Population-level exploration of alternative splicing and its unique role in controlling agronomic traits of rice.

Alternative splicing (AS) plays crucial roles in regulating various biological processes in plants. However, the genetic mechanisms underlying AS and its role in controlling important agronomic traits in rice (Oryza sativa) remain poorly understood. In this study, we explored AS in rice leaves and panicles using the rice minicore collection. Our analysis revealed a high level of transcript isoform diversity, with approximately one fifth of potential isoforms acting as major transcripts in both tissues. Regarding the genetic mechanism of AS, we found that the splicing of 833 genes in the leaf and 1,230 genes in the panicle was affected by cis-genetic variation. Twenty-one percent of these AS events could only be explained by large structural variations. Approximately 77.5% of genes with significant splicing quantitative trait loci (sGenes) exhibited tissue-specific regulation, and AS can cause 26.9% (leaf) and 23.6% (panicle) of sGenes to have altered, lost or gained functional domains. Additionally, through splicing-phenotype association analysis, we identified phosphate-starvation induced RING-type E3 ligase (OsPIE1; LOC_Os01g72480), whose splicing ratio was significantly associated with plant height. In summary, this study provides an understanding of AS in rice and its contribution to the regulation of important agronomic traits.

Evolutionary Dynamics of Chromatin Structure and Duplicate Gene Expression in Diploid and Allopolyploid Cotton.

Polyploidy is a prominent mechanism of plant speciation and adaptation, yet the mechanistic understandings of duplicated gene regulation remain elusive. Chromatin structure dynamics are suggested to govern gene regulatory control. Here, we characterized genome-wide nucleosome organization and chromatin accessibility in allotetraploid cotton, Gossypium hirsutum (AADD, 2n = 4X = 52), relative to its two diploid parents (AA or DD genome) and their synthetic diploid hybrid (AD), using DNS-seq. The larger A-genome exhibited wider average nucleosome spacing in diploids, and this intergenomic difference diminished in the allopolyploid but not hybrid. Allopolyploidization also exhibited increased accessibility at promoters genome-wide and synchronized cis-regulatory motifs between subgenomes. A prominent cis-acting control was inferred for chromatin dynamics and demonstrated by transposable element removal from promoters. Linking accessibility to gene expression patterns, we found distinct regulatory effects for hybridization and later allopolyploid stages, including nuanced establishment of homoeolog expression bias and expression level dominance. Histone gene expression and nucleosome organization are coordinated through chromatin accessibility. Our study demonstrates the capability to track high-resolution chromatin structure dynamics and reveals their role in the evolution of cis-regulatory landscapes and duplicate gene expression in polyploids, illuminating regulatory ties to subgenomic asymmetry and dominance.

The role of cannabinoid receptor 2 in bone remodeling during orthodontic tooth movement.

BACKGROUND: The purpose of this study is to explore the effects of CB2 on bone regulation during orthodontic tooth movement. METHODS: Thirty male mice were allocated into 2 groups (n = 15 in each group): wild type (WT) group and CB2 knockout (CB2-/-) group. Orthodontic tooth movement (OTM) was induced by applying a nickel-titanium coil spring between the maxillary first molar and the central incisors. There are three subgroups within the WT groups (0, 7 and 14 days) and the CB2-/- groups (0, 7 and 14 days). 0-day groups without force application. Tooth displacement, alveolar bone mass and alveolar bone volume were assessed by micro-CT on 0, 7 and 14 days, and the number of osteoclasts was quantified by tartrate-resistant acid phosphatase (TRAP) staining. Moreover, the expression levels of RANKL and OPG in the compression area were measured histomorphometrically. RESULTS: The WT group exhibited the typical pattern of OTM, characterized by narrowed periodontal space and bone resorption on the compression area. In contrast, the accelerated tooth displacement, increased osteoclast number (P < 0.0001) and bone resorption on the compression area in CB2-/- group. Additionally, the expression of RANKL was significantly upregulated, while OPG showed low levels in the compression area of the CB2 - / - group (P < 0.0001). CONCLUSIONS: CB2 modulated OTM and bone remodeling through regulating osteoclast activity and RANKL/OPG balance.

Positive association between urinary albumin-creatinine ratio and lower extremity peripheral arterial disease in Chinese diabetes patients: A cross-section study with propensity score matching analysis.

BACKGROUND AND AIMS: Elevated urinary albumin-creatinine ratio (ACR) is an established risk factor for lower extremity peripheral arterial disease (PAD) in non-diabetes individual. This study aimed to determine the relationship between urinary ACR level and PAD in diabetes population. METHODS AND RESULTS: A cross-section study with 1396 hospitalized diabetes participants from department of endocrinology and neurology were performed and the propensity score matching method was applied to reduce the effects of confounding factors between the matched PAD and Non-PAD groups. The relationship between urinary ACR and ankle-brachial index (ABI) was analyzed by linear curve fitting analyses and multiple logistic regression models. Our study showed that the prevalence of PAD (low ABI, ABI<0.9) was 7.09% in our diabetes patients. The ABI level was significantly lower in high ACR group compared with those in normal urinary ACR group (1.11 ± 0.17 vs 1.13 ± 0.15, p = 0.010). The prevalence of PAD was increased with the increased tertile's of log2-transformed ACR in total patients before and after propensity score matching (p < 0.001 and p = 0.007, respectively). The OR (95% CI) between log2-transformed ACR and PAD was 1.0 and 1.70 (1.08-2.69, p = 0.022) respectively in normal and high ACR levels in diabetes patients after adjusting for potential confounders. After propensity score matching, the OR (95% CI) between log2-transformed ACR and PAD was 1.0 and 1.85 (1.05-3.23, p = 0.031) respectively in normal and high ACR levels in diabetes patients after adjusting for potential confounders. CONCLUSION: The elevated urinary ACR level was associated with PAD in Chinese diabetes patients.

Efficacy and safety comparison between axillary lymph node dissection with no axillary surgery in patients with sentinel node-positive breast cancer: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to study the evidence on the efficacy and safety of omitting axillary lymph node dissection (ALND) for patients with clinically node-negative but sentinel lymph node (SLN)-positive breast cancer using all the available evidence. METHODS: The Embase, Medline, and Cochrane Library databases were searched through February 25, 2023. Original trials that compared only the sentinel lymph node biopsy (SLNB) with ALND as the control group for patients with clinically node-negative but SLN-positive breast cancer were included. The primary outcomes were axillary recurrence rate, total recurrence rate, disease-free survival (DFS), and overall survival (OS). Meta-analyses were performed to compare the odds ratio (OR) in rates and the hazard ratios (HR) in time-to-event outcomes between both interventions. Based on different study designs, tools in the revised Cochrane risk of bias tool were used for randomized trials and the risk of bias in nonrandomized studies of interventions to assess the risk of bias for each included article. Funnel plots and Egger's test were used for the publication's bias assessment. RESULTS: In total, 30 reports from 26 studies were included in the systematic review (9 reports of RCTs, 21 reports of retrospective cohort studies). According to our analysis, omitting ALND in patients with clinically node-negative but SLN-positive breast cancer had a similar axillary recurrence rate (OR = 0.95, 95% confidence interval (CI): 0.76-1.20), DFS (HR = 1.02, 95% CI: 0.89-1.16), and OS (HR = 0.97, 95% CI: 0.92-1.03), but caused a significantly lower incidence of adverse events and benefited in locoregional recurrence rate (OR = 0.76, 95% CI: 0.59-0.97) compared with ALND. CONCLUSION: For patients with clinically node-negative but SLN-positive breast cancer (no matter the number of the positive SLN), this review showed that SLNB alone had a similar axillary recurrence rate, DFS, and OS, but caused a significantly lower incidence of adverse events and showed a benefit for the locoregional recurrence compared with ALND. An OS benefit was found in the Macro subset that used SLNB alone versus complete ALND. Therefore, omitting ALND is feasible in this setting. TRIAL REGISTRATION: CRD 42023397963.

Synaptic loss in a mouse model of euthyroid Hashimoto's thyroiditis: possible involvement of the microglia.

BACKGROUND: Hashimoto's thyroiditis (HT) is an autoimmune illness that renders individuals vulnerable to neuropsychopathology even in the euthyroid state, the mechanisms involved remain unclear. We hypothesized that activated microglia might disrupt synapses, resulting in cognitive disturbance in the context of euthyroid HT, and designed the present study to test this hypothesis. METHODS: Experimental HT model was induced by immunizing NOD mice with thyroglobulin and adjuvant twice. Morris Water Maze was measured to determine mice spatial learning and memory. The synaptic parameters such as the synaptic density, synaptic ultrastructure and synaptic-markers (SYN and PSD95) as well as the interactions of microglia with synapses were also determined. RESULTS: HT mice had poorer performance in Morris Water Maze than controls. Concurrently, HT resulted in a significant reduction in synapse density and ultrastructure damage, along with decreased synaptic puncta visualized by immunostaining with synaptophysin and PSD-95. In parallel, frontal activated microglia in euthyroid HT mice showed increased engulfment of PSD95 and EM revealed that the synaptic structures were visible within the microglia. These functional alterations in microglia corresponded to structural increases in their attachment to neuronal perikarya and a reduction in presynaptic terminals covering the neurons. CONCLUSION: Our results provide initial evidence that HT can induce synaptic loss in the euthyroid state with deficits might be attributable to activated microglia, which may underlie the deleterious effects of HT on spatial learning and memory.

Fine-mapping and candidate gene analysis of qFL-c10-1 controlling fiber length in upland cotton (Gossypium hirsutum L.).

KEY MESSAGE: A fiber length QTL, qFL-c10-1, was fine-mapped to a 96.5-kb region containing one gene that has not been characterized in plants. Fiber length is an important component of cotton fiber quality, which is associated with other quality properties such as fiber strength, fiber maturity, and fineness. In our previous studies, a stable QTL qFL-c10-1 controlling fiber length had been identified on chromosome A10 in an upland cotton recombinant inbred line (RIL) population from a cross between Jimian5 and DH962. To fine-map qFL-c10-1, an F2 population with 1081 individual plants from a cross between a recombinant line DJ61 and Jimian5 was established. Using linkage analysis and progeny recombination experiment, qFL-c10-1 was mapped into a 96.5-kb genomic region that just contained one proper transcript Ghir_A10G022020 (described as GhFL10), an undescribed gene in plants. One 214-bp deletion was identified in the promoter region of DJ61 compared with Jimian5. Quantitative real-time PCR (qRT-PCR) and comparative analysis of parental sequences suggested that GhFL10 was the most promising candidate gene for qFL-c10-1. According to RNA-seq, yeast two-hybrid assay and bimolecular fluorescence complementation (BiFC), we speculate that GhFL10 interacts with NF-YA transcription factors to negatively regulate fiber elongation.

Lymphocyte Subsets Are Associated with Disease Status in Neuromyelitis Optica Spectrum Disorders.

OBJECTIVE: At present, studies on lymphocytes are mostly conducted on CD19+ B cells and CD27+ B cells in neuromyelitis optica spectrum disorders (NMOSDs), but the exact changes in lymphocyte subsets (CD19+ B cells, CD3+ T cells, CD4+ Th cells, CD8+ Ts cells, the CD4+/CD8+ ratio, and NK [CD56+ CD16] cells) have rarely been studied. This study aimed to assess lymphocyte subset changes in patients with NMOSD. METHODS: We performed a cross-sectional study of consecutive patients with acute NMOSD (n = 41), chronic NMOSD (n = 21), and healthy individuals (n = 44). Peripheral blood samples were obtained upon admission, and lymphocyte subsets were analyzed by flow cytometry. Levels of lymphocyte subsets among 3 groups were compared and its correlation with the length of spinal cord lesions was analyzed. RESULTS: The levels of peripheral blood CD19+ B cells were significantly higher in patients with acute and chronic NMOSD than in healthy controls (HCs) (17.91 ± 8.7%, 13.08 ± 7.562%, and 12.48 ± 3.575%, respectively; p < 0.001) and were positively correlated with the length of spinal cord lesions in acute NMOSD (r = 0.433, p < 0.05). The peripheral blood CD4+/CD8+ ratio was significantly lower in patients with acute NMOSD and chronic NMOSD than in HCs (1.497 ± 0.6387, 1.33 ± 0.5574, and 1.753 ± 0.659, respectively; p < 0.05), and the levels of peripheral blood NK (CD56+ CD16) cells were significantly lower in patients with acute and chronic NMOSD than in HCs (13.6 ± 10.13, 11.11 ± 7.057, and 14.7 [interquartile range = 9.28], respectively; p < 0.01). CONCLUSIONS: The levels of certain subsets of peripheral blood lymphocytes are associated with disease status in NMOSD.

Rhabdomyolysis-associated acute kidney injury: clinical characteristics and intensive care unit transfer analysis.

BACKGROUND: Information on rhabdomyolysis-associated acute kidney injury (AKI) in the emergency department or general ward is limited. AIM: To assess the risk factors, outcomes and clinical correlates with intensive care unit (ICU) transfer of patients with rhabdomyolysis-associated AKI. METHODS: Patients with rhabdomyolysis were divided into the rhabdomyolysis-associated AKI group and the rhabdomyolysis without AKI group. Inhospital outcomes, including ICU transfer, mortality, length of stay, daily cost and renal recovery were analysed. Multivariate regression analysis was performed to identify the association between rhabdomyolysis-associated AKI and ICU transfer. RESULTS: Among 149 patients with rhabdomyolysis, 68 (45.6%) developed AKI. Age and urine protein were important risk factors for incidence of rhabdomyolysis-associated AKI. Patients with rhabdomyolysis-associated AKI had higher levels of undergoing dialysis (19.1% vs 2.5%; P < 0.01), all-cause mortality (13.2% vs 1.2%; P < 0.01), cost of hospitalisation (10.8 1000 yuan, IQR (5.5, 3.5) vs 5.9 1000 yuan, IQR 5.9 (3.6, 9.9); P = 0.03), as well as longer length of hospital stay (8.0 days (5.0, 14.0)) versus (6.0 days (4.0, 11.0); P = 0.02). Additionally, the percentage of patients with AKI who transferred to ICU was higher than patients without AKI (33.8% vs 12.3%; P < 0.002) and rhabdomyolysis-associated AKI was an independent risk factor for ICU transfer (adjusted odds ratio = 2.58; 95% confidence interval, 1.12-6.8, P = 0.03). CONCLUSION: Rhabdomyolysis-associated AKI was common in the emergency department or general ward and led to more severe outcomes. It was also associated with an increased risk of ICU transfer.

Gossypium tomentosum genome and interspecific ultra-dense genetic maps reveal genomic structures, recombination landscape and flowering depression in cotton.

The high-quality reference-grade genome for Gossupium tomentosum can greatly promote the progress in biological research and introgression breeding for the mainly cultivated species, G. hirsutum. Here, we report a high-quality genome assembly for G. tomentosum by integrating PacBio and Hi-C technologies. Comparative genomic analysis revealed a large number of genetic variations. Two re-sequencing-based ultra-dense genetic maps were constructed which comprised 4,047,199 and 6,009,681 SNPs, 4120 and 4599 bins and covering 4126.36 cM and 4966.72 cM in the EMF2 (F2 from G. hirsutum × G. tomentosum) and GHF2 (F2 from G. hirsutum × G. barbadense). The EMF2 exhibited lower recombination rate at the whole-genome level as compared with GHF2. We mapped 22 and 33 QTL associated with crossover frequency and predicted Gh_MRE11 and Gh_FIGL1 as the candidate genes governing crossover in the EMF2 and GHF2, respectively. We identified 13 significant QTL that regulate the floral transition, and revealed that Gh_AGL18 was associated with the floral transition. Therefore, our study provides a valuable genomic resource to support a better understanding of cotton interspecific cross and recombination landscape for genetic improvement and breeding in cotton.

[Risk factors for early acute kidney injury after cardiac arrest in children in the pediatric intensive care unit and a prognostic analysis]. / é‡ç—‡ç›‘æŠ¤å®¤æ‚£å„¿å¿ƒè„åœæåŽæ—©æœŸå‡ºçŽ°æ€¥æ€§è‚¾æŸä¼¤çš„å±é™©å› ç´ åŠé¢„åŽåˆ†æž.

OBJECTIVES: To investigate the risk factors for acute kidney injury (AKI) in children with cardiac arrest (CA) and the influencing factors for prognosis. METHODS: A retrospective analysis was performed on the medical records of the children who developed CA in the pediatric intensive care unit (PICU) of Hunan Children's Hospital from June 2016 to June 2021. According to the presence or absence of AKI within 48 hours after return of spontaneous circulation (ROSC) for CA, the children were divided into two groups: AKI (n=50) and non-AKI (n=113). According to their prognosis on day 7 after ROSC, the AKI group was further divided into a survival group (n=21) and a death group (n=29). The multivariate logistic regression analysis was used to investigate the risk factors for early AKI in the children with CA and the influencing factors for prognosis. RESULTS: The incidence rate of AKI after CA was 30.7% (50/163). The AKI group had a 7-day mortality rate of 58.0% (29/50) and a 28-day mortality rate of 78.0% (39/50), and the non-AKI group had a 7-day mortality rate of 31.9% (36/113) and a 28-day mortality rate of 58.4% (66/113). The multivariate logistic regression analysis showed that long duration of cardiopulmonary resuscitation (OR=1.164, 95%CI: 1.088-1.246, P<0.001), low baseline albumin (OR=0.879, 95%CI: 0.806-0.958, P=0.003), and adrenaline administration before CA (OR=2.791, 95%CI: 1.119-6.961, P=0.028) were closely associated with the development of AKI after CA, and that low baseline pediatric critical illness score (OR=0.761, 95%CI: 0.612-0.945, P=0.014), adrenaline administration before CA (OR=7.018, 95%CI: 1.196-41.188, P=0.031), and mechanical ventilation before CA (OR=7.875, 95%CI: 1.358-45.672, P=0.021) were closely associated with the death of the children with AKI after CA. CONCLUSIONS: Albumin should be closely monitored for children with ROSC after CA, especially for those with long duration of cardiopulmonary resuscitation, low baseline pediatric critical illness score, adrenaline administration before CA, and mechanical ventilation before CA, and such children should be identified and intervened as early as possible to reduce the incidence of AKI and the mortality rate.

A global survey of the gene network and key genes for oil accumulation in cultivated tetraploid cottons.

To enrich our knowledge about gene network of fatty acid biosynthesis in cottonseed, we conducted comparative transcriptome to reveal the differences in gene expression between Gossypium hirsutum and Gossypium barbadense during cottonseed development. The prolonged expression period and increased expression abundance of oil-related genes are the main reasons for producing high seed oil content (SOC) in G. barbadense, which manifested as the bias of homeologous gene expression in Dt-subgenome after 25 day postanthesis (DPA). The dynamic expression profile showed that SAD6 and FATA are more important for oil biosynthesis in G. barbadense than that in G. hirsutum. Three key transcription factors, WRI1, NF-YB6 and DPBF2, showed their elite roles in regulating seed oil in cotton. We observed that sequence variations in the promoter region of BCCP2 genes might contribute to its divergence in expression level between the two species. Based on the quantitative trait loci (QTL) information of the seed oil content and utilizing additional G. barbadense introgression lines (ILs), we propose 21 candidate genes on the basis of their differential expression level, of which the GbSWEET and the GbACBP6 showed the potential functional to improve the oil content. Taken together, studying the different expression of oil-related genes and their genetic regulation mechanisms between G. hirsutum and G. barbadense provide new insights to understanding the mechanism of fatty acid biosynthesis network and fatty acid genetic improving breeding in cotton.

Genome-wide association mapping for agronomic traits in an 8-way Upland cotton MAGIC population by SLAF-seq.

KEY MESSAGE: One sub-MAGIC population was genotyped using SLAF-seq, and QTLs and candidate genes for agronomic traits were identified in Upland cotton. The agronomic traits of Upland cotton have serious impacts on cotton production, as well as economic benefits. To discover the genetic basis of important agronomic traits in Upland cotton, a subset MAGIC (multi-parent advanced generation inter-cross) population containing 372 lines (SMLs) was selected from an 8-way MAGIC population with 960 lines. The 372 lines and 8 parents were phenotyped in six environments and deeply genotyped by SLAF-seq with 60,495 polymorphic SNPs. The genetic diversity indexes of all SNPs were 0.324 and 0.362 for the parents and MAGIC lines, respectively. The LD decay distance of the SMLs was 600 kb (r2 = 0.1). Genome-wide association mapping was performed using 60,495 SNPs and the phenotypic data of the SMLs, and 177 SNPs were identified to be significantly associated with 9 stable agronomic traits in multiple environments. The identified SNPs were divided into 117 QTLs (quantitative trait loci) by LD decay distance, explaining 5.44% to 31.64% of the phenotypic variation. Among the 117 QTLs, 3 QTLs were stable in multiple environments, and 11 QTL regions were proven to have pleiotropism associated with multiple traits. Within QTL regions, 154 genes were preferentially expressed in correlated tissues, and 8 genes with known functions were identified as priori candidate genes. Two genes, GhACT1 and GhGASL3, reported to have clear functions, were, respectively, located in qFE-A05-4 and qFE-D04-3, two stable QTLs for FE. This study revealed the genetic basis of important agronomic traits of Upland cotton, and the results will facilitate molecular breeding in cotton.

Extensive Scarring Alopecia Treated Through a Single Dense-Packing Follicular Unit Extraction Megasession.

BACKGROUND: Follicular unit extraction (FUE) is becoming more popular in hair restoration. However, its potential for treating extensive scarring alopecia is unknown. METHODS: Patients with scarring alopecia larger than 100 cm2 were enrolled from 2015 to 2018. After assessing scar quality regarding vascularity, pliability, and thickness, dense-packing megasession (DPM)-FUE was performed on high-quality recipient sites. Patients were followed up at 1 week and 12 months postoperatively to evaluate complications, survival rates of grafts, and patient satisfactions. Cases of nonscarring alopecia were reviewed as controls. RESULTS: Fifty-two scarring alopecia and 55 nonscarring alopecia patients were enrolled. The mean scar area was 120 cm2, and the procedure required an average of 8 operative hours, with no difference between groups (p > .05). Graft amount and postoperative complications were similar as well (p > .05). The survival rate in scarring alopecia was lower than that in the control but was still 85% (p < .05). Follow-up photographs showed effective scar camouflage after DPM-FUE. Most patients were very satisfied with the final results (p > .05). CONCLUSION: DPM-FUE is a safe and effective treatment for extensive scarring alopecia.

Genetic dissection of an allotetraploid interspecific CSSLs guides interspecific genetics and breeding in cotton.

BACKGROUND: The low genetic diversity of Upland cotton limits the potential for genetic improvement. Making full use of the genetic resources of Sea-island cotton will facilitate genetic improvement of widely cultivated Upland cotton varieties. The chromosome segments substitution lines (CSSLs) provide an ideal strategy for mapping quantitative trait loci (QTL) in interspecific hybridization. RESULTS: In this study, a CSSL population was developed by PCR-based markers assisted selection (MAS), derived from the crossing and backcrossing of Gossypium hirsutum (Gh) and G. barbadense (Gb), firstly. Then, by whole genome re-sequencing, 11,653,661 high-quality single nucleotide polymorphisms (SNPs) were identified which ultimately constructed 1211 recombination chromosome introgression segments from Gb. The sequencing-based physical map provided more accurate introgressions than the PCR-based markers. By exploiting CSSLs with mutant morphological traits, the genes responding for leaf shape and fuzz-less mutation in the Gb were identified. Based on a high-resolution recombination bin map to uncover genetic loci determining the phenotypic variance between Gh and Gb, 64 QTLs were identified for 14 agronomic traits with an interval length of 158 kb to 27 Mb. Surprisingly, multiple alleles of Gb showed extremely high value in enhancing cottonseed oil content (SOC). CONCLUSIONS: This study provides guidance for studying interspecific inheritance, especially breeding researchers, for future studies using the traditional PCR-based molecular markers and high-throughput re-sequencing technology in the study of CSSLs. Available resources include candidate position for controlling cotton quality and quantitative traits, and excellent breeding materials. Collectively, our results provide insights into the genetic effects of Gb alleles on the Gh, and provide guidance for the utilization of Gb alleles in interspecific breeding.

Expression of the Clifednamide Biosynthetic Pathway in Streptomyces Generates 27,28-seco-Derivatives.

Polycyclic tetramate macrolactams (PoTeMs) are a group of hybrid PK-NRP natural products having a variable set of carbocyclic rings, a conserved assembly pathway, and diverse bioactivities. We report here the identification of seven new PoTeMs, clifednamides D-J (3-9), along with the known clifednamides A (1) and B (2) through rational pathway refactoring and heterologous expression. Remarkably, clifednamides D (3), G (6), and H (7) feature an unprecedented 27,28-seco skeleton. The cytotoxic activities of compounds 1-9 indicated that the hydroxy group of C-25, the methyl group of C-30, the inner five-membered ring, and the intact macrocycle are all critical for the activities. Meanwhile, the cytochrome P450 enzyme CftS023A and the hydroxylase CftS023E involved in oxidative tailoring of clifednamides were found to decorate the fused 5-6 bicyclic intermediates. Accordingly, the biosynthetic pathway for clifednamides was proposed.

Genetic Difference of Hypothyroidism-Induced Cognitive Dysfunction in C57BL/6j and 129/Sv Mice.

Adult-onset hypothyroidism induces cognitive impairments in learning and memory. Thyroxin (T4) replacement therapy appears to be effective in biochemically restoring euthyroidism, as evidenced by serum T4 and triiodothyronine concentrations within the normal range, although some the patients still exhibit cognitive dysfunctions. Here, we investigated the cognitive functions of propylthiouracil-induced hypothyroid mice in C57BL/6j and 129/Sv strains using the passive avoidance task and the novel object recognition test. Cognitive dysfunctions in hypothyroid mice were found only in the C57BL/6j strain, not in the 129/Sv strain. Further, we found that cholinergic neurons in the basal forebrain increased the membrane potential and input resistance with decreased capacitance, and that they decreased the amplitude and width of action potential in hypothyroid mice in the C57BL/6j strain but not in those in the 129/Sv strain, compared with the controls for each strain. Additionally, the excitability of cholinergic neurons in the basal forebrain was reduced in the hypothyroid mice in the C57BL/6j strain. These results indicated that transgenic mice with the C57BL/6j genetic background are more suitable for revealing the mechanism underlying hypothyroidism-induced cognitive dysfunction, and that the cholinergic basal forebrain may be the appropriate target for treating cognitive dysfunction in adult-onset hypothyroidism.

Fabrication of a cost effective and broadband self-powered photodetector based on Sb2Te3 and silicon.

The excellent conductive surface electronic states of topological insulators make them suitable candidates for the next generation optoelectronic devices. Moreover, their unique semiconducting properties are favorable for building heterojunctions with other semiconductors. Here, we fabricated a low cost and broadband self-powered photodetector based on Sb2Te3 and Si. The photolithography and thermal evaporation technique were combined to fabricate a series of asymmetric planar Sb2Te3 electrodes on the surface of an n-type silicon substrate. An obvious asymmetrical current voltage curve occurred under dark conditions, which is ascribed to the asymmetry of each electrode. During the photodetection test, self-powered photodetection was obtained upon 940 nm light irradiation. Moreover, the photodetector exhibited fast and broadband photodetection from 365 nm to 940 nm with a response time less than 40 ms.

Ameliorative effect of sevoflurane on endoplasmic reticulum stress mediates cardioprotection against ischemia-reperfusion injury 1.

We aimed to investigate whether the cardioprotection of sevoflurane against ischemia-reperfusion (IR) injury is via inhibiting endoplasmic reticulum stress. The rat in vivo model of myocardial IR injury was induced by ligation of the left anterior descending coronary artery. Sevoflurane significantly ameliorated the reduced cardiac function, increased infarct size, and elevated troponin I level and lactate dehydrogenase activity in plasma induced by IR injury. Sevoflurane suppressed the IR-induced myocardial apoptosis. The increased protein levels of glucose-regulated protein 78 and C/EBP homologous protein (CHOP) after myocardial IR were significantly reduced by sevoflurane. The protein levels of phosphorylated protein kinase RNA-like endoplasmic reticulum kinase (PERK), phosphorylated eukaryotic initiation factor 2 (eIF2α), and activating transcription factor 4 (ATF4) were significantly increased in rats with IR and attenuated by sevoflurane treatment. The phosphorylation of Akt was further activated by sevoflurane. The cardioprotection of sevoflurane could be blocked by wortmannin, a PI3K/Akt inhibitor. Our results suggest that the cardioprotection of sevoflurane against IR injury might be mediated by suppressing PERK/eIF2a/ATF4/CHOP signaling via activating the Akt pathway, which helps in understanding the novel mechanism of the cardioprotection of sevoflurane.

Enhanced N-acetyl-D-neuraminic production from glycerol and N-acetyl-D-glucosamine by metabolically engineered Escherichia coli with a two-stage pH-shift control strategy.

Typical N-acetyl-D-neuraminic acid (Neu5Ac) production uses N-acetyl-D-glucosamine (GlcNAc) and excess pyruvate as substrates in the enzymatic or whole-cell biocatalysis process. In a previous study, a Neu5Ac-producing biocatalytic process via engineered Escherichia coli SA-05/pDTrc-AB/pCDF-pck-ppsA was constructed without exogenous pyruvate. In this study, glycerol was found to be a good energy source compared with glucose for the catalytic system with resting cells, and Neu5Ac production increased to 13.97 ± 0.27 g L-1. In addition, a two-stage pH shift strategy was carried out, and the Neu5Ac yield was improved to 14.61 ± 0.31 g L-1. The GlcNAc concentration for Neu5Ac production was optimized. Finally, an integrated strategy was developed for Neu5Ac production, and the Neu5Ac yield reached as high as 18.17 ± 0.27 g L-1. These results provide a new biocatalysis technology for Neu5Ac production without exogenous pyruvate.