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Abstract Respiratory diseases are a growing concern in public health because of their potential to endanger the global community. Cell death contributes critically to the pathophysiology of respiratory diseases. Recent evidence indicates that necroptosis, a unique form of programmed cell death (PCD), plays a vital role in the molecular mechanisms underlying respiratory diseases, distinguishing it from apoptosis and conventional necrosis. Necroptosis is a type of inflammatory cell death governed by receptor-interacting serine/threonine protein kinase 1 (RIPK1), RIPK3, and mixed-lineage kinase domain-like protein (MLKL), resulting in the release of intracellular contents and inflammatory factors capable of initiating an inflammatory response in adjacent tissues. These necroinflammatory conditions can result in significant organ dysfunction and long-lasting tissue damage within the lungs. Despite evidence linking necroptosis to various respiratory diseases, there are currently no specific alternative treatments that target this mechanism. This review provides a comprehensive overview of the most recent advancements in understanding the significance and mechanisms of necroptosis. Specifically, this review emphasizes the intricate association between necroptosis and respiratory diseases, highlighting the potential use of necroptosis as an innovative therapeutic approach for treating these conditions.

Abstract The effective isolation of rare target cells, such as circulating tumor cells, from whole blood is still challenging due to the lack of a capturing surface with strong target-binding affinity and non-target-cell resistance. Here we present a solution leveraging the flexibility of bacterial virus (phage) nanofibers with their sidewalls displaying target circulating tumor cell-specific aptamers and their ends tethered to magnetic beads. Such flexible phages, with low stiffness and Young’s modulus, can twist and adapt to recognize the cell receptors, energetically enhancing target cell capturing and entropically discouraging non-target cells (white blood cells) adsorption. The magnetic beads with flexible phages can isolate and count target cells with significant increase in cell affinity and reduction in non-target cell absorption compared to magnetic beads having rigid phages. This differentiates breast cancer patients and healthy donors, with impressive area under the curve (0.991) at the optimal detection threshold (>4 target cells mL−1). Immunostaining of captured circulating tumor cells precisely determines breast cancer subtypes with a diagnostic accuracy of 91.07%. Our study reveals the power of viral mechanical attributes in designing surfaces with superior target binding and non-target anti-fouling.

Abstract Background The contractile phenotype of vascular smooth muscle cells (VSMCs) results in good diastolic and contractile capacities, and its altered function is the main pathophysiological basis for diseases such as hypertension. VSMCs exist as a synthetic phenotype in vitro, making it challenging to maintain a contractile phenotype for research. It is widely recognized that the common medium in vitro is significantly less crowded than in the in vivo environment. Additionally, VSMCs have a heightened sense for detecting changes in medium crowding. However, it is unclear whether macromolecular crowding (MMC) helps maintain the VSMCs contractile phenotype. Purpose This study aimed to explore the phenotypic, behavioral and gene expression changes of VSMCs after increasing the crowding degree by adding carrageenan (CR). Methods The degree of medium crowding was examined by a dynamic light scattering assay; VSMCs survival and activity were examined by calcein/PI cell activity and toxicity and CCK-8 assays; VSMCs phenotypes and migration were examined by WB and wound healing assays; and gene expression was examined by transcriptomic analysis and RT-qPCR. Results Notably, 225 μg/mL CR significantly increased the crowding degree of the medium and did not affect cell survival. Simultaneously, CR significantly promoted the contraction phenotypic marker expression in VSMCs, shortened cell length, decreased cell proliferation, and inhibited cell migration. CR significantly altered gene expression in VSMCs. Specifically, 856 genes were upregulated and 1207 genes were downregulated. These alterations primarily affect the cellular ion channel transport, microtubule movement, respiratory metabolism, amino acid transport, and extracellular matrix synthesis. The upregulated genes were primarily involved in the cytoskeleton and contraction processes of VSMCs, whereas the downregulated genes were mainly involved in extracellular matrix synthesis. Conclusions The in vitro study showed that VSMCs can maintain the contractile phenotype by sensing changes in the crowding of the culture environment, which can be maintained by adding CR. Graphical Abstract

Abstract Despite their crucial role in determining the fate of seeds, the type and breaking mode of seed dormancy in peatland plants in temperate Asia with a continental monsoon climate are rarely known. Fifteen common peatland plant species were used to test their seed germination response to various dormancy‐breaking treatments, including dry storage (D), gibberellin acid soaking (GA), cold stratification (CS), warm followed cold stratification (WCS), GA soaking + cold stratification (GA + CS) and GA soaking + warm followed cold stratification (GA + WCS). Germination experiment, viability and imbibition test, and morphological observation of embryos were conducted. Of the 15 species, nine showed physiological dormancy (PD), with non‐deep PD being the dominant type. Four species, Angelica pubescens, Cicuta virosa, Iris laevigata, and Iris setosa exhibited morphophysiological dormancy. Two species, Lycopus uniflorus and Spiraea salicifolia, demonstrated nondormancy. Overall, the effect hierarchy of dormancy‐breaking is: CS > GA > WCS > GA + CS > D > GA + WCS. Principal component analysis demonstrated that seed traits, including embryo length: seed length ratio, seed size, and monocot/eudicot divergence, are more likely to influence seed dormancy than environmental factors. Our study suggests that nearly 90% of the tested peatland plant species in the Changbai Mountains demonstrated seed dormancy, and seed traits (e.g. embryo‐to‐seed ratio and seed size) and abiotic environmental factors (e.g. pH and temperature seasonality) are related to germination behavior, suggesting seed dormancy being a common adaptation strategy for the peatland plants in the temperate montane environment.

Objective: Based on network pharmacology and experimental validation, this study aimed to screen the potential targets of Liuwei Dihuang decoction (LW) against mild cognitive impairment (MCI). Methods: Based on network pharmacology, this study preliminarily explored the targets and molecular mechanisms of LW in the treatment of MCI. The results showed that the mechanism of action of LW against MCI may be related to the cAMP pathway. Then, an aging cell and animal model was established to further verify its molecular mechanism. Results: A total of 23 active ingredients were identified in LW. In addition, through network pharmacological analysis, we found 22 anti-MCI active ingredients in LW, of which alisol B had the most significant effect, and predicted the potential mechanism pathway by which LW may improve MCI through the cAMP signaling pathway. Further in vivo and in vitro experiments confirmed that LW can alleviate cognitive dysfunction in aging mice and reduce D-galactose-induced senescent cells, which may be through activation of the cAMP/PKA/CREB signaling pathway. Conclusion: This study found that the traditional Chinese medicine formula LW may play a role in improving MCI by regulating the cAMP/PKA/CREB signaling pathway, which provides a reference for further clinical research on the anti-MCI effect of LW and its molecular mechanism.

Excessive oxidative stress and NLRP3 inflammasome activation are considered the main drivers of inflammatory bowel disease (IBD), and inhibition of inflammasomes ameliorates clinical symptoms and morphological manifestations of IBD. Herein, we examined the roles of NLRP3 activation in IBD and modulation of NLRP3 by sulforaphane (SFN), a compound with multiple pharmacological activities that is extracted from cruciferous plants. To simulate human IBD, we established a mouse colitis model by administering dextran sodium sulfate in the drinking water. SFN (25, 50 mg·kg−1·d−1, ig) or the positive control sulfasalazine (500 mg/kg, ig) was administered to colitis-affected mice for 7 days. Model mice displayed pathological alterations in colon tissue as well as classic symptoms of colitis beyond substantial tissue inflammation. Expression of NLRP3, ASC, and caspase-1 was significantly elevated in the colonic epithelium. The expression of NLRP3 inflammasomes led to activation of downstream proteins and increases in the cytokines IL-18 and IL-1β. SFN administration either fully or partially reversed these changes, thus restoring IL-18 and IL-1β, substantially inhibiting NLRP3 activation, and decreasing inflammation. SFN alleviated the inflammation induced by LPS and NLRP3 agonists in RAW264.7 cells by decreasing the levels of reactive oxygen species. In summary, our results revealed the pathological roles of oxidative stress and NLRP3 in colitis, and indicated that SFN might serve as a natural NLRP3 inhibitor, thereby providing a new strategy for alternative colitis treatment.

Abstract Background Carcinosarcoma of the parotid gland is an extremely rare malignancy comprising of 0.04–0.16% of all salivary gland tumors. This is the first case of an adenoid cystic carcinoma with chondrosarcoma to the best of our knowledge. They consist of distinct carcinomatous and sarcomatous components and may arise de novo or from a preexisting pleomorphic adenoma. Case presentation Herein we present a case of an 80-year-old white female who presented with progressively increasing left facial swelling over 6 weeks. Magnetic Resonance Imagining revealed a mass (3.4 cm) in the parotid gland with a predominant cystic/necrotic component. The cytology was atypical (Milan3) and a total parotidectomy and selective lymph node dissection was done. The resection showed extensive necrosis with high grade sarcomatous (chondrosarcoma) areas. The epithelial component was adenoid cystic carcinoma with perineural invasion. The patient is currently undergoing radiotherapy of the tumor bed and skull base due to propensity of perineural invasion of the adenoid cystic component. The most common carcinomas in carcinosarcomas of salivary glands are adenocarcinoma and squamous cell carcinoma. Conclusion Carcinosarcoma is a high-grade aggressive lesion with a poor prognosis and should be treated aggressively. More studies are needed to understand the origin of these tumors.

Abstract Background The adhesion and survival state of cells on scaffold material is a major problem in tissue-engineered blood vessel (TEBV) culture. Platelet-rich plasma (PRP) contains a large amount of biologically active factors and fibrin, which is expected to play an important role in TEBV culture. Purpose To combine PRP with cells and scaffold material to promote cell adhesion and biological activity on the scaffold material. Methods The adhesion status and migration of SMCs under the optimal concentration suitable for SMC growth and the optimal concentration of PRP were examined by scanning electron microscopy, HE staining, CCK-8 assays, qPCR, WB, and other experimental methods and compared with those under the conventional culture (20% FBS); finally, the effect of PRP on the deposition of ECM in vascular tissue engineering culture was verified by three-dimensional culture. Results PRP at 20% is a suitable concentration for SMCs. Compared with the control group, the 20% PRP group had better migration, and the number of SMC adhesions was significantly higher than that of the control group. In addition, collagen deposition in the experimental group was significantly higher than that in the control group. Conclusion PRP (20%) can promote SMC adhesion, migration, and collagen deposition on the scaffold material.

The low Earth orbit (LEO) satellite internet network (LEO-SIN) has become a heated issue for the next generation of mobile communications, serving as a crucial means to achieve global wide-area broadband coverage and, especially, mobile phone directly to satellite cell (MPDTSC) communication. The ultra-high-speed movement of LEO satellites relative to the Earth results in serious Doppler effects, leading to signal de-synchronization at the user end (UE), and relative high-speed motion leading to frequent satellite handovers. Satellite ephemeris, which indicates the satellite’s position, has the potential to determine the position of the transmit (Tx) within the LEO-SIN, thereby enhancing the reliability and efficiency of satellite communication. The adoption of ephemeris in the LEO-SIN has met some new challenges: (1) how UEs can acquire ephemerides before signal synchronization is complete, (2) how to minimize the frequency of ephemeris broadcasting, and (3) how to decrease the overhead of ephemeris broadcasting. To address the above challenges, this paper proposes a method for extrapolating the LEO-SIN orbit based on multi-satellite ephemeris coordination (MSEC) and the multi-stream fractional autoregressive integrated moving average (MS-FARIMA). First, a multi-factor global error analysis model for ephemeris-extrapolation error is established, which decomposes it into three types; namely, random error (RE), trending error (TE), and periodic error (PE), with a focus on increasing the extrapolation accuracy by improving RE and TE. Second, RE is eliminated by utilizing the ephemerides from multiple satellites received at the same UE at the same time, as well as multiple ephemerides from the same satellite at different times. Subsequently, we propose a new FARIMA algorithm with the innovation of a multi-stream data time-series forecast (TSF), which effectively improves ephemeris extrapolation errors. Finally, the simulation results show that the proposed method reduces ephemeris extrapolation errors by 33.5% compared to existing methods, which also contributes to a performance enhancement in the Doppler frequency offset (DFO) estimation of MPDTSC.

BackgroundIdiopathic scoliosis significantly affects the physical and mental health of children and adolescents, with varying prevalence rates in different regions. The occurrence of idiopathic scoliosis is associated with genetic regulation and biochemical factors, but the changes in exosome-derived miRNA profiles among idiopathic scoliosis patients remain unclear. This study aimed to determine the prevalence of idiopathic scoliosis in Yunnan Province, China, and identify key exosome-derived miRNAs in idiopathic scoliosis through a cohort study.MethodsFrom January 2018 to December 2020, a cross-sectional study on idiopathic scoliosis in children and adolescents was conducted in Yunnan Province. A total of 84,460 students from 13 cities and counties in Yunnan Province participated in a scoliosis screening program, with ages ranging from 7 to 19 years. After confirmation through screening and imaging results, patients with severe idiopathic scoliosis and normal control individuals were selected using propensity matching. Subsequently, plasma exosome-derived miRNA sequencing and RT-qPCR validation were performed separately. Based on the validation results, diagnostic performance analysis and target gene prediction were conducted for differential plasma exosome-derived miRNAs.ResultsThe overall prevalence of idiopathic scoliosis in children and adolescents in Yunnan Province was 1.10%, with a prevalence of 0.87% in males and 1.32% in females. The peak prevalence was observed at age 13. Among patients diagnosed with idiopathic scoliosis, approximately 12.8% had severe cases, and there were more cases of double curvature than of single curvature, with thoracolumbar curvature being the most common in the single-curvature group. Sequencing of plasma exosome-derived miRNAs associated with idiopathic scoliosis revealed 56 upregulated and 153 downregulated miRNAs. Further validation analysis confirmed that hsa-miR-27a-5p, hsa-miR-539-5p, and hsa-miR-1246 have potential diagnostic value.ConclusionsWe gained insights into the epidemiological characteristics of idiopathic scoliosis in Yunnan Province and conducted further analysis of plasma exosome-derived miRNA changes in patients with severe idiopathic scoliosis. This study has provided new insights for the prevention and diagnosis of idiopathic scoliosis, paving the way for exploring clinical biomarkers and molecular regulatory mechanisms. However, further validation and elucidation of the detailed biological mechanisms underlying these findings will be required in the future.

Neurocytomas are rare low-grade brain tumors predominantly affecting young adults, but their cellular origin and molecular pathogenesis is largely unknown. We previously reported a sellar neurocytoma that secreted excess arginine vasopressin causing syndrome of inappropriate anti-diuretic hormone (SIADH). Whole exome sequencing in 21 neurocytoma tumor tissues identified somatic mutations in the plant homeodomain finger protein 14 (PHF14) in 3/21 (14%) tumors. Of these mutations, two were missense mutations and 4 caused splicing site losses, resulting in PHF14 dysfunction. Employing shRNA-mediated knockdown and CRISPR/Cas9-based knockout approaches, we demonstrated that loss of PHF14 increased proliferation and colony formation in five different human, mouse and rat mesenchymal and differentiated cell lines. Additionally, we demonstrated that PHF14 depletion resulted in upregulation of platelet derived growth factor receptor-alpha (PDGFRα) mRNA and protein in neuroblastoma SHSY-5Y cells and led to increased sensitivity to treatment with the PDGFR inhibitor Sunitinib. Furthermore, in a neurocytoma primary culture harboring splicing loss PHF14 mutations, overexpression of wild-type PHF14 and sunitinib treatment inhibited cell proliferation. Nude mice, inoculated with PHF14 knockout SHSY-5Y cells developed earlier and larger tumors than control cell-inoculated mice and Sunitinib administration caused greater tumor suppression in mice harboring PHF-14 knockout than control SHSY-5Y cells. Altogether our studies identified mutations of PHF14 in 14% of neurocytomas, demonstrate it can serve as an alternative pathway for certain cancerous behavior, and suggest a potential role for Sunitinib treatment in some patients with residual/recurrent neurocytoma.

The conventional lithofacies and facies model of subaerial and marine pyroclastic rocks cannot reflect the characteristics of subaqueous volcanic edifice in lacustrine basins. In order to solve this problem, the lithofacies of subaqueous eruptive pyroclastic rocks is discussed and the facies model is established by taking the tuff cone of Cretaceous Huoshiling Formation in the Chaganhua area of the Changling fault depression, Songliao Basin as the research object. The results indicate that the subaqueous eruptive pyroclastic rocks in the Songliao Basin can be divided into two facies and four subfacies. The two facies are the subaqueous explosive facies and the volcanic sedimentary facies that is formed during the eruption interval. The subaqueous explosive facies can be further divided into three subfacies: gas-supported hot pyroclastic flow subfacies, water-laid density current subfacies and subaqueous fallout subfacies. The volcanic sedimentary facies consists of pyroclastic sedimentary rocks containing terrigenous clast subfacies. A typical facies model of the tuff cone that is formed by subaqueous eruptions in the Songliao Basin was established. The tuff cone is generally composed of multiple subaqueous eruption depositional units and can be divided into two facies associations: near-source facies association and far-source facies association. The complete vertical succession of one depositional unit of the near-source facies association is composed of pyroclastic sedimentary rocks containing terrigenous clast subfacies, gas-supported hot pyroclastic flow subfacies, water-laid density current subfacies and subaqueous fallout subfacies from bottom to top. The depositional unit of the far-source facies association is dominated by the subaqueous fallout subfacies and contains several thin interlayered deposits of the water-laid density current subfacies. The gas-supported hot pyroclastic flow subfacies and the pyroclastic sedimentary rocks containing terrigenous clast subfacies are favorable subaqueous eruptive facies for reservoirs in continental lacustrine basins.

Summary: Composite structures integrated with metasurfaces and nonlinear films have emerged as alternative candidates to enhance nonlinear response. The cooperative interaction between the two components is complicated. Herein, a split-ring resonator (SRR)-type metasurface was fabricated on a free-standing nanocrystal diamond (NCD) film utilizing electron beam lithography, electron beam evaporation, and a lift-off process. The terahertz (THz) radiation from the SRR-NCD under normal incidence originates from the high-order magnetic resonance of SRR because the NCD film cannot produce detectable THz radiation at this incident angle. As increasing the incident angle, the contribution of the THz radiation from the NCD film gradually increases until reaching 40° incident angle limitation. The results indicate that this angular-dependent THz radiation is induced by the interplay between the NCD film and SRR. This study offers a new approach to investigate nonlinear processes in composite structures.

Introduction: Rheumatoid arthritis (RA) is a common chronic autoimmune disease with high incidence rate and high disability rate. One of the top complications is cancer, especially lung adenocarcinoma (LUAD). However, the molecular mechanisms linking RA and LUAD are still not clear. Therefore, in this study, we tried to identify the shared genetic signatures and local immune microenvironment between RA and LUAD and construct a clinical model for survival prediction.Methods: We obtained gene expression profiles and clinical information of patients with RA and LUAD from GEO and TCGA datasets. We performed differential analysis and Weighted Gene Co-expression Network Analysis (WGCNA) to discover the shared genes between RA and LUAD. Then, COX regression and LASSO analysis were employed to figure out genes significantly associated with survival. qRT-PCR and Western blot were utilized to validate the expression level of candidate genes. For clinical application, we constructed a nomogram, and also explored the value of RALUADS in characterizing immune infiltration features by CIBERSORT and xCell. Finally, responses to different drug therapy were predicted according to different RALUADS.Results: Our analysis identified two gene sets from differentially expressed genes and WGCNA gene modules of RA and LUAD. Filtered by survival analysis, three most significant shared genes were selected, CCN6, CDCA4 and ERLIN1, which were all upregulated in tumors and associated with poor prognosis. The three genes constituted RA and LUAD score (RALUADS). Our results demonstrated that RALUADS was higher in tumor patients and predicted poor prognosis in LUAD patients. Clinical nomogram combining RALUADS and other clinicopathological parameters had superior performance in survival prediction (AUC = 0.722). We further explored tumor immune microenvironment (TME) affected by RALUADS and observed RALUADS was closely related to the sensitivity of multiple immune blockades, chemotherapy and targeted drugs.Conclusion: Our findings suggest that there are shared physiopathologic processes and molecular profiles between RA and LUAD. RALUADS represents an excellent prognosis predictor and immune-related biomarker, which can be applied to select potential effective drugs and for LUAD patients with RA.

This meta-analysis examined the predictive value of admission serum and urine carboxypeptidase-B activation peptide (CAPAP) in patients with severe acute pancreatitis. PubMed, Embase, and the Cochrane Library were searched for relevant studies published up to February 21, 2022. Seven studies (439 acute pancreatitis patients) were included. The summary sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), the area under the receiver operating characteristic curve (AUC) of admission serum CAPAP were 0.86 (95%CI: 0.76-0.93), 0.78 (95%CI: 0.68-0.85), 3.89 (95%CI: 2.56-5.91), 0.18 (95%CI: 0.09-0.33), 18.56 (95%CI: 6.99-49.30), and 0.90 (95%CI: 0.87-0.92), respectively; these values for admission urine CAPAP were 0.82 (95%CI: 0.50-0.95), 0.78 (95%CI: 0.68-0.86), 3.75 (95%CI: 2.40-5.85), 0.23 (95%CI: 0.07-0.79), 9.87 (95%CI: 3.71-26.22), and 0.84 (95%CI: 0.80-0.87), respectively. There were no significant differences between admission serum and urine CAPAP in sensitivity (1.05, 95%CI: 0.75-1.47; P = 0.781), specificity (1.00, 95%CI: 0.85-1.18; P = 1.000), PLR (1.04, 95%CI: 0.56-1.91; P = 0.906), NLR (0.78, 95%CI: 0.20-3.10; P = 0.727), and DOR (1.88, 95%CI: 0.47-7.49; P = 0.370). The AUC of serum CAPAP (1.07, 95%: 1.02-1.13; P = 0.007) was higher than that of urine CAPAP in predicting acute pancreatitis severity. Both admission serum and urine CAPAP had moderate predictive values for assessing the severity of acute pancreatitis. Key highlights Both admission serum and urine carboxypeptidase-B activation peptide (CAPAP) had moderate predictive values for assessing the severity of acute pancreatitis. The predictive value of admission serum CAPAP was higher than that of admission urine CAPAP in predicting acute pancreatitis severity. Including the measurement of serum CAPAP at admission in patients with suspected pancreatitis could help triage the patients and determine the course of management. Hospital policymakers could consider including it among the routine tests at admission for such patients.

Abstract Background Increasing evidence indicates that the tumor microenvironment (TME) is a crucial determinant of cancer progression. However, the clinical and pathobiological significance of stromal signatures in the TME, as a complex dynamic entity, is still unclear in esophageal squamous cell carcinoma (ESCC). Methods Herein, we used single-cell transcriptome sequencing data, imaging mass cytometry (IMC) and multiplex immunofluorescence staining to characterize the stromal signatures in ESCC and evaluate their prognostic values in this aggressive disease. An automated quantitative pathology imaging system determined the locations of the lamina propria, stroma, and invasive front. Subsequently, IMC spatial analyses further uncovered spatial interaction and distribution. Additionally, bioinformatics analysis was performed to explore the TME remodeling mechanism in ESCC. To define a new molecular prognostic model, we calculated the risk score of each patient based on their TME signatures and pTNM stages. Results We demonstrate that the presence of fibroblasts at the tumor invasive front was associated with the invasive depth and poor prognosis. Furthermore, the amount of α-smooth muscle actin (α-SMA)+ fibroblasts at the tumor invasive front positively correlated with the number of macrophages (MØs), but negatively correlated with that of tumor-infiltrating granzyme B+ immune cells, and CD4+ and CD8+ T cells. Spatial analyses uncovered a significant spatial interaction between α-SMA+ fibroblasts and CD163+ MØs in the TME, which resulted in spatially exclusive interactions to anti-tumor immune cells. We further validated the laminin and collagen signaling network contributions to TME remodeling. Moreover, compared with pTNM staging, a molecular prognostic model, based on expression of α-SMA+ fibroblasts at the invasive front, and CD163+ MØs, showed higher accuracy in predicting survival or recurrence in ESCC patients. Regression analysis confirmed this model is an independent predictor for survival, which also identifies a high-risk group of ESCC patients that can benefit from adjuvant therapy. Conclusions Our newly defined biomarker signature may serve as a complement for current clinical risk stratification approaches and provide potential therapeutic targets for reversing the fibroblast-mediated immunosuppressive microenvironment.

Abstracts Background Giant Cell Arteritis (GCA) is a large vessel vasculitis that most commonly presents with headache, scalp tenderness, jaw claudication, and vision changes. Various other, less common, manifestations have been reported in the literature such as scalp and tongue necrosis. Though most patients respond to corticosteroids, some cases of GCA are refractory to the high doses of corticosteroids. Case presentation We present a 73-year-old female with GCA refractory to corticosteroids presenting with tongue necrosis. This patient significantly improved with a dose of tocilizumab, an IL-6 inhibitor. Conclusion To the best of our knowledge, this is the first case report of a patient with refractory GCA presenting with tongue necrosis that had rapid improvement with tocilizumab. Prompt diagnosis and treatment can prevent severe outcomes such as tongue amputation in GCA patients with tongue necrosis, and tocilizumab may be effective for corticosteroid-refractory cases.

Abstract Background Among six extant tiger subspecies, the South China tiger (Panthera tigris amoyensis) once was widely distributed but is now the rarest one and extinct in the wild. All living South China tigers are descendants of only two male and four female wild-caught tigers and they survive solely in zoos after 60 years of effective conservation efforts. Inbreeding depression and hybridization with other tiger subspecies were believed to have occurred within the small, captive South China tiger population. It is therefore urgently needed to examine the genomic landscape of existing genetic variation among the South China tigers. Results In this study, we assembled a high-quality chromosome-level genome using long-read sequences and re-sequenced 29 high-depth genomes of the South China tigers. By combining and comparing our data with the other 40 genomes of six tiger subspecies, we identified two significantly differentiated genomic lineages among the South China tigers, which harbored some rare genetic variants introgressed from other tiger subspecies and thus maintained a moderate genetic diversity. We noticed that the South China tiger had higher F ROH values for longer runs of homozygosity (ROH > 1 Mb), an indication of recent inbreeding/founder events. We also observed that the South China tiger had the least frequent homozygous genotypes of both high- and moderate-impact deleterious mutations, and lower mutation loads than both Amur and Sumatran tigers. Altogether, our analyses indicated an effective genetic purging of deleterious mutations in homozygous states from the South China tiger, following its population contraction with a controlled increase in inbreeding based on its pedigree records. Conclusions The identification of two unique founder/genomic lineages coupled with active genetic purging of deleterious mutations in homozygous states and the genomic resources generated in our study pave the way for a genomics-informed conservation, following the real-time monitoring and rational exchange of reproductive South China tigers among zoos.

PURPOSETo explore the utility of four-phase computed tomography (CT) in distinguishing renal oncocytoma with central hypodense areas from clear cell renal cell carcinoma (ccRCC).METHODSEighteen patients with oncocytoma and 63 patients with ccRCC presenting with central hypodense areas were included in this study. All patients underwent four-phase CT imaging including the excretory phases later than 20 min after contrast injection. Two blinded experienced radiologists visually reviewed the enhancement features of the central hypodense areas in the excretory phase images and selected the area demonstrating the greatest degree of enhancement of the tumor in the corticomedullary phase images. Regions of interest (ROIs) were placed in the same location in each of the three contrast-enhanced imaging phases. Additionally, ROIs were placed in the adjacent normal renal cortex for normalization. The ratio of the lesion to cortex attenuation (L/C) for the three contrast-enhanced imaging phases and absolute de-enhancement were calculated. The receiver operating characteristic curve was used to obtain the cut-off values.RESULTSComplete enhancement inversion of the central areas was observed in 12 oncocytomas (66.67%) and 16 ccRCCs (25.40%) (P = 0.003). Complete enhancement inversion combined with L/C in the corticomedullary phase lower than 1.0 (P < 0.001) or absolute de-enhancement lower than 42.5 HU (P < 0.001) provided 86.42% and 85.19% accuracy, 61.11% and 55.56% sensitivity, 93.65% and 93.65% specificity, 73.33% and 71.43% positive predictive value (PPV), and 89.39% and 88.06% negative predictive value (NPV), respectively, for the diagnosis of oncocytomas. Combined with complete enhancement inversion, L/C in the corticomedullary phase lower than 1.0 and absolute de-enhancement lower than 42.5 HU provided 87.65%, 55.56%, 96.83%, 83.33%, and 88.41% of accuracy, sensitivity, specificity, PPV, and NPV, respectively, for the diagnosis of oncocytomas.CONCLUSIONThe combination of enhancement features of the central hypodense areas and the peripheral tumor parenchyma can help distinguish oncocytoma with central hypodense areas from ccRCC.

Inner coastal wetland ecosystems are generally eutrophic and are often exposed to both salinity stress and Escherichia coli pollution. However, the effects of these stressors on nutrient-cycling and microbial communities are under-researched. Here, we established a vegetated wetland ecosystem in a saline environment to understand the effects of E. coli pollution on nutrient removal and benthic microorganisms. The results show that E. coli significantly inhibited nutrient removal, especially total nitrogen (TN) and ammonium (78.89–84.98 and 3.45–44.65% were removed from the non-E. coli-treated and the E. coli-treated water, respectively). Compared with non-vegetated systems, archaeal community variations at both compositional and phylogenetic levels were weakened in vegetated systems (p < 0.05). Among all the environmental factors, the ratios of PO43--P to total phosphorus and NO3--N to TN contributed the most to archaeal and bacterial community structural variations, respectively. E. coli pollution affected archaeal community succession more than bacteria (p < 0.05). E. coli also weakened the trophic transferring efficiencies between Cyanobacteria and Myxobacteria (p < 0.05). Metabolically, E. coli inhibited bacterial genetic metabolic pathways but made human infection more likely (p < 0.05). Our findings provide new insights into aquatic ecological conservation and environmental management. HIGHLIGHTS The removal of TN and was significantly inhibited by E. coli.; Submerged vegetation weakened the archaeal community variations caused by E. coli.; Submerged vegetation enhanced the bacterial community variations caused by E. coli.; E. coli pollution affected archaeal community succession than bacteria.; E. coli weakened trophic transfers between Cyanobacteria and Myxobacteria.;

Background: To evaluate the clinical performance and clinical implementation of noninvasive prenatal testing (NIPT) using fetal fraction (FF) enrichment. Methods: Both standard NIPT and NIPT with FF enrichment were performed concurrently to 277 clinical samples. Results: On average, the FF of each sample processed by NIPT with FF enrichment was 1.9-fold higher than without enrichment. 88% (43/49) of samples with low FF in standard NIPT were recovered by the enrichment method. 11 more copy number variants (CNVs) which were confirmed by prenatal diagnosis were detected by NIPT with FF enrichment. NIPT with FF enrichment generated a positive predictive value of 75% for CNVs (≥3 Mb and 22q11.2 ≥1 Mb). NIPT with FF enrichment showed similar performance in the detection of common trisomy when compared with the standard method. Pregnant women with higher body mass indexes experienced significantly greater enriching effects on FF from NIPT with the enrichment protocol. Conclusions: NIPT with FF enrichment effectively elevated the FF level. This method is capable of detecting significantly more concordant CNVs with a positive predictive value (PPV) of 75%. Our data suggest that this enhanced version of NIPT can be used to improve the screening performance of clinically significant fetal CNVs but it should only be recommended when comprehensive counseling is available.