Long-term management and treatment of acute intermittent porphyria with recurring attacks using pharmacological prophylaxis.

BACKGROUND: There is no definitive guidance on whether patients with acute intermittent porphyria (AIP) with recurrent attacks need pharmacological prophylactic treatment. METHODS: The management strategies for patients with frequent (defined as ≥4 annualized attack rate (AAR) and less frequent attacks (<4 AAR), including treatment for acute attacks and duration of prophylaxis (weekly heme arginate 3 mg/kg body weight and/or investigational drug, givosiran), were summarized. The AAR for the following periods were presented: the first 2 years after diagnosis, before/after prophylaxis, and the most recent 2 years. RESULTS: A total of 29 patients with AIP were included, 19 (34.5%) had <4 AAR and 10 (65.6%) had ≥4 AAR in the first 2 years after diagnosis. All patients experienced reduced attacks during the treatment course, 23 (79.3%) were attack-free during the most recent 2 years. Among the 9 patients who received prophylaxis (7 heme arginate; 1 givosiran, 1 heme arginate followed by givosiran), 5 (55.6%) were attack-free in the most recent 2-year period and prophylaxis was discontinued because there had been no attacks for >1 year. For patients without prophylaxis (n = 20), 18 (90.0%) were attack-free in the most recent 2-year period and 15 (75.0%) experienced attacks only in the first 2 years after diagnosis. CONCLUSIONS: Prophylaxis could be considered for patients with AIP with ≥4 biochemically confirmed attacks/year after routine treatment of 1-2 years, during which the severity and frequency of attacks should be closely monitored to determine the necessity of pharmacologic prophylaxis. More studies are needed to reach a consensus on the use of pharmacological prophylaxis and treatment of AIP.

Progress on Z genome biosynthetic pathway of bacteriophage.

There are abundant base modifications in bacteriophages' genomes, mainly for avoiding the digestion of host endonucleases. More than 40 years ago, researchers discovered that 2-amino-adenine (Z) completely replaced adenine (A) and forms a complementary pairing with three hydrogen bonds with thymine (T) in the DNA of cyanophage S-2L, forming a distinct "Z-genome". In recent years, researchers have discovered and validated the biosynthetic pathway of Z-genome in various bacteriophages, constituting a multi-enzyme system. This system includes the phage-encoded enzymes deoxy-2'-aminoadenylosuccinate synthetase (PurZ), deoxyadenosine triphosphate hydrolase (dATPase/DatZ), deoxyadenosine/deoxyguanosine triphosphate pyrophosphatase (DUF550/MazZ) and DNA polymerase (DpoZ). In this review, we provide a concise overview of the historical discovery on diversely modified nucleosides in bacteriophages, then we comprehensively summarize the research progress on multiple enzymes involved in the Z-genome biosynthetic pathway. Finally, the potential applications of the Z-genome and the enzymes in its biosynthetic pathway are discussed in order to provide reference for research in this field.

Risk of Thrombosis Following the First Dose of ChAdOx1 nCoV-19 Vaccine in Patients Undergoing Maintenance Hemodialysis: A Self-Controlled Case Series Study.

Background: The ChAdOx1 nCoV-19 vaccine is associated with vaccine-induced thrombosis and thrombocytopenia (VITT). Patients with end-stage renal disease (ESRD) under hemodialysis are at elevated risk of heparin-induced thrombocytopenia, which shares similar mechanisms with VITT. We aimed to examine the risk of VITT after the first dose of ChAdOx1 nCoV-19 vaccine using a self-controlled case series analysis (SCCS) in the hemodialyzed ESRD population. Methods: Drawing from the largest multi-center electronic medical records database in Taiwan, we identified adult patients, with or without hemodialysis, between 1st December, 2020, and 31st December, 2021, who received a first dose of ChAdOx1 nCoV-19 vaccine and had an outcome of thrombocytopenia, venous thrombosis, or arterial thrombosis. We calculated the incident rate ratios (IRRs) of outcomes in different periods at risk, compared to periods not at risk. Results:  We identified 59 hemodialysis patients and 41 non-dialysis patients with an outcome. The SCCS analyses showed, for the hemodialysis group, a significantly increased risk of outcomes during the period 31 to 60 days post-exposure to ChAdOx1 nCoV-19 vaccine (IRR: 2.823; 95% CI: 1.423-5.600). However, in non-dialysis patients there was no increase in risks during any of the post-exposure risk periods. Conclusion: For ESRD patients under hemodialysis, the first dose of ChAdOx1 nCoV-19 vaccine was associated with a 2.8-fold increase in risk of thrombosis.

Association between antenatal corticosteroids and risk of serious infection in children: nationwide cohort study.

OBJECTIVE: To investigate the associations between exposure to antenatal corticosteroids and serious infection in children during the first three, six, and 12 months of life. DESIGN: Nationwide cohort study. SETTING: National Health Insurance Research Database, Birth Reporting Database, and Maternal and Child Health Database, 1 January 2008 to 31 December 2019, to identify all pregnant individuals and their offspring in Taiwan. PARTICIPANTS: 1 960 545 pairs of pregnant individuals and their singleton offspring. 45 232 children were exposed and 1 915 313 were not exposed to antenatal corticosteroids. MAIN OUTCOME MEASURES: Incidence rates were estimated for overall serious infection, sepsis, pneumonia, acute gastroenteritis, pyelonephritis, meningitis or encephalitis, cellulitis or soft tissue infection, septic arthritis or osteomyelitis, and endocarditis during the first three, six, and 12 months of life in children exposed versus those not exposed to antenatal corticosteroids. Cox proportional hazards models were performed to quantify adjusted hazard ratios with 95% confidence intervals for each study outcome. RESULTS: The study cohort was 1 960 545 singleton children: 45 232 children were exposed to one course of antenatal corticosteroids and 1 915 313 children were not exposed to antenatal corticosteroids. The adjusted hazard ratios for overall serious infection, sepsis, pneumonia, and acute gastroenteritis among children exposed to antenatal corticosteroids were significantly higher than those not exposed to antenatal corticosteroids during the first six months of life (adjusted hazard ratio 1.32, 95% confidence interval 1.18 to 1.47, P<0.001, for overall serious infection; 1.74, 1.16 to 2.61, P=0.01, for sepsis; 1.39, 1.17 to 1.65, P<0.001, for pneumonia; and 1.35, 1.10 to 1.65, P<0.001, for acute gastroenteritis).Similarly, the adjusted hazard ratios for overall serious infection (P<0.001), sepsis (P=0.02), pneumonia (P<0.001), and acute gastroenteritis (P<0.001) were significantly higher from birth to 12 months of life. In the sibling matched cohort, the results were comparable with those observed in the whole cohort, with a significantly increased risk of sepsis in the first six (P=0.01) and 12 (P=0.04) months of life. CONCLUSIONS: This nationwide cohort study found that children exposed to one course of antenatal corticosteroids were significantly more likely to have an increased risk of serious infection during the first 12 months of life. These findings suggest that before starting treatment, the long term risks of rare but serious infection associated with antenatal corticosteroids should be carefully weighed against the benefits in the perinatal period.

Efficacy of epidural analgesia for intractable cancer pain: A systematic review.

BACKGROUND: Epidural analgesia is a common technique for managing perioperative and obstetric pain. Patients with cancer who cannot tolerate opioids or not responding to conventional treatment may benefit from epidural analgesia. Therefore, this systematic review aimed to analyze the efficacy and safety of epidural analgesia in patients with intractable cancer pain. METHODS: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials to identify studies on patients with cancer who received epidural analgesia. We assessed the quality of all included studies using the risk-of-bias tool or Newcastle-Ottawa scale. The primary outcome was pain relief after epidural analgesia, and the secondary outcome was quality of life, analgesic consumption, and adverse events. The studies were grouped based on the medications used for epidural analgesia. A descriptive synthesis was performed following the Synthesis Without Meta-analysis reporting guideline. RESULTS: Our systematic review included nine randomized controlled trials (n = 340) and 15 observational studies (n = 926). Two randomized controlled trials suggested that epidural opioids were not superior to systemic opioids in relieving pain. Epidural opioids combined with local anesthetics or adjuvants, including calcitonin, clonidine, ketamine, neostigmine, methadone, and dexamethasone, offered better analgesic effects. No significant difference in pain relief between an intermittent bolus and a continuous infusion of epidural morphine was observed. Epidural opioids had more analgesic effects on nociceptive pain than neuropathic pain. The methods used to evaluate the quality of life and the corresponding results were heterogeneous among studies. Six observational studies demonstrated that some patients could have decreased opioid consumption after epidural analgesia. Adverse events, including complications and drug-related side effects, were reported in 23 studies. Five serious complications, such as epidural abscess and hematoma, required surgical management. The heterogeneity and methodological limitations of the studies hindered meta-analysis and evidence-level determination. CONCLUSION: Coadministration of epidural opioids, local anesthetics, and adjuvants may provide better pain relief for intractable cancer pain. However, we must assess the patients to ensure that the benefits outweigh the risks before epidural analgesia. Therefore, further high-quality studies are required.

Factors predictive of clinical outcome in advanced hepatocellular carcinoma patients receiving ramucirumab treatment: A real-world experience.

PURPOSE: The aim of this study was to investigate the factors predictive of clinical outcome in advanced hepatocellular carcinoma patients receiving ramucirumab treatment. METHODS: We conducted a retrospective study using a multi-institutional electronic medical records database in Taiwan. We included advanced HCC patients newly receiving ramucirumab as second-line or beyond systemic therapy between January 2016 and February 2022. The clinical outcomes were median progression-free survival (PFS) based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST), overall survival (OS) and adverse events. We applied Kaplan-Meier methods to estimate median PFS and OS. Uni-variable and multi-variable Cox regression models were applied to identify the prognostic factors. RESULTS: We included 39 ramucirumab naive users with a median age of 65.5 (IQR: 57.0-71.0) years and treatment time of 5.0 (3.0-7.0) cycles, of whom 82.1% were male and 84.6% were Barcelona Clinic Liver Cancer (BCLC) stage C. After median follow-up time of 6.0 months, 33.3% of patients' AFP level had decreased more than 20% within 12 weeks. The median PFS and OS were 4.1 months and non-reach, respectively. Moreover, tumor burden beyond the up-to-11 criteria (HR: 2.95, 95% CI: 1.04-8.38) and a decrease in estimated glomerular filtration rate of more than 10% within 12 weeks (HR: 0.31, 0.11-0.88) were significantly related to PFS in the multi-variable analysis. No patient discontinued ramucirumab during the treatment on account of side effects. CONCLUSION: Ramucirumab was an effective treatment option with good AFP response for advanced HCC patients in real-world experience. Tumor burden beyond the up-to-11 criteria and a decrease in estimated glomerular filtration rate were independent predictive factors for progression-free survival.

Renal Stones and Gallstones Correlated with the Ten-Year Risk Estimation of Atherosclerotic Cardiovascular Disease Based on the Pooled Cohort Risk Assessment of Males Aged 40-79.

BACKGROUND: The risk of developing atherosclerotic cardiovascular disease (ASCVD) is unknown for subjects with both gallstones and renal stones, nor is it known whether there is a difference in the risk between gallstones and renal stones. This study aimed to determine the risk relationship between gallstones and renal stones and the risk of ASCVD in a male population. METHODS: We recruited 6371 eligible males aged 40 to 79 years old who did not have a documented ASCVD history. The ten-year ASCVD risk was calculated using the pooled cohort equations developed by the American College of Cardiology (ACC) and the American Heart Association (AHA). The ASCVD risk score was classified as a low risk (<7.5%), an intermediate risk (7.5% to 19.9%), or a high risk (≥20%). The diagnosis of gallstones and renal stones was established based on the results of abdominal sonography. RESULTS: Both gallstones and renal stones were associated with a high level of intermediate risk (OR = 3.21, 95% CI = 1.89-5.49, p < 0.001) and high risk (OR = 3.01, 95% CI = 1.48-6.12, p < 0.001), compared to individuals with no stones at all, after adjusting for the effects of other clinical variables. The possession of gallstones was associated with a higher level of high ASCVD risk (OR = 1.84, 95% CI = 1.31-2.59, p < 0.05) than that of renal stones. CONCLUSIONS: The ASCVD risk was higher for males with gallstones than for those with renal stones. Men with both types of stones faced a risk of ASCVD that was three times higher than that of men without stones.

Carbapenem-resistant Enterobacteriaceae infection in children less than one year old in an Asian medical center.

BACKGROUND: The emergence of carbapenem-resistant Enterobacteriaceae (CRE) is a threat to public health worldwide. This study aimed to determine the risk factors and outcomes for CRE colonization and infection in infants. METHODS: Children aged <1 year hospitalized with CRE pathogens isolated from January 2016 to June 2019 were retrospectively analyzed. Demographic and clinical data were examined. RESULTS: A total of 48 infections were identified in 70 infants aged <1 year, and 66.7% (32/48) of these infants were born preterm. The infection rate in infants aged <1 month was higher than that of others (P = 0.005). The most commonly isolated CRE was Klebsiella pneumoniae (60.4%, 29/48), followed by Enterobacter cloacae complex (18.8%, 9/48). Sputum (37.5%, 18/48), blood (27.1%, 13/48), and urine (25.0%, 12/48) were the most common clinical samples. Urinary tract infection was common in infants aged 6-12 months. CRE infection was associated with mechanical ventilation (P = 0.037), central venous catheter (CVC) insertion (P = 0.034), and congenital heart disease (P = 0.027). The hospital stay of patients with CRE infection was longer (median, 75 days; SD, 66.4 days), and their all-cause mortality (6.4%) was higher than those with colonization. CONCLUSIONS: CRE infection was common in infants aged <1 month, and patients usually had longer hospitalization. Carbapenemase production was not common. Mechanical ventilation, CVC insertion, and congenital heart disease were associated with a higher risk of CRE acquisition in infants aged <1 year.

Formation of monodomain polymer-stabilized blue phase liquid crystals using surface acoustic waves.

This work uses surface acoustic waves (SAWs) that are generated by a piezoelectric substrate containing an interdigital transducer (IDT) to which a low voltage of 2 mV was applied at a frequency of 1 kHz to fabricate a polymer-stabilized blue phase liquid crystal (PS-BPLC) layer. The PS-BPLC layer has a more uniform optical microscope (OM) image at a voltage of 2 mV than at zero voltage, and its reflective spectrum exhibits a smaller full width at half maximum (FWHM) at the former than at the latter. The uniform OM image and small FWHM reveal that the lattices in the PS-BPLC layer have monodomain structure. The monodomain PS-BPLC layer is formed because the SAWs cause longitudinal and transverse vibrations of the PS-BPLC lattices in the vertical plane along their traveling direction. The proposed method for fabricating the monodomain PS-BPLC layer using the SAWs has potential for the development of reflective optical devices that consume low power during their fabrication.

Long-term use and risk of major adverse cardiac events: Comparing enzalutamide and abiraterone in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer.

This is a retrospective cohort study by analyzing a multi-institutional electronic medical records database in Taiwan to compare long-term effectiveness and risk of major adverse cardiac events (MACE) in chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) patients treated with enzalutamide (ENZ) or abiraterone (AA). Patients aged 20 years and older and newly receiving androgen receptor targeted therapies ENZ or AA from September 2016 to December 2019 were included. We followed patients from initiation of therapies to the occurrence of outcomes (prostate-specific antigen (PSA) response rate, PSA progression free survival (PFS), overall survival (OS), and MACE), death, the last clinical visit, or December 31, 2020. We performed multivariable Cox proportional hazard models to compare ENZ and AA groups for the measured outcomes. A total of 363 patients treated with either ENZ (n = 157) or AA (n = 206) were identified. The analysis found a significantly higher proportion of patients with a PSA response rate higher than 50% among those receiving ENZ than among those receiving AA (ENZ vs AA: 75.80% vs 63.59%, P = .01). However, there was no significant difference in PSA PFS (adjusted hazard ratio: 0.86; 95% CI 0.63-1.17) and OS (0.68: 0.41-1.14) between the use of ENZ and AA in chemotherapy-naïve mCRPC patients. Regarding the cardiovascular (CV) safety outcome, there was a significantly lower risk of MACE in patients receiving ENZ, compared to patients receiving AA (0.20: 0.07-0.55). The findings suggest that enzalutamide may be more efficacious for PSA response and suitable for chemotherapy-naïve mCRPC patients with high CV risk profile.

Diastereoselective Synthesis of Chromeno[3,2-d]isoxazoles via Brønsted Acid Catalyzed Tandem 1,6-Addition/Double Annulations of o-Hydroxyl Propargylic Alcohols.

A Brønsted acid catalyzed tandem process to access densely functionalized chromeno[3,2-d]isoxazoles with good to excellent yields and diastereoselectivities was disclosed. The procedure is proposed to involve a 1,6-conjugate addition/electrophilic addition/double annulations process of alkynyl o-quinone methides (o-AQMs) in situ generated from o-hydroxyl propargylic alcohols with nitrones. Mild conditions, good functional group compatibility, easy scale-up of the reaction, and further product transformation demonstrated its potential application.

Ameliorative effect and mechanism of Si-Ni-San on chronic stress-induced diarrhea-irritable bowel syndrome in rats.

Background: Chronic stress-induced diarrhea is a common clinical condition, characterized by an abnormal bowel movement and loose stools, which lacks effective treatment in the clinic. Si-Ni-San (SNS) is a compound traditional Chinese medicine extensively used in China for stress-related diarrhea. However, the mechanism is unclear. Methods: Male Wistar rats (200 ± 20 g) were placed in a restraint cylinder and fixed horizontally for 3 h once daily for 21 consecutive days to establish a chronic restraint stress (CRS) rat model. SNS (0.6944 g/kg or 1.3888 g/kg) was given by gavage 1 h before the restraint once daily for 21 consecutive days. We examined the fecal score, dopamine ß hydroxylase (DßH), and c-fos expression in locus coeruleus, norepinephrine (NE) content in ileum and plasma, expression of α1 adrenergic receptors, MLCK, MLC, and p-MLC in the colon and mesenteric arteries, contraction of isolated mesenteric arteries, The expression of subunit δ of ATP synthase (ATP5D) in intestinal tissues, ATP, ADP, and AMP content in the ileum and colon, occludin expression between ileum epithelial cells, the number of enterochromaffin cells (ECs) and mast cells (MCs) in the ileum, and 5-hydroxytryptamine (5-HT) content in the ileum and plasma. Results: After SNS treatment, the fecal score was improved. The increased expression of DßH and c-fos in locus coeruleus was inhibited. SNS suppressed the increased NE content in the ileum and plasma, down-regulated α1 adrenergic receptors in mesenteric arteries and MLCK, MLC, p-MLC in the colon and mesenteric arteries, and inhibited the contraction of mesenteric arteries. SNS also increased the ATP content in the ileum and colon, inhibited low expression of ATP5D in intestinal tissues, inhibited the decrease of ATP/ADP in the ileum and ATP/AMP in the colon, and up-regulated the occludin expression between ileum epithelial cells. In addition, SNS inhibited the increase of ECs and MCs in the ileum and the increase of 5-HT content in the ileum and plasma. Conclusion: This study demonstrated that SNS could improve CRS-induced abnormal feces in rats. This effect was related to the inhibition of CRS-induced increased expression of DßH and c-fos in the locus coeruleus, NE content in the ileum and plasma, and the contraction of isolated mesenteric arteries; inhibition of energy metabolism abnormality and decreased occludin expression; inhibition of increased ECs and MCs in the ileum, and 5-HT content in the ileum and plasma.

One-pot catalyst-free synthesis of benzopyrroxazine derivatives by a mutually activated sequential annulation process.

A one-pot catalyst-free reaction of o-hydroxyaryl azomethine ylides, vinyl pyridines and paraformaldehyde for the synthesis of benzopyrroxazines is reported, which offers a straightforward and atom-economical procedure for the preparation of benzopyrroxazine derivatives in moderate to excellent yields under mild conditions. A self-catalyzed [3 + 2] annulation through a mutual activation method and a sequential non-catalyzed [5 + 1] annulation process contribute to this strategy. The corresponding control experiments have been conducted to reveal the mechanism of this reaction.

Prenatal disruption of blood-brain barrier formation via cyclooxygenase activation leads to lifelong brain inflammation.

Gestational maternal immune activation (MIA) in mice induces persistent brain microglial activation and a range of neuropathologies in the adult offspring. Although long-term phenotypes are well documented, how MIA in utero leads to persistent brain inflammation is not well understood. Here, we found that offspring of mothers treated with polyriboinosinic­polyribocytidylic acid [poly(I:C)] to induce MIA at gestational day 13 exhibit blood­brain barrier (BBB) dysfunction throughout life. Live MRI in utero revealed fetal BBB hyperpermeability 2 d after MIA. Decreased pericyte­endothelium coupling in cerebral blood vessels and increased microglial activation were found in fetal and 1- and 6-mo-old offspring brains. The long-lasting disruptions result from abnormal prenatal BBB formation, driven by increased proliferation of cyclooxygenase-2 (COX2; Ptgs2)-expressing microglia in fetal brain parenchyma and perivascular spaces. Targeted deletion of the Ptgs2 gene in fetal myeloid cells or treatment with the inhibitor celecoxib 24 h after immune activation prevented microglial proliferation and disruption of BBB formation and function, showing that prenatal COX2 activation is a causal pathway of MIA effects. Thus, gestational MIA disrupts fetal BBB formation, inducing persistent BBB dysfunction, which promotes microglial overactivation and behavioral alterations across the offspring life span. Taken together, the data suggest that gestational MIA disruption of BBB formation could be an etiological contributor to neuropsychiatric disorders.

Comparative Effectiveness and Safety of Standard-Dose and Low-Dose Pembrolizumab in Patients with Non-Small-Cell Lung Cancer: A Multi-Institutional Cohort Study in Taiwan.

Fixed doses at 200 mg of pembrolizumab or 2 mg/kg every 3 weeks are the standard dosages for first- and second-line treatment of non-small-cell lung cancer (NSCLC); however, in clinical practice, patients with NSCLC may receive lower doses of pembrolizumab due to drug product availability or economic factors. To date, the comparative effectiveness and safety of the standard dose and lower doses of pembrolizumab in these patients still remains limited. We conducted a retrospective cohort study by analyzing electronic medical records data from the largest multi-institutional hospital system in Taiwan. Advanced NSCLC patients newly receiving pembrolizumab with or without chemotherapy were included. Patients were classified into: (1) the standard-dose group (≥2 mg/kg), and (2) the low-dose group (<2 mg/kg). We applied inverse probability of treatment weighting (IPTW) to compare the overall survival (OS) and immune-related adverse events (irAEs) between the two treatment groups, and to evaluate the minimum clinically effective dose of pembrolizumab. We included a total of 147 NSCLC patients receiving standard-dose pembrolizumab (mean [range] age: 63.7 [58.0−73.0] years; male: 62.6%; mean [range] body weight: 60.5 [58.0−73.0] kg) and 95 patients receiving low-dose pembrolizumab (mean [range] age: 62.0 [50.0−68.8] years; male: 64.2%; mean [range] body weight: 63.9 [55.0−73.8] kg). After IPTW adjustments, the median OS was similar for both the standard-dose and low-dose pembrolizumab groups (19.3 vs. 14.3 months, log-rank p = 0.15). Also, the rate for all classes of irAEs was similar for both groups. We found that patients with a pembrolizumab dose ≥1.8 mg/kg were associated with better OS than those receiving <1.8 mg/kg. Our findings suggested no significant difference in OS and irAEs between patients receiving pembrolizumab ≥2 mg/kg and <2 mg/kg in clinical practice. A pembrolizumab dose ≥1.8 mg/kg may be the clinically most efficient dose.

Stable reflective state induced by a disturbed planar texture in surface-treatment-free chiral nematic liquid crystals.

Chiral nematic liquid crystals possess a one-dimensional periodic helical structure and are one of the oldest known materials with the ability of selective reflection of light. Their helix orientation, determining their optical properties, can be changed by a variety of stimuli, and it is also dominated by the surface treatment, ratio of the elastic constants and cell thickness. Here, we present a simple method to realize an angular independence reflective state, induced by a stable disturbed planar texture, in a surface-treatment-free chiral nematic liquid crystal cell. The scattering state caused by the defect-rich focal-conic texture can be electrically tuned to the reflective state from the disturbed planar texture in a very short time, and vice versa. These two optical conditions are both stable states in the null field until the next trigger. We find that the disturbed planar texture in the chiral nematic can provide a 100° viewing angle without reflected wavelength shift. The gray level of the reflected intensity can be tuned via application of the voltage pulses. Moreover, in this work, we discuss the effect of the chiral concentration on stabilizing the disturbed planar texture. When the chiral concentration is higher to induce the blue phases, the change in the texture of the ChNLCs after removing the strong electric field can stop at the disturbed planar texture with high reflectivity. In this work, the optical performance and the bistability based on the disturbed planar texture exhibits great potential for many applications, such as tunable filters, see-through/reflective displays and large-area smart windows.

Guillain-​Barré Syndrome Associated with COVID-19 Vaccination.

We conducted a multi-institutional study in Taiwan and a systematic review of the literature for reports of Guillain-​Barré syndrome after coronavirus disease vaccination. This condition, mostly the classic form and the acute inflammatory demyelinating polyneuropathy subtype, has been reported in 39 cases and has occurred within 2 weeks of vaccine administration.

Potential transceptor AtNRT1.13 modulates shoot architecture and flowering time in a nitrate-dependent manner.

Compared with root development regulated by external nutrients, less is known about how internal nutrients are monitored to control plasticity of shoot development. In this study, we characterize an Arabidopsis thaliana transceptor, NRT1.13 (NPF4.4), of the NRT1/PTR/NPF family. Different from most NRT1 transporters, NRT1.13 does not have the conserved proline residue between transmembrane domains 10 and 11; an essential residue for nitrate transport activity in CHL1/NRT1.1/NPF6.3. As expected, when expressed in oocytes, NRT1.13 showed no nitrate transport activity. However, when Ser 487 at the corresponding position was converted back to proline, NRT1.13 S487P regained nitrate uptake activity, suggesting that wild-type NRT1.13 cannot transport nitrate but can bind it. Subcellular localization and ß-glucuronidase reporter analyses indicated that NRT1.13 is a plasma membrane protein expressed at the parenchyma cells next to xylem in the petioles and the stem nodes. When plants were grown with a normal concentration of nitrate, nrt1.13 showed no severe growth phenotype. However, when grown under low-nitrate conditions, nrt1.13 showed delayed flowering, increased node number, retarded branch outgrowth, and reduced lateral nitrate allocation to nodes. Our results suggest that NRT1.13 is required for low-nitrate acclimation and that internal nitrate is monitored near the xylem by NRT1.13 to regulate shoot architecture and flowering time.