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This study aims to uncover the heterogeneity of endothelial cells (ECs) in colorectal cancer (CRC) and their crucial role in angiogenesis, with a special focus on tip cells. Using single-cell RNA sequencing to profile ECs, our data suggests that CRC ECs predominantly exhibit enhanced angiogenesis and decreased antigen presentation, a shift in phenotype largely steered by tip cells. We also observed that an increase in the density and proportion of tip cells correlates with CRC occurrence, progression, and poorer patient prognosis. Furthermore, we identified endothelial cell-specific molecule 1 (ESM1), specifically expressed in tip cells, sustains a VEGFA-KDR-ESM1 positive feedback loop, promoting angiogenesis and CRC proliferation and migration. We also found the enrichment of KDR in tip cells and spotlight a unique long-tail effect in VEGFA expression: while VEGFA is primarily expressed by epithelial cells, the highest level of VEGFA expression is found in individual myeloid cells. Moreover, we observed that effective PD-1 blockade immunotherapy significantly reduced tip cells, disrupting the VEGFA-KDR-ESM1 positive feedback loop in the process. Our investigation into the heterogeneity of ECs in CRC at a single-cell level offers important insights that may contribute to the development of more effective immunotherapies targeting tip cells in CRC.
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Neoplasias Colorretais , Células Endoteliais , Neovascularização Patológica , Fator A de Crescimento do Endotélio Vascular , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/genética , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Neovascularização Patológica/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Proliferação de Células , Animais , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Linhagem Celular Tumoral , Análise de Célula Única , Movimento Celular , Camundongos , Regulação Neoplásica da Expressão Gênica , AngiogêneseRESUMO
Many deep learning approaches have been proposed to predict epigenetic profiles, chromatin organization, and transcription activity. While these approaches achieve satisfactory performance in predicting one modality from another, the learned representations are not generalizable across predictive tasks or across cell types. In this paper, we propose a deep learning approach named EPCOT which employs a pre-training and fine-tuning framework, and is able to accurately and comprehensively predict multiple modalities including epigenome, chromatin organization, transcriptome, and enhancer activity for new cell types, by only requiring cell-type specific chromatin accessibility profiles. Many of these predicted modalities, such as Micro-C and ChIA-PET, are quite expensive to get in practice, and the in silico prediction from EPCOT should be quite helpful. Furthermore, this pre-training and fine-tuning framework allows EPCOT to identify generic representations generalizable across different predictive tasks. Interpreting EPCOT models also provides biological insights including mapping between different genomic modalities, identifying TF sequence binding patterns, and analyzing cell-type specific TF impacts on enhancer activity.
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Epigenoma , Transcriptoma , Cromatina/genética , Genômica , GenomaRESUMO
Genomic Knowledgebase (GenomicKB) is a graph database for researchers to explore and investigate human genome, epigenome, transcriptome, and 4D nucleome with simple and efficient queries. The database uses a knowledge graph to consolidate genomic datasets and annotations from over 30 consortia and portals, including 347 million genomic entities, 1.36 billion relations, and 3.9 billion entity and relation properties. GenomicKB is equipped with a web-based query system (https://gkb.dcmb.med.umich.edu/) which allows users to query the knowledge graph with customized graph patterns and specific constraints on entities and relations. Compared with traditional tabular-structured data stored in separate data portals, GenomicKB emphasizes the relations among genomic entities, intuitively connects isolated data matrices, and supports efficient queries for scientific discoveries. GenomicKB transforms complicated analysis among multiple genomic entities and relations into coding-free queries, and facilitates data-driven genomic discoveries in the future.
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Genoma Humano , Reconhecimento Automatizado de Padrão , Humanos , Genômica , Bases de ConhecimentoRESUMO
Nitrogen (N) is a vital major nutrient for rice (Oryza sativa). Rice responds to different applications of N by altering its root morphology, including root elongation. Although ammonium ( NH 4 + ) is the primary source of N for rice, NH 4 + is toxic to rice roots and inhibits root elongation. However, the precise molecular mechanism that NH 4 + -inhibited root elongation of rice is not well understood. Here, we identified a rice T-DNA insert mutant of OsMADS5 with a longer seminal root (SR) under sufficient N conditions. Reverse-transcription quantitative PCR analysis revealed that the expression level of OsMADS5 was increased under NH 4 + compared with NO 3 - supply. Under NH 4 + conditions, knocking out OsMADS5 (cas9) produced a longer SR, phenocopying osmads5, while there was no significant difference in SR length between wild-type and cas9 under NO 3 - supply. Moreover, OsMADS5-overexpression plants displayed the opposite SR phenotype. Further study demonstrated that enhancement of OsMADS5 by NH 4 + supply inhibited rice SR elongation, likely by reducing root meristem activity of root tip, with the involvement of OsCYCB1;1. We also found that OsMADS5 interacted with OsSPL14 and OsSPL17 (OsSPL14/17) to repress their transcriptional activation by attenuating DNA binding ability. Moreover, loss of OsSPL14/17 function in osmads5 eliminated its stimulative effect on SR elongation under NH 4 + conditions, implying OsSPL14/17 may function downstream of OsMADS5 to mediate rice SR elongation under NH 4 + supply. Overall, our results indicate the existence of a novel modulatory pathway in which enhancement of OsMADS5 by NH 4 + supply represses the transcriptional activities of OsSPL14/17 to restrict SR elongation of rice.
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Compostos de Amônio , Oryza , Meristema/metabolismo , Oryza/metabolismo , Raízes de Plantas/metabolismo , Compostos de Amônio/metabolismo , Proliferação de Células , Regulação da Expressão Gênica de PlantasRESUMO
Metal-organic framework (MOF) membranes with high ion selectivity are highly desirable for direct lithium-ion (Li+) separation from industrial brines. However, very few MOF membranes can efficiently separate Li+ from brines of high Mg2+/Li+ concentration ratios and keep stable in ultrahigh Mg2+-concentrated brines. This work reports a type of MOF-channel membranes (MOFCMs) by growing UiO-66-(SH)2 into the nanochannels of polymer substrates to improve the efficiency of MOF membranes for challenging Li+ extraction. The resulting membranes demonstrate excellent monovalent metal ion selectivity over divalent metal ions, with Li+/Mg2+ selectivity up to 103 since Mg2+ should overcome a higher energy barrier than Li+ when transported through the MOF pores, as confirmed by molecular dynamics simulations. Under dual-ion diffusion, as the Mg2+/Li+ mole ratio of the feed solution increases from 0.2 to 30, the membrane Li+/Mg2+ selectivity decreases from 1516 to 19, corresponding to the purity of lithium products between 99.9 and 95.0%. Further research on multi-ion diffusion that involves Mg2+ and three monovalent metal ions (K+, Na+, and Li+, referred to as M+) in the feed solutions shows a significant improvement in Li+/Mg2+ separation efficiency. The Li+/Mg2+ selectivity can go up to 1114 when the Mg2+/M+ molar concentration ratio is 1:1, and it remains at 19 when the ratio is 30:1. The membrane selectivity is also stable for 30 days in a highly concentrated solution with a high Mg2+/Li+ concentration ratio. These results indicate the feasibility of the MOFCMs for direct lithium extraction from brines with Mg2+ concentrations up to 3.5 M. This study provides an alternative strategy for designing efficient MOF membranes in extracting valuable minerals in the future.
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BACKGROUND: Phosphatidylinositol 3-kinase (PI3K) inhibitors transformed management of various malignancies. This study preclinically characterized TQ-B3525 (dual PI3Kα/δ inhibitor) and assessed the recommended phase 2 dose (RP2D), safety, efficacy, and pharmacokinetics in relapsed or refractory (R/R) lymphoma or advanced solid tumors (STs). METHODS: Oral TQ-B3525 was given at eight dose levels on a 28-day cycle. Primary end points were dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and safety. RESULTS: TQ-B3525 showed high selectivity and suppressed tumor growth. Between June 12, 2018, and November 18, 2020, 80 patients were enrolled (63 in dose-escalation cohort; 17 in dose-expansion cohort). Two DLTs occurred in two (two of 63, 3.2%) DLT-evaluable patients; MTD was not identified. TQ-B3525 at 20 mg once daily was selected as RP2D. Grade 3 or worse treatment-related adverse events mainly included hyperglycemia (16.3%), neutrophil count decreased (15.0%), and diarrhea (10.0%). Two (2.5%) treatment-related deaths were reported. Sixty patients with R/R lymphoma and 11 advanced STs demonstrated objective response rates of 68.3% and 9.1%, disease control rates of 91.7% and 54.6%, median progression-free survivals of 12.1 and 1.1 months; median overall survivals were not reached. CONCLUSION: TQ-B3525 exhibited rapid absorption and a nearly proportional increase in exposure. Acceptable safety and promising efficacy support further investigation of TQ-B3525 (20 mg once daily) for R/R lymphoma.
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BACKGROUND: Mechano-growth factor (MGF), which is a growth factor produced specifically in response to mechanical stimuli, with potential of tissue repair and regeneration. Our previous research has shown that MGF plays a crucial role in repair of damaged periodontal ligaments by promoting differentiation of periodontal ligament stem cells (PDLSCs). However, the molecular mechanism is not fully understood. This study aimed to investigated the regulatory effect of MGF on differentiation of PDLSCs and its molecular mechanism. METHODS: Initially, we investigated how MGF impacts cell growth and differentiation, and the relationship with the activation of Fyn-p-YAPY357 and LATS1-p-YAPS127. Then, inhibitors were used to interfere Fyn phosphorylation to verify the role of Fyn-p-YAP Y357 signal after MGF stimulation; moreover, siRNA was used to downregulate YAP expression to clarify the function of YAP in PDLSCs proliferation and differentiation. Finally, after C3 was used to inhibit the RhoA expression, we explored the role of RhoA in the Fyn-p-YAP Y357 signaling pathway in PDLSCs proliferation and differentiation. RESULTS: Our study revealed that MGF plays a regulatory role in promoting PDLSCs proliferation and fibrogenic differentiation by inducing Fyn-YAPY357 phosphorylation but not LATS1-YAP S127 phosphorylation. Moreover, the results indicated that Fyn could not activate YAP directly but rather activated YAP through RhoA in response to MGF stimulation. CONCLUSION: The research findings indicated that the Fyn-RhoA-p-YAPY357 pathway is significant in facilitating the proliferation and fibrogenic differentiation of PDLSCs by MGF. Providing new ideas for the study of MGF in promoting periodontal regenerative repair.
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Due to the intrinsic flame-retardant, eutectic electrolytes are considered a promising candidate for sodium-metal batteries (SMBs). However, the high viscosity and ruinous side reaction with Na metal anode greatly hinder their further development. Herein, based on the Lewis acid-base theory, a new eutectic electrolyte (EE) composed of sodium bis(trifluoromethanesulfonyl)imide (NaTFSI), succinonitrile (SN), and fluoroethylene carbonate (FEC) is reported. As a strong Lewis base, the âC≡N group of SN can effectively weaken the interaction between Na+ and TFSI-, achieving the dynamic equilibrium and reducing the viscosity of EE. Moreover, the FEC additive shows a low energy level to construct thicker and denser solid electrolyte interphase (SEI) on the Na metal surface, which can effectively eliminate the side reaction between EE and Na metal anode. Therefore, EE-1:6 + 5% FEC shows high ionic conductivity (2.62 mS cm-1) and ultra-high transference number of Na+ (0.96). The Na||Na symmetric cell achieves stable Na plating/stripping for 1100 h and Na||Na3V2(PO4)3/C cell shows superior long-term cycling stability over 2000 cycles (99.1% retention) at 5 C. More importantly, the Na||NVP/C pouch cell demonstrates good cycling performance of 102.1 mAh g-1 after 135 cycles at 0.5 C with an average coulombic efficiency of 99.63%.
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Salmonella constitutes a prevalent alimentary pathogen, instigating zoonotic afflictions. Consequently, the prompt discernment of Salmonella in sustenance is of cardinal significance. Lateral flow assays utilizing colorimetric methodologies adequately fulfill the prerequisites of point-of-care diagnostics, however, their detection threshold remains elevated, generally permitting only qualitative discernment, an impediment to the preliminary screening of nascent pathogens. In response to this conundrum, we propose a lateral flow diagnostic predicated upon a streptavidin-biotin amplification system with recombinase polymerase amplification engineered for the expeditious and quantitative discernment of Salmonella enteritidis. Trace nucleic acids within a sample undergo exponential amplification via recombinase polymerase amplification to a level discernable, constituting the initial signal amplification. Subsequently, along the test line (T-line) of the lateral flow strip, the chromatic signal undergoes augmentation by securing a greater quantity of AuNPs through the magnification capacity of the streptavidin-biotin mechanism, affecting the second signal amplification. Quantitative results are procured via smartphone capture and transferred to computer software for precise calculation of the targeted quantity. The lateral flow strip exhibits a LOD at 19.41â CFU/mL for cultured S. enteritidis. The RSD of three varying concentrations were respectively 3.74 %, 5.96 %, and 4.25 %.
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Nanopartículas Metálicas , Salmonella enteritidis , Salmonella enteritidis/genética , Biotina , Estreptavidina , Recombinases , Ouro , Nucleotidiltransferases , Técnicas de Amplificação de Ácido Nucleico/métodos , Sensibilidade e EspecificidadeRESUMO
A vector optical field with inhomogeneous spatial polarization distribution offers what we believe to be a new paradigm to form controllable filaments. However, it is challenging to steer multiple performances (e.g. number, orientation, and interval) of filaments in transparent nonlinear media at one time. Herein, we theoretically self-design and generate a kind of believed to be novel ellipticity and orientation co-variant vector optical field to interact with Kerr medium to solve this issue. The collapsing behaviors of such a new hybrid vector optical field reveal that, by judiciously adjusting the inherent topological charge and initial phase of incident optical field, we are able to give access to stable collapsing filamentation with tunable numbers, orientations and interval. Additionally, the collapsing patterns presented are immune nearly to the extra random noise. The relevant mechanism behind the collapse of the vector optical field is elucidated as well. The findings in this work may have huge potential in optical signal processing, laser machining, and other related applications.
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Deficiency of adenosine deaminase 2 (DADA2) is a monogenic disease caused by biallelic mutations in adenosine deaminase 2 (ADA2). The varying phenotypes of the disease often lead to delayed diagnosis or misdiagnosis. We report an 11-year-old boy with DADA2 and provide a preliminary analysis of genotype-phenotype correlation. The age of onset of the disease was 8 years old. The disease successively involved the brainstem, muscles, joints, and cerebrum. After three relapse-remission episodes over 3 years, the patient was finally diagnosed with DADA2 by whole-exome sequencing. Compound heterozygous variants in the ADA2 gene (NM_001282225.2: c.1072G>A, p.Gly358Arg; c.419dupC, p.Arg141Lysfs*37) were found in the patient. He did not receive anti-TNF therapy and had no relapse after a 8-month follow-up. We identified a novel variant of the ADA2 gene, and the associated disease course may follow a relapse-remission pattern. Homozygous mutations of p.Gly358Arg can cause pure red cell aplasia, whereas compound heterozygous variations may lead to different phenotypes. Variants in the catalytic domain and frameshift mutations may also cause relatively benign phenotypes besides causing hematological disorders. Further studies are needed to clarify the genotypic-phenotypic relationship of this disease.
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Adenosina Desaminase , Estudos de Associação Genética , Doenças Hereditárias Autoinflamatórias , Peptídeos e Proteínas de Sinalização Intercelular , Mutação , Humanos , Adenosina Desaminase/genética , Adenosina Desaminase/deficiência , Masculino , Criança , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/deficiência , Mutação/genética , Fenótipo , Sequenciamento do Exoma , Recidiva , GenótipoRESUMO
We combine theory and experiments to explore the kinematics and actuation of intrinsically curved folds (ICFs) in otherwise developable shells. Unlike origami folds, ICFs are not bending isometries of flat sheets, but arise via non-isometric processes (growth/moulding) or by joining sheets along curved boundaries. Experimentally, we implement both, first making joined ICFs from paper, then fabricating flat liquid crystal elastomer (LCE) sheets that morph into ICFs upon heating/swelling via programmed metric changes. Theoretically, an ICF's intrinsic geometry is defined by the geodesic curvatures on either side, κgi. Given these, and a target 3D fold-line, one can construct the entire surface isometrically, and compute the bending energy. This construction shows ICFs are bending mechanisms, with a continuous family of isometries trading fold angle against fold-line curvature. In ICFs with symmetric κgi, straightening the fold-line culminates in a fully-folded flat state that is deployable but weak, while asymmetric ICFs ultimately lock with a mechanically strong finite-angle. When unloaded, freely-hinged ICFs simply adopt the (thickness t independent) isometry that minimizes the bend energy. In contrast, in LCE ICFs a competition between flank and ridge selects a ridge curvature that, unusually, scales as t-1/7. Finally, we demonstrate how multiple ICFs can be combined in one LCE sheet, to create a versatile intrinsically curved gripper that lifts a heavy weight.
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High-power LED lighting is a crucial challenge due to the notorious thermal quenching (TQ) effect of traditional phosphors at high operating currents, which would result in poor device performance and hamper practical optoelectronic application. Herein, we demonstrate ligand engineering of a cubane- versus staircase-like [Cu4I4] conformer as a node in coordination polymers, which remarkably suppresses the TQ effect of cluster-based photoluminescence. For complex 1 (the formula [Cu4I4(bbimb)2]n) with the cubane-like [Cu4I4] conformer as a node, the metallophilicity interaction enables ultrabright triplet emission with a photoluminescence quantum yield over 82%, and the phonon-assisted detrapping process of excitons effectively suppresses the TQ effect in the wide temperature range. In contrast, the staircase-like [Cu4I4] conformer as a node in complex 2 (the formula [Cu4I4(bbtmb)2]n) exhibits a serious TQ effect over the investigated temperature. Phosphor-converted white LEDs (pc-wLEDs) were fabricated by integrating the cluster-based coordination polymers as a color converter, and their electroluminescence performances were investigated under high bias currents. The prototype pc-wLED device by incorporating the phosphor with the suppressed TQ effect exhibits a continuous rise in brightness under a high bias current of 300 mA. The results demonstrate that ligand engineering of the cluster conformer via suppressing the TQ effect proves efficient in designing an ideal color converter for high-power pc-wLED lighting.
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BACKGROUND: Due to the global increase in aging populations and changes in modern lifestyles, the prevalence of neurodegenerative diseases, cerebrovascular disorders, neuropsychiatrcic conditions, and related ailments is rising, placing an increasing burden on the global public health system. MATERIALS AND METHODS: All studies on tetramethylpyrazine (TMP) and its derivatives were obtained from reputable sources such as PubMed, Elsevier, Library Genesis, and Google Scholar. Comprehensive data on TMP and its derivatives was meticulously compiled. RESULTS: This comprehensive analysis explains the neuroprotective effects demonstrated by TMP and its derivatives in diseases of the central nervous system. These compounds exert their influence on various targets and signaling pathways, playing crucial roles in the development of various central nervous system diseases. Their multifaceted mechanisms include inhibiting oxidative damage, inflammation, cell apoptosis, calcium overload, glutamate excitotoxicity, and acetylcholinesterase activity. CONCLUSION: This review provides a brief summary of the most recent advancements in research on TMP and its derivatives in the context of central nervous system diseases. It involves synthesizing analogs of TMP and evaluating their effectiveness in models of central nervous system diseases. The ultimate goal is to facilitate the practical application of TMP and its derivatives in the future treatment of central nervous system diseases.
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Doenças do Sistema Nervoso Central , Neuroproteção , Humanos , Acetilcolinesterase , Doenças do Sistema Nervoso Central/tratamento farmacológico , Pirazinas/farmacologia , Pirazinas/uso terapêuticoRESUMO
OBJECTIVE: Robot-assisted technology has been gradually applied to pedicle screw placement in spinal surgery. This study was designed to detailedly evaluate the learning curve of junior surgeons in robot-assisted spine surgery. METHODS: From December 2020 to February 2022, 199 patients requiring surgical treatment with posterior pedicle screw fixation were prospectively recruited into the study. The patients were randomized to the robot-assisted group (the RA group) or the conventional freehand group (the CF group). Under the senior specialist's supervision, pedicle screws were placed by two junior fellows without prior experience. Cumulative summation (CUSUM) analysis was performed on the learning curve of pedicle screw placement for performing quantitative assessment based on the time of screw insertion. RESULTS: In total, 769 and 788 pedicle screws were placed in the RA and CF groups. Compared with the CF group, the learning duration in the RA group was shorter in the upper thoracic region (57 vs. 70 screws), but longer in the lower thoracic (62 vs. 58 screws) and the lumbosacral region (56 vs. 48 screws). The slope of learning curve was lower in the RA group than in the CF group. The screw accuracy in the RA group was superior to that in the CF group, especially in upper thoracic region (89.4% vs. 76.7%, P < 0.001). This disparity of accuracy became wider in deformity cases. In the upper thoracic region, the mean placement time was 5.34 ± 1.96 min in the RA group and 5.52 ± 2.43 min in the CF groups, while in the lower thoracic and lumbosacral regions, the CF group's mean placement times were statistically shorter. Three screw-related neural complications occurred in the CF group. CONCLUSION: Robot-assisted technique has its advantages in the upper thoracic region and deformity cases, which is easier and safer to insert pedicle screws. The robot-assisted technique allowed a short learning curve for junior surgeons and exhibited consistently excellent results even in the early application period.
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Parafusos Pediculares , Procedimentos Cirúrgicos Robóticos , Robótica , Fusão Vertebral , Cirurgiões , Humanos , Estudos de Coortes , Curva de Aprendizado , Procedimentos Cirúrgicos Robóticos/métodos , Fusão Vertebral/métodos , Estudos RetrospectivosRESUMO
This is an acoustic and articulatory study of the two rhotic schwas in Southwestern Mandarin (SWM), i.e., the er-suffix (a functional morpheme) and the rhotic schwa phoneme. Electromagnetic Articulography (EMA) and ultrasound results from 10 speakers show that the two rhotic schwas were both produced exclusively with the bunching of the tongue body. No retroflex versions of the two rhotic schwas were found, nor was retraction of the tongue root into the pharynx observed. On the other hand, the er-suffix and the rhotic schwa, though homophonous, significantly differ in certain types of acoustic and articulatory measurements. In particular, more pronounced lip protrusion is involved in the production of the rhotic schwa phoneme than in the er-suffix. It is equally remarkable that contrast preservation is not an issue because the two rhotic schwas are in complementary distribution. Taken together, the present results suggest that while morphologically-induced phonetic variation can be observed in articulation, gestural economy may act to constrain articulatory variability, resulting in the absence of retroflex tongue variants in the two rhotic schwas, the only two remaining r-colored sounds in SWM.
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Acústica , Laringe , Humanos , Acústica da Fala , Fonética , LínguaRESUMO
Objective: To examine the characteristics of the prevalence of congenital cleft lip with/without cleft palate in the ethnic Tibetan population and to provide support for the precise prevention and treatment of cleft lip with/without cleft palate in the Tibetan population. Methods: The clinical data of Tibetan patients with cleft lip with/without cleft palate were collected and the clinical characteristics of the patients were analyzed. The patients' age ranged from 2 months to 51 years old. All the subjects were admitted to West China Stomatology Hospital, Sichuan University for the treatment of cleft lip with/without cleft palate between January 2016 and August 2023. Most of the subjects came from Sichuan Province and the Tibet Autonomous Region. Results: A total of 1051 patients were enrolled and children aged under 12 months (460 cases) accounted for the largest proportion. Among the subjects, 383 had cleft lip only (36.44%), 140 had cleft palate only (13.32%), and 528 had cleft lip with cleft palate (50.24%). The male-to-female ratios of patients with cleft lip only (0.99â¶1), cleft palate only (0.54â¶1), and cleft lip with cleft palate (1.67â¶1) exhibited significant differences (P<0.001). However, there was no significant difference in the male-to-female ratio in patients with cleft lip only or those with cleft lip with cleft palate when the subjects were divided into two groups according to whether they had unilateral or bilateral cleft lip with/without cleft palate. Most of the patients with bilateral cleft lip were female, while most of the patients with unilateral cleft lip and unilateral or bilateral cleft lip with cleft palate were male. The unilateral cleft lip with/without cleft palate was located predominantly on the left side. Syndromic cleft lip with/without cleft palate accounted for 3.43% of all the cases and the most common concomitant deformity was congenital heart disease. 3.81% (40 cases) of the patients had a family history. In the patients with cleft lip only and those with cleft palate only, the proportion of patients having parents with corresponding phenotypes was higher than those of other phenotypes of cleft lip with/without cleft palate. Regarding the birth time distribution of the children with cleft lip with/without cleft palate, Spring saw the highest number of births of these children (311 cases, 29.59%), while Winter saw the lowest number of births (231 cases, 21.98%). Conclusion: The cases of cleft lip with/without cleft palate in the ethnic Tibetan population are predominantly cleft lip and palate. Unilateral cleft lip only or cleft lip with palate is predominantly located on the left side. Lip disease phenotypes may be more heritable.
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Fenda Labial , Fissura Palatina , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Fenda Labial/epidemiologia , Fenda Labial/complicações , Fissura Palatina/epidemiologia , Etnicidade , Prevalência , Tibet/epidemiologiaRESUMO
Objective: Congenital cleft lip and palate is a common birth defect that seriously affects the lives of the afflicted children and their families. Previously, no research has been done to investigate the pathogenic characteristics of cleft lip and palate among ethnic minorities, for example, Tibetans, a minority ethnic group with a large population in China. This study aims to investigate the relationship between the occurrence of cleft lip and palate in Tibetans and Han Chinese in western China and the distribution of ABO blood groups and Rh blood groups to provide a theoretical basis for the precise prevention and treatment of cleft lip and palate. Methods: In this study, statistics on Tibetan patients with cleft lip and palate, some Han patients with cleft lip and palate, and normal controls from western China were retrospectively collected. All participants were patients from West China Stomatology Hospital, Sichuan University. All patients with cleft lip and palate received treatment at the hospital between January 2016 and September 2023. The normal controls were outpatients or inpatients who did not have cleft lip and palate, and who received treatment at the hospital between January 2020 and October 2023. Information on the A, B, O, and AB blood groups and Rh positive and negative blood groups of the patients was collected and compared with that of the normal controls. The incidence of different phenotypes, including cleft lip alone, cleft palate alone, and cleft lip with cleft palate, in patients of blood groups A, B, O and AB were statistically analyzed by Chi-square test. Results: A total of 1227 Tibetan patients with cleft lip and palate, 4064 Han patients with cleft lip and palate, and 5360 normal controls were included in the study. Among all the patients with cleft lip and palate, 1863 had cleft lip alone, 1425 had cleft palate alone, and 2003 had cleft lip with cleft palate. The ABO blood group distribution of Tibetan patients with cleft lip and palate was characterized as O>B>A>AB, with Rh positive blood group accounting for 100%, blood type O accounting for 41.15%, and blood type B accounting for 30.64%. The blood group distribution of the Han patients with cleft lip and palate was characterized as O>A>B>AB, with Rh positive blood group accounting for 99.58%, blood type O accounting for 35.78%, and type A accounting for 30.54%. There was a significant difference in ABO blood groups between Tibetan and Han patients with cleft lip and palate (P<0.005), but no significant difference in Rh blood groups. The ABO blood group distribution of the Tibetan patients with cleft lip and palate showed an obvious difference from that of the control group, while those of the Han patients with cleft lip and cleft palate and the control group did not show obvious differences. In the analysis of the subtypes, it was found that the blood group distribution in the subtypes of cleft lip alone, cleft palate alone, and cleft lip with cleft palate in the Tibetan population was O>B>A>AB, while that in the Han Chinese population was O>A>B>AB. There were differences in blood group distribution between Tibetans and Hans of the subtypes of cleft lip alone and cleft lip with cleft palate (P<0.001), but there was no difference in blood group distribution in the population of cleft palate-only subtype. The proportion of blood type O in Tibetan patients with cleft lip and palate was significantly higher than that in the Han patients with cleft lip and palate. The blood group distribution of Tibetan patients with cleft lip and palate in Sichuan Province, Xizang Autonomous Region, and Qinghai Province was always O>B>A>AB. Tibetan patients from Shiqu County and Baiyu County, Ganzi Tibetan Autonomous Prefecture and Chaya County, Qamdo City were predominantly of blood type B, and those from other regions were mainly of blood type O. Conclusion: There were significant differences in the phenotype composition and ABO blood group distribution between the Tibetan and Han populations with cleft lip and palate in western China. The distribution of blood group O in the population with cleft lip and palate was higher than that in the normal population, and the same trend was observed for different phenotypes. However, differences between Tibetan and Han populations in ABO blood group distribution were only found in the phenotypes of cleft lip only and cleft lip with palate. Tibetans with blood type O are more prone to cleft lip deformity than Han people, and the effect in the phenotype of cleft lip with palate is less pronounced than that in the phenotype of cleft lip only.
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Sistema ABO de Grupos Sanguíneos , Fenda Labial , Fissura Palatina , Sistema do Grupo Sanguíneo Rh-Hr , Centros de Atenção Terciária , Humanos , Fenda Labial/sangue , Fissura Palatina/sangue , Tibet/epidemiologia , China/epidemiologia , Estudos Retrospectivos , Centros de Atenção Terciária/estatística & dados numéricos , Feminino , Masculino , Etnicidade , Povo Asiático , CriançaRESUMO
The first total syntheses of polycyclic diterpenes phomopsene (1), methyl phomopsenonate (2), and iso-phomopsene (3) have been accomplished through the unusual cascade reorganization of C-C single bonds. This approach features: (i) a synergistic Nazarov cyclization/double ring expansions in one-step, developed by authors, to rapid and stereospecific construction of the 5/5/5/5 tetraquinane scaffold bearing contiguous quaternary centers and (ii) a one-pot strategic ring expansion through Beckmann fragmentation/recombination to efficiently assemble the requisite 5/5/6/5 tetracyclic skeleton of the target molecules 1-3. This work enables us to determine that the correct structure of iso-phomopsene is, in fact, the C7 epimer of the originally assigned structure. Finally, the absolute configurations of three target molecules were confirmed through enantioselective synthesis.
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All-solid-state sodium metal batteries paired with solid polymer electrolytes (SPEs) are considered a promising candidate for high energy-density, low-cost, and high-safety energy storage systems. However, the low ionic conductivity and inferior interfacial stability with Na metal anode of SPEs severely hinder their practical applications. Herein, an anion-trapping 3D fiber network enhanced polymer electrolyte (ATFPE) is developed by infusing poly(ethylene oxide) matrix into an electrostatic spun fiber framework loading with an orderly arranged metal-organic framework (MOF). The 3D continuous channel provides a fast Na+ transport path leading to high ionic conductivity, and simultaneously the rich coordinated unsaturated cation sites exposed on MOF can effectively trap anions, thus regulating Na+ concentration distribution for constructing stable electrolyte/Na anode interface. Based on such advantages, the ATFPE exhibits high ionic conductivity and considerable Na+ transference number, as well as enhanced interfacial stability. Consequently, Na/Na symmetric cells using this ATFPE possess cyclability over 600 h at 0.1 mA cm-2 without discernable Na dendrites. Cooperated with Na3 V2 (PO4 )3 cathode, the all-solid-state sodium metal batteries (ASSMBs) demonstrate significantly improved rate and cycle performances, delivering a high discharge capacity of 117.5 mAh g-1 under 0.1 C and rendering high capacity retention of 78.2% after 1000 cycles even at 1 C.