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Abstract Background This study aimed to investigate the differential expression levels of the cGAS-STING pathway in peripheral blood mononuclear cells (PBMCs) of spinal tuberculosis (TB) patients with different progression and its feasibility as a diagnostic marker. Methods Peripheral blood and medical records of 25 patients with spinal TB and 10 healthy individuals, were prospectively collected and analyzed. PBMCs and serum were extracted from peripheral blood and the expression levels of the cGAS-STING pathway in PBMCs were measured by real-time PCR (RT-PCR) and serum interferon β (IFN-β) expression levels were measured by enzyme-linked immunosorbent assay (ELISA). The expression of Interferon regulatory Factor 3 (IRF3) in PBMCs was measured using western blot. Statistical analysis was performed using the SPSS 26.0 statistical package. Results The results showed that the expression level of the TANK-binding kinase 1 (TBK1) and IRF3 was significantly higher in PBMCs (P 0.05), and the serum IFN-β concentration was elevated (P < 0.05). The calculated AUC values for TBK1 and IRF3 in PBMCs, IFN-β in serum and erythrocyte sedimentation rate (ESR) to distinguish between patients with active and stable lesions were 0.732, 0.714, 0.839, and 0.714 respectively. Conclusions The expression level of TBK1 and IRF3 in PBMCs, and IFN-β in the serum of patients with spinal TB is positively correlated with disease activity. TBK1 has higher specificity and IFN-β in serum has higher sensitivity when used to differentiate between patients with active and stable lesions.

Abstract This study aimed to assess the current status and changing trends of the disease burden of stroke and its subtypes due to low dietary fiber intake in China from 1990 to 2019. In cases of stroke and its subtypes attributable to low dietary fiber, deaths, disability-adjusted life-years (DALYs), age-standardized mortality rates (ASMR), age-standardized DALYs rates (ASDR), and percentage change were used to assess disease burden. Data were obtained from the 2019 global burden of disease study. Trends were assessed using Joinpoint regression and age-period-cohort analysis. Between 1990 and 2019, there was a declining trend in stroke and its subtypes, ASDR and ASMR, as well as the corresponding number of deaths and DALYs, due to low dietary fiber intake in China. Subarachnoid hemorrhage (SH) showed the greatest decrease, followed by intracerebral hemorrhage (IH) and ischemic stroke (IS). Local drift curves showed a U-shaped distribution of stroke, IS, and IH DALYs across the whole group and sex-based groups. For mortality, the overall and male trends were similar to those for DALYs, whereas female stroke, IH, and IS showed an upward trend. The DALYs for stroke and IH showed a clear bimodal distribution, IS showed an increasing risk with age. For mortality, the SH subtype showed a decreasing trend, whereas other subtypes showed an increasing risk with age. Both the period and cohort rates of stroke DALYs and motality due to low dietary fiber have declined. Males had a higher risk of DALYs and mortality associated with low fiber levels. The burden of stroke and its subtypes associated with a low-fiber diet in China has been declining over the past 30 years, with different patterns of change for different stroke subtypes and a higher burden for males, highlighting the differential impact of fiber intake on stroke and its subtypes.

Abstract Despite the advent of genomic sequencing, molecular diagnosis remains unsolved in approximately half of patients with Mendelian disorders, largely due to unclarified functions of noncoding regions and the difficulty in identifying complex structural variations. In this study, we map a unique form of central iris hypoplasia in a large family to 6q15-q23.3 and 18p11.31-q12.1 using a genome-wide linkage scan. Long-read sequencing reveals a balanced translocation t(6;18)(q22.31;p11.22) with intergenic breakpoints. By performing Hi-C on induced pluripotent stem cells from a patient, we identify two chromatin topologically associating domains spanning across the breakpoints. These alterations lead the ectopic chromatin interactions between APCDD1 on chromosome 18 and enhancers on chromosome 6, resulting in upregulation of APCDD1. Notably, APCDD1 is specifically localized in the iris of human eyes. Our findings demonstrate that noncoding structural variations can lead to Mendelian diseases by disrupting the 3D genome structure and resulting in altered gene expression.

Background: Femur fracture is a type of fracture with high disability and mortality. There is no comprehensive analysis and prediction of the global distribution of femur fractures, so we conducted this study. Methods: Age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), and years living with disability (YLDs) of femur fractures (excluding femoral neck) were downloaded from the Global burden of disease database. Trend analysis was performed, and 6 time-series machine learning algorithms were applied to predict the global ASIR, ASPR, and YLDs. Results: ASPR for femur fracture had been increasing in most countries worldwide from 1990 to 2019, with the highest in East Asia (AAPC = 1.25 95%Confidence Interval (1.2, 1.3)) and lowest in Central Latin America (AAPC = −0.74 95%CI (−0.81, −0.67)). However, ASIR showed a significant downward trend worldwide, with East Saharan Africa decreasing the most (AAPC = −4.04 95%CI (−5.56, −2.47)), and East Asia elevating the most (AAPC = 1.11 95%CI (0.87, 1.42)). YLDs were increasing over the world, with East Asia still elevating the most AAPC= (3.9 95%CI (3.85, 3.95)), with the only region of decrease being Eastern Europe (AAPC = −0.28 95%CI (−0.3, −0.26)). Both ASPR and ASIR were higher in women than in men in the >75 year group, whereas YLDs was lower in women than in men in the >60 year group. Globally, the ARIMA model was optimal in the prediction of ASPR, the PROPHET model effected in the prediction of ASIR, and the PROPHET WITH XGBOOST model was the best in the prediction of YLDs. The projections showed increase in both ASPR and YLDs, except for ASIR decreasing by 2030. Conclusions: Our study found a rise in femur fracture ASPR and ASIR from 1990 to 2019 in war conflict areas and East Asia, meanwhile, the YLDs of femur fracture increased in populous countries. In both 1990 and 2019, both ASPR and ASIR were higher in women over 75 years than that in men, but YLDs was higher in men over 60 years than that in women. In 2020–2030, while global femur fracture ASIR might decline, both ASPR and YLDs might rise. The Translational Potential of this article: Femur fracture is a high-energy injury due to direct violence, and in war, conflicting and underdeveloped regions such as East Asia. Accidental injuries may occur due to the rapid development of industry and the frequent traffic accidents. This study suggests that we should focus on elderly women (≥75 years) in the above regions in the future. For older men (>60 years old), more attention should be paid to post-fracture functional rehabilitation and early reintegration into society to reduce the disability rate and lower the socio-economic burden.

Abstract Hearing preservation (HP) during vestibular schwannomas (VSs) surgery poses a significant challenge. Although brainstem auditory evoked potentials (BAEPs) on the affected side are commonly employed to monitor cochlear nerve function, their low signal-to-noise ratio (SNR) renders them susceptible to interferences, compromising their reliability. We retrospectively analyzed the data of patients who underwent tumor resection, while binaural brainstem auditory evoked potentials (BAEPs) were simultaneously recorded during surgery. To standardize BAEPs on the affected side, we incorporated the synchronous healthy side as a reference (interval between affected and healthy side ≤ 3 min). A total of 127 patients were enrolled. Comparison of the raw BAEPs data pre- and post-tumor resection revealed that neither V-wave amplitude (Am-V) nor latency (La-V) could serve as reliable predictors of HP simultaneously. However, following standardization, V-wave latency (STIAS-La-V) and amplitude (STIAS-Am-V) emerged as stable predictors of HP. Furthermore, the intraoperative difference in V-wave amplitude (D-Am-V) predicted postoperative HP in patients with preoperative HP and remained predictive after standardization. The utilization of intraoperative synchronous healthy side BAEPs as a reference to eliminate interferences proves to be an effective approach in enhancing the reliability of BAEPs for predicting HP in VSs patients.

Abstract Background Postoperative central diabetes insipidus (CDI) is commonly observed in craniopharyngioma (CP) patients, and the inflammatory response plays an important role in CPs. We aimed to evaluate the predictive value of preoperative peripheral inflammatory markers and their combinations regarding CDI occurrence in CPs. Methods The clinical data including preoperative peripheral inflammatory markers of 208 CP patients who underwent surgical treatment were retrospectively collected and analyzed. The preoperative peripheral white blood cells (WBC), neutrophils, lymphocytes, monocytes, platelet (PLT), neutrophil-to-lymphocyte ratio (NLR), derived-NLR (dNLR), monocyte-to-lymphocyte ratio (MLR) and PLT-to-lymphocyte ratio (PLR) were assessed in total 208 CP patients and different age and surgical approach CP patient subgroups. Their predictive values were evaluated by the receiver operator characteristic curve analysis. Results Preoperative peripheral WBC, neutrophils, NLR, dNLR, MLR, and PLR were positively correlated and lymphocyte was negatively associated with postoperative CDI occurrence in CP patients, especially when WBC ≥ 6.66 × 109/L or lymphocyte ≤ 1.86 × 109/L. Meanwhile, multiple logistic regression analysis showed that WBC > 6.39 × 109/L in the > 18 yrs age patients, WBC > 6.88 × 109/L or lymphocytes ≤ 1.85 × 109/L in the transcranial approach patients were closely associated with the elevated incidence of postoperative CDI. Furthermore, the area under the curve obtained from the receiver operator characteristic curve analysis showed that the best predictors of inflammatory markers were the NLR in total CP patients, the MLR in the ≤ 18 yrs age group and the transsphenoidal group, the NLR in the > 18 yrs age group and the dNLR in the transcranial group. Notably, the combination index NLR + dNLR demonstrated the most valuable predictor in all groups. Conclusions Preoperative peripheral inflammatory markers, especially WBC, lymphocytes and NLR + dNLR, are promising predictors of postoperative CDI in CPs.

Objective: To explore the clinical application of submandibular endotracheal intubation in craniomaxillofacial fractures. Methods: The submandibular endotracheal intubation was used to treat 10 patients with cranio-maxillofacial fractures and contraindications to nasal intubation.Ventilator monitoring data including SPO2(oxygen saturation of blood), Freq,VT,MV,PEEP, PLAT and PEAK were monitored before and after the operation of submandibular endotracheal intubation. The technique of submandibular intubation was assessed intraoperatively and in the postoperative period. The outcomes and complications are presented. Results: The study included 10 patients aged between 18 and 63 years(6 males and 4 females). All patients had mandibular fractures, with 6 midface fractures (60 %), 5 nasal bone fractures (50 %), 6 zygomatic bone fractures (60 %). The procedure time ranged from 6 to 10 min (mean, 7.9 min). NO delayed extubation was performed in 10 cases. The technique has proved to be straightforward and satisfactory. A postoperative superficial infection occurred in 1 patients, whereas hypertrophic scars occurred in another 1 patients. Conclusion: Submandibular endotracheal intubation is a safe procedure for intraoperative airway control in maxillofacial trauma patients who present contraindication to nasotracheal intubation.

Defect detection in aluminum profiles helps to ensure product quality. However, aluminum defects suffer from variable object scales and high defect-background similarity issues. To address these issues, an improved multiscale semantic enhancement YOLOv5 defect detection method, namely CW-YOLOv5, has been proposed. First, to reduce missed defections, a cross layer link network (CLLN) is introduced into YOLOv5 to capture complete and comprehensive features during the feature extraction process. To accurately detect small-size defects, the weighted feature fusion mechanism (WFFM) is proposed to be added to shallow and high-level feature fusion networks. Finally, the soft non-maximum suppression (Soft-NMS) module is introduced into YOLOv5 to tackle the feature candidate box filtering task to reduce false and missed detections. The proposed defect detection network is applied to the public Tianchi aluminum profile defect dataset (TCAPD), and CW-YOLOv5 gain the improvement of mAP@0.5 by 2.3% compared to the baseline network. Moreover, the experimental results demonstrate that CW-YOLOv5 can effectively detect aluminum surface defects.

An efficient, cost-effective and environmentally friendly ultrasound-assisted hot water method for Imperata cylindrica polysaccharide (ICPs) extraction was developed. According to the response surface results, the optimal ultrasonic time was 85 min, ultrasonic power was 192.75 W, temperature was 90.74 °C, liquid–solid ratio was 26.1, and polysaccharide yield was 28.50 %. The polysaccharide mainly consisted of arabinose (Ara), galactose (Gal), and glucose (Glc), with a molecular weight of 62.3 kDa. Ultrasound-assisted extraction of Imperata cylindrica polysaccharide (UICP) exhibited stronger anti-oxidant activity and ability to ameliorate cellular damage due to uric acid stimulation compared with traditional hot water extraction of Imperata cylindrica polysaccharide (ICPC-b). It also exhibited higher thermal stability, indicating its potential value for applications in the food industry.

Abstract Sampling restrictions have hindered the comprehensive study of invasive non-enhancing (NE) high-grade glioma (HGG) cell populations driving tumor progression. Here, we present an integrated multi-omic analysis of spatially matched molecular and multi-parametric magnetic resonance imaging (MRI) profiling across 313 multi-regional tumor biopsies, including 111 from the NE, across 68 HGG patients. Whole exome and RNA sequencing uncover unique genomic alterations to unresectable invasive NE tumor, including subclonal events, which inform genomic models predictive of geographic evolution. Infiltrative NE tumor is alternatively enriched with tumor cells exhibiting neuronal or glycolytic/plurimetabolic cellular states, two principal transcriptomic pathway-based glioma subtypes, which respectively demonstrate abundant private mutations or enrichment in immune cell signatures. These NE phenotypes are non-invasively identified through normalized K2 imaging signatures, which discern cell size heterogeneity on dynamic susceptibility contrast (DSC)-MRI. NE tumor populations predicted to display increased cellular proliferation by mean diffusivity (MD) MRI metrics are uniquely associated with EGFR amplification and CDKN2A homozygous deletion. The biophysical mapping of infiltrative HGG potentially enables the clinical recognition of tumor subpopulations with aggressive molecular signatures driving tumor progression, thereby informing precision medicine targeting.

Abstract T-lymphocytes are prevalent in the tumor microenvironment of follicular lymphoma (FL). However, the phenotype of T-cells may vary, and the prevalence of certain T-cell subsets may influence tumor biology and patient survival. We therefore analyzed a cohort of 82 FL patients using CyTOF to determine whether specific T-cell phenotypes were associated with distinct tumor microenvironments and patient outcome. We identified four immune subgroups with differing T-cell phenotypes and the prevalence of certain T-cell subsets was associated with patient survival. Patients with increased T cells with early differentiation stage tended to have a significantly better survival than patients with increased T-cells of late differentiation stage. Specifically, CD57+ TFH cells, with a late-stage differentiation phenotype, were significantly more abundant in FL patients who had early disease progression and therefore correlated with an inferior survival. Single cell analysis (CITE-seq) revealed that CD57+ TFH cells exhibited a substantially different transcriptome from CD57− TFH cells with upregulation of inflammatory pathways, evidence of immune exhaustion and susceptibility to apoptosis. Taken together, our results show that different tumor microenvironments among FL patients are associated with variable T-cell phenotypes and an increased prevalence of CD57+ TFH cells is associated with poor patient survival.

Abstract Background N6-methyladenosine (m6A) and 5-methylcytosine (m5C) are the main RNA methylation modifications involved in the oncogenesis of cancer. However, it remains obscure whether m6A/m5C-related long non-coding RNAs (lncRNAs) affect the development and progression of low grade gliomas (LGG). Methods We summarized 926 LGG tumor samples with RNA-seq data and clinical information from The Cancer Genome Atlas and Chinese Glioma Genome Atlas. 105 normal brain samples with RNA-seq data from the Genotype Tissue Expression project were collected for control. We obtained a molecular classification cluster from the expression pattern of sreened lncRNAs. The least absolute shrinkage and selection operator Cox regression was employed to construct a m6A/m5C-related lncRNAs prognostic signature of LGG. In vitro experiments were employed to validate the biological functions of lncRNAs in our risk model. Results The expression pattern of 14 sreened highly correlated lncRNAs could cluster samples into two groups, in which various clinicopathological features and the tumor immune microenvironment were significantly distinct. The survival time of cluster 1 was significantly reduced compared with cluster 2. This prognostic signature is based on 8 m6A/m5C-related lncRNAs (GDNF-AS1, HOXA-AS3, LINC00346, LINC00664, LINC00665, MIR155HG, NEAT1, RHPN1-AS1). Patients in the high-risk group harbored shorter survival times. Immunity microenvironment analysis showed B cells, CD4 + T cells, macrophages, and myeloid-derived DC cells were significantly increased in the high-risk group. Patients in high-risk group had the worse overall survival time regardless of followed TMZ therapy or radiotherapy. All observed results from the TCGA-LGG cohort could be validated in CGGA cohort. Afterwards, LINC00664 was found to promote cell viability, invasion and migration ability of glioma cells in vitro. Conclusion Our study elucidated a prognostic prediction model of LGG by 8 m6A/m5C methylated lncRNAs and a critical lncRNA regulation function involved in LGG progression. High-risk patients have shorter survival times and a pro-tumor immune microenvironment.

The content and proportion of sugars and acids in tomato fruit directly affect its flavor quality. Previous studies have shown that 5-aminolevulinic acid (ALA) could promote fruit ripening and improve its aroma quality. In order to explore the effect of ALA on sugar and acid quality during tomato fruit development, 0, 100, and 200 mg L−1 ALA solutions were sprayed on the fruit surface 10 days after pollination of the fourth inflorescence, and the regulation of ALA on sugar, acid metabolism and flavor quality of tomato fruit was analyzed. The results showed that ALA treatment could enhance the activities of acid invertase (AI), neutral invertase (NI), and sucrose synthase (SS), reduce the activity of sucrose phosphate synthase (SPS), up-regulate the expression of SlAI, SlNI and SlSS, change the composition and content of sugar in tomato fruit at three stages, significantly increase the content of sugars in fruit, and promote the accumulation of sugars into flesh. Secondly, ALA treatments increased the activities of phosphoenolpyruvate carboxykinase (PEPC), malic enzyme (ME), and citrate synthase (CS), up-regulated the expression of SlPPC2, SlME1, and SlCS, and reduced the citric acid content at maturity stage, thereby reducing the total organic acid content. In addition, ALA could also increase the number and mass fraction of volatile components in mature tomato fruits. These results indicated that exogenous application of ALA during tomato fruit development could promote the formation of fruit aroma quality and were also conducive to the formation of fruit sugar and acid quality.

Abstract Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications.

Flavonoids and alkaloids are the major active ingredients in mulberry leaves that have outstanding medicinal value. Bacillus subtilis can effectively activate the plants defense response and regulate the plant secondary metabolism. In this study, we explored the effects of soil application of B. subtilis on the content of flavonoids and the most important alkaloids (1-deoxynojirimycin, DNJ) in mulberry leaves. Significant decreases in flavonoid content were observed in tender leaves and mature leaves after treatment with B. subtilis; at the same time, significant increases in DNJ content were observed in tender leaves. Based on widely targeted LC-MS/MS and high-throughput approaches, we screened out 904 differentially synthesized metabolites (DSMs) and 9715 differentially expressed genes (DEGs). KEGG analyses showed that these DSMs and DEGs were both significantly enriched in the biosynthesis of secondary metabolites, flavonoid synthesis and plant hormone signal transduction. Further correlation analysis of DEMs and DEGs showed that 40 key genes were involved in flavonoid biosynthesis, with 6 key genes involved in DNJ biosynthesis. The expression of CHS, CHI, F3H, F3′H, FLS, UGT and AOC significantly responded to B. subtilis soil application. This study broadens our understanding of the molecular mechanisms underlying the accumulation of flavonoids and alkaloids in mulberry leaves.

Bombyx mori silk fibroin is a natural biomacromolecule that can be assembled into nanoparticles. Manganese dioxide (MnO2) is responsive to tumor microenvironment (TME). Herein, SF and MnO2 is integrated to develop novel TME‐responsive drug carriers. Specifically, silk fibroin nanoparticles (SF‐NPs) are used as a biotemplates to regulate the nucleation and self‐assembly of MnO2 for designing the complex drug delivery (SM‐NPs). The SM‐NPs are further modified by polyethylene glycol and folic acid to improve their stability and tumor targeting. The resultant nanocarriers (SMPF‐NPs) present a raspberry‐like structure with lamellar MnO2 nanoparticles coating on its surface. The SMPF‐NPs show a high drug‐loading capability and selectively release drugs in acidic TME. Due to the catalytic activity of MnO2, the SMPF‐NPs generate high levels of oxygen under H2O2 and produce more reactive oxygen after loading Ce6. In vivo and in vitro analysis prove that SMPF‐NPs can accumulate in breast tumor tissues, efficiently kill cancer cells, and destroy breast cancer tumors by a combination of chemotherapy and photodynamic therapy (PDT). Moreover, the SMPF‐NPs also provide fluorescence and magnetic resonance (MR) imaging for guiding cancer therapy. These results suggest that the self‐assembled SF and MnO2 nanocomplex could be a novel TME‐responsive nanodrug delivery system.

Our objective was to transform the text data in migraine diagnosis and treatment guidelines into a visualized knowledge graph by using knowledge graph technology, visually display the clinical diagnosis and treatment process, and provide assistance for the standardization of diagnosis and treatment of migraine with integrative medicine.

Owing to the small size of the defect pixel area and poor defect-background contrast issues in industrial images, noise and missed detection can easily occur. Therefore, automated defect detection is both necessary and challenging. To address these issues, with parallel attention mechanism (PAM) and dual-channel spatial pyramid pooling-fast block (DC_SPPF), a novel defect detection network, namely, PDDD-Net, is proposed in this paper. First, to make the detection network emphasize small defect areas better, the PAM block is proposed to be embedded into YOLOv5 to obtain more low-level visual features and improve the detection accuracy of microdefects. Meanwhile, by fusing multi-channel features, the DC_SPPF block is proposed to replace the raw spatial pyramid pooling-fast block to acquire richer discriminative features of the defect areas. Finally, The soft non-maximum suppression (Soft-NMS) module is used to undertake the feature candidate box filtering task in YOLOv5 to reduce missed detection. Two public datasets are adopted for the model evaluation: the Tianchi aluminum profile defects dataset (APDDD) and the power line insulator dataset (CPLID). The experimental results indicate that the proposed PDDD-Net network exhibits remarkable defect detection performance compared with other related detection methods.

IntroductionRetinal degenerative or inflammatory changes may occur with hereditary immunological disorders (HID) due to variants in approximately 20 genes. This study aimed to investigate if such retinopathy may present as an initial sign of immunological disorders in eye clinic.MethodsThe variants in the 20 genes were selected from in-house exome sequencing data from 10,530 individuals with different eye conditions. Potential pathogenic variants were assessed by multistep bioinformatic analysis. Pathogenic variants were defined according to the ACMG/AMP criteria and confirmed by Sanger sequencing, co-segregation analysis, and consistency with related phenotypes. Ocular clinical data were thoroughly reviewed, especially fundus changes.ResultsA total of seven pathogenic variants in four of the 20 genes were detected in six probands from six families, including three with hemizygous nonsense variants p.(Q308*), p.(Q416*), and p.(R550*) in MSN, one with homozygous nonsense variants p.(R257*) in AIRE, one with compound heterozygous nonsense variants p.(R176*) and p.(T902*) in LAMB2, and one with a known c.1222T>C (p.W408R) heterozygous variant in CBL. Ocular presentation, as the initial signs of the diseases, was mainly retinopathy mimicking other forms of hereditary retinal degeneration, including exudative vitreoretinopathy in the three patients with MSN variants or tapetoretinal degeneration in the other three patients. Neither extraocular symptoms nor extraocular manifestations were recorded at the time of visit to our eye clinic. However, of the 19 families in the literature with retinopathy caused by variants in these four genes, only one family with an AIRE homozygous variant had retinopathy as an initial symptom, while the other 18 families had systemic abnormalities that preceded retinopathy.DiscussionThis study, for the first time, identified six unrelated patients with retinopathy as their initial and only presenting sign of HID, contrary to the previous reports where retinopathy was the accompanying sign of systemic HID. Recognizing such phenotype of HID may facilitate the clinical care of these patients. Follow-up visits to such patients and additional studies are expected to validate and confirm our findings.

Abstract A biosynthetic precursor of tetrapyrrol, 5-aminolevulinic acid (ALA), is widely used in agricultural production, as an exogenous regulatory substance that effectively regulates plant growth. Previous studies have shown that heme and chlorophyll accumulate in plants under salt stress, when treated with exogenous ALA. In this study, we explored the regulatory role of heme in plants, by spraying 25 mg L–1 ALA onto the leaves of cucumber seedlings treated with heme synthesis inhibitor (2,2'-dipyridyl, DPD) and heme scavenger (hemopexin, Hx), under 50 mmol L–1 NaCl stress. The results showed that NaCl alone and DPD + Hx treatments to cucumber seedlings subjected to salt stress adversely affected their growth, by decreasing biomass accumulation, root activity, and root morphology. In addition, these treatments induced an increase in membrane lipid oxidation, as well as enhancement of anti-oxidase activities, proline content, and glutamate betaine. However, exogenous ALA application increased the plant growth and root architecture indices under NaCl stress, owing to a lack of heme in the seedlings. In addition, cucumber seedlings treated with DPD and Hx showed inhibition of growth under salt stress, but exogenous ALA effectively improved cucumber seedling growth as well as the physiological characteristics; moreover, the regulation of ALA in plants was weakened when heme synthesis was inhibited. Heme biosynthesis and metabolism genes, HEMH and HO1, which are involved in the ALA metabolic pathway, were upregulated under salinity conditions, when ferrochelatase activity was inhibited. Application of exogenous ALA increased the heme content in the leaves. Thus, exogenous ALA may supplement the substrates for heme synthesis. These results indicated that heme plays a vital role in the response of plants to salinity stress. In conclusion, heme is involved in ALA-mediated alleviation of damage caused to cucumber seedlings and acts as a positive regulator of plant adaption.

Atomically dispersed Pt atoms encapsulated inside ZSM‐5 zeolites are synthesized via thermally induced dispersion under oxygen atmosphere. Dispersion of Pt clusters within ZSM‐5 and silicate‐1 is compared to investigate its dependence on the support and calcination temperature. Detailed density functional theory (DFT) calculations are applied to rationalize the dispersion process, which includes the detachment of Pt species from the bulk and the migration of volatile PtO x species, both of which are accelerated by thermal treatment at high temperature. DFT results also indicate that Al atoms within zeolites provide the anchoring sites to retain the dominated PtO species, though their interaction with the support is weakened with the increase in temperature. Our findings suggest that successful dispersion depends on the strong metal–support interaction and thermal treatment at moderate temperature (500 °C) which is crucial to balance the detachment and fixation of Pt atoms. This study paves the way to further understand the dispersion mechanism and assist in the development of stable single‐atom catalysts.

BackgroundSchwannomas of the trochlear nerve with the absence of systemic neurofibromatosis are considerably uncommon, especially complicated by intra-tumoral hemorrhage. Due to the lack of typical clinical manifestations and imaging findings, a definite diagnosis of trochlear schwannomas before surgery is particularly difficult.Case presentationWe report the case of a 64-year-old female patient who presented with a unilaterally intermittent headache of 2-month duration and without a remarkable neurological deficit at admission. Imaging studies revealed a well-demarcated cystic-solid lesion with mixed signals beside the brainstem and suprasellar cisterna. The patient underwent a surgical operation with total resection of the tumor by a subtemporal surgical approach. The tumor was intraoperatively found to originate from the trochlear nerve and was pathologically confirmed as a hemorrhagic schwannoma with cystic degeneration.ConclusionsWe describe this case in detail and conduct a concomitant survey of the literature, summarizing the clinical presentations, radiological features, surgical treatment, and the possible mechanisms of hemorrhage in relevance to trochlear nerve schwannoma.

The wrinkled pepper (Capsicum annuum L.) is a type of chili pepper domesticated in northwestern China, with a characteristic flavor. Fifteen wrinkled and four smooth-skinned pepper varieties were evaluated for morphology, texture, color, nutrients, capsaicinoids, and volatile compounds at the mature fruit stage. The sensory evaluation showed wrinkled pepper was superior to smooth pepper in texture, and it has a highly significant correlation (p < 0.01) with cuticle thickness, maximum penetrating force, lignin content, and moisture content. Citric acid was the major organic acid in peppers, accounting for 39.10–63.55% of the total organic acids, followed by quininic acid. The average oxalic acid content of smooth peppers was 26.19% higher than that of wrinkled peppers. The pungency of wrinkled pepper fruits ranged from 1748.9 to 25529.4 SHU, which can be considered slightly to very spicy, while the four smooth varieties ranged between 866.63 and 8533.70 SHU, at slightly to moderately spicy. A total of 199 volatile compounds were detected in the 19 pepper varieties. The average volatile content of wrinkled pepper was 39.79% higher than that of smooth pepper. Twenty-nine volatile compounds, including 14 aldehydes, four alcohols, three esters, three ketones, two furans, one pyrazine, one acid, and one phenol, contributed to the fragrance of peppers and could be regarded as aroma-active compounds, with 2-isobutyl-3-methoxypyrazine being the major contributor among the 19 pepper varieties. Wrinkled pepper can be confidently distinguished from smooth pepper and is of superior quality. The current findings outlined the major texture-related characteristics of pepper as well as the main aroma-active compounds, providing valuable information for pepper quality breeding and consumer guidelines.

As the urbanization is being rapidly boosted, the urban habitat quality has been significantly disturbed by human activities through land use, which highly affects the urban ecological environment and sustainable development of social economy. However, the change characteristics of the habitat quality and human activities in different topographic gradients in rapidly urbanized mountainous cities remain unclear. Accordingly, Guiyang in China, is selected as the representative of typical mountain cities. The change characteristics of the habitat quality, the human activity intensity and their correlation in mountainous cities from 2000 to 2020, are analyzed using the Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) model, as well as the ArcGIS software based on the remote sensing interpretation data in 2000, 2010 and 2020. The results demonstrate that the overall habitat quality in Guiyang decreased by 0.0304, while the human activity intensity increased by 0.0287 from 2000 to 2020. The amount of changes of the habitat quality and the human activity intensity in Guiyang from 2010 to 2020, are higher than those from 2000 to 2010. The amount of changes of the habitat quality and the human activity intensity in Guiyang decreases with the increase of the slope. The central and southern parts of Guiyang are the highlight areas with a significant decline of habitat quality and significant increase of human activity intensity. The areas with an increased habitat quality and decreased human activity intensity are sporadically distributed. A significant negative correlation is reported between the change of the habitat quality and human activity intensity in Guiyang. In addition, a prominent spatial heterogeneity is identified in the local indicators of the spatial association (LISA) map. The significant increase in the artificial land and the decrease in the natural land as affected by the rapid urbanization, act as crucial factors leading to the decline of the habitat quality and the increase in the human activity intensity in mountainous cities.

5-Aminolevulinic acid (ALA) plays a vital role in promoting plant growth, enhancing stress resistance, and improving fruit yield and quality. In the present study, tomato fruits were harvested at mature green stage and sprayed with 200 mg L–1 ALA on fruit surface. During ripening, the estimation of primary and secondary metabolites, carotenoids, and chlorophyll contents, and the expression levels of key genes involved in their metabolism were carried out. The results showed that ALA significantly promoted carotenoids accumulation by upregulating the gene expression levels of geranylgeranyl diphosphate synthase (GGPPS, encoding geranylgeranyl diphosphate synthase), phytoene synthase 1 (PSY1, encoding phytoene synthase), phytoene desaturase (PDS, encoding phytoene desaturase), and lycopeneβ-cyclase (LCYB, encoding lycopene β-cyclase), whereas chlorophyll content decreased by downregulating the expression levels of Mg-chelatase (CHLH, encoding Mg-chelatase) and protochlorophyllide oxidoreductase (POR, encoding protochlorophyllide oxidoreductase). Besides, the contents of soluble solids, vitamin C, soluble protein, free amino acids, total soluble sugar, organic acid, total phenol, and flavonoid were increased in ALA-treated tomato fruit, but the fruit firmness was decreased. These results indicated that the exogenous ALA could not only promote postharvest tomato fruit ripening but also improve the internal nutritional and flavor quality of tomato fruit.

Focal segmental glomerulosclerosis (FSGS) has an over 30% risk of recurrence after kidney transplantation (Ktx) and is associated with an extremely high risk of graft loss. However, mechanisms remain largely unclear. Thus, this study identifies novel genes related to the recurrence of FSGS (rFSGS). Whole genome-wide sequencing and next-generation RNA sequencing were used to identify the candidate mutant genes associated with rFSGS in peripheral blood mononuclear cells (PBMCs) from patients with biopsy-confirmed rFSGS after KTx. To confirm the functional role of the identified gene with the MDH2 c.26C >T mutation, a homozygous MDH2 c.26C >T mutation in HMy2.CIR cell line was induced by CRISPR/Cas9 and co-cultured with podocytes, mesangial cells, or HK2 cells, respectively, to detect the potential pathogenicity of the c.26C >T variant in MDH2. A total of 32 nonsynonymous single nucleotide polymorphisms (SNPs) and 610 differentially expressed genes (DEGs) related to rFSGS were identified. DEGs are mainly enriched in the immune and metabolomic-related pathways. A variant in MDH2, c.26C >T, was found in all patients with rFSGS, which was also accompanied by lower levels of mRNA expression in PBMCs from relapsed patients compared with patients with remission after KTx. Functionally, co-cultures of HMy2.CIR cells overexpressing the mutant MDH2 significantly inhibited the expression of synaptopodin, podocin, and F-actin by podocytes compared with those co-cultured with WT HMy2.CIR cells or podocytes alone. We identified that MDH2 is a novel rFSGS susceptibility gene in patients with recurrence of FSGS after KTx. Mutation of the MDH2 c.26C >T variant may contribute to progressive podocyte injury in rFSGS patients.

Tomatoes (Lycopersicon esculentum) are the most valuable vegetable crop in the world. This study identified the morphological characteristics, vitamin content, etc., from 15 tomato varieties in total, that included five each from the three experimental types, during the commercial ripening period. The results showed that the hardness with peel and the moisture content of tasty tomatoes were 157.81% and 54.50%, and 3.16% and 1.90% lower than those of regular tomatoes and cherry tomatoes, respectively, while the soluble solids were 60.25% and 20.79% higher than those of the latter two types. In addition, the contents of vitamin C, lycopene, fructose, glucose, and total organic acids of tasty tomatoes were higher than those of regular tomatoes and cherry tomatoes. A total of 110 volatile compounds were detected in the 15 tomato varieties. The average volatile compound content of tasty tomatoes was 57.94% higher than that of regular tomatoes and 15.24% higher than that of cherry tomatoes. Twenty of the 34 characteristic tomato aroma components were identified in tasty tomatoes, with fruity and green being the main odor types. Ten characteristic aroma components in regular tomatoes were similar to those of tasty tomatoes; ten types of cherry tomatoes had floral and woody aromas as the main odor types. The flavor sensory score was significantly positively correlated with the content of soluble solids, fructose, glucose, citric acid, fumaric acid, and β-ionone (p < 0.01), and significantly negatively correlated with water content and firmness without peel. Regular, tasty, and cherry tomatoes were separated using principal component analysis, and the quality of tasty tomatoes was found to be better than cherry tomatoes, followed by regular tomatoes. These results provide valuable information for a comprehensive evaluation of fruit quality among tomato varieties to develop consumer guidelines.

Abstract Drug‐induced QT prolongation, primarily antiarrhythmic drugs, is a common cause of torsade de pointes (TdP). Although there have been previous reports of drug‐induced TdP in patients, it has not been well documented when caused by citalopram during the pacemaker battery‐depletion phase. To improve delirium recognition, we report a case of citalopram‐induced TdP during the pacemaker battery‐depletion phase. An 84‐year‐old Chinese female was brought to the hospital presenting recurrent syncope. She lost consciousness and was admitted after her syncope TdP was documented. Her pacemaker was inspected and found to be operating in an extremely ineffective manner. Although she had prolonged QT interval after the pacemaker was replaced, she did not suffer another syncope attack, and ECG monitoring revealed no cardiac arrhythmia or TdP. During her admission, she was treated with citalopram for depression. Citalopram was discontinued when the QT interval shortened progressively. In this study, we described a case of citalopram‐induced TdP during the depletion phase of a pacemaker battery. This case should serve as a cautionary lesson to clinicians to avoid using citalopram during the pacemaker battery‐depletion phase.

Early adverse life events (EALs), such as maternal separation (MS), can cause visceral hypersensitivity, which is thought to be a key pathophysiological mechanism of irritable bowel syndrome (IBS). Previous studies mainly focused on EALs-induced visceral hypersensitivity in adulthood but did not consider that it may have occurred in the preadult period. We previously found that rats who experienced MS suffered from visceral hypersensitivity starting from the post-weaning period. Moreover, the hippocampus is considered to be critical in regulating the formation of visceral hypersensitivity induced by MS. But the underlying mechanisms throughout different life periods are unclear. In this study, behavioral tests, RNA-seq, lentiviral interference, and molecular biology techniques were applied to investigate the molecular mechanism in the hippocampus underlying MS-induced long-lasting visceral hypersensitivity. It was found that both visceral sensitivity and anxiety-like behaviors were significantly increased in MS rats in post-weaning, prepubertal, and adult periods, especially in the prepubertal period. Subsequently, RNA-seq targeting the hippocampus identified that the expression level of Netrin-1 was significantly increased in all periods, which was further confirmed by quantitative real-time PCR and Western blot. Knocking-down hippocampal Netrin-1 in the post-weaning period by lentivirus interference alleviated visceral hypersensitivity and anxiety-like behaviors of MS rats in the later phase of life. In addition, deleted in colorectal cancer (DCC), instead of neogenin-1(Neo-1) or uncoordinated (UNC5), was proved to be the specific functional receptor of Netrin-1 in regulating visceral hypersensitivity, whose upregulation may result in the most severe symptoms in the prepubertal period. Furthermore, the activation of the Netrin-1/DCC pathway could enhance long-term potentiation (LTP) in the hippocampus, probably via recruitment of the AMPA receptor subunit GluA1, which finally resulted in the formation of visceral hypersensitivity. These novel findings suggest that long-lasting over-expression of Netrin-1 can mediate visceral hypersensitivity and anxiety disorder from the post-weaning period to adulthood by activating DCC/GluA1 pathway in the hippocampus. Moreover, early intervention of Netrin-1 in the post-weaning period could lead to significant symptom relief afterward, which provides evidence that the Netrin-1/DCC/GluA1 signaling pathway may be a potential therapeutic target for the treatment of visceral hypersensitivity in clinics.

ObjectivePrimary ventricular lymphoma (PVL) is an extremely rare and commonly misdiagnosed disease. Previous studies were predominantly case reports, and literature regarding the diagnosis and treatment of PVL is limited. Therefore, this study aimed to evaluate the characteristics of patients with PVL.MethodsThe data of patients with pathologically confirmed PVL were assessed. Epidemiological data, imaging findings, surgery, pathological results, and prognosis were retrospectively analyzed. A systematic review of relevant literature was also conducted.ResultsA total of eight patients with PVL were identified. The main symptom was increased intracranial pressure. Radiographically, five patients had single lesion and three had multiple lesions; typical findings on magnetic resonance imaging included hypointensity on T1- and T2-weighted imaging, adjacent brain edema, and homogeneous enhancement on contrast-enhanced T1-weighted images. Preoperatively, six cases were misdiagnosed and two cases did not get a definite diagnosis. Craniotomy was performed on all patients, and four achieved gross total resection. Hydrocephalus was relieved after surgical resection in four patients. Pathology revealed diffuse large B-cell lymphoma in all patients. Only one patient had a severe complication. A total of three patients received concomitant adjuvant treatment, whereas five patients refused any adjuvant therapy. At the time of follow-up, the median survival time of patients was 15 months.ConclusionPrimary ventricular lymphoma mainly presented with symptoms of increased intracranial pressure and had several imaging characteristics for the diagnosis, but the condition still tends to be misdiagnosed. Surgical resection is a feasible treatment for patients with isolated nodules, especially those with acute obstructive hydrocephalus.

Abstract Background The aim of this study was to evaluate the effect of surgical resection and stereotactic biopsy on the complication rate, progression-free survival (PFS) and overall survival (OS) of 70 patients diagnosed at a single institution with primary central nervous system lymphoma (PCNSL) and to explore the predictors of selection for resection and the prognostic factors of PCNSL. Methods A retrospective analysis was performed of 70 patients with PCNSL that was diagnosed by surgical resection or stereotactic brain biopsy in our department from January 2013 to May 2019. We divided the patients into two groups: a resection group (n = 28) and a stereotactic biopsy group (n = 42). Data on clinical characteristics, imaging findings, complication rates, PFS and OS were retrospectively reviewed and compared between these two groups. We also analysed the predictors of selection for resection and prognostic factors of PCNSL by multivariate analysis. Results The median age was 53.3 ± 14.3 years, and there was a male predominance with a sex ratio of 1.33:1. The most common clinical manifestation was a headache. The complication rate in the resection group was 10.7% versus 7.1% in the stereotactic biopsy group, and there was no statistically significant difference. The rate of improvement in symptoms of the resection group was significantly higher than that of the stereotactic biopsy group. Multivariable analysis identified a single tumour and not involving deep structures as predictors of selection for resection. With a median follow-up of 30 months (range 1–110), the mean OS and PFS of all patients were 16.1 months and 6.2 months, respectively. Patients who underwent surgical resection had a mean OS of 23.4 months and PFS of 8.6 months versus 11.2 months and 4.6 months for those who had a brain biopsy performed. In addition, multivariable analysis showed that not involving deep structures and resection were favourable prognostic factors for PCNSL. Conclusions The outcomes of patients with PCNSL treated in our cohort are still poor. In our series, surgical resection might play a role in significantly improving OS and PFS compared with stereotactic biopsy in a subset of patients. The type of surgery and tumour location are prognostic factors for PCNSL.

Abstract Background Targeted sequencing using oncopanels requires comprehensive assessments of accuracy and detection sensitivity to ensure analytical validity. By employing reference materials characterized by the U.S. Food and Drug Administration-led SEquence Quality Control project phase2 (SEQC2) effort, we perform a cross-platform multi-lab evaluation of eight Pan-Cancer panels to assess best practices for oncopanel sequencing. Results All panels demonstrate high sensitivity across targeted high-confidence coding regions and variant types for the variants previously verified to have variant allele frequency (VAF) in the 5–20% range. Sensitivity is reduced by utilizing VAF thresholds due to inherent variability in VAF measurements. Enforcing a VAF threshold for reporting has a positive impact on reducing false positive calls. Importantly, the false positive rate is found to be significantly higher outside the high-confidence coding regions, resulting in lower reproducibility. Thus, region restriction and VAF thresholds lead to low relative technical variability in estimating promising biomarkers and tumor mutational burden. Conclusion This comprehensive study provides actionable guidelines for oncopanel sequencing and clear evidence that supports a simplified approach to assess the analytical performance of oncopanels. It will facilitate the rapid implementation, validation, and quality control of oncopanels in clinical use.

Regulatory B cells have been shown to play critical roles in the modulation of the immune system. Here, the authors implicate TIGIT expression in B cells with the process of immuno-regulation.

Variants in PRPH2 are a common cause of inherited retinal dystrophies with high genetic and phenotypic heterogeneity. In this study, variants in PRPH2 were selected from in-house exome sequencing data, and all reported PRPH2 variants were evaluated with the assistance of online prediction tools and the comparative validation of large datasets. All variants were classified based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines. Individuals with pathogenic or likely pathogenic variants of PRPH2 were confirmed by Sanger sequencing. Clinical characteristics were summarized. Ten pathogenic or likely pathogenic variants of PRPH2 were identified in 14 families. In our cohort, the most frequent variant was p.G305Afs*19, accounting for 33.3% (5/15) of alleles, in contrast to the literature, where p.R172G (11.6%, 119/1028) was the most common variant. Nine in-house families (63.8%) were diagnosed with retinitis pigmentosa (RP), distinct from the phenotypic spectrum in the literature, which shows that RP accounts for 27.9% (283/1013) and macular degeneration is more common (45.2%, 458/1013). Patients carrying missense variants predicted as damaging by all seven prediction tools and absent in the gnomAD database were more likely to develop RP compared to those carrying missense variants predicted as damaging with fewer tools or with more than one allele number in the gnomAD database (p = 0.001). The population-specific genetic and phenotypic spectra of PRPH2 were explored, and novel insight into the genotype–phenotype correlation of PRPH2 was proposed. These findings demonstrated the importance of assessing PRPH2 variants in distinct populations and the value of providing practical suggestions for the genetic interpretation of PRPH2 variants.

Corneal dystrophies (CDs) represent a group of inherited diseases characterized by the progressive deposit of abnormal materials in the cornea. This study aimed to describe the variant landscape of 15 genes responsible for CDs based on a cohort of Chinese families and a comparative analysis of literature reports. Families with CDs were recruited from our eye clinic. Their genomic DNA was analyzed using exome sequencing. The detected variants were filtered using multi-step bioinformatics and confirmed using Sanger sequencing. Previously reported variants in the literature were summarized and evaluated based on the gnomAD database and in-house exome data. In 30 of 37 families with CDs, 17 pathogenic or likely pathogenic variants were detected in 4 of the 15 genes, including TGFBI, CHST6, SLC4A11, and ZEB1. A comparative analysis of large datasets revealed that 12 of the 586 reported variants are unlikely causative of CDs in monogenic mode, accounting for 61 of 2933 families in the literature. Of the 15 genes, the gene most frequently implicated in CDs was TGFBI (1823/2902, 62.82% of families), followed by CHST6 (483/2902, 16.64%) and SLC4A11 (201/2902, 6.93%). This study presents, for the first time, the landscape of pathogenic and likely pathogenic variants in the 15 genes responsible for CDs. Awareness of frequently misinterpreted variants, such as c.1501C>A, p.(Pro501Thr) in TGFBI, is crucial in the era of genomic medicine.

Abstract Radiogenomics uses machine-learning (ML) to directly connect the morphologic and physiological appearance of tumors on clinical imaging with underlying genomic features. Despite extensive growth in the area of radiogenomics across many cancers, and its potential role in advancing clinical decision making, no published studies have directly addressed uncertainty in these model predictions. We developed a radiogenomics ML model to quantify uncertainty using transductive Gaussian Processes (GP) and a unique dataset of 95 image-localized biopsies with spatially matched MRI from 25 untreated Glioblastoma (GBM) patients. The model generated predictions for regional EGFR amplification status (a common and important target in GBM) to resolve the intratumoral genetic heterogeneity across each individual tumor—a key factor for future personalized therapeutic paradigms. The model used probability distributions for each sample prediction to quantify uncertainty, and used transductive learning to reduce the overall uncertainty. We compared predictive accuracy and uncertainty of the transductive learning GP model against a standard GP model using leave-one-patient-out cross validation. Additionally, we used a separate dataset containing 24 image-localized biopsies from 7 high-grade glioma patients to validate the model. Predictive uncertainty informed the likelihood of achieving an accurate sample prediction. When stratifying predictions based on uncertainty, we observed substantially higher performance in the group cohort (75% accuracy, n = 95) and amongst sample predictions with the lowest uncertainty (83% accuracy, n = 72) compared to predictions with higher uncertainty (48% accuracy, n = 23), due largely to data interpolation (rather than extrapolation). On the separate validation set, our model achieved 78% accuracy amongst the sample predictions with lowest uncertainty. We present a novel approach to quantify radiogenomics uncertainty to enhance model performance and clinical interpretability. This should help integrate more reliable radiogenomics models for improved medical decision-making.

Lili Ren et al. investigate antibody response from 176 COVID-19 patients who presented different stages of their disease. This study suggests the late onset of antibody response as a risk factor for disease severity and a limited role of antibody titers in predicting the disease severity of COVID-19.

BackgroundBecause of the low incidence and the constantly changing diagnostic and classification criteria, the clinical features, management, and prognostic factors of intracranial solitary fibrous tumor (ISFT) remain unclear and were thus analyzed in this study.MethodA total of 38 patients with ISFTs who were diagnosed in our institution were enrolled in this study. Patient data including age, gender, clinical presentation, histopathological features, immunohistochemistry staining, tumor location, tumor size, treatment methods, and prognosis were extracted and retrospectively analyzed.ResultsThe median age at diagnosis was 45.5 years (range 28–66 years) and the male-to-female ratio was 1:1.53 in our series. The 3-, 5-, and 10-year progression-free survival (PFS) rate was 82.2%, 62.8%, and 21.4%, respectively; and the 3-, 5-, and 10-year overall survival rate was 97.1%, 86.9%, and 64.2%, respectively. Patients with high WHO grade (grade 3) ISFTs experienced impaired PFS (p < 0.05) and OS (p < 0.01). Subtotal resection (STR) was associated with worse PFS and OS (p < 0.001, respectively). Postoperative radiotherapy (PORT) improved PFS, especially local control rate, in patients with WHO grade 3 ISFTs (P = 0.025) or STR (p = 0.027). Moreover, CD34-negative immunostaining and a high Ki-67 index (>10%) were associated with impaired PFS in ISFTs.ConclusionOur study provides evidence that high tumor grade, subtotal tumor resection, CD34 negative immunostaining, and high Ki-67 index (>10%) were independent predictors for the poor prognosis of ISFTs. PORT can improve local control rate, and should be recommended for patients with high-grade ISFTs or STR.

To evaluate the impact of straw mulching on the production of open field loose-curd cauliflower, this study analyzed the “Feicui No.9” cauliflower variety, grown in field trials in Northwest China, in 2019 and 2020. Plots in an open field were prepared without mulch (CK1) and with plastic film mulch (CK2), as experimental controls, along with three experimental mulching methods, including dual straw and plastic film mulch (T1), inter-row straw mulch (T2), and full straw mulch (T3). The effects of the different ground cover alternatives on loose-curd cauliflower's dry matter accumulation, yield, quality, and volatile compounds, were explored. The results showed that, compared with CK2 treatment, T1 treatment promoted the accumulation of dry matter, and increased the economic and biological yield, by 12.98 and 6.51%, respectively. The soluble sugar and vitamin C content in loose-curd cauliflower heads, subjected to T1 treatment, increased by 18.46 and 8.12%, respectively, and the nitrate content decreased by 25.57%. Moreover, the T1, T2, and T3 treatments significantly increased the levels of macro-, meso-, and microelements. Headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) was used to determine the volatile substances in loose-curd cauliflower heads from the 2020 harvesting period. Detected compounds included 17 aldehydes, 15 ketones, 10 alcohols, 15 esters, 29 hydrocarbons, 12 nitrogen-containing compounds, and 17 other substances. T1, T2, and T3 treatments increased the volatile substance content, whereas T1 treatment increased the quantity of volatile substances. In summary, dual mulching with straw and plastic film could promote dry matter accumulation, significantly increase the yield and quality, and effectively improve the flavor of loose-curd cauliflower. This mulching technique can be applied to open field vegetable and corn production areas, providing technical and theoretical support for the realization of high-yield, high-quality production models and a new straw recycling method.

The crystal structure of solvated [Mn(TPP)(NO3)] (TPP = 5,10,15,20-tetraphenylporphyrinato, C44H28N4), [Mn(C44H28N4O3)(NO3)]·0.5C6H14·0.5C6H6, has been determined in the space group Pccn. The MnIII atom has a distorted square-pyramidal environment, being coordinated by four pyrrole N atoms of the porphyrin ligand in the basal plane and an O atom of the nitrato ligand in the apical site. The MnIII atom is displaced out of the porphyrin plane by 0.22 (4) Å with the average Mn—Np distance being 2.011 (6) Å (where Np is a porphyrin N atom). The Mn—O bond length is 2.1246 (18) Å. Two kinds of intermolecular C—H...O hydrogen bonds exist in the crystal structure, with the apical nitrato ligands interacting with solvent molecules and adjacent molecules, respectively.

BackgroundCraniopharyngioma (CP) with tumoral hemorrhage is a very rare syndrome presenting with various manifestation and unfavorable outcomes. The current retrospective study was performed to summarize the clinical features of CP with tumoral hemorrhage.MethodsIn this study, 185 patients with pathological diagnosis of CP (18 patients with hemorrhage) were enrolled. Clinical characteristics, radiological and surgical treatments, and post-operative complications were analyzed. In addition, the correlations between sexual hormones and tumor volume were explored.ResultsDrowsiness, acute syndrome, and pituitary deficiency were more frequent in patients with hemorrhage patients. Prothrombin time (PT) were higher in patients with hemorrhage. Luteinizing hormone (LH) and testosterone (T) were lower in male patients with hemorrhage. Post-operative electrolyte disturbances, hypothalamic syndrome, and death appeared more frequently in the hemorrhage group. Moreover, prolactin (PRL) and cortisol 8AM were found to be correlated with the volume of the tumor and the hematoma, respectively.ConclusionThe current study presented the clinical features of CP apoplexy from the aspects of clinical characteristics, radiography, surgical treatment, and post-operative complications. Patients with CP apoplexy could benefit from the proper processing of peritumoral hemorrhage and post-operative monitoring of the electrolyte.

Abstract Background The polymorphisms rs6885224 and rs634990 have been reported to be associated with high myopia in many populations. As there is still no report on whether these two SNPs are associated with myopia in the Tujia and Miao minority areas of China, we conducted a replication study to evaluate the association of single-nucleotide polymorphisms in the regions 5p15.2 and 15q14 with high myopia in Tujia and Miao Chinese populations. Methods We performed a comprehensive meta-analysis of 5831 cases and 7055 controls to assess whether rs6885224 in the 5p15.2 region and rs634990 in the 15q14 region are associated with high myopia. Our replication study enrolled 804 individuals. Genomic DNA was extracted from venous leukocytes, and these two SNPs were genotyped by Sanger sequencing. Allele and genotype frequencies were analysed using χ 2 tests, and ORs and 95% CIs were calculated. Results According to the results of the meta-analysis, rs6885224 in the CTNND2 gene showed no association with myopia [p = 0.222, OR = 1.154, 95% CI (0.917–1.452)]. Conversely, rs634990 in the 15q14 region did exhibit a significant correlation with myopia [p = 7.270 × 10− 7, OR = 0.817, 95% CI (0.754–0.885)]. In our replication study, no association with high myopia in the Tujia and Miao populations was found for rs634990 or rs6885224. The following were obtained by allele frequency analysis: rs6885224, p = 0.175, OR = 0.845, and 95% CI = 0.662–1.078; rs634990, p = 0.087, OR = 0.84, and the 95% CI = 0.687–1.026. Genotype frequency analysis yielded p = 0.376 for rs6885224 and p = 0.243 for rs634990. Conclusions Our meta-analysis results show that rs634990 was significantly associated with myopia but that rs6885224 was not. Nevertheless, in our replication study, these two SNPs showed no association with myopia in the Tujia and Miao Chinese populations. This is the first report involving Tujia and Miao ethnic groups from Enshi minority areas. However, the sample size needs to be expanded and more stringent inclusion and exclusion criteria need to be formulated to verify the findings.

Background: Brainstem tumors are rare and extremely heterogeneous and present significant challenges in surgical treatment. Thus, biopsies often set the foundation for the diagnosis of brainstem tumors. Multimodal, image-guided, robot-assisted frameless stereotactic biopsies are increasingly popular in neurosurgery centers. This study aimed to compare the safety, efficacy, and duration of the Remebot robot-assisted (Remebot) frameless brainstem tumor biopsy versus those of frame-based stereotactic biopsy. Method: A retrospective analysis of 33 patients with brainstem tumors who underwent stereotactic brainstem biopsies in the department of neurosurgery from January 2016 to January 2021 was conducted. The patients were divided into two groups: the Remebot group (n = 22) and the frame-based group (n = 11). The clinical characteristics, trajectory strategy, duration of procedure, diagnostic yielding, histopathological diagnosis, and postoperative complications were retrospectively analyzed and compared between the groups. Results: More pediatric patients performed Remebot frameless brainstem tumor biopsy than frame-based biopsy, with a mean age of 17.3 ± 18.7 vs. 32.8 ± 17.1 (p = 0.027). The diagnostic yield had no significant difference in the two groups, with the diagnostic yield of frame-based biopsy and Remebot frameless brain biopsy being 90.9% and 95.5%, respectively. The time of the total process was 124.5 min for the frame-based biopsy and 84.7 min for the Remebot frameless brain biopsy (p < 0.001). There were no significant differences with respect to the occurrence of complication or the duration of the operation between the two groups. Conclusion: Remebot frameless stereotactic brainstem biopsy is as safe and efficacious as frame-based stereotactic biopsy. However, Remebot frameless biopsy can reduce the total duration of the procedure and has better application in young pediatric patients. Remebot frameless stereotactic biopsies can be a better option towards the safe and efficient treatment of brainstem tumors.

The maintenance of neural stem cells (NSCs) plays a critical role in neurodevelopment and has been implicated in neurodevelopmental disorders (NDDs). However, the underlying mechanisms linking defective human neural stem cell self-renewal to NDDs remain undetermined. Our previous study found that Supt16 haploinsufficiency causes cognitive and social behavior deficits by disrupting the stemness maintenance of NSCs in mice. However, its effects and underlying mechanisms have not been elucidated in human neural stem cells (hNSCs). Here, we generated Supt16+/− induced pluripotent stem cells (iPSCs) and induced them into hNSCs. The results revealed that Supt16 heterozygous hNSCs exhibit impaired proliferation, cell cycle arrest, and increased apoptosis. As the RNA-seq analysis showed, Supt16 haploinsufficiency inhibited the PI3K/AKT/mTOR pathway, leading to rising autophagy, and further resulted in the dysregulated expression of multiple proteins related to cell proliferation and apoptotic process. Furthermore, the suppression of Supt16 heterozygous hNSC self-renewal caused by autophagy activation could be rescued by MHY1485 treatment or reproduced in rapamycin-treated hNSCs. Thus, our results showed that Supt16 was essential for hNSC self-renewal and its haploinsufficiency led to cell cycle arrest, impaired cell proliferation, and increased apoptosis of hNSCs by regulating the PI3K/AKT/mTOR/autophagy pathway. These provided a new insight to understand the causality between the Supt16 heterozygous NSCs and NDDs in humans.

Objective: This study aimed to investigate the clinical efficacy of robot-assisted neuroendoscopic hematoma evacuation combined intracranial pressure (ICP) monitoring for the treatment of hypertensive intracerebral hemorrhage (HICH).Patients and Methods: A retrospective analysis of 53 patients with HICH undergoing neuroendoscopic hematoma evacuation in our department from January 2016 to December 2020 was performed. We divided the patients into two groups: the neuroendoscopic group (n = 32) and the robot-assisted neuroendoscopic combined ICP monitoring group (n = 21). Data on clinical characteristics, treatment effects, and outcomes were retrospectively reviewed and analyzed between these two groups.Results: The operation time of the procedure of the neuroendoscopic group was significantly longer than that of the robot-assisted neuroendoscopic combined ICP-monitoring group (mean time 153.8 ± 16.8 vs. 132.8 ± 15.7 min, P < 0.001). The intraoperative blood loss was significantly less in the robot-assisted neuroendoscopic combined ICP-monitoring group than in the neuroendoscopic group (215.4 ± 28.3 vs. 190.1 ± 25.6 ml, P = 0.001). However, the patients undergoing neuroendoscopic had a comparable hematoma clearance rate with those undergoing robot-assisted neuroendoscopic combined ICP monitoring (85.2 ± 4.8 vs. 89.2 ± 5.4%, P = 0.997). The complications rate was greater in the endoscopic group (25%) than in the robot-assisted neuroendoscopic combined ICP-monitoring group (9.5%) but without significant difference (P = 0.159). We also found that the dose of used mannitol was significantly less in the ICP monitoring group (615.2 ± 63.8 vs. 547.8 ± 65.3 ml, P < 0.001) and there was a significant difference in modified Rankin scale (mRS) score at discharge, patients with less mRS score in the robot-assisted neuroendoscopic combined ICP monitoring group than in the neuroendoscopic group (3.0 ± 1.0 vs. 3.8 ± 0.8, p = 0.011). Patients undergoing robot-assisted neuroendoscopic combined ICP monitoring had better 6-month functional outcomes, and there was a significant difference between the two groups (p = 0.004). Besides, multivariable analysis shows younger age, no complication, and robot-assisted neuroendoscopic combined ICP monitoring were predictors of 6-month favorable outcomes for the patients with HICH.Conclusion: Robot-assisted neuroendoscopic hematoma evacuation combined with ICP monitoring appears to be safer and more effective as compared to the neuroendoscopic hematoma evacuation in the treatment of HICH. Robot-assisted neuroendoscopic hematoma evacuation combined with ICP monitoring might improve the clinical effect and treatment outcomes of the patients with HICH.

Melatonin plays key roles in improving fruit quality and yield by regulating various aspects of plant growth. However, the effects of how melatonin regulates primary and secondary metabolites during fruit growth and development are poorly understood. In this study, the surfaces of tomato fruit were sprayed with different concentrations of melatonin (0, 50, and 100 µmol·L−1) on the 20th day after anthesis; we used high-performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry (LC/MS) to determine the changes in primary and secondary metabolite contents during fruit development and measured the activity of sucrose metabolizing enzymes during fruit development. Our results showed that 100 µmol·L−1 melatonin significantly promoted the accumulation of soluble sugar in tomato fruit by increasing the activities of sucrose synthase (SS), sucrose phosphate synthase (SPS), and acid convertase (AI). The application of 100 µmol·L−1 melatonin also increased the contents of ten amino acids in tomato fruit as well as decreased the contents of organic acids. In addition, 100 µmol·L−1 melatonin application also increased the accumulation of some secondary metabolites, such as six phenolic acids, three flavonoids, and volatile substances (including alcohols, aldehydes, and ketones). In conclusion, melatonin application improves the internal nutritional and flavor quality of tomato fruit by regulating the accumulation of primary and secondary metabolites during tomato fruit ripening. In the future, we need to further understand the molecular mechanism of melatonin in tomato fruit to lay a solid foundation for quality improvement breeding.

Abstract Background Cervical cancer (CC) is the second leading cause of cancer death among women worldwide. Epigenetic regulation of gene expression through DNA methylation and hydroxymethylation plays a pivotal role during tumorigenesis. In this study, to analyze the epigenomic landscape and identify potential biomarkers for CCs, we selected a series of samples from normal to cervical intra‐epithelial neoplasia (CINs) to CCs and performed an integrative analysis of whole‐genome bisulfite sequencing (WGBS‐seq), oxidative WGBS, RNA‐seq, and external histone modifications profiling data. Results In the development and progression of CC, there were genome‐wide hypo‐methylation and hypo‐hydroxymethylation, accompanied by local hyper‐methylation and hyper‐hydroxymethylation. Hydroxymethylation prefers to distribute in the CpG islands and CpG shores, as displayed a trend of gradual decline from health to CIN2, while a trend of increase from CIN3 to CC. The differentially methylated and hydroxymethylated region‐associated genes both enriched in Hippo and other cancer‐related signaling pathways that drive cervical carcinogenesis. Furthermore, we identified eight novel differentially methylated/hydroxymethylated‐associated genes (DES, MAL, MTIF2, PIP5K1A, RPS6KA6, ANGEL2, MPP, and PAPSS2) significantly correlated with the overall survival of CC. In addition, no any correlation was observed between methylation or hydroxymethylation levels and somatic copy number variations in CINs and CCs. Conclusion Our current study systematically delineates the map of methylome and hydroxymethylome from CINs to CC, and some differentially methylated/hydroxymethylated‐associated genes can be used as the potential epigenetic biomarkers in CC prognosis.

5-Aminolevulinic acid (ALA) plays an important role in plant growth and development. It can also be used to enhance crop resistance to environmental stresses and improve the color and internal quality of fruits. However, there are limited reports regarding the effects of ALA on tomato fruit color and its regulatory mechanisms. Therefore, in this study, the effects of exogenous ALA on the quality and coloration of tomato fruits were examined. Tomato (Solanum lycopersicum “Yuanwei No. 1”) fruit surfaces were treated with different concentrations of ALA (0, 100, and 200 mg⋅L–1) on the 24th day after fruit setting (mature green fruit stage), and the content of soluble sugar, titratable acid, soluble protein, vitamin C, and total free amino acids, as well as amino acid components, intermediates of lycopene synthetic and metabolic pathways, and ALA metabolic pathway derivatives were determined during fruit ripening. The relative expression levels of genes involved in lycopene synthesis and metabolism and those involved in ALA metabolism were also analyzed. The results indicated that exogenous ALA (200 mg⋅L–1) increased the contents of soluble sugars, soluble proteins, total free amino acids, and vitamin C as well as 11 kinds of amino acid components in tomato fruits and reduced the content of titratable acids, thus improving the quality of tomato fruits harvested 4 days earlier than those of the control plants. In addition, exogenous ALA markedly improved carotenoid biosynthesis by upregulating the gene expression levels of geranylgeranyl diphosphate synthase, phytoene synthase 1, phytoene desaturase, and lycopene β-cyclase. Furthermore, exogenous ALA inhibited chlorophyll synthesis by downregulating the genes expression levels of Mg-chelatase and protochlorophyllide oxidoreductase. These findings suggest that supplementation with 200 mg⋅L–1 ALA not only enhances the nutritional quality and color of the fruit but also promotes early fruit maturation in tomato.

Abstract Background Scarf osteotomy (SO) was broadly applied in moderate to severe hallux valgus (MSHV), and the results were satisfactory. However, due to the complicated pathologic changes in hallux valgus, the ideal surgical treatment is still controversial. Transfer of the abductor hallucis tendon combined with Scarf osteotomy (TAHTCSO) was an innovative alternative technique. This retrospective cohort study aimed to define if TAHTCSO mode resulted in improved outcomes as compared with the single SO in MSHV. Methods Of 73 patients (92 ft) with MSHV, 36 (45 ft) were treated through TAHTCSO and 37 ones (47 ft) through SO. The patients were assessed clinically and radiographically with a 24-month follow-up. They were assessed pre-operatively and post-operatively with intermetatarsal angle (IMA), hallux valgus angle (HVA), distal metatarsal articular angle (DMAA), first metatarsophalangeal joint range of motion (1#MTP ROM), as well as American Orthopaedic Foot and Ankle Society (AOFAS) forefoot scores and postoperative complications of surgery. Results Both cohorts had the same baseline feathures. All patients were followed up from 24 to 40 months, with a mean of 28.3 months. Patients in the TAHTCSO cohort had significantly decreased HVA at 6 months (p 0.05). IMA, DMAA and AOFAS also had not significantly difference at all followed time after surgery as compared with the SO cohort. The healing of osteotomies was observed within 8 weeks in the two cohorts. Two cases of hallus varus had been found in SO cohort and there were no cases of delayed healing and bone non-union in both cohorts. Conclusion In this retrospective cohort study, TAHTCSO had sufficient maintenance of the correction and improved functional performance thereby was a good alternative for MSHV, though it did not display a better result for MSHV compared to SO.

Firstly,the scope of research was expanded,the development trend of future internet and forward-looking application were analyzed,including the 5G era and beyond 5G era,and the overall architecture of future internet with its key technologies was proposed.Then the technical requirement for industrial internet in the 5G era was researched,including future industrial internet architecture,industrial edge cloud,deterministic delay industrial connection,future industrial internet cloud platform,digital transformation,network security,industrial identification and resolution.