Brassinosteroid regulates stomatal development in etiolated Arabidopsis cotyledons via transcription factors BZR1 and BES1.

Brassinosteroids (BRs) are phytohormones that regulate stomatal development. In this study, we report that BR represses stomatal development in etiolated Arabidopsis (Arabidopsis thaliana) cotyledons via transcription factors BRASSINAZOLE RESISTANT 1 (BZR1) and bri1-EMS SUPPRESSOR1 (BES1), which directly target MITOGEN-ACTIVATED PROTEIN KINASE KINASE 9 (MKK9) and FAMA, 2 important genes for stomatal development. BZR1/BES1 bind MKK9 and FAMA promoters in vitro and in vivo, and mutation of the BZR1/BES1 binding motif in MKK9/FAMA promoters abolishes their transcription regulation by BZR1/BES1 in plants. Expression of a constitutively active MKK9 (MKK9DD) suppressed overproduction of stomata induced by BR deficiency, while expression of a constitutively inactive MKK9 (MKK9KR) induced high-density stomata in bzr1-1D. In addition, bzr-h, a sextuple mutant of the BZR1 family of proteins, produced overabundant stomata, and the dominant bzr1-1D and bes1-D mutants effectively suppressed the stomata-overproducing phenotype of brassinosteroid insensitive 1-116 (bri1-116) and brassinosteroid insensitive 2-1 (bin2-1). In conclusion, our results revealed important roles of BZR1/BES1 in stomatal development, and their transcriptional regulation of MKK9 and FAMA expression may contribute to BR-regulated stomatal development in etiolated Arabidopsis cotyledons.

Tyrosine phosphorylation-mediated YAP1-TFAP2A interactions coordinate transcription and trastuzumab resistance in HER2+ breast cancer.

Trastuzumab resistance in HER2+ breast cancer (BC) is the major reason leading to poor prognosis of BC patients. Oncogenic gene overexpression or aberrant activation of tyrosine kinase SRC is identified to be the key modulator of trastuzumab response. However, the detailed regulatory mechanisms underlying SRC activation-associated trastuzumab resistance remain poorly understood. In the present study, we discover that SRC-mediated YAP1 tyrosine phosphorylation facilitates its interaction with transcription factor AP-2 alpha (activating enhancer binding protein 2 alpha, TFAP2A), which in turn promotes YAP1/TEAD-TFAP2A (YTT) complex-associated transcriptional outputs, thereby conferring trastuzumab resistance in HER2+ BC. Inhibition of SRC kinase activity or disruption of YTT complex sensitizes cells to trastuzumab treatment in vitro and in vivo. Additionally, we also identify YTT complex co-occupies the regulatory regions of a series of genes related to trastuzumab resistance and directly regulates their transcriptions, including EGFR, HER2, H19 and CTGF. Moreover, YTT-mediated transcriptional regulation is coordinated by SRC kinase activity. Taken together, our study reveals that SRC-mediated YTT complex formation and transcriptions are responsible for multiple mechanisms associated with trastuzumab resistance. Therefore, targeting HER2 signaling in combination with the inhibition of YTT-associated transcriptional outputs could serve as the treatment strategy to overcome trastuzumab resistance caused by SRC activation.

Saccharin Sodium Coupling Fluorinated Solvent Enabled Stable Interface for High-Voltage Li-Metal Batteries.

Optimizing the electrode/electrolyte interface structure is the key to realizing high-voltage Li-metal batteries (LMBs). Herein, a functional electrolyte is introduced to synergetically regulate the interface layer structures on the high-voltage cathode and the Li-metal anode. Saccharin sodium (NaSH) as a multifunctional electrolyte additive is employed in fluorinated solvent-based electrolyte (FBE) for robust interphase layer construction. On the one hand, combining the results of ex-situ techniques and in-situ electrochemical dissipative quartz crystal microbalance (EQCM-D) technique, it can be seen that the solid electrolyte interface (SEI) layer constructed by NaSH-coupled fluoroethylene carbonate (FEC) on Li-metal anode significantly inhibits the growth of lithium dendrites and improves the cyclic stability of the anode. On the other hand, the experimental results also confirm that the cathode-electrolyte interface (CEI) layer induced by NaSH-coupled FEC effectively protects the active materials of LiCoO2 and improves their structural stability under high-voltage cycling, thus avoiding the material rupture. Moreover, theoretical calculation results show that the addition of NaSH alters the desolvation behavior of Li+ and enhances the transport kinetics of Li+ at the electrode/electrolyte interface. In this contribution, the LiCoO2 ǁLi full cell containing FBE+NaSH results in a high capacity retention of 80% after 530 cycles with a coulombic efficiency of 99.8%.

Evaluating the global impact of low physical activity on type 2 diabetes: Insights from the global burden of disease 2019 study.

AIM: We aimed to assess the global implications of low physical activity (LPA) on type 2 diabetes mellitus (T2DM) by utilizing data from the Global Burden of Disease (GBD) 2019. METHODS: The analysis was conducted by examining the age-standardized disability-adjusted life years (DALYs) rates over a 30-year period. To assess the trends, we utilized estimated annual percentage changes (EAPCs). RESULTS: The study revealed a notable increase in the burden of DALYs attributable to T2DM resulting from LPA, with an EAPC of 0.84 (95% confidence interval 0.78-0.89). Among the regions examined, Oceania showed the highest burden, whereas Eastern Europe exhibited the lowest burden. Specifically, within the Central Asia region, a considerable increase in T2DM-LPA DALYs was observed, with an EAPC of 3.18 (95% confidence interval 3.01-3.36). The burden associated with T2DM-LPA DALYs was found to be similar between genders and increased across all age groups, peaking in the 80-84 years. Furthermore, there was a clear association between the socio-demographic index (SDI) and the age-standardized DALYs rate. Regions categorized as low-middle and middle SDI experienced a substantial rise in burden. CONCLUSION: This study highlights a substantial increase in the T2DM-LPA DALYs in low-middle and middle SDI regions, as well as among individuals aged 80-84 years. These findings emphasize the importance of implementing comprehensive global health interventions that promote physical activity, particularly targeting high-risk populations and regions.

Tyrosine kinase SRC-induced YAP1-KLF5 module regulates cancer stemness and metastasis in triple-negative breast cancer.

SRC is the first identified oncogene, and its aberrant activation has been implicated as a driving event in tumor initiation and progression. However, its role in cancer stemness regulation and the underlying regulatory mechanism are still elusive. Here, we identified a YAP1 tyrosine phosphorylation-dependent YAP1-KLF5 oncogenic module, as the key downstream mediator of SRC kinase regulating cancer stemness and metastasis in triple-negative breast cancer (TNBC). SRC was overexpressed in TNBC patient tissues and its expression level was highly correlated with the tumor malignancy. SRC activation induced, while inhibition of SRC kinase reduced the cancer stemness, tumor cell growth and metastasis in vitro and in vivo. Transcriptomic and proteomic analysis revealed that SRC-mediated YAP1 tyrosine phosphorylation induced its interaction with Kruppel-like factor 5 (KLF5) to form a YAP1/TEAD-KLF5 complex in TNBC cells. YAP1-KLF5 association further promoted TEAD-mediated transcriptional program independently of canonical Hippo kinases, which eventually gave rise to the enhanced cancer stemness and metastasis. Disruption of YAP1-KLF5 module in TNBC cells dramatically attenuated the SRC-induced cancer stemness and metastasis in vitro and in vivo. Accordingly, co-upregulations of SRC and YAP1-KLF5 module in TNBC tissues were significantly positively correlated with the tumor malignance. Altogether, our work presents a novel tyrosine phosphorylation-dependent YAP1-KLF5 oncogenic module governing SRC-induced cancer stemness and metastasis in TNBC. Therefore, targeting YAP1/KLF5-mediated transcription may provide a promising strategy for TNBC treatment with SRC aberrantly activation.

Comprehensive quality evaluation of Lysimachia christinae Hance via fingerprint, spectrum-effect relationship, and quantitative analyses of multiple components by single marker.

BACKGROUND: Lysimachia christinae Hance (LCH) is a traditional medicine used to treat gallstone disease and cholecystitis. Despite its known anti-inflammatory and choleretic effects, its quality has not been extensively evaluated. OBJECTIVE: In this study, we aimed to establish a reliable quality evaluation method for LCH via fingerprint, spectrum-effect relationship, and quantitative analyses of multicomponents by a single marker (QAMS). METHODS: First, the fingerprints and anti-inflammatory and choleretic activities of 14 LCH batches were determined. Then, the gray relation analysis method was used to analyze the peak areas of the fingerprint profile and pharmacodynamic data. Subsequently, the characteristic peaks were tentatively identified using high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Finally, rutin was selected as the internal reference material, and QAMS was used to analyze the LCH components. RESULTS: Pharmacodynamic experiments confirmed that LCH exerted anti-inflammatory and choleretic effects. Moreover, 15 flavonoids related to the anti-inflammatory and choleretic effects of LCH were identified. Notably, relative error percentage between the QAMS and external standard method was less than 5%. CONCLUSION: This study successfully established a comprehensive evaluation method for the qualitative and quantitative analyses of LCH.

The oncogenic roles and clinical implications of YAP/TAZ in breast cancer.

Breast cancer (BC) is the most commonly diagnosed form of cancer and a leading cause of cancer-related deaths among women worldwide. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are homologous transcriptional coactivators and downstream effectors of Hippo signalling. YAP/TAZ activation has been revealed to play essential roles in multiple events of BC development, including tumour initiation, progression, metastasis, drug resistance and stemness regulations. In this review, we will first give an overview of YAP/TAZ-mediated oncogenesis in BC, and then systematically summarise the oncogenic roles of YAP/TAZ in various BC subtypes, BC stem cells (BCSCs) and tumour microenvironments (TMEs). Based on these findings, we will further discuss the clinical implications of YAP/TAZ-based targeted therapies in BC and the potential future direction.

Cytosine base editors (CBEs) for inducing targeted DNA base editing in Nicotiana benthamiana.

BACKGROUND: The base editors can introduce point mutations accurately without causing double-stranded DNA breaks or requiring donor DNA templates. Previously, cytosine base editors (CBEs) containing different deaminases are reported for precise and accurate base editing in plants. However, the knowledge of CBEs in polyploid plants is inadequate and needs further exploration. RESULTS: In the present study, we constructed three polycistronic tRNA-gRNA expression cassettes CBEs containing A3A, A3A (Y130F), and rAPOBEC1(R33A) to compare their base editing efficiency in allotetraploid N. benthamiana (n = 4x). We used 14 target sites to compare their editing efficiency using transient transformation in tobacco plants. The sanger sequencing and deep sequencing results showed that A3A-CBE was the most efficient base editor. In addition, the results showed that A3A-CBE provided most comprehensive editing window (C1 ~ C17 could be edited) and had a better editing efficiency under the base background of TC. The target sites (T2 and T6) analysis in transformed N. benthamiana showed that only A3A-CBE can have C-to-T editing events and the editing efficiency of T2 was higher than T6. Additionally, no off-target events were found in transformed N. benthamiana. CONCLUSIONS: All in all, we conclude that A3A-CBE is the most suitable vector for specific C to T conversion in N. benthamiana. Current findings will provide valuable insights into selecting an appropriate base editor for breeding polyploid plants.

Prognosis of Concurrent Versus Sequential Chemo-Radiotherapy Induction Followed by Surgical Resection in Patients with Advanced Thymic Epithelial Tumors: A Retrospective Study.

BACKGROUND: This study aimed to evaluate the prognosis of concurrent chemo-radiotherapy (CCRT) versus sequential chemo-radiotherapy (SCRT) induction followed by surgical resection in patients with advanced thymic epithelial tumors (TETs). METHODS: This retrospective study included patients with advanced TETs who underwent CCRT or SCRT induction followed by surgical resection at the Second General Hospital of Guangdong Province between January 2008 and December 2019. The primary outcomes were induction response rate and surgical complete resection rate. The secondary outcomes were surgery combined resection, post-induction T staging, postoperative TNM staging, postoperative pathological tumor regression grade, progression-free survival (PFS) and overall survival (OS), and adverse events (AEs). RESULTS: A total of 31 patients were included, 15 of whom received CCRT and the other 16 SCRT. The induction response rates were 80.0 and 62.5%, respectively, the post-induction step-down rates were 46.7 and 31.3%, respectively, and the post-induction R0 resection rates were 80.0 and 68.8%, respectively, without significant differences between CCRT and SCRT groups (all P > 0.05). The 5-year OS rate was 64.2 and 51.6%, respectively, and PFS was 42.3 and 21.4%, respectively, without significant differences between CCRT and SCRT groups (both P > 0.05). AEs in the hematologic system were significantly higher with CCRT compared with SCRT (P = 0.009). CONCLUSIONS: Patients with advanced TETs might have a good prognosis with both CCRT and SCRT induction therapy, while SCRT induction may result in a lower probability of AEs in the hematologic system.

Integrating the serum proteomic and fecal metaproteomic to analyze the impacts of overweight/obesity on IBD: a pilot investigation.

BACKGROUND: Inflammatory bowel disease (IBD) encompasses a group of chronic relapsing disorders which include ulcerative colitis (UC) and Crohn's disease (CD). The incidences of IBD and overweight/obesity are increasing in parallel. Here, we investigated alterations in proteomic in serum and metaproteomic in feces of IBD patients with overweight/obesity and aimed to explore the effect of overweight/ obesity on IBD and the underlying mechanism. METHODS: This prospective observational study (n = 64) comprised 26 health control subjects (HC, 13 with overweight/obesity) and 38 IBD patients (19 with overweight/obesity) at a tertiary hospital. Overweight/obesity was evaluated by body mass index (BMI) and defined as a BMI greater than 24 kg/m2. The comprehensive serum proteomic and fecal metaproteomic analyses were conducted by ultra-performance liquid chromatography-Orbitrap Exploris 480 mass spectrometry. RESULTS: UC and CD presented similar serum molecular profiles but distinct gut microbiota. UC and CD serum exhibited higher levels of cytoskeleton organization- associated and inflammatory response-related proteins than the HC serum. Compared the serum proteome of UC and CD without overweight/obesity, inflammatory response-associated proteins were dramatically decreased in UC and CD with overweight/obesity. Fecal metaproteome identified 66 species in the feces. Among them, Parasutterella excrementihominis was increased in CD compared with that in HC. UC group had a significant enrichment of Moniliophthora roreri, but had dramatically decreased abundances of Alistipes indistinctus, Clostridium methylpentosum, Bacteroides vulgatus, and Schizochytrium aggregatum. In addition, overweight/obesity could improve the microbial diversity of UC. Specifically, the UC patients with overweight/obesity had increased abundance of some probiotics in contrast to those without overweight/obesity, including Parabacteroides distasonis, Alistipes indistincus, and Ruminococcus bromii. CONCLUSION: This study provided high-quality multi-omics data of IBD serum and fecal samples, which enabled deciphering the molecular bases of clinical phenotypes of IBD, revealing the impacts of microbiota on IBD, and emphasizing the important role of overweight/obesity in IBD.

Novel Classification System of Adenoids Based on Appearance and Its Relationship with Drug Therapy.

INTRODUCTION: Adenoidectomy is a common procedure in children who have adenoid hypertrophy (AH), but anesthesia risks should be considered. We proposed a novel classification system for adenoids based on their appearance. Additionally, we explored whether the novel classification of adenoids correlates with the response to therapy and thus might be helpful for further treatment recommendations. METHODS: We used fiberoptic nasal endoscopy to determine the degree and appearance of AH. Obstructive Sleep Apnea Questionnaire (OSA-18) was used to assess the quality of life of children with AH. The adenoids were divided into three types: edematous type, common type, and fibrous type. In adenoid tissues, the eosinophils were counted. Immunohistochemistry and Western blot were done to determine the expression of CysLTR1, CysLTR2, CGR-α, and CGR-ß in different types of adenoids. RESULTS: 70.67% (106/150) of AH patients presented with allergic rhinitis (AR), and of them, 68% (72/106) of adenoids were the edematous type. The expressions of CGR-α, CGR-ß, and eosinophil count were higher in the edematous compared with the common and fibrous types. The expression of the leukotriene receptor was similar in all types. Upon montelukast combined with nasal glucocorticoid therapy, improvement of OSA-18 scores and AH grade was significantly compared to montelukast monotherapy for edematous type. There was not any statistically significant difference between the scores upon montelukast combined with nasal glucocorticoid and montelukast monotherapy for common and fibrous type. We observed a positive correlation between eosinophil count in the blood and in the adenoid tissue. CONCLUSION: AR was the risk factor for the development of edematous AH. All subtypes of AH responded to montelukast, while there was an additional effect of nasal glucocorticoid in the edematous type. A combination therapy of nasal glucocorticoid with leukotriene receptor antagonist can be recommended for AH patients with AR, patients with edematous adenoids, and/or patients with increased eosinophils in blood routine.

Preparation of high performance porous carbon by microwave synergistic nitrogen/phosphorus doping for efficient removal of Cu2+ via capacitive deionization.

Sargassum biochar has potential advantages as an electrode material due to its natural microscopic pore channels. However, conventional pyrolysis method is prone to thermal damage to the biochar, and incapable to form a complete pore structure resulting in poor biochar electrode performance. In this study, a strategy of microwave pyrolysis coupled with KOH activation was used to prepare nitrogen/phosphorus double-doped graded porous biochar (STC) using ammonium dihydrogen phosphate as dopant. The carbon material STC-1.24-800 prepared by the optimal parameters had a high specific surface area (SSA) of 1367.6 m2 g -1 and a total pore volume of 1.499 cm3 g-1. The precise inside-out heating characteristics of microwave facilitated the generation of suitable meso-micropore distribution ratios in carbon, and the graded porous structure provided abundant active sites for charge accumulation and ion diffusion. The doped nitrogen/phosphorus atoms responding to the microwave field, generated spin to promote microwave absorption, introducing surface structural defects to produce electron density differences. The change in the nature of the electron donor and its electron density enhanced the electrical conductivity and chemical stability of STC. Nitrogen/phosphorus polar surface functional groups improved hydrophilicity and wettability. STC-1.24-800 had a higher specific capacitance of 531 F g-1 and exhibits great cycle performance in capacitive deionization (CDI) applications (1.0 V, 50 mg L-1 Cu2+) as well as adsorption performance (56.16 mg g -1). The present work can provide a novel feasible idea for preparing diatomically doped graded porous biochar for CDI electrode application by microwave irradiation.

Study on the interaction mechanism between Crocus sativus and Fusarium oxysporum based on dual RNA-seq.

KEY MESSAGE: The saffron phenylpropane synthesis pathway and Fusarium oxysporum cell wall-degrading enzymes play key roles in their early interactions. Saffron (Crocus sativus) is a highly important crop with diverse medicinal properties. F. oxysporum is a widely-distributed soil-borne fungus, causing the serious saffron rot disease. Currently, there is no effective management strategy to control this disease because of no resistant cultivars and limited information about the resistance and pathogenic mechanisms. In this study, we first characterized the infection process and physiological responses of saffron infected by F. oxysporum. The molecular mechanism of these infection interactions was revealed by dual RNA-seq analysis. On the 3rd day of infection, the hyphae completely entered, colonized and spread in the corm cells; while on the 6th day of infection, hyphae had appeared in the xylem cells, blocking these vessels. Transcriptome results indicate that within the host, phenylpropanoid metabolism, plant hormone signal transduction and plant pathogen interaction pathways were activated during infection. These pathways were conducive to the enhancement of cell wall, the occurrence of hypersensitivity, and the accumulation of various antibacterial proteins and phytoantitoxins. Meanwhile, in the fungus, many up-regulated genes were related to F. oxysporum cell wall degrading enzymes, toxin synthesis and pathogenicity gene, showing its strong pathogenicity. This study provides new ideas for the control of saffron corm rot, and also provides a theoretical basis for mining the key functional genes.

Quality evaluation of Hawk tea from different months and regions based on quantitative analysis of multiple components with a single marker (QAMS) combined with HPLC fingerprint.

BACKGROUND: Hawk tea, a medicinal and edible plant, has been consumed for thousands of years in Southwest China. To date, no unified food safety standard for Hawk tea has been established, and systematic research on the quality of Hawk tea is lacking. OBJECTIVE: The aim of this study was to develop a comprehensive evaluation method for the quality of Hawk tea based on inclusions content, high-performance liquid chromatography (HPLC) fingerprinting combined with the quantitative analysis of multiple components with a single marker (QAMS) method. METHODS: The contents of total flavonoids, total phenols, total polysaccharides, and total protein were determined using the colorimetric method. An effective comprehensive evaluation method was established to classify the 16 batches of samples based on HPLC fingerprint analysis combined with similarity analysis (SA), hierarchical cluster analysis (HCA), principal component analysis (PCA), partial least-squares discrimination analysis (PLS-DA), and the QAMS method. RESULTS: Flavonoids were the main chemical components of Hawk tea. The accuracy of the QAMS method was verified by comparing the calculated results with those of the external standard method (ESM). No significant differences were found between the two methods. Additionally, the fingerprint of Hawk tea was also established. CONCLUSION: The method established in this study can be used for the comprehensive quality evaluation of Hawk tea and can also provide a reference for the quality evaluation of other herbal medicines.

Genome-Wide Identification of Kiwifruit SGR Family Members and Functional Characterization of SGR2 Protein for Chlorophyll Degradation.

The STAY-GREEN (SGR) proteins play an important role in chlorophyll (Chl) degradation and are closely related to plant photosynthesis. However, the availability of inadequate studies on SGR motivated us to conduct a comprehensive study on the identification and functional dissection of SGR superfamily members in kiwifruit. Here, we identified five SGR genes for each of the kiwifruit species [Actinidia chinensis (Ac) and Actinidia eriantha (Ae)]. The phylogenetic analysis showed that the kiwifruit SGR superfamily members were divided into two subfamilies the SGR subfamily and the SGRL subfamily. The results of transcriptome data and RT-qPCR showed that the expression of the kiwifruit SGRs was closely related to light and plant developmental stages (regulated by plant growth regulators), which were further supported by the presence of light and the plant hormone-responsive cis-regulatory element in the promoter region. The subcellular localization analysis of the AcSGR2 protein confirmed its localization in the chloroplast. The Fv/Fm, SPAD value, and Chl contents were decreased in overexpressed AcSGR2, but varied in different cultivars of A. chinensis. The sequence analysis showed significant differences within AcSGR2 proteins. Our findings provide valuable insights into the characteristics and evolutionary patterns of SGR genes in kiwifruit, and shall assist kiwifruit breeders to enhance cultivar development.

[Clinical and genetic analysis of a child with Schaaf-Yang syndrome].

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with Schaaf-Yang syndrome (SYS). METHODS: Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing. Sanger sequencing was used for family constellation verification, and bioinformatic analysis was performed for the candidate variant. RESULTS: The child, a 1-year-and-9-month-old boy, had clinical manifestations of retarded growth, small penis, and unusual facies. Genetic testing revealed that the child has harbored a novel heterozygous variant of c.3078dupG (p.Leu1027Valfs*28) of the MAGEL2 gene. Sanger sequencing showed that neither parent of the child carried the same variant. The c.3078dupG(p.Leu1027Valfs*28) variant of the MAGEL2 gene has not been included in the databases of ESP, 1000 Genomes and ExAC. According to the Standards and Guidelines for the Interpretation of Sequence Variants of the American College of Medical Genetics and Genomics (ACMG), the variant was judged to be pathogenic. CONCLUSION: The c.3078dupG (p.Leu1027Valfs*28) variant of the MAGEL2 gene probably underlay the SYS in this child, which has further expanded the spectrum of the MAGEL2 gene variants.

SRC kinase-mediated signaling pathways and targeted therapies in breast cancer.

Breast cancer (BC) has been ranked the most common malignant tumor throughout the world and is also a leading cause of cancer-related deaths among women. SRC family kinases (SFKs) belong to the non-receptor tyrosine kinase (nRTK) family, which has eleven members sharing similar structure and function. Among them, SRC is the first identified proto-oncogene in mammalian cells. Oncogenic overexpression or activation of SRC has been revealed to play essential roles in multiple events of BC progression, including tumor initiation, growth, metastasis, drug resistance and stemness regulations. In this review, we will first give an overview of SRC kinase and SRC-relevant functions in various subtypes of BC and then systematically summarize SRC-mediated signaling transductions, with particular emphasis on SRC-mediated substrate phosphorylation in BC. Furthermore, we will discuss the progress of SRC-based targeted therapies in BC and the potential future direction.

Titanium-Mediated Domino Cross-Coupling/Cyclodehydration and Aldol-Addition/Cyclocondensation: Concise and Regioselective Synthesis of Polysubstituted and Fused Furans.

Titanium enolates, in situ-generated from readily available ketones and titanium tetraisopropoxide, undergo domino cross-coupling/cyclodehydration or domino Aldol-addition/cyclocondensation with α-chloroketones to provide synthetically valuable furan derivatives. The domino process tolerates a variety of cyclic and acyclic ketones and chloroketones, producing polysubstituted furans and bi-, tri-, and tetracyclic fused furans.

Rostro-Caudal Specificity of Corticospinal Tract Projections in Mice.

Rostro-caudal specificity of corticospinal tract (CST) projections from different areas of the cortex was assessed by retrograde labeling with fluorogold and retrograde transfection following retro-AAV/Cre injection into the spinal cord of tdT reporter mice. Injections at C5 led to retrograde labeling of neurons throughout forelimb area of the sensorimotor cortex and a region in the dorsolateral cortex near the barrel field (S2). Injections at L2 led to retrograde labeling of neurons in the posterior sensorimotor cortex (hindlimb area) but not the dorsolateral cortex. With injections of biotinylated dextran amine (BDA) into the main sensorimotor cortex (forelimb region), labeled axons terminated selectively at cervical levels. With BDA injections into caudal sensorimotor cortex (hindlimb region), labeled axons passed through cervical levels without sending collaterals into the gray matter and then elaborated terminal arbors at thoracic sacral levels. With BDA injections into the dorsolateral cortex near the barrel field, labeled axons terminated at high cervical levels. Axons from medial sensorimotor cortex terminated primarily in intermediate laminae and axons from lateral sensorimotor cortex terminated primarily in laminae III-V of the dorsal horn. One of the descending pathways seen in rats (the ventral CST) was not observed in most mice.

Experience of the Wang procedure in treating pectus excavatum in two hundred fifty-six paediatric patients.

INTRODUCTION: To analyze and summarize the orthopaedic effect and application experience of the Wang procedure in the treatment of pectus excavatum in paediatric patients. METHODS: The clinical data of 256 children ranging from 0.83~14 years (4.89±2.83 years) who underwent the Wang procedure for pectus excavatum from January 2017 to September 2020 in our hospital were analyzed retrospectively. A 1~2-cm incision was made in front of the xiphoid, and a tunnel was constructed on the deep surface of the thoracic cage. Steel wires were inserted through the bilateral costal arch and the lower sternum, and a steel bar was placed in the tunnel. The wires were pulled taut and fixed to the bar, and the incision was sutured. RESULTS: All the procedures were performed using one steel bar. The range of the procedure duration, the intra-operative bleeding volume, and the hospitalization stays of the patients were 18 to 45 (24.02±4.89) minutes, one to ten (2.16±1.68) mL, and three to nine days (5.71±1.35 days) respectively. Post-operative pneumothorax occurred in three cases without other complications. All the cases received follow-up for one to 45 months after discharge, during which six cases experienced poor wound healing, removed steel plate in 82 cases, and three cases of pectus excavatum recurrence. CONCLUSIONS: The Wang procedure is a good option for treating pectus excavatum, secondary pectus excavatum, or recurrent pectus excavatum in paediatric patients.