Acyloxyacyl hydrolase promotes pulmonary defense by preventing alveolar macrophage tolerance.

Although alveolar macrophages (AMs) play important roles in preventing and eliminating pulmonary infections, little is known about their regulation in healthy animals. Since exposure to LPS often renders cells hyporesponsive to subsequent LPS exposures ("tolerant"), we tested the hypothesis that LPS produced in the intestine reaches the lungs and stimulates AMs, rendering them tolerant. We found that resting AMs were more likely to be tolerant in mice lacking acyloxyacyl hydrolase (AOAH), the host lipase that degrades and inactivates LPS; isolated Aoah-/- AMs were less responsive to LPS stimulation and less phagocytic than were Aoah+/+ AMs. Upon innate stimulation in the airways, Aoah-/- mice had reduced epithelium- and macrophage-derived chemokine/cytokine production. Aoah-/- mice also developed greater and more prolonged loss of body weight and higher bacterial burdens after pulmonary challenge with Pseudomonas aeruginosa than did wildtype mice. We also found that bloodborne or intrarectally-administered LPS desensitized ("tolerized") AMs while antimicrobial drug treatment that reduced intestinal commensal Gram-negative bacterial abundance largely restored the innate responsiveness of Aoah-/- AMs. Confirming the role of LPS stimulation, the absence of TLR4 prevented Aoah-/- AM tolerance. We conclude that commensal LPSs may stimulate and desensitize (tolerize) alveolar macrophages in a TLR4-dependent manner and compromise pulmonary immunity. By inactivating LPS in the intestine, AOAH promotes antibacterial host defenses in the lung.

Learning of the same task subserved by substantially different mechanisms between patients with body dysmorphic disorder and healthy individuals.

It has remained unclear whether individuals with psychiatric disorders involving altered visual processing employ similar neuronal mechanisms during perceptual learning of a visual task. We investigated this question by training patients with body dysmorphic disorder, a psychiatric disorder characterized by distressing or impairing preoccupation with nonexistent or slight defects in one's physical appearance, and healthy controls on a visual detection task for human faces with low spatial frequency components. Brain activation during task performance was measured with functional magnetic resonance imaging before the beginning and after the end of behavioral training. Both groups of participants improved performance on the trained task to a similar extent. However, neuronal changes in the fusiform face area were substantially different between groups such that activation for low spatial frequency faces in the right fusiform face area increased after training in body dysmorphic disorder patients but decreased in controls. Moreover, functional connectivity between left and right fusiform face area decreased after training in patients but increased in controls. Our results indicate that neuronal mechanisms involved in perceptual learning of a face detection task differ fundamentally between body dysmorphic disorder patients and controls. Such different neuronal mechanisms in body dysmorphic disorder patients might reflect the brain's adaptations to altered functions imposed by the psychiatric disorder.

The Effect of Frailty on the Efficacy and Safety of Intensive Blood Pressure Control: A Post Hoc Analysis of the SPRINT Trial.

BACKGROUND: Frailty is associated with an increased risk of all-cause death and cardiovascular events. However, it is uncertain whether frailty modifies the efficacy and safety of intensive blood pressure control. METHODS: Data from SPRINT (Systolic Blood Pressure Intervention Trial) were used to construct a frailty index. Subgroup differences in intensive blood pressure control treatment effects and safety outcomes were measured on a relative and an absolute scale in patients with and without frailty (defined as a frailty index >0.21) using Cox proportional hazard models and generalized linear models, respectively. The primary outcome was a composite of myocardial infarction, acute coronary syndrome without myocardial infarction, stroke, heart failure, and cardiovascular death. RESULTS: A total of 9306 patients (mean age, 67.9±9.4 years), 2560 (26.7%) of whom had frailty, were included in our study. Over a median follow-up of 3.22 years, 561 primary outcomes were observed. Patients with frailty had a significantly higher risk of primary outcome in both the intensive and standard blood pressure control arms (adjusted hazard ratio, 2.10 [95% CI, 1.59-2.77] and 1.85 [95% CI, 1.46-2.35], respectively). Intensive treatment effects on primary and secondary outcomes were not significantly different on a relative scale (except for cardiovascular death [hazard ratio in patients with and without frailty, 0.91 (95% CI, 0.52-1.60) versus 0.30 (95% CI, 0.16-0.59), respectively; Pinteraction=0.01]) or absolute scale. There was no significant interaction between frailty and risks for serious adverse events with intensive treatment. CONCLUSIONS: Frailty status was a marker of high cardiovascular risk. Patients with frailty benefit similarly to other patients from intensive blood pressure control without an increased risk of serious adverse events.

Screening and functional verification of drought resistance-related genes in castor bean seeds.

Drought is one of the natural stresses that greatly impact plants. Castor bean (Ricinus communis L.) is an oil crop with high economic value. Drought is one of the factors limiting castor bean growth. The drought resistance mechanisms of castor bean have become a research focus. In this study, we used castor germinating embryos as experimental materials, and screened genes related to drought resistance through physiological measurements, proteomics and metabolomics joint analysis; castor drought-related genes were subjected to transient silencing expression analysis in castor leaves to validate their drought-resistant functions, and heterologous overexpression and backward complementary expression in Arabidopsis thaliana, and analysed the mechanism of the genes' response to the participation of Arabidopsis thaliana in drought-resistance.Three drought tolerance-related genes, RcECP 63, RcDDX 31 and RcA/HD1, were obtained by screening and analysis, and transient silencing of expression in castor leaves further verified that these three genes corresponded to drought stress, and heterologous overexpression and back-complementary expression of the three genes in Arabidopsis thaliana revealed that the function of these three genes in drought stress response.In this study, three drought tolerance related genes, RcECP 63, RcDDX 31 and RcA/HD1, were screened and analysed for gene function, which were found to be responsive to drought stress and to function in drought stress, laying the foundation for the study of drought tolerance mechanism in castor bean.

Orthostatic blood pressure changes do not influence cognitive outcomes following intensive blood pressure control.

BACKGROUND: Effects of intensive blood pressure (BP) control on cognitive outcomes in patients with excess orthostatic BP changes are unclear. We aimed to evaluate whether orthostatic BP changes modified the effects of BP intervention on cognitive impairment. METHODS: We analyzed 8547 participants from the Systolic Blood Pressure Intervention Trial Memory and cognition IN Decreased Hypertension. Associations between orthostatic BP changes and incident cognitive outcomes were evaluated by restricted cubic spline curves based on Cox models. The interactions between orthostatic BP changes and intensive BP intervention were assessed. RESULTS: The U-shaped associations were observed between baseline orthostatic systolic BP changes and cognitive outcomes. However, there were insignificant interactions between either change in orthostatic systolic BP (P for interaction = 0.81) or diastolic BP (P for interaction = 0.32) and intensive BP intervention for the composite outcome of probable dementia or mild cognitive impairment (MCI). The hazard ratio of intensive versus standard target for the composite cognitive outcome was 0.82 (95% CI 0.50-1.35) in those with an orthostatic systolic BP reduction of >20 mmHg and 0.41 (95% CI 0.21-0.80) in those with an orthostatic systolic BP increase of >20 mmHg. Results were similar for probable dementia and MCI. The annual changes in global cerebral blood flow (P for interaction = 0.86) consistently favored intensive BP treatment across orthostatic systolic BP changes. CONCLUSION: Intensive BP control did not have a deteriorating effect on cognitive outcomes among hypertensive patients experiencing significant postural BP changes.

Endophytic Streptomyces sp. NEAU-DD186 from Moss with Broad-Spectrum Antimicrobial Activity: Biocontrol Potential Against Soilborne Diseases and Bioactive Components.

Soilborne diseases cause significant economic losses in agricultural production around the world. They are difficult to control because a host plant is invaded by multiple pathogens, and chemical control often does not work well. In this study, we isolated and identified an endophytic Streptomyces sp. NEAU-DD186 from moss, which showed broad-spectrum antifungal activity against 17 soilborne phytopathogenic fungi, with Bipolaris sorokiniana being the most prominent. The strain also exhibited strong antibacterial activity against soilborne phytopathogenic bacteria Ralstonia solanacearum. To evaluate its biocontrol potential, the strain was prepared into biofertilizer by solid-state fermentation. Response surface methodology was employed to optimize the fermentation conditions for maximizing spore production and revealed that the 1:1 ratio of vermicompost to wheat bran, a temperature of 28°C, and 50% water content with an inoculation amount of 15% represented the optimal parameters. Pot experiments showed that the application of biofertilizer with a spore concentration of 108 CFU/g soil could effectively suppress the occurrence of tomato bacterial wilt caused by R. solanacearum and wheat root rot caused by B. sorokiniana, and the biocontrol efficacy was 81.2 and 72.2%, respectively. Chemical analysis of strain NEAU-DD186 extracts using nuclear magnetic resonance spectrometry and mass analysis indicated that 25-O-malonylguanidylfungin A and 23-O-malonylguanidylfungin A were the main active constituents, which showed high activity against R. solanacearum (EC50 of 2.46 and 2.58 µg ml-1) and B. sorokiniana (EC50 of 3.92 and 3.95 µg ml-1). In conclusion, this study demonstrates that Streptomyces sp. NEAU-DD186 can be developed as biofertilizer to control soilborne diseases.

Identification of Xuanfei Baidu granule constituents by liquid chromatography-quadruple-time-of-flight-mass spectrometry and its anti-inflammatory active constituents using a lipopolysaccharide-induced RAW264.7 cell model.

The Xuanfei Baidu (XFBD) prescription, a traditional Chinese medicine prescription, has demonstrated significant anti-inflammatory activities; however, the number of its reported constituents is limited, and its anti-inflammatory constituents are unclear. In this study, the constituents of XFBD granule, a granule dosage of XFBD prescription, were thoroughly examined in vitro and in vivo using liquid chromatography-quadruple-time-of-flight-mass spectrometry, and the anti-inflammatory constituents were screened. A total of 214 constituents were identified from the XFBD granule, 62 of which were confirmed via comparison with reference standards. After intragastric administration of XFBD granule, 63 and 28 constituents were absorbed into the rat sera and lungs in prototype form, respectively. XFBD granule and XFBD-containing serum were found to significantly reduce nitric oxide (NO) and interleukin-6 (IL-6) secretion in lipopolysaccharide-induced RAW264.7 cells. Five anti-inflammatory constituents (verbasoside, scutellarin, luteolin, apigenin, and pogostone) were found to reduce the concentration of NO and IL-6 in a dose-dependent manner. Moreover, the combination of these five constituents could significantly reduce NO secretion even when the concentration of each constituent was two to three orders of magnitude lower than their individual minimum effective concentrations. Overall, this study provides a valuable reference for the discovery of effective constituents from the XFBD granule.

Basic and Informative Photographic Standards for Cleft Lip Patients.

BACKGROUND: Standardized and reliable medical photographs are crucial for preoperative and postoperative comparisons and academic communication in the medical field. There is limited research on photographic techniques in patients with cleft lip. Deformities of the lip and nose in patients with cleft lip are not only associated with morphological abnormalities but also with abnormalities of muscle function. METHODS: Considering the morphology and function of the lips and nose in cleft lip patients, the study captured the deformity of cleft lip patients in 6 positions: frontal view, 45 degrees left-right tilted side view, 90 degrees left-right tilted side view, and basal view, and in 5 facial expressions: tightly closed lips, slightly open mouth, smiling, teeth bared, and pout. RESULTS: In 6 different positions and 5 different expressions, we took pictures of lip and nasal deformities covering most of the common deformities in patients with cleft lip, such as white lip scarring, interruption of continuity of vermillion border, lip prolapse, asymmetric corners of the mouth, collapsed ala nasi, loss of the nasal base and deviated nasal septum. CONCLUSIONS: This paper suggests a set of effective, easy-to-follow, and precise photographic protocols to assist cleft lip surgeons in capturing suitable and informative, high-quality 2D digital photographs. LEVEL OF EVIDENCE: Level-V.

Chronic Sacral Nerve Stimulation Inhibits Visceral Hypersensitivity in Diarrhea-Predominant Irritable Bowel Syndrome Rats Model.

OBJECTIVE: Sacral nerve stimulation (SNS) is emerging as a novel treatment for irritable bowel syndrome (IBS). However, its effects are limited, and the underlying mechanisms remain largely unknown. MATERIALS AND METHODS: In this study, rats were divided into three groups (n = 12 rats per group): 1) the SNS group; 2) the sham SNS group (the sham group for short); and 3) the control group. The SNS and sham groups were exposed to chronic and acute stress to establish an IBS model. Electrode implantation surgery was performed in rats with the IBS model. The SNS group received electrical stimulation for 30 minutes every day for seven days. Abdominal withdrawal reflex (AWR) was used to evaluate the effect of SNS on visceral sensitivity in diarrhea-predominant IBS (IBS-D) rats. The frequency domain of heart rate variability (HRV) was analyzed to assess the effect of SNS on regulating the autonomic function. The expression of transient receptor potential vanilloid 1 (TRPV1) in the colon, spinal cord, and hippocampus was detected by immunohistochemistry to explore the mechanism of SNS in IBS-D rats. RESULTS: Compared with the sham group, AWR scores were significantly decreased under different gas volumes of stimulation of 0.4, 0.6, and 0.8 ml for rectal distention in the SNS group (all p < 0.05). However, there was no significant difference <1.0 ml between the two groups (p > 0.05). Compared with the sham group, the frequency domain indexes of HRV were significantly altered. Normalized low-frequency power and low frequency-to-high frequency ratio were significantly decreased, and normalized high-frequency power was significantly increased in the SNS group (all p < 0.05). Moreover, the expression of TRPV1 in the spinal cord and colon in the SNS group was significantly decreased compared with the sham group (both p < 0.05). These results suggested that chronic SNS not only improved the visceral sensitivity and autonomic dysfunction but also decreased the expression of TRPV1 in the spinal cord-gut tissue in IBS-D rats. CONCLUSION: Chronic SNS was found to have an inhibitory effect on visceral hypersensitivity in IBS-D rats, providing experimental evidence for its potential clinical application in IBS.

Biomolecular Condensates Decipher Molecular Codes of Cell Fate: From Biophysical Fundamentals to Therapeutic Practices.

Cell fate is precisely modulated by complex but well-tuned molecular signaling networks, whose spatial and temporal dysregulation commonly leads to hazardous diseases. Biomolecular condensates (BCs), as a newly emerging type of biophysical assemblies, decipher the molecular codes bridging molecular behaviors, signaling axes, and clinical prognosis. Particularly, physical traits of BCs play an important role; however, a panoramic view from this perspective toward clinical practices remains lacking. In this review, we describe the most typical five physical traits of BCs, and comprehensively summarize their roles in molecular signaling axes and corresponding major determinants. Moreover, establishing the recent observed contribution of condensate physics on clinical therapeutics, we illustrate next-generation medical strategies by targeting condensate physics. Finally, the challenges and opportunities for future medical development along with the rapid scientific and technological advances are highlighted.

The First High-Quality Genome Assembly of Freshwater Pearl Mussel Sinohyriopsis cumingii: New Insights into Pearl Biomineralization.

China leads the world in freshwater pearl production, an industry in which the triangle sail mussel (Sinohyriopsis cumingii) plays a pivotal role. In this paper, we report a high-quality chromosome-level genome assembly of S. cumingii with a size of 2.90 Gb-the largest yet reported among bivalves-and 89.92% anchorage onto 19 linkage groups. The assembled genome has 37,696 protein-coding genes and 50.86% repeat elements. A comparative genomic analysis revealed expansions of 752 gene families, mostly associated with biomineralization, and 237 genes under strong positive selection. Notably, the fibrillin gene family exhibited gene family expansion and positive selection simultaneously, and it also exhibited multiple high expressions after mantle implantation by transcriptome analysis. Furthermore, RNA silencing and an in vitro calcium carbonate crystallization assay highlighted the pivotal role played by one fibrillin gene in calcium carbonate deposition and aragonite transformation. This study provides a valuable genomic resource and offers new insights into the mechanism of pearl biomineralization.

Deep brain stimulation in the lateral habenula reverses local neuronal hyperactivity and ameliorates depression-like behaviors in rats.

Deep brain stimulation (DBS) is a promising therapy for treatment-resistant depression, while mechanisms underlying its therapeutic effects remain poorly defined. Increasing evidence has revealed an intimate association between the lateral habenula (LHb) and major depression, and suggests that the LHb might be an effective target of DBS therapy for depression. Here, we found that DBS in the LHb effectively decreased depression-like behaviors in rats experienced with chronic unpredictable mild stress (CUMS), a well-accepted paradigm for modeling depression in rodents. In vivo electrophysiological recording unveiled that CUMS increased neuronal burst firing, as well as the proportion of neurons showing hyperactivity to aversive stimuli in the LHb. Nevertheless, DBS downregulated local field potential power, reversed the CUMS-induced increase of LHb burst firing and neuronal hyperactivity to aversive stimuli, and decreased the coherence between LHb and ventral tegmental area (VTA). Our results demonstrate that DBS in the LHb exerts antidepressant-like effects and reverses local neural hyperactivity, supporting the LHb as a target of DBS therapy for depression.

Synovial inducible costimulator is correlated with severity in knee osteoarthritis.

Osteoarthritis (OA) is a joint disease characterized by articular cartilage loss, which afflicts many people worldwide. Knowing the disease severity can improve the recovery rate of OA. Antibody array technology was utilized for protein expression profiling of synovial fluid from eight mild knee OA patients, eight severe knee OA patients and 16 healthy persons. Subsequently, 48 mild OA patients, 56 severe OA patients and 24 healthy controls were utilized for validation by ELISA. In the protein expression profiling, inducible costimulator (ICOS) levels were markedly higher in OA patients compared with those in the healthy population, and were significantly higher in severe OA than those in mild OA. Furthermore, ICOS levels were shown to be significantly correlated with WOMAC, MRI-MOAKS and MRI-UTE-T2* scores. The multivariate logistic regression analysis indicated that higher levels of ICOS could significantly increase the risk of severe OA. Synovial ICOS levels were positively correlated with the radiographic severity of OA. ICOS may represent a biomarker for predicting the OA severity and may be involved in the development and progression of knee OA.

Right Ventricular Function in Takayasu's Arteritis Patients With Pulmonary Artery Involvement Using MRI Feature Tracking.

BACKGROUND: Pulmonary artery involvement (PAI) is not rare in Takayasu arteritis (TA). Persistently elevated pulmonary arterial pressure in TA-PAI patients leads to pulmonary hypertension (PH), and eventually cardiac death. Thus, the early detection of right ventricular dysfunction before the onset of PH is important. PURPOSE: To explore the potential of right ventricular global peak longitudinal and circumferential strain (RVGLS and RVGCS, respectively) in detecting right ventricular myocardial damage in TA-PAI patients without PH. STUDY TYPE: Retrospective. POPULATION: One hundred and six TA patients (39.6 ± 13.9 years), of whom 52 were non-PAI and 54 were PAI patients (36 without PH and 18 with PH), along with 58 sex- and age-matched healthy volunteers (HVs) (36.7 ± 13.2 years). The involved arteries were validated by aorta magnetic resonance (MR) angiography and pulmonary artery computed tomography angiography. FIELD STRENGTH/SEQUENCE: 3 T/Cine imaging sequence with a steady-state free precession readout. ASSESSMENT: Cardiac MRI-derived parameters measured by two radiologists independently were compared among HVs, and TA patients with and without PAI. In addition, these indices were further compared among HVs, and TA-PAI patients with and without PH. STATISTICAL TESTS: Student's t test, one-way ANOVA analysis, Pearson and Spearman correlation analysis, and reproducibility analysis. A P-value of <0.05 was considered statistically significant. RESULTS: Although the TA-PAI patients without PH had a similar RV ejection fraction (RVEF) with HV (P = 0.348), RVGLS (non-PH 20.6 ± 3.7% vs. HV 24.0 ± 3.1%) was significantly lower and RVGCS (non-PH 14.8 ± 3.9% vs. HV 13.0 ± 2.7%) higher. The TA-PAI patients with PH had significantly poorer RVGLS (PH 13.5 ± 3.8% vs. non-PH 20.6 ± 3.7%) and RVGCS (PH 10.9 ± 3.2% vs. non-PH 14.8 ± 3.9%) than those without PH. DATA CONCLUSION: Right ventricular dysfunction was detected in the TA-PAI patients without PH. MR-feature tracking may be an effective method for detecting early cardiac damage in the TA-PAI patients without PH. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 3.

Nuclear Tkt promotes ischemic heart failure via the cleaved Parp1/Aif axis.

Transketolase (Tkt), an enzyme in pentose phosphate pathway, has been reported to regulate genome instability and cell survival in cancers. Yet, the role of Tkt after myocardial ischemic injury remains to be elucidated. Label-free proteomics revealed dramatic elevation of Tkt in murine hearts after myocardial infarction (MI). Lentivirus-mediated Tkt knockdown ameliorated cardiomyocyte apoptosis and preserved the systolic function after myocardial ischemic injury. In contrast, Tkt overexpression led to the opposite effects. Inducible conditional cardiomyocyte Tkt-knockout mice were generated, and cardiomyocyte-expressed Tkt was found to play an intrinsic role in the ischemic heart failure of these model mice. Furthermore, through luciferase assay and chromatin immunoprecipitation, Tkt was shown to be a direct target of transcription factor Krüppel-like factor 5 (Klf5). In cardiomyocytes under ischemic stress, Tkt redistributed into the nucleus. By binding with the full-length poly(ADP-ribose) polymerase 1 (Parp1), facilitating its cleavage, and activating apoptosis inducible factor (Aif) subsequently, nuclear Tkt demonstrated its non-metabolic functions. Overall, our study confirmed that elevated nuclear Tkt plays a noncanonical role in promoting cardiomyocyte apoptosis via the cleaved Parp1/Aif pathway, leading to the deterioration of cardiac dysfunction.

Almost perfect sequence modulated multiplexing ion mobility spectrometry.

RATIONALE: Multiplexing ion mobility spectrometry with multiple ion injection pulses was used to achieve a high duty cycle and thus improve the signal-to-noise (S/N) ratio while maintaining high resolving power compared with the traditional single-pulse signal averaging method. Historically, an ion mobility spectrum was reconstructed by various multiplexing methods including Fourier transform ion mobility spectrometry (FT-IMS), Hadamard transform ion mobility spectrometry (HT-IMS), and linear frequency modulation correlation ion mobility spectrometry (LFM-CIMS) sequence or Barker code. METHODS: To achieve an artifact-free multiplexing ion mobility spectrum, an almost perfect sequence (APS) with correlation technique was proposed to modulate the Bradbury-Nielson ion gate and was compared with FT-IMS, HT-IMS, LFM-IMS, and the traditional single-pulse signal averaging method. RESULTS: Experimental results showed that there are no artifact peaks in the APS-IMS spectra except an inverted mirror peak, and the S/N ratio was improved 5-8 times with a repetition time of 40-60 ms, corresponding to the improvement in the duty cycle. With the same duty cycle and similar acquisition time, APS-IMS showed a higher S/N ratio than HT-IMS for its unique autocorrelation response. CONCLUSIONS: The APS-IMS technique offered a higher duty cycle and relatively shorter modulation period compared with reported multiplexing methods and is suitable to track rapidly changing signals without losing information and adding extra transformation artifact peaks.

Isolation and Biosynthesis of Phenazine-Polyketide Hybrids from Streptomyces sp. KIB-H483.

A phenazine-polyketide hybrid compound, nexphenazine A (1), was isolated from Streptomyces sp. KIB-H483. The bioinformatic analysis of the draft genome of the producing strain and gene inactivation experiments revealed that the biosynthesis of 1 involves a phenazine-polyketide hybrid gene cluster. The abolished production of 1 as well as the accumulation of shunt metabolites 4-7 in mutant strain ΔnpzI revealed the key role of the npzI gene, which encodes an NAD(P)H-dependent ketoreductase, in nexphenazine biosynthesis. The structures and absolute configurations of the isolated intermediates were established on the basis of spectroscopic data analysis, single-crystal X-ray diffraction, chiral chromatography, and chemical conversion experiments. NpzI exhibited stereochemical selectivity in reducing the carbonyl group of 4. Nexphenazine biosynthesis is proposed to involve a condensation of the carboxyl group of phenazine with one molecule of methylmalonyl-CoA by a type I PKS, followed by a ketone reduction by NpzI and an unknown methylation reaction.

Three-Dimensional Evaluation of Deformed Noses in Patients With Unilateral Cleft Lip and Palate: A Meta-Analysis.

ABSTRACT: Multiple surgeries for patients with cleft lip and palate may be required to repair secondary deformities after the completion of cleft repair. This meta-analysis aimed to evaluate the three-dimensional nasal morphology in patients with unilateral cleft palate who underwent cleft lip and palate repair but did not undergo terminal nasal repair. PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang Data, and SINOMED databases were searched from inception until December 2020. Studies involving patients ages ≥6 years with cleft lip and palate who did not undergo terminal nasal repair were included. Quantitative data were obtained through three-dimensional evaluation. Mean weighted effect sizes with 95% confidence intervals, heterogeneities, and publication biases were assessed using raw data obtained from 13 studies. In general, patients with unilateral cleft lip and palate had a significantly wider nose; shorter bridge length and nasal height; larger forehead-nose angle, nasal tip angle, and alar slope angle; and smaller nasolabial angle. The number of studies that included patients with unilateral cleft lip, unilateral cleft lip and alveolus, and unclassified deformities was limited, and their results were similar to those involving patients with unilateral cleft lip and palate. Patients with unilateral cleft tend to have short, flat, and wide noses. Nasal tip elevation and alar base adduction should be prioritized during terminal nasal repair to achieve more normalized cleft-side nostrils.

Streptomyces typhae sp. nov., a novel endophytic actinomycete with antifungal activity isolated the root of cattail (Typha angustifolia L.).

A novel endophytic actinomycete with antagonistic activity against various phytopathogenic fungi, designated strain p1417T, was isolated from the root of cattail (Typha angustifolia L.) collected from Yunnan Province, Southwest China. A polyphasic taxonomic study was carried out to establish the taxonomic status of this strain. Strain p1417T was found to have morphological and chemotaxonomic characteristics typical of the genus Streptomyces. The diamino acid present in the cell wall was LL-diaminopimelic acid. Xylose and arabinose occurred in whole cell hydrolysates. The menaquinones were identified as MK-9(H8), MK-9(H6) and MK-9(H4). The polar lipid profile was found to contain diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannoside. The major fatty acids were found to be iso-C16:0, anteiso-C15:0, iso-C15:0 and C16:0. The genomic DNA G + C content of strain p1417T based on the genome sequence was 72.0 mol%. Based on 16 S rRNA gene, five housekeeping genes and whole genome sequences analysis, strain p1417T was most closely related to Streptomyces flavofungini JCM 4753T (99.4% 16 S rRNA gene sequence similarity), Streptomyces alboflavus JCM 4615T (98.8%) and Streptomyces aureoverticillatus JCM 4347T (98.2%). However, the average nucleotide identity values, the digital DNA-DNA hybridization values and the multilocus sequence analysis evolutionary distances between this strain and its closely related strains showed that it belonged to one distinct species. In addition, these results were also supported by differences in the phenotypic and chemotaxonomic characteristics between strain p1417T and three closely related type strains. Therefore, it is concluded that strain p1417T represents a novel species of the genus of Streptomyces, for which the name Streptomyces typhae sp. nov. is proposed. The type strain is p1417T (= CCTCC AA 2019091T = DSM 110636T).

Processing neutral tone under the non-attentional condition: a mismatch negativity study.

The neutral tone is a unique tone form in Mandarin as it distinguishes from four canonical tones or full tones on the one hand and integrates phonetic, morphological, syntactical and prosodic information on the other hand. Research to date has been focusing on its unique and variant acoustic features. However, little is known about how native Mandarin speakers process such a unique tone. In the present study, the mismatch negativity was used to explore the comparison-based pre-attentive change detection of Mandarin neutral tone. The mismatch negativity at the time window of 400-800 ms post-first-tone onset was obtained by subtracting event-related potentials to standard neutral tone from event-related potentials to a deviant natural tone. The source analysis of mismatch negativity showed the cortex generator was located at the left temporal lobe. The data suggest that Chinese native speakers process neutral tone automatically under non-attentional conditions, as revealed by the mismatch negativity data aligned with a neutral tone, and that neutral tone does exist as an automatically recognizable one in native Mandarin speakers' tone system.