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The spatial layout and arrangement of obstacles in the built environment significantly affect its evacuation performance. However, few researchers focus on pedestrian simulation-based design optimization of built environment under emergency evacuation conditions. In this paper, we aim to evaluate the evacuation performance of optimized design solutions for traffic space in the teaching building of a primary school based on a pedestrian simulation approach and to quantify the effect of design parameters on evacuation time. Firstly, the level of traffic space design parameters was determined and optimized design solutions for the traffic space of the school building were generated. Secondly, based on the Anylogic simulation platform, the environment module and pedestrian evacuation behaviour rules of the teaching building were built to realize the evacuation behaviour simulation. Thirdly, the effect of the traffic space design parameters on the evacuation time of the teaching building was evaluated and the most significant design parameters were identified. Finally, the optimal combination of traffic space design parameters was proposed under evacuation performance orientation. The results show that the sensitivity of the traffic space design parameters to evacuation time is 31.85%. The effect of corridor width on evacuation time is 49.06 times greater than the staircase width. The optimal design combination for the traffic space in the teaching building of the primary school is a 3.0 m wide trapezoidal corridor combined with a 3.6 m wide staircase, and a 3.0 m wide fish maw corridor combined with 3.6 m wide staircase, guided by evacuation performance. The framework developed in this paper provides technical support for the development of evacuation performance-oriented design optimization of the built environment, and the results are intended to supplement the building design specifications.

A local long-lived convective system developed at midnight over inland South China, producing record-breaking rainfall in Guangzhou on 7 May 2017. This study examines the physical processes responsible for nocturnal convection initiation (CI) and growth. Observational analyses show that the CI occurs in the warm sector under weakly forced synoptic conditions at 500 hPa, while moderate but nocturnally enhanced low-level southeasterlies with a mesoscale moist tongue at 925 hPa intrude inland from the northern South China Sea. Convection-permitting model results show that mesoscale low-level convergence and increased moisture at the leading edge of the southeasterlies are favorable for CI dynamically and thermodynamically. Local ascent and potential instability are further enhanced by orographic lifting and warm moist air from the urban surface, respectively, which trigger convection in northern Guangzhou. The mesoscale moist tongue of southeasterly flows then meets convectively generated outflows, thereby maintaining strong updrafts and continuously triggering back-building convective cells in eastern Guangzhou. Sensitivity tests are conducted to estimate the relative roles of ambient southeasterly moist tongue and urban thermal effects. The southeasterly moist tongue provides moisture that is crucial for CI, while warm moist air from the urban surface is lifted at the leading edge of the southeasterlies and locally facilitates convection. Therefore, the mesoscale processes of lifting and moistening due to nocturnal southeasterlies and their strong interaction with the local factors (orographic lifting, urban heating, and cold-pool-related ascent) provide the sustained lifting and instability crucial for triggering the local long-lived convective systems. The multiscale processes shed light on the understanding of the nocturnal warm-sector heavy rainfall inland.

The TDP-43 proteinopathies, which include amyotrophic lateral sclerosis and frontotemporal dementia, are a devastating group of neurodegenerative disorders that are characterized by the mislocalization and aggregation of TDP-43. Here we demonstrate that RNA-targeting CRISPR effector proteins, a programmable class of gene silencing agents that includes the Cas13 family of enzymes and Cas7-11, can be used to mitigate TDP-43 pathology when programmed to target ataxin-2, a modifier of TDP-43-associated toxicity. In addition to inhibiting the aggregation and transit of TDP-43 to stress granules, we find that thein vivodelivery of an ataxin-2-targeting Cas13 system to a mouse model of TDP-43 proteinopathy improved functional deficits, extended survival, and reduced the severity of neuropathological hallmarks. Further, we benchmark RNA-targeting CRISPR platforms against ataxin-2 and find that high-fidelity forms of Cas13 possess improved transcriptome-wide specificity compared to Cas7-11 and a first-generation effector. Our results demonstrate the potential of CRISPR technology for TDP-43 proteinopathies.

The risk of early recurrent events after stroke remains high despite currently established secondary prevention strategies. Risk is particularly high in patients with atherosclerosis, with more than 10% of patients experiencing early recurrent events. However, despite the enormous medical burden of this clinical phenomenon, the underlying mechanisms leading to increased vascular risk and recurrent stroke are largely unknown. Here, using a novel mouse model of stroke-induced recurrent ischemia, we show that stroke leads to activation of the AIM2 inflammasome in vulnerable atherosclerotic plaques via an increase of circulating cell-free DNA from the ischemic tissue. Enhanced plaque inflammation post-stroke results in plaque destabilization and atherothrombosis, finally leading to arterio-arterial embolism and recurrent stroke within days after the index stroke. We confirm key steps of plaque destabilization also after experimental myocardial infarction and in carotid artery plaque samples from patients with acute stroke. Neutralization of cell-free DNA by DNase treatment or inhibition of inflammasome activation reduced the rate of stroke recurrence after experimental stroke. Our findings present an explanation for the high recurrence rate after incident ischemic events in atherosclerotic patients. The detailed mechanisms uncovered here provide so far clinically uncharted therapeutic targets for which we show high efficacy to prevent recurrent events. Targeting DNA-mediated inflammasome activation after remote tissue injury represents a promising avenue for further clinical development in the prevention of early recurrent events.

The binary polyhydrides of heavy rare earth lutetium that shares a similar valence electron configuration to lanthanum have been experimentally discovered to be superconductive. The lutetium polyhydrides were successfully synthesized at high pressure and high temperature conditions using a diamond anvil cell in combinations with the in-situ high pressure laser heating technique. The resistance measurements as a function of temperature were performed at the same pressure of synthesis in order to study the transitions of superconductivity (SC). The superconducting transition with a maximum onset temperature (Tc) 71 K was observed at pressure of 218 GPa in the experiments. The Tc decreased to 65 K when pressure was at 181 GPa. From the evolution of SC at applied magnetic fields, the upper critical field at zero temperature {\mu}0Hc2(0) was obtained to be ~36 Tesla. The in-situ high pressure X-ray diffraction experiments imply that the high Tc SC should arise from the Lu4H23 phase with Pm-3n symmetry that forms a new type of hydrogen cage framework different from those reported for previous light rare earth polyhydride superconductors.

Xiaolong Tang,1,2,* YingYing Guo,2,* Sijia Zhang,2 Xin Wang,2 Yuhao Teng,3 Qingjiang Jin,2 Qinglei Jin,2 Wei Shen,2,* Ruiping Wang1,3,* 1The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 2Department of Oncology, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, Jiangsu, People’s Republic of China; 3Department of Oncology, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Shen, Department of Oncology, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, 39 Xiashatang Road, Wuzhong District, Suzhou, Jiangsu, People’s Republic of China, Email sw196611@163.com Ruiping Wang, Department of Oncology, the Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Qinhuai District, Nanjing, Jiangsu, People’s Republic of China, Tel +13815883181, Email ruipingwang61@hotmail.comPurpose: Solanine is the main component of the plant Solanum, which has been shown to provide growth-limiting activities in a variety of human cancers. However, little is known about its function in gastric cancer (GC).Methods: We investigated the effect of solanine on GC in vivo and in vitro. The inhibition rate of solanine on the tumor was observed by constructing a subcutaneous tumor in nude mice. Morphological changes were analyzed with H&E staining. The expression of ATF4 was detected by IF analysis. MTT assays, EdU staining, and colony formation assays were used to detect the inhibition rate of solanine on GC cells. Matrigel transwells were used to detect the invasion of GC cells. Cell migration was measured using the wound healing assay. The flow cytometric analysis was used to monitor changes in the cell cycle and cell apoptosis. Western blotting was used to detect major proteins in cells and tumors.Results: Solanine suppressed gastric tumorigenesis. Solanine also inhibited the proliferation, invasion and mitigation of GC cells, and induced cell cycle arrest and apoptosis in vitro. Moreover, the growth-limiting activities of solanine in gastric cancer were related to the suppression of the AAMDC/MYC/ATF4/Sesn2 pathway-mediated autophagy. Overexpression of AAMDC reversed the inhibitory effect of solanine on autophagy and gastric cancer.Conclusion: In summary, our findings indicate that solanine confers growth-limiting activities by deactivating the AAMDC-regulated autophagy in gastric cancer.Keywords: gastric cancer, autophagy, AAMDC, solanine

BACKGROUND: Sacubitril/valsartan has been approved for the management of heart failure (HF) with reduced ejection fraction in adults. PANORAMA-HF trial (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF) investigated its effects on clinical outcomes in pediatric patients with HF. METHODS: PANORAMA-HF is a multicenter, Phase II/III study using an adaptive, seamless, 2-part design. The study aimed to evaluate the pharmacokinetics and pharmacodynamics of single doses of sacubitril/valsartan (Part 1), and the efficacy and safety of sacubitril/valsartan versus enalapril administered twice daily for 52 weeks (Part 2) in pediatric patients with HF due to left ventricular systolic dysfunction with biventricular heart physiology. An innovative trial design using a novel global rank assessment of severity was employed. For analysis, eligible patients were stratified into 3 age groups (Group 1, 6 to RESULTS: We report the key demographic, baseline, and clinical characteristics of 375 pediatric patients randomized to receive the study medication. The mean age for patients in Groups 1, 2a, and 3a was 12.2, 3.2, and 1.3 years, respectively. About 70% of patients had a prior HF hospitalization, 85% had New York Heart Association/Ross class I/II HF, and ≈8% were angiotensin-converting enzyme inhibitor/angiotensin receptor blocker naïve. CONCLUSIONS: Compared to other pediatric HF studies, PANORAMA-HF recruited a relatively homogeneous pediatric HF population across 3 age groups, enabling a more robust evaluation of pharmacokinetics/pharmacodynamics and efficacy/safety of sacubitril/valsartan. Most patients had mildly symptomatic HF at baseline. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02678312.

Thymomas and thymic carcinomas are rare and primary tumors of the mediastinum which is derived from the thymic epithelium. Thymomas are the most common primary anterior mediastinal tumor, while ectopic thymomas are rarer. Mutational profiles of ectopic thymomas may help expand our understanding of the occurrence and treatment options of these tumors. In this report, we sought to elucidate the mutational profiles of two ectopic thymoma nodules to gain deeper understanding of the molecular genetic information of this rare tumor and to provide guidance treatment options. We presented a case of 62-year-old male patient with a postoperative pathological diagnosis of type A mediastinal thymoma and ectopic pulmonary thymoma. After mediastinal lesion resection and thoracoscopic lung wedge resection, the mediastinal thymoma was completely removed, and the patient recovered from the surgery and no recurrence was found by examination until now. Whole exome sequencing was performed on both mediastinal thymoma and ectopic pulmonary thymoma tissue samples of the patient and clonal evolution analysis were further conducted to analyze the genetic characteristics. We identified eight gene mutations that were co-mutated in both lesions. Consistent with a previous exome sequencing analysis of thymic epithelial tumor, HRAS was also observed in both mediastinal lesion and lung lesion tissues. We also evaluated the intratumor heterogeneity of non-silent mutations. The results showed that the mediastinal lesion tissue has higher degree of heterogeneity and the lung lesion tissue has relatively low amount of variant heterogeneity in the detected variants. Through pathology and genomics sequencing detection, we initially revealed the genetic differences between mediastinal thymoma and ectopic thymoma, and clonal evolution analysis showed that these two lesions originated from multi-ancestral regions.

This study aims to understand the epidemiological characteristics of SARS-CoV-2 infection in the paediatric population during the outbreak of the Omicron variant in Shanghai. We retrospectively analysed the population-based epidemiological characteristics and clinical outcome of SARS-CoV-2 Omicron variant infection in children in Minhang District, Shanghai, based on the citywide surveillance system during the outbreak period in 2022 (March to May). During this time, a total of 63,969 cases of SARS-CoV-2 infection were notified in Minhang District, out of which 4,652 (7.3%) were children and adolescents

The culture medium plays an important role in embryonic development and subsequent pregnancy outcomes of in vitro fertilization (IVF) cycles. The sequential culture media of Vitrolife and Cook are the two most commonly used reagents in China. This study aimed to assess their effects on IVF success rates, obstetric outcomes and neonatal outcomes.This was a retrospective cohort study on 6352 patients undergoing first IVF attempts between January 2018 and December 2019, resulting in 3153 clinical pregnancies, 2646 live births, and 2668 babies. Patients were grouped according to the culture media they used. There were 4680 patients in the Vitrolife group and 1672 patients in the Cook group. The primary outcome measures were maternal and neonatal outcomes. ANOVA and Chi-square tests were used for statistical comparison, and multivariate logistic regression and multivariate general linear model were used to adjust for potential confounders.The rates of live birth, clinical pregnancy, monozygotic twins, miscarriage, and ectopic pregnancy were all comparable between the groups of Vitrolife and Cook. The incidence of placenta previa was higher in the Vitrolife group [4.86 vs. 3.09%, adjusted odds ratio = 2.048 (1.146-3.657)]. The incidence of macrosomia was higher in the Cook group [7.51 vs. 5.39%, adjusted odds ratio = 1.445 (1.010-2.069)].The culture media of Vitrolife and Cook are comparably effective in IVF success. Vitrolife is associated with a higher risk of placenta previa, while Cook is associated with a higher risk of macrosomia.

A novel hydrophilic porous biocomposite was fabricated by incorporating graphene oxide (GO) @chitosan (CS) foam substrate (GO@CS@ZIF-8 foam) with ZIF-8 crystals in situ via a facile stirring method for simultaneous enrichment of glycopeptides and phosphopeptides from complex biological samples. The experimental results demonstrated that GO@CS@ZIF-8 foam exhibited favorable specificity for simultaneous enrichment of N-glycopeptides and phosphopeptides under the same condition for HRP and β-casein tryptic digest mixtures. The novel material was further applied to enriching both glycopeptides and phosphopeptides simultaneously from 4 μL complex human serum, and 423 N-glycopeptides and 40 phosphopeptides corresponding to 133 glycoproteins and 29 phosphoproteins were identified, respectively.

Background and Aims: Liver fibrosis has been recognized as a significant risk factor for short-term outcomes after hepatectomy. Magnetic resonance elastography (MRE) showed higher diagnostic performance in staging liver fibrosis than other elastography modalities. This study aimed to assess the accuracy of predicting postoperative complications in patients with malignant liver tumors using liver stiffness measurement (LSM) by MRE. Methods: After a systematic review of the relevant studies, the sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and area under the curve (AUC) for the diagnosis of postoperative complications were pooled using bivariate meta-analysis. Meanwhile, the pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the effect. Heterogeneity was explored by sensitivity analysis, univariate meta-regression, and subgroup analysis. The potential publication bias was evaluated by the Deek’s funnel plot test. Results: Eight studies comprising a total of 1,154 patients that predicted postoperative outcomes as their purpose were ultimately included in the quantitative analysis. The pooled results of the meta-analysis revealed that the pooled sensitivity, specificity, and AUC were 78% (95% CI: 69–85%, Higgins’s inconsistency index [I2] = 43.00), 75% (95% CI: 70–80%, Higgins’s inconsistency index [I2] = 72.53), and 0.83 (95% CI: 0.80–0.86), respectively. Preoperative LSM by MRE was significantly associated with the development of overall postoperative outcomes (OR 1.78, 95% CI: 1.49–2.08). Univariate meta-regression showed that advanced fibrosis stage (≥F3), HCC patient proportion and cut-off value significantly influenced the heterogeneity of the included studies. The AUC of several novel prediction models based on LSM by MRE ranged from 0.818 to 0.911. Conclusions: In conclusion, liver stiffness measured by MRE was a significant predictor of postoperative outcomes in patients undergoing liver resection. Future studies could focus on setting a prognostic model integrated with LSM by MRE in distinguishing patients at high risk of posthepatectomy complications.

Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a rare and highly aggressive cancer with a very poor prognosis. The proper treatment decision and possible prognosis outcome for advanced LCNEC is always an enormous challenge due to its scarcity. Here, we presented a 59-year-old male patient with advanced LCNEC with a non-neuroendocrine immunophenotype who received endostar plus pembrolizumab combined with a platinum-based dual chemotherapy regime as a first-line treatment. At present, the patient’s condition is well controlled by medication only and has a progression-free survival of more than 2 years. Adverse effects recorded for this patient during treatment courses include nausea, vomiting, II–III quality bone marrow toxicity, and PD-1 blockage-related hypothyroidism. This case report discussed the feasibility of immunotherapy, anti-angiogenesis agents, and chemotherapy as a first-line therapy in advanced LCNEC.

Clean, efficient and economical separation of yttrium (Y) from heavy rare earth elements (HREEs) has always attracted attention.

Tumor nanovaccines have potential applications in the prevention and treatment of malignant tumors. However, it remains a longstanding challenge in exploiting efficient nanocarriers for inducing potent specifically cellular immune responses. Toward this objective, we herein explore an intensive tumor immunotherapeutic strategy by combining mannosylated nanovaccines and gene regulated PD-L1 blockade for immune stimulation and killing activity. Here, we fabricate a mannose modified PLL-RT (Man-PLL-RT) mediated nanovaccines with dendritic cells (DCs) targeting capacity. Man-PLL-RT is capable of co-encapsulating with antigen (ovalbumin, OVA) and adjuvant (unmethylated cytosine-phosphate-guanine, CpG) by electrostatic interaction. This positively charged Man-PLL-RT/OVA/CpG nanovaccines can facilitate the endocytosis, maturation and cross presentation in DCs. However, the nanovaccines arouse limited inhibition of tumor growth, which is mainly due to the immunosuppressed microenvironment of tumors. Combining tumor nanovaccines with gene regulated PD-L1 blockade leads to an obvious tumor remission in B16F10 melanoma bearing mice. The collaborative strategy provides essential insights to boost the benefits of tumor vaccines by regulating the checkpoint blockade with gene therapy., Graphical abstract Image 1, Highlights • The nanovaccines are composed of polypeptides, which are bio-safe and biodegradable. • The nanovaccines have APCs target function. • Blocking PD-1/PD-L1 through gene therapy can reverse the tumor immune-tolerant microenvironment. • The combined strategy provides a potentially effective strategy for the clinical treatment of tumors.

A novel super-hydrophilic hydrogel (ZIF-8/SAP) was first proposed and facilely fabricated to capture N-glycopeptides from complex biological samples with excellent selectivity and sensitivity.

Kiwifruit is an economically and nutritionally important fruit crop with extremely high contents of vitamin C. However, the previously released versions of kiwifruit genomes all have a mass of unanchored or missing regions. Here, we report a highly continuous and completely gap-free reference genome of Actinidia chinensis cv. ‘Hongyang’, named Hongyang v4.0, which is the first to achieve two de novo haploid-resolved haplotypes, HY4P and HY4A. HY4P and HY4A have a total length of 606.1 and 599.6 Mb, respectively, with almost the entire telomeres and centromeres assembled in each haplotype. In comparison with Hongyang v3.0, the integrity and contiguity of Hongyang v4.0 is markedly improved by filling all unclosed gaps and correcting some misoriented regions, resulting in ~38.6–39.5 Mb extra sequences, which might affect 4263 and 4244 protein-coding genes in HY4P and HY4A, respectively. Furthermore, our gap-free genome assembly provides the first clue for inspecting the structure and function of centromeres. Globally, centromeric regions are characterized by higher-order repeats that mainly consist of a 153-bp conserved centromere-specific monomer (Ach-CEN153) with different copy numbers among chromosomes. Functional enrichment analysis of the genes located within centromeric regions demonstrates that chromosome centromeres may not only play physical roles for linking a pair of sister chromatids, but also have genetic features for participation in the regulation of cell division. The availability of the telomere-to-telomere and gap-free Hongyang v4.0 reference genome lays a solid foundation not only for illustrating genome structure and functional genomics studies but also for facilitating kiwifruit breeding and improvement.

Aims High systolic blood pressure (HSBP), a significant public health challenge, has not been systematically studied in the elderly population in the context of global aging. Understanding the temporal trends of the disease burden associated with HSBP in the elderly population is essential to control and mitigate the harm caused by HSBP. Methods and results We used the estimated data derived from the Global Burden of Disease Study to analyse the disease burden of HSBP among the elderly population by region, sex, and temporal changes from 1990 to 2019. We found that the number of deaths due to HSBP increased to 7.86 (95% UI: 6.89–8.82) million, with an increase of 54.1%, and the number of disability-adjusted life years (DALYs) increased to 146 (95% UI: 130–162) million, with an increase of 52.4%. Conversely, the death and DALY rates of HSBP decreased by −27.0 and −27.8%, respectively. At the national and regional levels, Australasia and other high socio-demographic index regions have made significant improvements in the burden of HSBP, while it remains high in other regions of the world. Additionally, the burden of HSBP in older men is greater than that in older women. Conclusion Our findings indicate that the current prevention and control of HSBP in older adults is poor, with the total burden increasing significantly. There is an urgent need to implement feasible measures to resist HSBP and lessen the disparity of the global HSBP burden for older adults.

The genus

As the largest family within the order Saxifragales, Crassulaceae contains about 34 genera with 1400 species. Mitochondria play a critical role in cellular energy production. Since the first land plant mitogenome was reported in

In this Letter, we report that two amines can be coupled together rapidly and quantitatively through amine-thiol scrambling using a bisvinylogous thioester conjugate acceptor under mild conditions. The resulting bisvinylogous amide conjugate acceptors can be decoupled via an ethylene diamine-induced cyclization. Four representative conjugate acceptors have been utilized in the couple-decouple reactions, which were monitored and characterized by nuclear magnetic resonance, high-resolution mass spectrometry, and UV-vis spectroscopy. Further, we applied these small-molecule-based "click-declick" reactions to polymer synthesis and degradation. Highly cross-linked polymers, i.e., plastics, were quantitatively synthesized by simple reactions between commercial tris(2-aminoethyl)amine and the conjugate acceptors without solvent and any initiator or catalyst through ball milling within 60 min. Significantly, these thermosetting plastics can be degraded within 3-24 h via addition of ethylene diamine. The multiple architectures, application to plastics synthesis, and chemically triggered clean degradation to the thermosets at mild conditions with little input of energy herald a new generation of "intelligent" materials.

To improve the efficiency of nucleic acid and protein delivery by cationic polymers, there is a trade-off between increasing the positive charge density of cationic polymers and decreasing cytotoxicity. In this work, a strategy to introduce multiple interactions between the cell membrane and a delivery system based on cationic polymers was proposed. A novel delivery system consisting of PEI1.8k and an enhancer (LA-RT) was fabricated. The introduction of LA-RT contributed to multiple interactions between the delivery system and the cell membrane including electrostatic interactions, hydrogen bonding, hydrophobic interaction, and dynamic sulfur exchange reactions, which enabled efficient intracellular delivery of nucleic acids and proteins. For nucleic acid delivery, plasmid DNA and mRNA were loaded to realize CRISPR/Cas 9 gene editing

A systematic review of implementation evaluation methods in healthcare, and an institution on how to evaluate a project.

Stroke has a high incidence and is a disabling condition that can lead to severe cognitive, motor, and sensory dysfunction. In this study, we employed a drug repurposing strategy to investigate the neuroprotective effect of lomitapide on focal ischemic brain injury and explore its potential mechanism of action.Experimental cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in adult male C57BL/6 mice and simulated by oxygen-glucose deprivation in N2a-BV2 cells in co-cultivation.Lomitapide significantly increased the survival rate, reduced the neuronal tissue loss, and improved the neurological function after MCAO. Furthermore, lomitapide could increase the expression of LC3-II, reduce the expression of P62 and LAMP2, promote autophagic flux, and inhibit apoptosis by increasing and inhibiting the expression of the apoptosis-associated proteins Bcl-2 and Bax, respectively. In addition, lomitapide inhibited the migration of pro-inflammatory microglia.Lomitapide is a lipid-lowering drug, and this is the first study to explore its protective effect on ischemic nerve injury in vitro and in vivo. Our results suggest that lomitapide can be repositioned as a potential therapeutic drug for the treatment of stroke.

BackgroundThere are no widely accepted pediatric guidelines on who should undergo biopsy of the nail apparatus to screen for subungual melanoma (SUM). Reported cases of pre-adolescent children diagnosed with SUM presenting as melanonychia remain controversial. Further, observed age differences in the incidence of acral lentiginous melanoma are complicated by reported ethnic differences in adult prevalence and survival rates.MethodsWe conducted a retrospective chart review of Rady Children’s Hospital San Diego, a tertiary hospital system, with over 2 million patients in its electronic health records to identify patients diagnosed with melanonychia younger than 12 years and biopsies in these children, between January 1, 2010, and July 31, 2021.ResultsThere were 623,805 patients younger than 12 years of age seen in the outpatient setting. Average age was 7.2 years for melanonychia diagnosis, and 5.1 years for those biopsied. Nail apparatus biopsies were performed in 22 different individuals and involved the hand 17/22 (77%) and the foot 5/22 (23%). The presence of Hutchinson’s sign was documented in 9/22 (41%) patients. Males were diagnosed with melanonychia and underwent biopsy more often than females. Many of the biopsies were performed in Hispanic/Latino 11/22 (50%) and Asian/Pacific Islander 3/22 (14%) patients.DiscussionRegardless of reported ethnicity, biopsy of nail apparatus is highly unlikely to uncover invasive ALM in children younger than 12 years. Prospective studies are needed to understand how incidence of melanonychia, age, gender, and ethnicity/race influence parental and clinicians’ perceptions of melanoma risk.

The genus

Mass spectrometry (MS) data is susceptible to random noises and alternating baseline, posing great challenges to spectral peak detection, especially for weak peaks and overlapping peaks. Herein, an efficient peak detection algorithm combining continuous wavelet transform (CWT) and genetic algorithm-based threshold segmentation (denoted as WSTGA) for mass spectrometry was proposed. Firstly, Mexican Hat wavelet was selected as the mother wavelet by comparing the matching degree between the difference of Gaussian (DOG) and different wavelets. Subsequently, the ridges and valleys were identified from 2D wavelet coefficient matrix. Afterward, an improved threshold segmentation method, Otsu method based on genetic algorithm, was introduced to find optimal segmentation threshold and achieve better image segmentation, overcoming the deficiency of traditional Otsu method that cannot handle long-tailed unimodal histograms. Finally, the characteristic peaks were successfully identified by utilizing the ridge-valley lines in wavelet space and original spectrum. Receiver operating characteristic (ROC) curve, area under curve (AUC) and F₁ measure are used as criterions to evaluate performance of peak detection algorithms. Compared with multi-scale peak detection (MSPD) and CWT and image segmentation (CWT-IS) methods, all the results showed that WSTGA can achieve better peak detection. More importantly, the experimental results from MALDI-TOF spectra demonstrated that WSTGA can effectively detect more weak peaks and overlapping peaks while maintaining a lower false peak detection rate than MSPD and CWT-IS methods, indicating its great advantages in characteristic peak identification.

The mammalian Y chromosome offers a unique perspective on the male reproduction and paternal evolutionary histories. However, further understanding of the Y chromosome biology for most mammals is hindered by the lack of a Y chromosome assembly. This study presents an integrated in silico strategy for identifying and assembling the goat Y‐linked scaffolds using existing data. A total of 11.5 Mb Y‐linked sequences were clustered into 33 scaffolds, and 187 protein‐coding genes were annotated. We also identified high abundance of repetitive elements. A 5.84 Mb subset was further ordered into an assembly with the evidence from the goat radiation hybrid map (RH map). The existing whole‐genome resequencing data of 96 goats (worldwide distribution) were utilized to exploit the paternal relationships among bezoars and domestic goats. Goat paternal lineages were clearly divided into two clades (Y1 and Y2), predating the goat domestication. Demographic history analyses indicated that maternal lineages experienced a bottleneck effect around 2,000 YBP (years before present), after which goats belonging to the A haplogroup spread worldwide from the Near East. As opposed to this, paternal lineages experienced a population decline around the 10,000 YBP. The evidence from the Y chromosome suggests that male goats were not affected by the A haplogroup worldwide transmission, which implies sexually unbalanced contribution to the goat trade and population expansion in post‐Neolithic period., In this paper, we first assembled goat Y chromosome into 33 scaffolds totaling 11.5 Mb, and a subset of 5.84 Mb was further ordered into an assembly with the validation of goat radiation hybrid map. Then, we identified SNPs of 96 goat samples worldwide to exploit the paternal relationships among wild bezoars and domestic goats. The paternal lineages showed a clear division of bezoars and goats into two clades, and they were independent of goat domestication. Further demographical history of paternal and maternal lineages showed evident differences, with a bottleneck effect in mtDNA around 2,000 YBP, which may be related to the worldwide dispersal of goat in the post‐Neolithic period, implied the possibility of gender preference in goat domestication. Our research provided a new perspective of goat evolution history.

We empirically examine the initial loan announcement period of 96 zero-leverage firms listed on the FTSE 350 index. Our research demonstrates that there is a clear tendency that trades are executed at the ask price during the initial loan announcement period, which are regarded as favorable firm-level news. Similar results are observed for subsamples formed on the basis of trade size. Order flow disruption causes a bias in the calculation of returns around the company event announcement.

In this paper, the pollen morphology characteristics, chromosome karyotype characteristics, floral and fruity pigment compositions of 13 species and hybrids of Lonicera L. were analyzed by means of scanning electron microscopy, root tip squash method, HPLC-MS and GC-MS, and then they were classified separately to discuss their genetic relationship and taxonomic relationship. According to the morphological taxonomy, Lonicera L. distributed in northern are divided into two categories by whether the branchlets are hollow or not. In this experiment, Lonicera chrysanthaTurcz. ex Ledeb., Lonicera maackii (Rupr.) Maxim., Lonicera ruprechtiana Regel., Lonicera tatarica Linn. and Lonicera korolkowi ‘Zabelii’. belongsto the category of hollow branchlets; and Lonicera edulisTurcz. and Lonicera tatarinowiiMaxim. belongs to the category of branchlets with solid white pith. Through the analysis of pollen morphology characteristics, chromosome karyotype characteristics, floral and fruit pigment compositions, and using the above four indexes for clustering, Lonicera ruprechtiana Regel. and Lonicera tatarica Linn. can always be clustered together. Five hybrids such as Lonicera korolkow‘Zabelii’.×Lonicera maackii (Rupr.) Maxim., Lonicera korolkow‘Zabelii’.×Lonicera tatarica Linn.No.8 etal. can basically clustered with their parents, which is conform to the morphological taxonomy. These results indicate that the analysis of pollen morphology characteristics, chromosome karyotype characteristics, floral and fruit pigment compositions, has certain value and significance for the study of system classification and genetic relationship of Lonicera L., and the conclusions of this study partially support morphological taxonomy. Among the four clusters, the clustering result of pollen morphology characteristics was in the highest agreement with morphological taxonomy.

Vesicles, also known as "microparticles", are vesicle-like structures that are released outside the cell in a "sprouting" manner when the cytoskeleton is changed during cell activation or apoptosis, with a diameter of about 100-1000 nm, and are carriers of material information exchange between cells. Tumor-derived extracellular vesicles can effectively deliver drugs to the nucleus of tumor stem cells, thus effectively killing them without toxic side effects. The underlying mechanism involves the soft nature of tumor stem cells that allows better uptake of vesicles, and the entry of drug-carrying vesicles into lysosomes and facilitation of lysosomal movement toward the nucleus to deliver drugs to the nucleus. Drug-loaded vesicles have unique advantages, such as low immunogenicity, homing targeting ability, and the ability to break through the physiological barrier to tumor therapy. Tumor-derived drug-delivery vesicles have entered clinical trials for the treatment of malignant pleural effusions. In this review, we summarized the progress of basic and clinical research on tumor cell-derived drug-loaded vesicles for the treatment of malignant pleural effusion in recent years.