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Evidence mapping was performed to systematically search and review the clinical studies about the treatment of insomnia with Chinese patent medicines. The evidence distribution in this field was analyzed and the problems of the studies were summarized. Chinese-and English-language articles of the studies involving the Chinese patent medicines specified in three national drug catalogs for the treatment of insomnia were searched against the databases with the time interval from inception to August 2023. Figures and tables were established to present the results. Finally, 23 Chinese patent medicines were screened out, which were mentioned in 299 articles involving 236 randomized controlled trials(RCTs), 35 non-randomized controlled trials(non-RCTs), 7 retrospective studies, 17 systematic reviews/Meta-analysis, and 4 guidelines/expert recommendations or consensus. Bailemian Capsules, Wuling Capsules, and Yangxue Qingnao Granules were mentioned in a large proportion of articles. The outcome indicators included sleep rating scale, clinical response rate, safety indicators, and anxiety and depression scores. The results showed that the studies about the treatment of insomnia with Chinese patent medicines were growing. However, there was a scarcity of research evidence, and the available studies were single-center with small sample sizes and short periods. These studies spanned broad clinical scopes with inadequately emphasized advantages of TCM and insufficient outcome indicators about quality of life, follow-up, and recurrence rate. RCT exhibited a high risk of bias, and the systematic reviews/Meta-analysis demonstrated low overall quality. The retrospective studies received suboptimal scores, and the non-RCT failed to mention follow-up time, loss rate to follow-up, and sample size estimations, which compromised result reliability. It is recommended that the research protocol for Chinese patent medicines in treating insomnia should adhere to the clinical research standards of TCM. The TCM syndrome score can serves as a crucial outcome measure, and emphasis should be placed on patients' quality of life, follow-up, and recurrence prevention. Measures should be taken to enhance the accessibility and affordability of Chinese patent medicines and strengthen the connection between medical insurance policies and the policies pertaining to Chinese patent medicines. Furthermore, it is advisable to reasonably increase the inclusion of Chinese patent medicines with well-established efficacy and safety evidence in the category A list of medical insurance.
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Medicamentos Herbarios Chinos , Trastornos del Inicio y del Mantenimiento del Sueño , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Humanos , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos sin Prescripción/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
We report an H-bond donor controlled diastereoselective switchable intramolecular aza-Henry reaction of ketimines derived from α-ketoesters and 2-(2-nitroethyl)anilines, allowing facile access to chiral tetrahydroquinolines bearing an aza-quaternary carbon stereocenter, which are privileged scaffold for medicinal researches. While newly developed cinchona alkaloid derived phosphoramide-bearing quaternary ammonium salt C2 selectively give cis-adducts in up to 20:1 dr and 99% ee, the corresponding urea-bearing analogue C8 preferentially give trans-adducts in up to 20:1 dr and 99% ee.
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Plant phenology, the timing of recurrent biological events, shows key and complex response to climate warming, with consequences for ecosystem functions and services. A key challenge for predicting plant phenology under future climates is to determine whether the phenological changes will persist with more intensive and long-term warming. Here, we conducted a meta-analysis of 103 experimental warming studies around the globe to investigate the responses of four phenophases - leaf-out, first flowering, last flowering, and leaf coloring. We showed that warming advanced leaf-out and flowering but delayed leaf coloring across herbaceous and woody plants. As the magnitude of warming increased, the response of most plant phenophases gradually leveled off for herbaceous plants, while phenology responded in proportion to warming in woody plants. We also found that the experimental effects of warming on plant phenology diminished over time across all phenophases. Specifically, the rate of changes in first flowering for herbaceous species, as well as leaf-out and leaf coloring for woody species, decreased as the experimental duration extended. Together, these results suggest that the real-world impact of global warming on plant phenology will diminish over time as temperatures continue to increase.
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Silicon-stereogenic chiral organosilanes have found increasing applications in synthetic chemistry, medicinal chemistry, and materials science. In this context, various asymmetric catalytic methods have been established for the diverse synthesis of silicon-stereogenic silanes. In particular, asymmetric organocatalysis is emerging as an important and complementary synthetic tool for the enantioselective construction of silicon-stereocenters, along with the rapid development of chiral-metal catalyzed protocols. Its advent provides a powerful platform to achieve functionalized silicon-stereogenic organosilanes with structural diversity, and should lead to great development in chiral organosilicon chemistry. In this Tutorial Review, we highlight these latest achievements from two aspects: desymmetrizations of prochiral tetraorganosilanes and dynamic kinetic asymmetric transformations of racemic organosilanes by employing five organocatalytic activation modes. The advantages, limitations and synthetic value of each protocol, as well as the synthetic opportunities still open for further exploration, are also discussed.
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Despite its significant potential in various disease treatments and diagnostics, microbiotherapy is consistently plagued by multiple limitations ranging from manufacturing challenges to in vivo functionality. Inspired by the strategy involving nonproliferating yet metabolically active microorganisms, we report an intracellular gelation approach that can generate a synthetic polymer network within bacterial cells to solve these challenges. Specifically, poly(ethylene glycol dimethacrylate) (PEGDA, 700 Da) monomers are introduced into the bacterial cytosol through a single cycle of freeze-thawing followed by the initiation of intracellular free radical polymerization by UV light to create a macromolecular PEGDA gel within the bacterial cytosol. The molecular crowding resulting from intracytoplasmic gelation prohibits bacterial division and confers robust resistance to simulated gastrointestinal fluids and bile acids while retaining the ability to secrete functional proteins. Biocompatibility assessments demonstrate that the nondividing gelatinized bacteria are effective in alleviating systemic inflammation triggered by intravenous Escherichia coli injection. Furthermore, the therapeutic efficacy of gelatinized Lactobacillus rhamnosus in colitis mice provides additional support for this approach. Collectively, intracellular gelation indicates a universal strategy to manufacture next-generation live biotherapeutics for advanced microbiotherapy.
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Escherichia coli , Polietilenglicoles , Animales , Ratones , Escherichia coli/efectos de los fármacos , Polietilenglicoles/química , Geles/química , Modelos Animales de Enfermedad , Colitis/tratamiento farmacológico , Colitis/inducido químicamente , Metacrilatos/químicaRESUMEN
Transformers are widely used in computer vision areas and have achieved remarkable success. Most state-of-the-art approaches split images into regular grids and represent each grid region with a vision token. However, fixed token distribution disregards the semantic meaning of different image regions, resulting in sub-optimal performance. To address this issue, we propose the Token Clustering Transformer (TCFormer), which generates dynamic vision tokens based on semantic meaning. Our dynamic tokens possess two crucial characteristics: (1) Representing image regions with similar semantic meanings using the same vision token, even if those regions are not adjacent, and (2) concentrating on regions with valuable details and represent them using fine tokens. Through extensive experimentation across various applications, including image classification, human pose estimation, semantic segmentation, and object detection, we demonstrate the effectiveness of our TCFormer. The code and models for this work are available at https://github.com/zengwang430521/TCFormer.
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BACKGROUND: The rate of distant metastasis in patients with pancreatic neuroendocrine tumors (PNETs) is 20%-50% at the time of initial diagnosis. However, whether tumor size can predict distant metastasis for PNETs remains unknown up to date. METHODS: We used Surveillance, Epidemiology, and End Results (SEER) population-based data to collect 6089 patients with PNETs from 2010 to 2019. The optimal cut-off point of tumor size to predict distant metastasis was calculated by Youden's index. Multivariate logistic regression analysis was used to figure out the association between tumor size and distant metastasis patterns. RESULTS: The most common metastatic site was liver (27.2%), followed by bone (3.0%), lung (2.3%) and brain (0.4%). Based on an optimal cut-off value of tumor size (25.5 mm) for predicting distant metastasis determined by Youden's index, patients were categorized into groups of tumor size < 25.5 mm and ≥ 25.5 mm. Multivariate logistic regression analyses showed that, compared with < 25.5 mm, tumor size ≥ 25.5 mm was an independent risk predictor of overall distant metastasis [odds ratio (OR) = 4.491, 95% confidence interval (CI): 3.724-5.416, P < 0.001] and liver metastasis (OR = 4.686, 95% CI: 3.886-5.651, P < 0.001). CONCLUSIONS: Tumor size ≥ 25.5 mm was significantly associated with more overall distant and liver metastases. Timely identification of distant metastasis for tumor size ≥ 25.5 mm may provide survival benefit for timely and precise treatment.
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Global climate change can shape the interactions among soil microbes and, in turn, mediate ecosystem functions. However, how these interactions were regulated remains to be investigated. This study utilized 16S rRNA, ITS, and 18S rRNA high-throughput sequencing to investigate the effects of simulated warming and precipitation changes on the major components of soil micro-food webs in the Qinghai-Tibetan Plateau through a field experiment. Adonis and non-metric multidimensional scaling (NMDS) analyses showed that compositions of bacteria, fungi and protists were all affected by changes in temperature and precipitation. Correlation and cross-trophic network analyses revealed that warming and decreased precipitation, both separately and together, enhanced the relationships between bacteria and protists, especially protistan predators. We found that the modified stochasticity ratio of the bacterial community assembly was best predicted by protists. The potential functional structures of bacteria were positively correlated with protistan predators under warming and decreased precipitation condition, suggesting enhanced predator-prey relationships between protists and bacteria might further influence the potential functional characteristics of bacterial communities. Our study indicated that climate change altered bacterial compositional and functional structure via enhanced predator-prey interactions. Therefore, in the context of global climate change, broader and more comprehensive studies on protist-regulated soil bacterial and fungal communities are imperative.
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BACKGROUND: For the treatment of coronoid process fractures, medial, lateral, anterior, anteromedial, and posterior approaches have been increasingly reported; however, there is no general consensus on the method of fixation of coronal fractures. Here, we present a highly-extensile minimally invasive approach to treat coronoid process fractures using a mini-plate that can achieve anatomic reduction, stable fixation, and anterior capsular repair. Further, the study aimed to determine the complication rate of the anterior minimally invasive approach and to evaluate functional and clinical patient-reported outcomes during follow-up. METHODS: Thirty-one patients diagnosed with coronoid fractures accompanied with a "terrible triad" or posteromedial rotational instability between April 2012 and October 2018 were included in the analysis. Anatomical reduction and mini-plate fixation of coronoid fractures were performed using an anterior minimally invasive approach. Patient-reported outcomes were evaluated using the Mayo Elbow Performance Index (MEPI) score, range of motion (ROM), and the visual analog score (VAS). The time of fracture healing and complications were recorded. RESULTS: The mean follow-up time was 26.7 months (range, 14-60 months). The average time to radiological union was 3.6 ± 1.3 months. During the follow-up period, the average elbow extension was 6.8 ± 2.9° while the average flexion was 129.6 ± 4.6°. According to Morrey's criteria, 26 (81%) elbows achieved a normal desired ROM. At the last follow-up, the mean MEPI score was 98 ± 3.3 points. There were no instances of elbow instability, elbow joint stiffness, subluxation or dislocation, infection, blood vessel complications, or nerve palsy. Overall, 10 elbows (31%) experienced heterotopic ossification. CONCLUSION: An anterior minimally invasive approach allows satisfactory fixation of coronoid fractures while reducing incision complications due to over-dissection of soft tissue injuries. In addition, this incision does not compromise the soft tissue stability of the elbow joint and allows the patient a more rapid return to rehabilitation exercises.
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Placas Óseas , Articulación del Codo , Fijación Interna de Fracturas , Fracturas Conminutas , Rango del Movimiento Articular , Fracturas del Cúbito , Humanos , Masculino , Femenino , Fracturas del Cúbito/cirugía , Fracturas del Cúbito/diagnóstico por imagen , Fijación Interna de Fracturas/métodos , Fijación Interna de Fracturas/instrumentación , Persona de Mediana Edad , Adulto , Fracturas Conminutas/cirugía , Fracturas Conminutas/diagnóstico por imagen , Articulación del Codo/cirugía , Articulación del Codo/diagnóstico por imagen , Articulación del Codo/fisiopatología , Resultado del Tratamiento , Estudios Retrospectivos , Estudios de Seguimiento , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/instrumentación , Curación de Fractura , Anciano , Medición de Resultados Informados por el Paciente , Adulto JovenRESUMEN
OBJECTIVE: To investigate whether heavy metal cadmium acts as a risk factor for temporomandibular joint disorder disease and to study its pathogenic mechanism. METHODS: A total of 57 rats were allocated into 6 distinct groups, distinguished by 2 interventions: occlusal elevation and cadmium water gavage. These groups included a blank control group, occlusal elevation group, occlusal elevation + 0.42 mg/mL cadmium water gavage group, occlusal elevation + 4.2 mg/mL cadmium water gavage group, no occlusal elevation + 0.42 mg/mL cadmium water gavage group, and no occlusal elevation + 4.2 mg/mL cadmium water gavage group. The impact of cadmium exposure on cartilage oxidative stress was evaluated through the assessment of SOD, CAT, GST, and GSH-Px enzyme activities. In addition, the influence of cadmium exposure on alterations in the extracellular matrix and inflammatory mediators was examined by analyzing the expression levels of type II collagen, protein aggregation polysaccharide, glycosaminoglycan, IL1ß, IL-6, and TNF-α. Histologic examination of the condylar process cartilage of rats in the occlusal elevation + cadmium water gavage group was conducted to ascertain the occurrence of osteoarthritis. RESULTS: The variance in the expression levels of inflammatory factors did not demonstrate statistical significance between the occlusal elevation group and the blank control group; however, statistical significance was observed between the occlusal elevation + cadmium water gavage group and both the control and occlusal elevation groups. CONCLUSION: The severity of inflammation and condylar lesions correlates directly with the concentration of cadmium.
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Cerebral palsy (CP) has historically been attributed to acquired insults, but emerging research suggests that genetic variations are also important causes of CP. While microarray and whole-exome sequencing based studies have been the primary methods for establishing new CP-gene relationships and providing a genetic etiology for individual patients, the cause of their condition remains unknown for many patients with CP. Recent advancements in genomic technologies offer additional opportunities to uncover variations in human genomes, transcriptomes, and epigenomes that have previously escaped detection. In this review, we outline the use of these state-of-the-art technologies to address the molecular diagnostic challenges experienced by individuals with CP. We also explore the importance of identifying a molecular etiology whenever possible, given the potential for genomic medicine to provide opportunities to treat patients with CP in new and more precise ways.
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Parálisis Cerebral , Genómica , Humanos , Parálisis Cerebral/genética , Genómica/métodos , Predisposición Genética a la Enfermedad , Genoma Humano , Variación Genética , Secuenciación del Exoma , TranscriptomaRESUMEN
Noble gas xenon (Xe) is an excellent anesthetic gas, but its rarity, high cost and constrained production prohibits wide use in medicine. Here, we have developed a closed-circuit anesthetic Xe recovery and reusage process with highly effective CO2-specific adsorbent CUPMOF-5 that is promising to solve the anesthetic Xe supply problem. CUPMOF-5 possesses spacious cage cavities interconnected in four directions by confinement throat apertures of ~3.4â Å, which makes it an ideal molecular sieving of CO2 from Xe, O2, N2 with the benchmark selectivity and high uptake capacity of CO2. In situ single-crystal X-ray diffraction (SCXRD) and computational simulation solidly revealed the vital sieving role of the confined throat and the sorbent-sorbate induced-fit strengthening binding interaction to CO2. CUPMOF-5 can remove 5 % CO2 even from actual moist exhaled anesthetic gases, and achieves the highest Xe recovery rate (99.8 %) so far, as verified by breakthrough experiments. This endows CUPMOF-5 great potential for the on-line CO2 removal and Xe recovery from anesthetic closed-circuits.
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PURPOSE: Aging contributes significantly to cardiovascular diseases and cardiac dysfunction, leading to the upregulation of matrix metalloproteinase-9 (MMP-9) in the heart and a significant decrease in hydrogen sulfide (H2S) content, coupled with impaired cardiac diastolic function. This study explores whether supplementing exogenous hydrogen sulfide during aging ameliorates the decline in H2S concentration in the heart, suppresses MMP-9 expression, and improves the age-associated impairment in cardiac morphology and function. METHODS: We collected plasma from healthy individuals of different ages to determine the relationship between aging and H2S and MMP-9 levels through Elisa detection and liquid chromatography-tandem mass spectrometry (LC/MC) detection of plasma H2S content. Three-month-old mice were selected as the young group, while 18-month-old mice were selected as the old group, and sodium hydrosulfide (NaHS) was injected intraperitoneally from 15 months old until 18 months old as the old + NaHS group. Plasma MMP-9 content was detected using Elisa, plasma H2S content, cardiac H2S content, and cystathionine gamma-lyase (CSE) activity were detected using LC/MC, and cardiac function was detected using echocardiography. Heart structure was assessed using hematoxylin and eosin staining, Masone staining was used to detect the degree of cardiac fibrosis, while western blot was used to detect the expression of MMP-9, CSE, and aging marker proteins. Knockdown of MMP-9 and CSE in H9c2 cells using small interfering RNA was carried out to determine the upstream-downstream relationship between MMP-9 and CSE. RESULTS: H2S content in the plasma of healthy individuals decreases with escalating age, whereas MMP-9 level rises with age progression. Aging leads to a decrease in H2S levels in the heart and plasma of mice, severe impairment of cardiac diastolic function, interstitial relaxation, and fibrosis of the heart. Supplementing with exogenous H2S can improve these phenomena. CONCLUSION: H2S maintains the structure and function of the heart by inhibiting the expression of MMP-9 during the aging process.
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Enlargement of the cerebrospinal fluid (CSF)-filled brain ventricles (cerebral ventriculomegaly), the cardinal feature of congenital hydrocephalus (CH), is increasingly recognized among patients with autism spectrum disorders (ASD). KATNAL2, a member of Katanin family microtubule-severing ATPases, is a known ASD risk gene, but its roles in human brain development remain unclear. Here, we show that nonsense truncation of Katnal2 (Katnal2Δ17) in mice results in classic ciliopathy phenotypes, including impaired spermatogenesis and cerebral ventriculomegaly. In both humans and mice, KATNAL2 is highly expressed in ciliated radial glia of the fetal ventricular-subventricular zone as well as in their postnatal ependymal and neuronal progeny. The ventriculomegaly observed in Katnal2Δ17 mice is associated with disrupted primary cilia and ependymal planar cell polarity that results in impaired cilia-generated CSF flow. Further, prefrontal pyramidal neurons in ventriculomegalic Katnal2Δ17 mice exhibit decreased excitatory drive and reduced high-frequency firing. Consistent with these findings in mice, we identified rare, damaging heterozygous germline variants in KATNAL2 in five unrelated patients with neurosurgically treated CH and comorbid ASD or other neurodevelopmental disorders. Mice engineered with the orthologous ASD-associated KATNAL2 F244L missense variant recapitulated the ventriculomegaly found in human patients. Together, these data suggest KATNAL2 pathogenic variants alter intraventricular CSF homeostasis and parenchymal neuronal connectivity by disrupting microtubule dynamics in fetal radial glia and their postnatal ependymal and neuronal descendants. The results identify a molecular mechanism underlying the development of ventriculomegaly in a genetic subset of patients with ASD and may explain persistence of neurodevelopmental phenotypes in some patients with CH despite neurosurgical CSF shunting.
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Cilios , Hidrocefalia , Microtúbulos , Animales , Femenino , Humanos , Masculino , Ratones , ATPasas Asociadas con Actividades Celulares Diversas/genética , ATPasas Asociadas con Actividades Celulares Diversas/metabolismo , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/patología , Trastorno del Espectro Autista/metabolismo , Cilios/metabolismo , Cilios/patología , Epéndimo/metabolismo , Epéndimo/patología , Hidrocefalia/genética , Hidrocefalia/patología , Hidrocefalia/metabolismo , Katanina/metabolismo , Katanina/genética , Microtúbulos/metabolismo , Neuronas/metabolismo , Células Piramidales/metabolismo , Células Piramidales/patologíaRESUMEN
Metal-organic frameworks (MOFs) have emerged as attractive candidates for Li+ conducting electrolytes due to their regular channels and controllable morphology, making their presence prominent in the field of solid-state lithium batteries. However, most MOF-based electrolytes are researched at or near room temperature, which poses a challenge to their practical applications at low temperatures. Herein, a thin layer flower-shaped 2D Cu-MOF (CuBDC-10)-based solid-state electrolytes (SSEs) for lithium-ion batteries (LIBs) are developed for facilitating Li+ transport at lower temperatures, which achieve an ion conductivity of 10-4 S cm-1 at -30 °C. The CuBDC-10-based SSE exhibits outstanding ionic conductivity over a wide temperature range of -40 to 100 °C (0.073-3.68 × 10-3 S cm-1). This work provides strategies for exploring MOF-based SSEs with high ionic transport performances at low temperatures.
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Sympathetic activation is a hallmark of heart failure and the underlying mechanism remains elusive. Butyrate is generated by gut microbiota and influences numerous physiological and pathological processes in the host. The present study aims to investigate whether the intestinal metabolite butyrate reduces sympathetic activation in rats with heart failure (HF) and the underlying mechanisms involved. Sprague-Dawley rats (220â250â g) are anaesthetized with isoflurane, and the left anterior descending artery is ligated to model HF. Then, the rats are treated with or without butyrate sodium (NaB, a donor of butyrate, 10â g/L in water) for 8 weeks. Blood pressure and renal sympathetic nerve activity (RSNA) are recorded to assess sympathetic outflow. Cardiac function is improved (mean ejection fraction, 22.6%±4.8% vs 38.3%±5.3%; P<0.05), and sympathetic activation is decreased (RSNA, 36.3%±7.9% vs 23.9%±7.6%; P<0.05) in HF rats treated with NaB compared with untreated HF rats. The plasma and cerebrospinal fluid levels of norepinephrine are decreased in HF rats treated with NaB. The infusion of N-methyl-D-aspartic acid (NMDA) into the paraventricular nucleus (PVN) of the hypothalamus of HF model rats increases sympathetic nervous activity by upregulating the NMDA receptor. Microglia polarized to the M2 phenotype and inflammation are markedly attenuated in the PVN of HF model rats after NaB administration. In addition, HF model rats treated with NaB exhibit enhanced intestinal barrier function and increased levels of GPR109A, zona occludens-1 and occludin, but decreased levels of lipopolysaccharide-binding protein and zonulin. In conclusion, butyrate attenuates sympathetic activation and improves cardiac function in rats with HF. The improvements in intestinal barrier function, reductions in microglia-mediated inflammation and decreases in NMDA receptor 1 expression in the PVN are all due to the protective effects of NaB.
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Purpose: The purpose of this study was to compare the clinical and radiographic outcomes with use of short-curved stems versus standard-length single wedged stems over a minimum follow-up period of five years. Materials and Methods: A retrospective study of primary total hip arthroplasties performed using the Fitmore® stem (127 hips, 122 patients) and the M/L taper® stem (195 hips, 187 patients) between October 2012 and June 2014 was conducted. The clinical and radiographic outcomes were obtained for evaluation over a minimum follow-up period of five years. Results: In both the Fitmore® and M/L taper® groups, the mean Harris hip score improved from 52.4 and 48.9 preoperatively to 93.3 and 94.5 at the final follow-up, respectively (P=0.980). The mean Western Ontario and McMaster Universities Osteoarthritis Index scores also improved from 73.3 and 76.8 preoperatively to 22.9 and 25.6 at the final follow-up, respectively (P=0.465). Fifteen hips (Fitmore®: 14 hips; M/L taper®: one hip, P<0.001) developed intraoperative cracks and were treated simultaneously with cerclage wiring. Radiography showed a radiolucent line in 24 hips in the Fitmore® group and 12 hips in the M/L taper® group (P=0.125). Cortical hypertrophy was detected in 29 hips (Fitmore® group: 28 hips; M/L taper® group: one hip, P<0.001). Conclusion: Similarly favorable clinical and radiographic outcomes were achieved with use of both short-curved stems and standard-length single wedged stems. However, higher cortical hypertrophy and a higher rate of femoral crack were observed with use of Fitmore® stems.
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Congenital hydrocephalus (CH), characterized by cerebral ventriculomegaly, is one of the most common reasons for pediatric brain surgery. Recent studies have implicated lin-41 (lineage variant 41)/TRIM71 (tripartite motif 71) as a candidate CH risk gene, however, TRIM71 variants have not been systematically examined in a large patient cohort or conclusively linked with an OMIM syndrome. Through cross-sectional analysis of the largest assembled cohort of patients with cerebral ventriculomegaly, including neurosurgically-treated CH (totaling 2,697 parent-proband trios and 8,091 total exomes), we identified 13 protein-altering de novo variants (DNVs) in TRIM71 in unrelated children exhibiting variable ventriculomegaly, CH, developmental delay, dysmorphic features, and other structural brain defects including corpus callosum dysgenesis and white matter hypoplasia. Eight unrelated patients were found to harbor arginine variants, including two recurrent missense DNVs, at homologous positions in RPXGV motifs of different NHL domains. Seven additional patients with rare, damaging, unphased or transmitted variants of uncertain significance were also identified. NHL-domain variants of TRIM71 exhibited impaired binding to the canonical TRIM71 target CDKN1A; other variants failed to direct the subcellular localization of TRIM71 to processing bodies. Single-cell transcriptomic analysis of human embryos revealed expression of TRIM71 in early first-trimester neural stem cells of the brain. These data show TRIM71 is essential for human brain morphogenesis and that TRIM71 mutations cause a novel neurodevelopmental syndrome featuring ventriculomegaly and CH.
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The visual information regarding the road environment can influence drivers' perception and judgment, often resulting in frequent speeding incidents. Identifying speeding hotspots in cities can prevent potential speeding incidents, thereby improving traffic safety levels. We propose the Dual-Branch Contextual Dynamic-Static Feature Fusion Network based on static panoramic images and dynamically changing sequence data, aiming to capture global features in the macro scene of the area and dynamically changing information in the micro view for a more accurate urban speeding hotspot area identification. For the static branch, we propose the Multi-scale Contextual Feature Aggregation Network for learning global spatial contextual association information. In the dynamic branch, we construct the Multi-view Dynamic Feature Fusion Network to capture the dynamically changing features of a scene from a continuous sequence of street view images. Additionally, we designed the Dynamic-Static Feature Correlation Fusion Structure to correlate and fuse dynamic and static features. The experimental results show that the model has good performance, and the overall recognition accuracy reaches 99.4%. The ablation experiments show that the recognition effect after the fusion of dynamic and static features is better than that of static and dynamic branches. The proposed model also shows better performance than other deep learning models. In addition, we combine image processing methods and different Class Activation Mapping (CAM) methods to extract speeding frequency visual features from the model perception results. The results show that more accurate speeding frequency features can be obtained by using LayerCAM and GradCAM-Plus for static global scenes and dynamic local sequences, respectively. In the static global scene, the speeding frequency features are mainly concentrated on the buildings and green layout on both sides of the road, while in the dynamic scene, the speeding frequency features shift with the scene changes and are mainly concentrated on the dynamically changing transition areas of greenery, roads, and surrounding buildings. The code and model used for identifying hotspots of urban traffic accidents in this study are available for access: https://github.com/gwt-ZJU/DCDSFF-Net.