was approved by the Research Ethics Committee of National Taiwan University Hospital (202202066RINC), retrospectively registered from January 1, 2010 to December 31, 2019.

Alpha event-related decreases during encoding in adults with ADHD - An investigation of sustained attention and working memory processes.

BACKGROUND: Executive functioning deficits are central to established neuropsychological models of ADHD. Oscillatory activity, particularly the alpha rhythm (8-12 Hz) has been associated with cognitive impairments in ADHD. However, most studies to date examined such neural mechanisms underlying executive dysfunction in children and adolescents with ADHD, raising the question of whether and to what extent those ADHD-related working memory impairments are still present in adults. To this end, the current study aimed to investigate the role of alpha event-related decreases (ERD) during working memory processes in adults with and without ADHD. METHODS: We collected electroencephalographic (EEG) data from 85 adults with a lifetime diagnosis of ADHD and 105 controls (aged 32-64), while they performed a continuous performance (CPT) and a spatial delayed response working memory task (SDRT). Time-frequency and independent component analysis (ICA) was used to identify alpha (8-12 Hz) clusters to examine group and condition effects during the temporal profile of sustained attention and working memory processes (encoding, maintenance, retrieval), loads (low and high) and trial type (go and nogo). RESULTS: Individuals with ADHD exhibited higher reaction time-variability in SDRT, and slower response times in SDRT and CPT, despite no differences in task accuracy. Although working memory load was associated with stronger alpha ERD in both tasks and both groups (ADHD, controls), we found no consistent evidence for attenuated alpha ERD in adults with ADHD, failing to replicate effects reported in children. In contrast, when looking at the whole sample, the correlations of alpha power during encoding with inattention and hyperactivity-impulsivity symptoms were significant, replicating prior findings in children with ADHD, but suggesting an alternate source for these effects in adults. CONCLUSIONS: Our results corroborate the robustness of alpha as a marker of visual attention and suggest that occipital alpha ERD normalizes in adulthood, but with unique contributions of centro-occipital alpha ERD, suggesting a secondary source. This implies that deviations in processes other than previously reported visuospatial cortex engagement may account for the persistent symptoms and cognitive deficits in adults with a history of ADHD.

An importance-performance analysis of teachers' perception of STEM engineering design education.

There is an increasing worldwide trend toward the development of science, technology, engineering, and mathematics (STEM) education using engineering design (ED) practice. Considering that teachers play pivotal roles in terms of student interest in STEM subjects and careers, it is important to explore teachers' perceptions of STEM-ED education. We analysed survey data from 184 technology teachers who participated in empowerment training (using a STEM-ED curriculum) in 2017, 2018, 2021, and 2022. We used an importance-performance analytical model to investigate the teachers' perceptions of STEM-ED itself, its impact on students, and the challenges experienced during implementation. The results showed that various improvements were required for STEM-ED promotion and for the preparation of STEM-ED lessons. Analysis of variance revealed that the age groups taught and the number of weekly teaching hours significantly affected the teachers' perceptions of STEM-ED. These findings will assist educational institutions worldwide in planning future education policies, designing teacher empowerment courses, and understanding teachers' needs in efforts to improve STEM-ED.

Sequential provocation of Ekbom's syndrome and acute mania following AstraZeneca COVID-19 vaccination.

ChAdOx1 nCoV-19 vaccine (so called AZ vaccine), is widely used to prevent the SARS-CoV-2 pandemic and shows powerful effectiveness to deter community transmission. There are common immunogenicity-related side effects such as fever, myalgia, lethargy, and headache; however, rare report on the neuropsychiatric problems (Ramasamy et al., 2021). In Taiwan, more than 15,200,000 doses of AZ vaccine were injected by the end of 2022. Here we presented a unique case with separated episode of Ekbom's syndrome, also called delusion of parasitosis, and mania following successive AZ vaccination in three-month interval.

Age, Dose, and Locomotion: Decoding Vulnerability to Ketamine in C57BL/6J and BALB/c Mice.

Ketamine has been abused as a psychedelic agent and causes diverse neurobehavioral changes. Adolescence is a critical developmental stage but vulnerable to substances and environmental stimuli. Growing evidence shows that ketamine affects glutamatergic neurotransmission, which is important for memory storage, addiction, and psychosis. To explore diverse biological responses, this study was designed to assess ketamine sensitivity in mice of different ages and strains. Male C57BL/6J and BALB/c mice were studied in adolescence and adulthood separately. An open field test assessed motor behavioral changes. After a 30-min baseline habituation, mice were injected with ketamine (0, 25, and 50 mg/kg), and their locomotion was measured for 60 min. Following ketamine injection, the travelled distance and speed significantly increased in C57BL/6J mice between both age groups (p < 0.01), but not in BALB/c mice. The pattern of hyperlocomotion showed that mice were delayed at the higher dose (50 mg/kg) compared to the lower dose (25 mg/kg) of ketamine treatment. Ketamine accentuated locomotor activation in adolescent C57BL/6J mice compared to adults, but not in the BALB/c strain. Here, we show that ketamine-induced locomotor behavior is modulated by dose and age. The discrepancy of neurobehaviors in the two strains of mice indicates that sensitivity to ketamine is biologically determined. This study suggests that individual vulnerability to ketamine's pharmacological responses varies biologically.

Hysteroscopic removal, with or without laparoscopic assistance, of first-trimester cesarean scar pregnancy.

OBJECTIVE: To demonstrate the implementation and potential benefits of hysteroscopic removal, with or without concomitant laparoscopic assistance, of first-trimester cesarean scar pregnancies (CSPs). DESIGN: Patients with prior cesarean deliveries may have scar formation at the muscular wall of the uterine isthmus, resulting in a cesarean scar defect (CSD), also known as an isthmocele or diverticulum. When implantation of a trophoblast occurs at the CSD, a CSP develops, and with progression onto higher gestational age, it carries risks for serious complications, such as placenta previa spectrum, life-threatening bleeding, uterine rupture, and cesarean hysterectomy. Therefore, early termination is often recommended. Given that the chorionic frondosum only penetrates the decidual basalis layer during the first trimester and does not invade the distal myometrial segment until early second trimester, operative hysteroscopy can be a reliable and efficient treatment modality for early intervention. This narrated video features the systematic approach and surgical management for patients with first-trimester CSPs. SETTING: Academic tertiary hospital. PATIENT(S): Three multiparous women between 34 and 38 years of age diagnosed with CSPs within the first trimester. INTERVENTION(S): Initial assessment with transvaginal ultrasonography and color Doppler flow identifies the site of implantation and measures the residual myometrial thickness (RMT), which are important parameters for classifying the CSPs into type I or type II. Type I CSPs often present at an earlier gestational age, have a thicker RMT, and grow toward the uterine cavity, while type II CSPs are frequently noted at a higher gestational age, have a thinner RMT, demonstrate obvious scar dehiscence, and often invade toward the bladder. The patients received either operative hysteroscopy alone or with concomitant laparoscopic assistance and repair of CSD dehiscence. For all hysteroscopic operations, misoprostol (200 µg) was given 4 hours before the procedure while oxytocin (20 U in 1000 mL isotonic solution, intravenous infusion) was infused immediately after removal of the placental tissue. For laparoscopic excision and repair of the dehiscent scar, local injection of 5 mL terlipressin acetate (1 mg) was added before the initiation of laparoscopic CSD excision. MAIN OUTCOME MEASURE(S): Appraisal of the parameters used for preoperative assessment, the efficacy of the surgical procedures, and the intention to minimize the associated risks and morbid sequalae were evaluated. RESULT(S): Most of the type I CSPs or type II CSPs with gestational age <8 weeks and RMT >3 mm can be successfully treated with operative hysteroscopy alone. In contrast to blind dilatation and curettage, operative hysteroscopy offers direct visualization to ensure complete removal of the chorionic villi, which can occasionally be buried deep within the concavity of the CSD. It is worth noting that gently sweeping the decidua basalis from the myometrium with the loop resectoscope is more than enough to separate the chorionic villi within and completely displace the placental tissues without causing massive hemorrhage. For type II CSPs in late first-trimesters showing distended CSDs and diminished RMT, laparoscopy can be established before the hysteroscopic procedure for better surveillance and to prevent inadvertent myometrial perforation. Then, hysteroscopic removal of CSP can further induce uterine contractions to help reduce blood loss during subsequent laparoscopic repair of CSD. CONCLUSION(S): Accurate diagnosis and timely management of CSPs during the first trimester are crucial for preventing significant morbidities associated with advanced gestational age. Operative hysteroscopy offers the benefit of direct visualization for competent detachment of the decidua basalis of the CSP from the steep concavity of the CSD. Furthermore, the employment of laparoscopy for type II CSPs helps avoid inadvertent complications related to the thin RMT and allows concomitant repair of the extensive dehiscence.

A siRNA targets and inhibits a broad range of SARS-CoV-2 infections including Delta variant.

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants has altered the trajectory of the COVID-19 pandemic and raised some uncertainty on the long-term efficiency of vaccine strategy. The development of new therapeutics against a wide range of SARS-CoV-2 variants is imperative. We, here, have designed an inhalable siRNA, C6G25S, which covers 99.8% of current SARS-CoV-2 variants and is capable of inhibiting dominant strains, including Alpha, Delta, Gamma, and Epsilon, at picomolar ranges of IC50 in vitro. Moreover, C6G25S could completely inhibit the production of infectious virions in lungs by prophylactic treatment, and decrease 96.2% of virions by cotreatment in K18-hACE2-transgenic mice, accompanied by a significant prevention of virus-associated extensive pulmonary alveolar damage, vascular thrombi, and immune cell infiltrations. Our data suggest that C6G25S provides an alternative and effective approach to combating the COVID-19 pandemic.

Event-Related Potentials During Decision-Making in a Mixed-Strategy Game.

The decisions we make are sometimes influenced by interactions with other agents. Previous studies have suggested that the prefrontal cortex plays an important role in decision-making and that the dopamine system underlies processes of motivation, motor preparation, and reinforcement learning. However, the physiological mechanisms underlying how the prefrontal cortex and the dopaminergic system are involved in decision-making remain largely unclear. The present study aimed to determine how decision strategies influence event-related potentials (ERPs). We also tested the effect of levodopa, a dopamine precursor, on decision-making and ERPs in a randomized double-blind placebo-controlled investigation. The subjects performed a matching-pennies task against an opposing virtual computer player by choosing between right and left targets while their ERPs were recorded. According to the rules of the matching-pennies task, the subject won the trial when they chose the same side as the opponent, and lost otherwise. We set three different task rules: (1) with the alternation (ALT) rule, the computer opponent made alternating choices of right and left in sequential trials; (2) with the random (RAND) rule, the opponent randomly chose between right and left; and (3) with the GAME rule, the opponent analyzed the subject's past choices to predict the subject's next choice, and then chose the opposite side. A sustained medial ERP became more negative toward the time of the subject's target choice. A biphasic potential appeared when the opponent's choice was revealed after the subject's response. The ERPs around the subject's choice were greater in RAND and GAME than in ALT, and the negative peak was enhanced by levodopa. In addition to these medial ERPs, we observed lateral frontal ERPs tuned to the choice direction. The signals emerged around the choice period selectively in RAND and GAME when levodopa was administered. These results suggest that decision processes are modulated by the dopamine system when a complex and strategic decision is required, which may reflect decision updating with dopaminergic prediction error signals.

Endosperm cell size reduction caused by osmotic adjustment during nighttime warming in rice.

High night temperature (HNT) often reduces yield in field crops. In rice, HNT during the ripening stage diminishes endosperm cell size, resulting in a considerable reduction in final kernel weight; however, little is known about the underlying mechanisms at cell level. In this study, we performed picolitre pressure-probe-electrospray-ionization mass spectrometry to directly determine metabolites in growing inner endosperm cells of intact seeds produced under HNT conditions, combining with 13C feeding and water status measurements including in situ turgor assay. Microscopic observation in the inner zone suggested that approximately 24.2% of decrease in cell expansion rate occurred under HNT at early ripening stage, leading to a reduction in cell volume. It has been shown that HNT-treated plants were subjected to mild shoot water deficit at night and endosperm cell turgor was sustained by a decline in osmotic potential. Cell metabolomics also suggests that active solute accumulation was caused by a partial inhibition of wall and starch biosynthesis under HNT conditions. Because metabolites were detected in the single cells, it is concluded that a partial arrest of cell expansion observed in the inner endosperms was caused by osmotic adjustment at mild water deficit during HNT conditions.

The effect of a music programme during lunchtime on the problem behaviour of the older residents with dementia at an institution in Taiwan.

AIMS: To study the effect of a music programme during lunchtime on problem behaviour among institutionalised older residents with dementia. BACKGROUND: Symptoms of dementia among older people include depression, problems with memory, insomnia and problem behaviours. Problem behaviour has been identified by families and nurses as the greatest challenge that needs to be addressed. Several studies have found that music therapy can reduce problem behaviours among dementia sufferers and, based on this finding, music has been recommended for incorporation as part of dementia management. DESIGN: This study used a quasi-experimental design with an eight-week time series follow-up. The intervention was background music when residents had their lunch meal. METHODS: A purposive sampling technique was used. Forty-one participants were selected from an institution housing residents with dementia located in a city in Taiwan. RESULTS: The mean age of participants was 81.68 (SD 6.39) years old. The mean score for Mini-Mental State Examination (MMSE) was 10.66 (SD 6.85). The mean of Barthel Activity of Daily Living score was 56.83 (SD 38.12). The results showed that the music programme reduced, significantly, physical and verbal aggressive behaviour among the older residents with dementia. The study identified that there was a one-week time lag between the implementation of the music programme and a significant effect on the residents. CONCLUSIONS: The results from this study suggested that music is able to reduce the degree of problem behaviours among the older residents with dementia and this helps to ease work-load of nurse aides and nurses during meal times. RELEVANCE TO CLINICAL PRACTICE: The results may serve as a reference for the future treatment of problem behaviour among the older with dementia.