Multiple serum anti-glutamate receptor antibody levels in clozapine-treated/naïve patients with treatment-resistant schizophrenia.

BACKGROUND: Glutamatergic function abnormalities have been implicated in the etiology of treatment-resistant schizophrenia (TRS), and the efficacy of clozapine may be attributed to its impact on the glutamate system. Recently, evidence has emerged suggesting the involvement of immune processes and increased prevalence of antineuronal antibodies in TRS. This current study aimed to investigate the levels of multiple anti-glutamate receptor antibodies in TRS and explore the effects of clozapine on these antibody levels. METHODS: Enzyme linked immunosorbent assay (ELISA) was used to measure and compare the levels of anti-glutamate receptor antibodies (NMDAR, AMPAR, mGlur3, mGluR5) in clozapine-treated TRS patients (TRS-C, n = 37), clozapine-naïve TRS patients (TRS-NC, n = 39), and non-TRS patients (nTRS, n = 35). Clinical symptom severity was assessed using the Positive and Negative Symptom Scale (PANSS), while cognitive function was evaluated using the MATRICS Consensus Cognitive Battery (MCCB). RESULT: The levels of all four glutamate receptor antibodies in TRS-NC were significantly higher than those in nTRS (p < 0.001) and in TRS-C (p < 0.001), and the antibody levels in TRS-C were comparable to those in nTRS. However, no significant associations were observed between antibody levels and symptom severity or cognitive function across all three groups after FDR correction. CONCLUSION: Our findings suggest that TRS may related to increased anti-glutamate receptor antibody levels and provide further evidence that glutamatergic dysfunction and immune processes may contribute to the pathogenesis of TRS. The impact of clozapine on anti-glutamate receptor antibody levels may be a pharmacological mechanism underlying its therapeutic effects.

How to determine the optimal proximal fusion level for Scheuermann kyphosis.

OBJECTIVE: To determine optimal proximal fusion levels for instrumented spinal fusion for Scheuermann kyphosis. METHODS: We reviewed 86 patients (33 women) who underwent corrective instrumented spinal fusion for Scheuermann kyphosis. All patients had long-cassette upright lateral radiographs taken preoperatively, postoperatively, and at 2 years and the last follow-up. Demographic, radiographic, and surgical parameters were compared between patients with and without PJK. RESULTS: PJK occurred in 28 patients (32%). The mean maximum Cobb angle was 85.8° ± 11.7° preoperatively, 54.8° ± 14.2° postoperatively, and 59.7° ± 16.8° at the last follow-up. Age and sex did not differ between the PJK and non-PJK groups (P > 0.05). The preoperative curve characteristics, fusion levels, and corrective ratio were similar in both groups (P > 0.05). The maximal Cobb angle at 2 years and the last follow-up significantly differed between the 2 groups (P < 0.05). The proportion of patients with the uppermost instrumented vertebra (UIV) at or above the proximal end vertebra (PEV) was similar in both groups (P > 0.05). The proportion of patients with UIV at or above T2 was significantly greater in the non-PJK group (P < 0.05). PJK was significantly associated with a C7 plumb line (C7PL)-sacrum distance ≥ 50 mm (P < 0.05). CONCLUSION: PJK is the main cause of postoperative correction loss. Proper fusion-level selection can reduce PJK occurrence. We recommend having the UIV at T2 or above, especially when the C7PL-sacrum distance ≥ 50 mm.

KF-Containing Interphase Formation Enables Better Potassium Ion Storage Capability.

Rechargeable potassium ion batteries have long been regarded as one alternative to conventional lithium ion batteries because of their resource sustainability and cost advantages. However, the compatibility between anodes and electrolytes remains to be resolved, impeding their commercial adoption. In this work, the K-ion storage properties of Bi nanoparticles encapsulated in N-doped carbon nanocomposites have been examined in two typical electrolyte solutions, which show a significant effect on potassium insertion/removal processes. In a KFSI-based electrolyte, the N-C@Bi nanocomposites exhibit a high specific capacity of 255.2 mAh g-1 at 0.5 A g-1, which remains at 245.6 mAh g-1 after 50 cycles, corresponding to a high capacity retention rate of 96.24%. In a KPF6-based electrolyte, the N-C@Bi nanocomposites show a specific capacity of 209.0 mAh g-1, which remains at 71.5 mAh g-1 after 50 cycles, corresponding to an inferior capacity retention rate of only 34.21%. Post-investigations reveal the formation of a KF interphase derived from salt decomposition and an intact rod-like morphology after cycling in K2 electrolytes, which are responsible for better K-ion storage properties.

Optical noise-resistant nonreciprocal phonon blockade in a spinning optomechanical resonator.

A scheme of nonreciprocal conventional phonon blockade (PB) is proposed in a spinning optomechanical resonator coupled with a two-level atom. The coherent coupling between the atom and breathing mode is mediated by the optical mode with a large detuning. Due to the Fizeau shift caused by the spinning resonator, the PB can be implemented in a nonreciprocal way. Specifically, when the spinning resonator is driven from one direction, the single-phonon (1PB) and two-phonon blockade (2PB) can be achieved by adjusting both the amplitude and frequency of the mechanical drive field, while phonon-induced tunneling (PIT) occurs when the spinning resonator is driven from the opposite direction. The PB effects are insensitive to cavity decay because of the adiabatic elimination of the optical mode, thus making the scheme more robust to the optical noise and still feasible even in a low-Q cavity. Our scheme provides a flexible method for engineering a unidirectional phonon source with external control, which is expected to be used as a chiral quantum device in quantum computing networks.

Suicidal ideation in Chinese patients with chronic schizophrenia: prevalence, clinical correlates, and relationship with alexithymia.

Suicidal ideation (SI) is common among people with schizophrenia. However, it has received less attention than suicide attempts (SA), especially in the Chinese population. Alexithymia is a well-established risk factor for SI across different populations. Nevertheless, very few studies evaluated their relationship in schizophrenia patients. We aimed to determine the prevalence and clinical correlates of SI and its relationship with alexithymia in 812 Chinese chronic schizophrenia inpatients. We assessed SI, clinical symptoms, and alexithymia by the Beck Scale for Suicidal Ideation, the Positive and Negative Syndrome Scale (PANSS), and the Toronto Alexithymia Scale, respectively. A multiple logistic regression model was conducted to identify independent correlates of SI. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were performed to determine the ability of our model to distinguish between patients with and without SI. 10% (n = 84) reported current SI. Lifetime SA (OR, 4.68; 95% CI 2.76-7.94, p < 0.001), PANSS depressive factor (OR, 1.24; 95% CI 1.12-1.38, p < 0.001), PANSS positive subscale (OR, 1.055; 95% CI 1.004-1.108, p = 0.035), and difficulty identifying emotions (OR, 1.07; 95% CI 1.03-1.12, p = 0.002) were associated with SI. The AUC value was 0.80, indicating excellent distinguishing capabilities. Timely assessments of these factors may help identify schizophrenia patients who are at risk for SI.

Sex differences in the association of treatment-resistant schizophrenia and serum interleukin-6 levels.

BACKGROUND: Low-grade inflammation and altered inflammatory markers have been observed in treatment-resistant schizophrenia (TRS). Interleukin-6 (IL-6) is one of the pro-inflammatory cytokines linked with TRS and receives increasing attention. Previous studies showed that patients with TRS might have higher IL-6 levels compared with healthy individuals and treatment-responsive patients. Besides, emerging evidence has suggested that there are sex differences in the associations between IL-6 levels and various illnesses, including chronic hepatitis C, metabolic syndrome, etc.; however, there is limited study on TRS. In this present study, we aimed to compare the serum IL-6 levels of TRS and partially responsive schizophrenia (PRS) and explore potential sex differences in the association of TRS and IL-6 levels. METHODS: The study population consisted of a total of 90 patients with schizophrenia: 64 TRS patients (45.3% males and 54.7% females) and 26 PRS patients (46.2% males and 53.8% females). We measured serum IL-6 levels using enzyme-linked immunosorbent assay (ELISA) and analyzed them separately by gender, controlling for confounders (age, education, medication, body mass index, and PANSS scores) rigorously. RESULT: The results showed that patients with TRS had higher serum IL-6 levels than patients with PRS (p = 0.002). In females, IL-6 levels increased significantly in the TRS group compared with the PRS group (p = 0.005). And a positive correlation tendency was observed between IL-6 levels and PANSS general sub-scores (r = 0.31, p = 0.039), although this correlation was not significant after correcting for multiple comparisons. Whereas, there were no differences in IL-6 levels between the TRS and PRS (p = 0.124) in males. CONCLUSION: Our findings provided evidence supporting the hypothesis that the inflammatory response system (IRS) may play a role in the pathogenesis of TRS in a sex-dependent manner. In addition, sex differences in the immune dysfunction of individuals with schizophrenia cannot be neglected, and inflammation in male and female TRS should be discussed separately.

Comparisons of potential values of D-dimer and the neutrophil- to-lymphocyte ratio in patients with suspected acute aortic syndrome.

OBJECTIVES: This study aimed to investigate and compare the discriminative performance and clinical utility of D-dimer and the neutrophil-to-lymphocyte ratio (NLR) in the early differential diagnosis of acute aortic syndrome (AAS). METHODS: The consecutive patients presenting to Tianjin Chest Hospital for suspected AAS were retrospectively investigated between June 2018 and December 2021. The baseline values of D-dimer and NLR were analyzed and compared in the study population. The discriminative ability of D-dimer and NLR was illustrated and compared using the area under the receiver operating characteristic (ROC) curve (AUC), net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Clinical utility was evaluated by means of decision curve analysis (DCA). RESULTS: In the study period, a total of 697 participants suspected of having AAS were enrolled and 323 had a final diagnosis of AAS. The baseline level of NLR as well as D-dimer was higher in patients with AAS. The use of NLR showed excellent overall diagnostic performance for AAS with a comparable AUC to that of D-dimer (0.845 vs. 0.822, P > 0.05). The reclassification analyses further confirmed that NLR had better discriminative properties for AAS with a significant NRI of 66.1% and IDI of 12.4% (P < 0.001). Moreover, NLR provided higher net benefit than D-dimer as shown by DCA. Similar results were observed in subgroup analyses according to the different classes of AAS. CONCLUSIONS: NLR outperformed D-dimer with improved discriminative performance and superior clinical utility in identifying AAS. As a more readily available biomarker, NLR may be a reliable alternative to D-dimer for the screening of suspected AAS in clinical practice.

Tracking the Progression of the Simulated Bronze Disease-A Laboratory X-ray Microtomography Study.

The internal three-dimensional characteristics of X-ray microtomography (micro-CT) has great application potential in the field of bronze corrosion. This work presents a method of simulating bronze disease based on an in situ micro-CT image to study the characteristics of the oxidative hydrolysis reactions of copper(I) chloride and copper(II) chloride dihydrate. A series of high-resolution reconstruction images were obtained by carrying out micro-CT at three key points throughout the experiment. We found that the reactions of copper(I) chloride and copper(II) chloride dihydrate showed different characteristics at different stages of the simulation in the micro-CT view. The method proposed in this work specifically simulated one single type of bronze corrosion and characterized the evolution characteristics of simulated bronze disease. It provides a new perspective to investigate bronze disease and can help improve the subsequent use of micro-CT to distinguish real bronze corrosions.

The traditional herb Polygonum hydropiper from China: a comprehensive review on phytochemistry, pharmacological activities and applications.

CONTEXT: Polygonum hydropiper L. (Polygonaceae) (PH) is a traditional Chinese traditional medicine with a pungent flavor and mild drug properties. PH is mainly distributed in the channel tropism in the stomach and large intestine. PH has multiple uses and can be used to treat a variety of diseases for a long time. OBJECTIVE: This review summarizes the phytochemical and pharmacological activities, and applications of PH from 1980 to 2022. We also provide suggestions for promoting further research and developing additional applications of PH. METHODS: The data and information on PH from 1980 to 2022 reviewed in this article were obtained from scientific databases, including Science Direct, PubMed, Science Citation Index, SciFinder Scholar (SciFinder), Springer, American Chemical Society (ACS) Publications, and China National Knowledge Infrastructure (CNKI), etc. Some information was obtained from classic literature on traditional Chinese medicines. The search terms were Polygonum hydropiper, phytochemistry compositions of Polygonum hydropiper, pharmacological activities of Polygonum hydropiper, and applications of Polygonum hydropiper. RESULTS: The comprehensive analysis of the literature resulted in 324 compounds being isolated, identified, and reported from PH. Regarding traditional uses, the majority of phytochemical and pharmacological studies have indicated the diverse bioactivities of PH extracts, flavonoids, and volatile oil elements, including antibacterial, antifungal, insecticidal, antioxidant, and anti-inflammatory. CONCLUSIONS: PH has a long history of diversified medicinal uses, some of which have been verified in modern pharmacological studies. Further detailed studies are required to establish scientific and reasonable quality evaluation standards and action mechanisms of active constituents from PH.

[A new dihydrochalcone from Humulus scandens].

To study the chemical constituents from the stems and leaves of Humulus scandens, this study isolated thirteen compounds by different chromatographic methods including silica gel column, ODS, Sephadex LH-20 and preparative HPLC. Based on comprehensive analysis, the chemical structures were elucidated and identified as citrunohin A(1), chrysosplenetin(2), casticin(3), neoechinulin A(4), ethyl 1H-indole-3-carboxylate(5), 3-hydroxyacetyl-indole(6),(1H-indol-3-yl) oxoacetamide(7), inonotusic acid(8), arteannuin B(9), xanthotoxol(10), α-tocopherol quinone(11), eicosanyl-trans-p-coumarate(12), and 9-oxo-(10E,12E)-octadecadienoic acid(13). Among them, compound 1 was a new dihydrochalcone, and the other compounds were obtained from H. scandens for the first time.

[Clinical features of autoimmune encephalitis secondary to epidemic encephalitis B in 5 children]. / 5ä¾‹æµè¡Œæ€§ä¹™åž‹è„‘ç‚Žå„¿ç«¥ç»§å‘è‡ªèº«å ç–«æ€§è„‘ç‚Žçš„ä¸´åºŠåˆ†æž.

OBJECTIVES: To study the clinical features of children with autoimmune encephalitis (AE) secondary to epidemic encephalitis B (EEB). METHODS: A retrospective analysis was performed on the medical data of five children with EEB with "bipolar course" who were treated in Children's Hospital Affiliated to Zhengzhou University from January 2020 to June 2022. RESULTS: Among the five children, there were three boys and two girls, with a median age of onset of 7 years (range 3 years 9 months to 12 years) and a median time of 32 (range 25-37) days from the onset of EEB to the appearance of AE symptoms. The main symptoms in the AE stage included dyskinesia (5/5), low-grade fever (4/5), mental and behavioral disorders (4/5), convulsion (2/5), severe disturbance of consciousness (2/5), and limb weakness (1/5). Compared with the results of cranial MRI in the acute phase of EEB, the lesions were enlarged in 3 children and unchanged in 2 children showed on cranial MRI in the AE stage. In the AE stage, four children were positive for anti-N-methyl-D-aspartate receptor antibody (one was also positive for anti-γ-aminobutyric acid type B receptor antibody), and one was negative for all AE antibodies. All five children in the AE stage responded to immunotherapy and were followed up for 3 months, among whom one almost recovered and four still had neurological dysfunction. CONCLUSIONS: EEB can induce AE, with anti-N-methyl-D-aspartate receptor encephalitis as the most common disease. The symptoms in the AE stage are similar to those of classical anti-N-methyl-D-aspartate receptor encephalitis. Immunotherapy is effective for children with AE secondary to EEB, and the prognosis might be related to neurological dysfunction in the acute phase of EEB.

Pbrm1 intrinsically controls the development and effector differentiation of iNKT cells.

Under static condition, the pool size of peripheral invariant natural killer T (iNKT) cells is determined by their homeostatic proliferation, survival and thymic input. However, the underlying mechanism is not fully understood. In the present study, we found that the percentage and number of iNKT cells were significantly reduced in the spleen, but not in the thymus of mice with deletion of polybromo-1 (Pbrm1) compared to wild type (WT) mice. Pbrm1 deletion did not affect iNKT cell proliferation and survival, instead significantly impaired their development from stage 1 to stage 2. Importantly, loss of Pbrm1 led to a dysfunction of RORγt expression and iNKT17 cell differentiation, but not iNKT1 and iNKT2 proportion. Collectively, our study reveals a novel mechanism of Pbrm1 controlling the peripheral size of iNKT cells through regulating their development and differentiation.

Field-Tuning Mechanisms of Spin Switching and Spin Reorientation Transition in Praseodymium-Erbium Orthoferrite Single Crystals.

Field-tuning mechanisms of spin switching and spin reorientation (SR) transition were investigated in a series of high-quality single crystal samples of PrxEr1-xFeO3 (x = 0, 0.1, 0.3, 0.5) prepared using the optical floating zone method. The single crystal quality, structure, and axis orientation were determined by room-temperature powder X-ray diffraction, back-reflection Laue X-ray diffraction, and Raman scattering at room temperature. Magnetic measurements indicate that the type and temperature region of SR transition are tuned by introducing different ratios of Pr3+ doping (x = 0, 0.1, 0.3, 0.5). The trigger temperatures of spin switching and magnetization compensation temperature of PrxEr1-xFeO3 crystals can be adjusted by doping with different proportions of Pr3+. Furthermore, the trigger temperature of the two types of spin switching in Pr0.3Er0.7FeO3 along the a-axis can be regulated by an external field. Meanwhile, the isothermal magnetic field-triggered spin switching effect is also observed along the a and c-axes of Pr0.3Er0.7FeO3. An in-depth understanding of the magnetic coupling and competition between the R3+ and Fe3+ magnetic sublattices, within the RFeO3 system, has important implications for advancing the practical applications of the relevant spin switching materials.

Nomogram-based risk prediction of macrosomia: a case-control study.

BACKGROUND: Macrosomia is closely associated with poor maternal and fetal outcome. But there is short of studies on the risk of macrosomia in early pregnancy. The purpose of this study is to establish a nomogram for predicting macrosomia in the first trimester. METHODS: A case-control study involving 1549 pregnant women was performed. According to the birth weight of newborn, the subjects were divided into macrosomia group and non-macrosomia group. The risk factors for macrosomia in early pregnancy were analyzed by multivariate logistic regression. A nomogram was used to predict the risk of macrosomia. RESULTS: The prevalence of macrosomia was 6.13% (95/1549) in our hospital. Multivariate logistic regression analysis showed that prepregnancy overweight (OR: 2.13 95% CI: 1.18-3.83)/obesity (OR: 3.54, 95% CI: 1.56-8.04), multiparity (OR:1.88, 95% CI: 1.16-3.04), the history of macrosomia (OR: 36.97, 95% CI: 19.90-68.67), the history of GDM/DM (OR: 2.29, 95% CI: 1.31-3.98), the high levels of HbA1c (OR: 1.76, 95% CI: 1.00-3.10) and TC (OR: 1.36, 95% CI: 1.00-1.84) in the first trimester were the risk factors of macrosomia. The area under ROC (the receiver operating characteristic) curve of the nomogram model was 0.807 (95% CI: 0.755-0.859). The sensitivity and specificity of the model were 0.716 and 0.777, respectively. CONCLUSION: The nomogram model provides an effective mothed for clinicians to predict macrosomia in the first trimester.

SMRI: A New Method for siRNA Design for COVID-19 Therapy.

First discovered in Wuhan, China, SARS-CoV-2 is a highly pathogenic novel coronavirus, which rapidly spread globally and became a pandemic with no vaccine and limited distinctive clinical drugs available till March 13th, 2020. Ribonucleic Acid interference (RNAi) technology, a gene-silencing technology that targets mRNA, can cause damage to RNA viruses effectively. Here, we report a new efficient small interfering RNA (siRNA) design method named Simple Multiple Rules Intelligent Method (SMRI) to propose a new solution of the treatment of COVID-19. To be specific, this study proposes a new model named Base Preference and Thermodynamic Characteristic model (BPTC model) indicating the siRNA silencing efficiency and a new index named siRNA Extended Rules index (SER index) based on the BPTC model to screen high-efficiency siRNAs and filter out the siRNAs that are difficult to take effect or synthesize as a part of the SMRI method, which is more robust and efficient than the traditional statistical indicators under the same circumstances. Besides, to silence the spike protein of SARS-CoV-2 to invade cells, this study further puts forward the SMRI method to search candidate high-efficiency siRNAs on SARS-CoV-2's S gene. This study is one of the early studies applying RNAi therapy to the COVID-19 treatment. According to the analysis, the average value of predicted interference efficiency of the candidate siRNAs designed by the SMRI method is comparable to that of the mainstream siRNA design algorithms. Moreover, the SMRI method ensures that the designed siRNAs have more than three base mismatches with human genes, thus avoiding silencing normal human genes. This is not considered by other mainstream methods, thereby the five candidate high-efficiency siRNAs which are easy to take effect or synthesize and much safer for human body are obtained by our SMRI method, which provide a new safer, small dosage and long efficacy solution for the treatment of COVID-19. Supplementary Information: The online version contains supplementary material available at 10.1007/s11390-021-0826-x.

Induced secretion system mutation alters rhizosphere bacterial composition in Sorghum bicolor (L.) Moench.

MAIN CONCLUSION: A novel inducible secretion system mutation in Sorghum named Red root has been identified. The mutant plant root exudes pigmented compounds that enriches Actinobacteria in its rhizosphere compared to BTx623. Favorable plant-microbe interactions in the rhizosphere positively influence plant growth and stress tolerance. Sorghum bicolor, a staple biomass and food crop, has been shown to selectively recruit Gram-positive bacteria (Actinobacteria) in its rhizosphere under drought conditions to enhance stress tolerance. However, the genetic/biochemical mechanism underlying the selective enrichment of specific microbial phyla in the sorghum rhizosphere is poorly known due to the lack of available mutants with altered root secretion systems. Using a subset of sorghum ethyl methanesulfonate (EMS) mutant lines, we have isolated a novel Red root (RR) mutant with an increased accumulation and secretion of phenolic compounds in roots. Genetic analysis showed that RR is a single dominant mutation. We further investigated the effect of root-specific phenolic compounds on rhizosphere microbiome composition under well-watered and water-deficit conditions. The microbiome diversity analysis of the RR rhizosphere showed that Actinobacteria were enriched significantly under the well-watered condition but showed no significant change under the water-deficit condition. BTx623 rhizosphere showed a significant increase in Actinobacteria under the water-deficit condition. Overall, the rhizosphere of RR genotype retained a higher bacterial diversity and richness relative to the rhizosphere of BTx623, especially under water-deficit condition. Therefore, the RR mutant provides an excellent genetic resource for rhizosphere-microbiome interaction studies as well as to develop drought-tolerant lines. Identification of the RR gene and the molecular mechanism through which the mutant selectively enriches microbial populations in the rhizosphere will be useful in designing strategies for improving sorghum productivity and stress tolerance.

Axonal iron transport in the brain modulates anxiety-related behaviors.

Iron is essential for a broad range of biochemical processes in the brain, but the mechanisms of iron metabolism in the brain remain elusive. Here we show that iron functionally translocates among brain regions along specific axonal projections. We identified two pathways for iron transport in the brain: a pathway from ventral hippocampus (vHip) to medial prefrontal cortex (mPFC) to substantia nigra; and a pathway from thalamus (Tha) to amygdala (AMG) to mPFC. While vHip-mPFC transport modulates anxiety-related behaviors, impairment of Tha-AMG-mPFC transport did not. Moreover, vHip-mPFC iron transport is necessary for the behavioral effects of diazepam, a well-known anxiolytic drug. By contrast, genetic or pharmacological promotion of vHip-mPFC transport produced anxiolytic-like effects and restored anxiety-like behaviors induced by repeated restraint stress. Taken together, these findings provide key insights into iron metabolism in the brain and identify the mechanisms underlying iron transport in the brain as a potential target for development of novel anxiety treatments.

[Optimization of polysaccharide extraction from Hippocampus by deep neural network and Box-Behnken design-response surface methodology].

In this paper, the extraction rate of crude polysaccharides and the yield of polysaccharides from Hippocampus served as test indicators. The comprehensive evaluation indicators were assigned by the R language combined with the entropy weight method. The Box-Behnken design-response surface methodology(BBD-RSM) and the deep neural network(DNN) were employed to screen the optimal parameters for the polysaccharide extraction from Hippocampus. These two modeling methods were compared and verified experimentally for the process optimization. This study provides a reference for the industrialization of effective component extraction from Chinese medicinals and achieves the effective combination of modern technology and traditional Chinese medicine.

The Photoperiodic Flowering Time Regulator FKF1 Negatively Regulates Cellulose Biosynthesis.

Cellulose synthesis is precisely regulated by internal and external cues, and emerging evidence suggests that light regulates cellulose biosynthesis through specific light receptors. Recently, the blue light receptor CRYPTOCHROME 1 (CRY1) was shown to positively regulate secondary cell wall biosynthesis in Arabidopsis (Arabidopsis thaliana). Here, we characterize the role of FLAVIN-BINDING KELCH REPEAT, F-BOX 1 (FKF1), another blue light receptor and well-known photoperiodic flowering time regulator, in cellulose biosynthesis. A phenotype suppression screen using a cellulose deficient mutant cesa1aegeus,cesa3ixr1-2 (c1,c3), which carries nonlethal point mutations in CELLULOSE SYNTHASE A 1 (CESA1) and CESA3, resulted in identification of the phenotype-restoring large leaf (llf) mutant. Next-generation mapping using the whole genome resequencing method identified the llf locus as FKF1 FKF1 was confirmed as the causal gene through observation of the llf phenotype in an independent triple mutant c1,c3,fkf1-t carrying a FKF1 T-DNA insertion mutant. Moreover, overexpression of FKF1 in llf plants restored the c1,c3 phenotype. The fkf1 mutants showed significant increases in cellulose content and CESA gene expression compared with that in wild-type Columbia-0 plants, suggesting a negative role of FKF1 in cellulose biosynthesis. Using genetic, molecular, and phenocopy and biochemical evidence, we have firmly established the role of FKF1 in regulation of cellulose biosynthesis. In addition, CESA expression analysis showed that diurnal expression patterns of CESAs are FKF1 independent, whereas their circadian expression patterns are FKF1 dependent. Overall, our work establishes a role of FKF1 in the regulation of cell wall biosynthesis in Arabidopsis.

Perineural Invasion is a Better Prognostic Indicator than Lymphovascular Invasion and a Potential Adjuvant Therapy Indicator for pN0M0 Esophageal Squamous Cell Carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) at pN0M0 can be more locally aggressive and disseminated than those with lymph node and distant metastasis. Perineural invasion (PNI) is reported as a poor prognostic factor in cancer and is thought to be related to regional tumor spread and metastasis. However, its clinicopathological role and meaning for treatment in pN0M0 ESCC are unknown. PATIENTS AND METHODS: We applied scoring methods of PNI and lymphatic and vascular invasion (LI, VI) based on immunohistochemistry staining on tumor tissues of pN0M0 ESCC patients. ROC analyses, Kaplan-Meier analyses, Cox regression, and χ2 test were performed for survival analysis, comparison of PNI with LI and VI, and exploration of the relevance between PNI and other clinicopathological features. RESULTS: Presence of PNI was significantly associated with poor survival in pN0M0 patients, whereas LI and VI were not predictive of outcome (P > 0.05). Neural invasion index (NII), defined as the ratio of the number of tumor-invaded nerves to the total number of nerves per tumor microsection, was the most consistent measure of PNI (P = 0.006, HR = 6.892, 1.731-27.428). Postoperative radiotherapy significantly improved survival in high-NII patients (P = 0.035, HR = 0.390, 0.163-0.936). CONCLUSIONS: PNI is an important risk factor for the outcome of pN0M0 ESCC patients. NII can be used for risk assessment and to tailor adjuvant radiotherapy in this population.