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Abstract Disorders of gallbladder motility can lead to serious pathology. Bitter tastants acting upon bitter taste receptors (TAS2R family) have been proposed as a novel class of smooth muscle relaxants to combat excessive contraction in the airways and other organs. To explore whether this might also emerge as an option for gallbladder diseases, we here tested bitter tastants for relaxant properties and profiled Tas2r expression in the mouse gallbladder. In organ bath experiments, the bitter tastants denatonium, quinine, dextromethorphan, and noscapine, dose-dependently relaxed the pre-contracted gallbladder. Utilizing gene-deficient mouse strains, neither transient receptor potential family member 5 (TRPM5), nor the Tas2r143/Tas2r135/Tas2r126 gene cluster, nor tuft cells proved to be required for this relaxation, indicating direct action upon smooth muscle cells (SMC). Accordingly, denatonium, quinine and dextromethorphan increased intracellular calcium concentration preferentially in isolated gallbladder SMC and, again, this effect was independent of TRPM5. RT-PCR revealed transcripts of Tas2r108, Tas2r126, Tas2r135, Tas2r137, and Tas2r143, and analysis of gallbladders from mice lacking tuft cells revealed preferential expression of Tas2r108 and Tas2r137 in tuft cells. A TAS2R143-mCherry reporter mouse labeled tuft cells in the gallbladder epithelium. An in silico analysis of a scRNA sequencing data set revealed Tas2r expression in only few cells of different identity, and from in situ hybridization histochemistry, which did not label distinct cells. Our findings demonstrate profound tuft cell- and TRPM5-independent relaxing effects of bitter tastants on gallbladder smooth muscle, but do not support the concept that these effects are mediated by bitter receptors.

Abstract Skeletonema tropicum is a marine diatom of the genus Skeletonema that also includes many well-known species including S. marinoi. S. tropicum is a high temperature preferring species thriving in tropical ocean regions or temperate ocean regions during summer-autumn. However, mechanisms of ecological adaptation of S. tropicum remain poorly understood due partially to the lack of a high-quality whole genome assembly. Here, we report the first high-quality chromosome-scale genome assembly for S. tropicum, using cutting-edge technologies including PacBio single molecular sequencing and high-throughput chromatin conformation capture. The assembled genome has a size of 78.78 Mb with a scaffold N50 of 3.17 Mb, anchored to 23 pseudo-chromosomes. In total, 20,613 protein-coding genes were predicted, of which 17,757 (86.14%) genes were functionally annotated. Collinearity analysis of the genomes of S. tropicum and S. marinoi revealed that these two genomes were highly homologous. This chromosome-level genome assembly of S. tropicum provides a valuable genomic platform for comparative analysis of mechanisms of ecological adaption.

Summary: The phytoplankton Phaeocystis globosa plays an important role in sulfur cycling and climate control, and can develop harmful algal blooms (HABs). Here we report a chromosome-scale reference genome assembly of P. globosa, which enable in-depth analysis of molecular underpinnings of important ecological characteristics. Comparative genomic analyses detected two-rounds of genome duplications that may have fueled evolutionary innovations. The genome duplication may have resulted in the formation of dual HiDP and LoDP dimethylsulphoniopropionate (DMSP) biosynthesis pathways in P. globosa. Selective gene family expansions may have strengthened biological pathways critical for colonial formation that is often associated with the development of algal blooms. The copy numbers of rhodopsin genes are variable in different strains, suggesting that rhodopsin genes may play a role in strain-specific adaptation to ecological factors. The successful reconstruction of the P. globosa genome sets up an excellent platform that facilitates in-depth research on bloom development and DMSP metabolism.

Asthma is a heterogeneous airway inflammatory disease that can be classified according to the inflammatory phenotype. The pathogenesis, clinical features, response to hormone therapy, and prognosis of different inflammatory phenotypes differ significantly. This condition also refers to age-related chronic ailments. Here, we intend to identify the function of aging-related genes in different inflammatory phenotypes of asthma using bioinformatic analyses. Initially, the research adopted the GSEA analysis to understand the fundamental mechanisms that govern different inflammatory phenotypes of asthma pathogenesis and use the CIBERSORT algorithm to assess the immune cell composition. The differentially expressed genes (DEGs) of eosinophilic asthma (EA), neutrophilic asthma (NA), and paucigranulocytic asthma (PGA) were identified through the limma R package. Aging-related genes, screened from multiple databases, were intersected with DEGs of asthma to obtain the asthma-aging-related DEGs. Then, the GO and KEGG pathway enrichment analyses showed that the NA- and EA-aging-related DEGs are involved in the various cytokine-mediated signaling pathways. PPI network and correlation analysis were performed to identify and evaluate the correlation of the hub genes. Further, the clinical characteristics of asthma-aging-related DEGs were explored through ROC analysis. 3 and 12 aging-related DEGs in EA and NA patients show high diagnostic accuracy, respectively (AUC >0.7). This study provided valuable insights into aging-related gene therapy for phenotype-specific asthma. Moreover, the study suggests that effective interventions against asthma may operate by disrupting the detrimental cycle of “aging induces metabolic diseases, which exacerbate aging''.

Abstract Uterine leiomyosarcoma (uLMS) is an aggressive mesenchymal neoplasm associated with a poor prognosis. Systemic chemotherapy is the standard therapy for patients with uLMS. However, it is unclear which treatment regimen results in the most favorable clinical outcome. We performed a meta‐analysis and meta‐regression analysis to assess the efficiency of different treatments received by patients with advanced, metastatic, and relapsing uLMS by evaluating the objective response rate (ORR) and disease control rate (DCR) as primary endpoints. The frequentist random effects meta‐analysis model was used to compare the outcomes of different treatment regimens for advanced uLMS. A meta‐regression analysis was performed to estimate the association between the study‐specific hazard ratios and specific demographic variables. A meta‐analysis of 51 reports including 1664 patients was conducted. Among patients who received adjuvant chemotherapy (916 patients; 55%), gemcitabine and docetaxel were the most frequently used drugs. First‐line monotherapy with alkylating agents (pooled ORR = 0.48; 95% confidence interval [CI]: 0.44–0.52) and second‐line monotherapy with protein kinase inhibitors (pooled ORR = 0.45; 95% CI: 0.39–0.52) resulted in favorable prognoses. The combinations of anthracycline plus alkylating therapy (pooled DCR = 0.74; 95% CI: 0.67–0.79) and of gemcitabine plus docetaxel (pooled DCR = 0.70; 95% CI: 0.63–0.75) showed the greatest benefits when used as first‐line and second‐line chemotherapies, respectively. Subgroup meta‐analysis results revealed that dual‐regimen therapies comprising anthracycline plus alkylating therapy and gemcitabine plus docetaxel are practical therapeutic choices for International Federation of Gynecology and Obstetrics stages III–IVb with distant metastases when assessed by computed tomography (p = 0.001). Furthermore, neoadjuvant chemotherapy and local radiotherapy resulted in favorable outcomes for patients with earlier stages of distant relapsed uLMS (p

Abstract Background Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, and histopathologic glomerular lesions are among the earliest structural alterations of DN. However, the signaling pathways that initiate these glomerular alterations are incompletely understood. Methods To delineate the cellular and molecular basis for DN initiation, we performed single-cell and bulk RNA sequencing of renal cells from type 2 diabetes mice (BTBR ob/ob) at the early stage of DN. Results Analysis of differentially expressed genes revealed glucose-independent responses in glomerular cell types. The gene regulatory network upstream of glomerular cell programs suggested the activation of mechanosensitive transcriptional pathway MRTF-SRF predominantly taking place in mesangial cells. Importantly, activation of MRTF-SRF transcriptional pathway was also identified in DN glomeruli in independent patient cohort datasets. Furthermore, ex vivo kidney perfusion suggested that the regulation of MRTF-SRF is a common mechanism in response to glomerular hyperfiltration. Conclusions Overall, our study presents a comprehensive single-cell transcriptomic landscape of early DN, highlighting mechanosensitive signaling pathways as novel targets of diabetic glomerulopathy.

Abstract Background Regenerative endodontic procedures (REPs) have achieved clinical success on the immature permanent teeth with pulp necrosis, and can promote root development. However, preoperative factors and their effects on root development of REPs have not been definitely concluded. The aim of this study was to investigate the preoperative factors that may influence the root development of REPs. Methods A total of 116 teeth in 110 patients treated with REPs in the Paediatric Dentistry Department and Endodontics Department from 2013 to 2017 were included in this study. Preoperative factors including aetiology, age, diagnosis and initial root morphology were collected retrospectively, and the associations between these factors and root development after REPs were analysed by Fisher's exact test and multivariate logistic regression model. Results The overall rate of root development after REPs was 89.7%. The dens evaginatus group showed a higher rate (98.8%) in root development than the trauma group (67.6%) (P 0.05). And it showed in the trauma group that the teeth with apical foramen sizes larger than 3 mm significantly promoted root development than those smaller than 3 mm (P

Interleukin-10 (IL-10) is a pleiotropic cytokine with both immune enhancement and immunosuppression activities, but the main role is immunosuppression and anti-inflammatory ability. In order to use the immunosuppressive function of IL-10, many viruses, such as SARS-CoV-2, hepatitis B virus and EB virus, can evade the host’s immune surveillance and clearance by increasing the expression of host IL-10. However, it has not been reported whether the aquatic animal infection virus can upregulate the expression of host IL-10 and the mechanisms are still unknown. Spring viremia of carp (SVC) is a fatal viral disease for many fish species and is caused by spring viremia of carp virus (SVCV). This disease has caused significant economic losses in the aquaculture industry worldwide. In this study, the expression of carp IL-10 with or without infection of SVCV in epithelioma papulosum cyprinid (EPC) cells, carp head kidney (cHK) primary cells and common carp tissues were analyzed using RT-PCR and ELISA. The results show that SVCV infection induced carp IL-10 mRNA and protein expression, both in vitro and in vivo. However, the upregulation of carp IL-10 by SVCV was hindered by specific inhibitors of the JAK inhibitor (CP-690550), STAT3 inhibitor (STA-21), NF-κB inhibitor (BAY11-7082) and p38 MAPK (mitogen-activated protein kinase) inhibitor (SB202190), but not JNK inhibitor (SP600125). Furthermore, the results demonstrated that JAK1, JAK2, JAK3, TYK2 and STAT5 played important roles in carp IL-10 production induced by SVCV infection. Taken together, SVCV infection significantly induced carp IL-10 expression and the upregulation trigged in JAK-STAT, NF-κB and p38MAPK pathways. To our knowledge, this is the first time that a fish infection virus upregulated the host IL-10 expression through the JAK-STAT, NF-κB and p38MAPK pathways. Altogether, fish viruses may have a similar mechanism as human or other mammalian viruses to escape host immune surveillance and clearance.

Molecular luminescent materials with optical waveguide have wide application prospects in light-emitting diodes, sensors, and logic gates. However, the majority of traditional optical waveguide systems are based on brittle molecular crystals, which limited the fabrication, transportation, storage, and adaptation of flexible devices under diverse application situations. To date, the design and synthesis of photofunctional materials with high flexibility, novel optical waveguide, and multi-port color-tunable emission in the same solid-state system remain an open challenge. Here, we have constructed new types of zero-dimensional organic metal halides (Au-4-dimethylaminopyridine [DMAP] and In-DMAP) with a rarely high elasticity and rather low loss coefficients for optical waveguide. Theoretical calculations on the intermolecular interactions showed that the high elasticity of 2 molecular crystalline materials was original from their herringbone structure and slip plane. Based on one-dimensional flexible microrods of 2 crystals and the 2-dimensional microplate of the Mn-DMAP, heterojunctions with multi-color and space-resolved optical waveguides have been fabricated. The formation mechanism of heterojunctions is based on the surface selective growth on account of the low lattice mismatch ratio between contacting crystal planes. Therefore, this work describes the first attempt to the design of metal-halide-based crystal heterojunctions with high flexibility and optical waveguide, expanding the prospects of traditional luminescent materials for smart optical devices, such as logic gates and multiplexers.

Abstract Background Skeletonema species are prominent primary producers, some of which can also cause massive harmful algal blooms (HABs) in coastal waters under specific environmental conditions. Nevertheless, genomic information of Skeletonema species is currently limited, hindering advanced research on their role as primary producers and as HAB species. Mitochondrial genome (mtDNA) has been extensively used as “super barcode” in the phylogenetic analyses and comparative genomic analyses. However, of the 21 accepted Skeletonema species, full-length mtDNAs are currently available only for a single species, S. marinoi. Results In this study, we constructed full-length mtDNAs for six strains of five Skeletonema species, including S. marinoi, S. tropicum, S. grevillei, S. pseudocostatum and S. costatum (with two strains), which were isolated from coastal waters in China. The mtDNAs of all of these Skeletonema species were compact with short intergenic regions, no introns, and no repeat regions. Comparative analyses of these Skeletonema mtDNAs revealed high conservation, with a few discrete regions of high variations, some of which could be used as molecular markers for distinguishing Skeletonema species and for tracking the biogeographic distribution of these species with high resolution and specificity. We estimated divergence times among these Skeletonema species using 34 mtDNAs genes with fossil data as calibration point in PAML, which revealed that the Skeletonema species formed the independent clade diverging from Thalassiosira species approximately 48.30 Mya. Conclusions The availability of mtDNAs of five Skeletonema species provided valuable reference sequences for further evolutionary studies including speciation time estimation and comparative genomic analysis among diatom species. Divergent regions could be used as molecular markers for tracking different Skeletonema species in the fields of coastal regions.

The glomerular filtration barrier (GFB) produces primary urine and is composed of a fenestrated endothelium, a glomerular basement membrane (GBM), podocytes, and a slit diaphragm. Impairment of the GFB leads to albuminuria and microhematuria. The GBM is generated via secreted proteins from both endothelial cells and podocytes and is supposed to majorly contribute to filtration selectivity. While genetic mutations or variations of GBM components have been recently proposed to be a common cause of glomerular diseases, pathways modifying and stabilizing the GBM remain incompletely understood. Here, we identified prolyl 3-hydroxylase 2 (P3H2) as a regulator of the GBM in an a cohort of patients with albuminuria. P3H2 hydroxylates the 3′ of prolines in collagen IV subchains in the endoplasmic reticulum. Characterization of a P3h2ΔPod mouse line revealed that the absence of P3H2 protein in podocytes induced a thin basement membrane nephropathy (TBMN) phenotype with a thinner GBM than that in WT mice and the development of microhematuria and microalbuminuria over time. Mechanistically, differential quantitative proteomics of the GBM identified a significant decrease in the abundance of collagen IV subchains and their interaction partners in P3h2ΔPod mice. To our knowledge, P3H2 protein is the first identified GBM modifier, and loss or mutation of P3H2 causes TBMN and focal segmental glomerulosclerosis in mice and humans.

Abstract BRAF and NRAS are the most reported mutations associated to melanomagenesis. The lack of accurate diagnostic markers in response to therapeutic treatment in BRAF/NRAS-driven melanomagenesis is one of the main challenges in melanoma personalized therapy. In order to assess the diagnostic value of phosphatidylserine-specific phospholipase A1-alpha (PLA1A), a potent lysophospholipid mediating the production of lysophosphatidylserine, PLA1A mRNA and serum levels were compared in subjects with malignant melanoma (n = 18), primary melanoma (n = 13), and healthy subjects (n = 10). Additionally, the correlation between histopathological subtypes of BRAF/NRAS-mutated melanoma and PLA1A was analyzed. PLA1A expression was significantly increased during melanogenesis and positively correlated to disease severity and histopathological markers of metastatic melanoma. PLA1A mRNA and serum levels were significantly higher in patients with BRAF-mutated melanoma compared to the patients with NRAS-mutated melanoma. Notably, PLA1A can be used as a diagnostic marker for an efficient discrimination between naïve melanoma samples and advanced melanoma samples (sensitivity 91%, specificity 57%, and AUC 0.99), as well as BRAF-mutated melanoma samples (sensitivity 62%, specificity 61%, and AUC 0.75). Our findings suggest that PLA1A can be considered as a potential diagnostic marker for advanced and BRAF-mutated melanoma.

Diatoms (Bacillariophyta) constitute one of the most diverse and ecologically significant groups of phytoplankton, comprising 100,000–200,000 species in three classes Bacillariophyceae, Mediophyceae, and Coscinodiscophyceae. However, due to the limited resolution of common molecular markers including 18S rDNA, 28S rDNA, ITS, rbcL, and cox1, diatom biodiversity has not been adequately ascertained. Organelle genomes including mitochondrial genomes (mtDNAs) have been proposed to be “super barcodes” for distinguishing diatom species because of their rich genomic content, and the rapid progress of DNA sequencing technologies that has made it possible to construct mtDNAs with increasing throughout and decreasing cost. Here, we constructed complete mtDNAs of 15 diatom species including five Coscinodiscophyceae species (Guinardia delicatula, Guinardia striata, Stephanopyxis turris, Paralia sulcata, and Actinocyclus sp.), four Mediophyceae species (Hemiaulus sinensis, Odontella aurita var. minima, Lithodesmioides sp., and Helicotheca tamesis), and six Bacillariophyceae species (Nitzschia ovalis, Nitzschia sp., Nitzschia traheaformis, Cylindrotheca closterium, Haslea tsukamotoi, and Pleurosigma sp.) to test the practicality of using mtDNAs as super barcodes. We found that mtDNAs have much higher resolution compared to common molecular markers as expected. Comparative analysis of mtDNAs also suggested that mtDNAs are valuable in evolutionary studies by revealing extensive genome rearrangement events with gene duplications, gene losses, and gains and losses of introns. Synteny analyses of mtDNAs uncovered high conservation among species within an order, but extensive rearrangements including translocations and/or inversions between species of different orders within a class. Duplication of cox1 was discovered for the first time in diatoms in Nitzschia traheaformis and Haslea tsukamotoi. Molecular dating analysis revealed that the three diatom classes split 100 Mya and many diatom species appeared since 50 Mya. In conclusion, more diatom mtDNAs representing different orders will play great dividends to explore biodiversity and speciation of diatoms in different ecological regions.

Thalassiosira is a species-rich genus with about 170 described species, many of which are harmful algal species with significant negative ecological impact. However, genome data of these species remain limited. In this study, the complete mitochondrial genome of Thalassiosira profunda (Hendey) Hasle 1973 was determined for the first time. The circular genome was 40,470 bp in length with GC content of 30.98%. It encodes 63 genes including 36 protein-coding genes (PCGs), 25 tRNA genes, and two rRNA genes. Phylogenetic analysis using concatenated PCGs suggested that T. profunda had a closer evolutionary relationship with Skeletonema marinoi of a different family (Skeletonemataceae) than Thalassiosira pseudonana, suggesting complex evolutionary relationship among species in these two families. Colinearity analysis also revealed fewer genome rearrangements between T. profunda and S. marinoi than that between T. profunda and T. pseudonana. This study suggests that mitochondrial genomes of many more species in the Thalassiosiraceae and Skeletonemataceae families are needed to disentangle the complex evolutionary relationships in the order of Thalassiosirales.

Thalassiosira nordenskioeldii is a common harmful algal bloom (HAB) species with worldwide distribution. Although barcode sequences of this ecologically important species have been published, no genome data have been published for T. nordenskioeldii. In this study, we constructed the complete mitochondrial genome (mtDNA) of a T. nordenskioeldii strain isolated from the East China Sea. The T. nordenskioeldii mtDNA is circular and has a length of 47,038 bp and a GC content of 30.84%. The mtDNA encodes 69 genes, including 40 protein-coding (PCGs), 27 tRNA and two rRNA genes. Phylogenetic analysis using concatenated amino acid sequences of 31 shared PCGs from 37 diatom mtDNAs revealed that the mtDNA of T. nordenskioeldii was fully resolved in a clade with that of Thalassiosira profunda. The mtDNA of T. nordenskioeldii showed high collinearity with those of T. profunda and Skeletonema marinoi with only minor rearrangements. The completion of Thalassiosira mtDNAs will facilitate evolutionary studies on species of the order Thalassiosirales and the class Mediophyceae.

Molecular luminescence is generally significantly quenched at high temperature. Here the authors report a zero-dimensional metal halide hybrid that exhibits zero-thermal-quenching ultralong phosphorescence over a wide temperature range of 220 K, and demonstrate use for Morse code encryption and logic gates.

This study aimed to identify a novel disease-associated differentially co-expressed mRNA-microRNA (miRNA) that is associated with vasculogenic mimicry (VM) and epithelial-to-mesenchymal transition (EMT) network at different stages of melanoma. By applying weighted gene co-expression network analysis, we constructed a VM+EMT biological network with the available microarray dataset downloaded from a public database. Quantitative real-time PCR, immunohistochemical staining, and CD31-periodic acid solution dual staining were performed to confirm the expression of genes associated with EMT and VM formation in subjects with malignant melanoma (n = 18) and primary melanoma (n = 13) and in healthy subjects (n = 10). Our findings suggested that phosphatidylserine-specific phospholipase A1-alpha (PLA1A) and dermokine (DMKN) genes function as oncogenes that trigger VM and EMT processes during melanomagenesis on interaction with miR-370, miR-563, and miR-770–5p. PLA1A and DMKN genes can be considered potential VM+EMT network-based diagnostic biomarkers for distinguishing between melanoma patients. We postulate that a network with altered PLA1A/miR-563 and DMNK/miR-770–5p/miR-370 may contribute to melanomagenesis by triggering the EMT signaling pathway and VM formation. This study provides a potentially valuable approach for the early diagnosis and prognosis of melanoma progression.

Skeletonema species are cosmopolitan coastal diatoms that exhibit important roles in ecological system. The chloroplast genomes (cpDNAs) have been proven to be important in the study of molecular evolution and genetic diversity. However, cpDNA of only a single Skeletonema species (S. pseudocostatum) has been constructed, hindering in-depth investigation on Skeletonema species. In this study, complete cpDNAs of five Skeletonema species were constructed with cpDNAs of four species S. marinoi, S. tropicum, S. costatum, and S. grevillea constructed for the first time. These cpDNAs had similar sizes and same numbers of genes. These cpDNAs were highly syntenic with no substantial expansions, contractions, or inversions. Interestingly, two copies of petF, which encodes ferredoxin with critical role in iron dependency, were found in all five Skeletonema species, with one copy in the cpDNA and another copy in the nuclear genome of each species. Selection analysis revealed that all PCGs of cpDNAs were undergoing purifying selection. Despite the high conservation of these cpDNAs, nine genomic regions with high sequence divergence were identified, which illustrated substantial variations that could be used as markers for phylogenetic inference and for tracking Skeletonema species in the field. Additionally, the numbers of simple sequence repeats varied among different cpDNAs, which were useful for detecting genetic polymorphisms. The divergence times estimated using PCGs of cpDNAs revealed that most of these species were established within ∼33 Mya, consistent with that estimated using mtDNAs. Overall, the current study deepened our understanding about the molecular evolution of Skeletonema cpDNAs.

Thalassiosira is a species-rich genus in Bacillariophyta with important ecological contribution to primary productivity but can also pose negative impact on ecology by developing harmful algal blooms (HABs). However, genomic resources of only a few Thalassiosira species are currently available. Here, we constructed complete chloroplast genomes (cpDNAs) of six Thalassiosira strains (representing six Thalassiosira species T. rotula, T. profunda, T. nordenskioeldii, T. tenera, T. weissflogii, and Thalassiosira sp.), and compared them with published cpDNAs of other diatoms. Comparative analysis revealed that Thalassiosira cpDNAs have generally conventional and conserved quadripartite structure with important exceptions. Gene orders of cpDNAs of Thalassiosira sp. (CNS00561) and T. oceanica were different from that of other Thalassiosira species. Additionally, endosymbiotic gene transfers (EGT) were found to occur in the evolution of Thalassiosira cpDNAs. Furthermore, genomic regions of cpDNAs were found to be highly variable, which could be used to construct molecular markers for distinguishing Thalassiosira species with high resolution and high specificity. This study also demonstrated that Thalassiosira species emerged roughly around 51 MYA and diversified 17–28 MYA. Thalassiosira cpDNAs are not only valuable as super-barcode for phylogenetic analysis, but also important for functional and evolutionary analysis of diatoms.

The Fenwei Plain plays an essential role for China’s three-year action plan to protect the air environment. At present, the high-value area and maximum value of atmospheric aerosol have been effectively controlled, but the governance situation is not stable. Therefore, based on the daily ultraviolet aerosol index (UVAI) data retrieved by Ozone Monitoring Instrument (OMI) from 2012 to 2020, combined with precipitation and temperature and air pressure and lifting index data, this paper analyzes the spatiotemporal distribution characteristics and some influencing factors of UVAI in the Fenwei Plain. The results show that the overall trend of the annual average UVAI value of the Fenwei Plain in 9 years showed two “peaks” in 2013 and 2018, respectively. The high UVAI values are mainly concentrated in the southwest and central areas of the Fenwei Plain. In the study area, UVAI was highest in winter, followed by autumn and spring, and lowest in summer. There were significant negative correlations between precipitation and UVAI and between temperature and UVAI. There were significant positive correlations between air pressure and UVAI and between lifting index and UVAI. According to the backward trajectory clustering results, during the autumn and winter seasons in this area, due to the sand and dust brought by the northwest and the input of aerosols in the coal-producing area and coal-fired heating area, the UVAI value of this time period is higher.

In this study, we perform a meta-analysis and meta-regression analysis for the article entitled “Prognostic value of systemic hemato-immunological indices in uterine cervical cancer: A systemic review, meta-analysis, and meta-regression of observational studies.” [1] We implemented quantitative meta-analyses and time series meta-regression analysis to determine whether systemic hemato-immunological indices, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), thrombocyte-to-lymphocyte ratio (TLR), and C-reactive protein/albumin ratio (CAR) are associated with an increased risk of cervical collision cancer. In all, 9558 patients from 22 studies were included after a systematic data search, performed comprehensively using the following databases: MEDLINE, Web of Science, Embase, and Cochrane. The meta-analysis was conducted with a random-effects model using the Review Manager software (Revman version 5.3). The overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) data were compared among each observational study. All data are expressed as hazard ratios (HRs) and 95% confidence intervals (CIs), and were calculated using the generic inverse of variance method. Statistical heterogeneity was quantified using Cochrane's Q statistic and Higgins I2 statistic. Subgroup analysis was performed to investigate the sources of heterogeneity. Furthermore, quality assessment of the included datasets was presented according to the Newcastle-Ottawa Scale method. Additionally, sensitivity analysis was conducted to explore the sources of heterogeneity and analyze whether the results were stable and reliable. Meta-analysis random-effect approach was used for the regression to evaluate the effect of age, presence of squamous cell carcinoma patients, and number of evaluated NLR and PLR parameters on patient survival.

Selecting the flow accumulation threshold (FAT) plays a central role in extracting drainage networks from Digital Elevation Models (DEMs). This work presents the MR-AP (Multiple Regression and Adaptive Power) method for choosing suitable FAT when extracting drainage from DEMs. This work employs 36 sample sub-basins in Hubei (China) province. Firstly, topography, the normalized difference vegetation index (NDVI), and water storage change are used in building multiple regression models to calculate the drainage length. Power functions are fit to calculate the FAT of each sub-basin. Nine randomly chosen regions served as test sub-basins. The results show that: (1) water storage change and NDVI have high correlation with the drainage length, and the coefficient of determination (R2) ranges between 0.85 and 0.87; (2) the drainage length obtained from the Multiple Regression model using water storage change, NDVI, and topography as influence factors is similar to the actual drainage length, featuring a coefficient of determination (R2) equal to 0.714; (3) the MR-AP method calculates suitable FATs for each sub-basin in Hubei province, with a drainage length error equal to 5.13%. Moreover, drainage network extraction by the MR-AP method mainly depends on the water storage change and the NDVI, thus being consistent with the regional water-resources change.

Comprehensively evaluating satellite precipitation products (SPPs) for hydrological simulations on watershed scales is necessary given that the quality of different SPPs varies remarkably in different regions. The Yellow River source region (YRSR) of China was chosen as the study area. Four SPPs were statistically evaluated, namely, the Tropical Rainfall Measurement Mission (TRMM) Multisatellite Precipitation Analysis (TMPA) 3B42V7, Precipitation Estimation from Remotely Sensed Information using Artificial Neural Networks Climate Data Record (PERSIANN-CDR), Integrated Multisatellite Retrievals for Global Precipitation Measurement final run (IMERG-F), and gauge-corrected Global Satellite Mapping of Precipitation (GSMaP-Gauge) products. Subsequently, the hydrological utility of these SPPs was assessed via the variable infiltration capacity hydrological model on a daily temporal scale. Results show that the four SPPs generally demonstrate similar spatial distribution pattern of precipitation to that of the ground observations. In the period of January 1998 to December 2016, 3B42V7 outperforms PERSIANN-CDR on basin scale. In the period of April 2014 to December 2016, GSMaP-Gauge demonstrates the highest precipitation monitoring capability and hydrological utility among all SPPs on grid and basin scales. In general, 3B42V7, IMERG-F, and GSMaP-Gauge show a satisfactory hydrological performance in streamflow simulations in YRSR. IMERG-F has an improved hydrological utility than 3B42V7 in YRSR.

High-resolution precipitation field has been widely used in hydrological and meteorological modeling. This paper establishes the spatial and temporal distribution model of precipitation in Hubei Province from 2006 through 2014, based on the data of 75 meteorological stations. This paper applies a geographically and temporally weighted regression kriging (GTWRK) model to precipitation and assesses the effects of timescales and a time-weighted function on precipitation interpolation. This work’s results indicate that: (1) the optimal timescale of the geographically and temporally weighted regression (GTWR) precipitation model is daily. The fitting accuracy is improved when the timescale is converted from months and years to days. The average mean absolute error (MAE), mean relative error (MRE), and the root mean square error (RMSE) decrease with scaling from monthly to daily time steps by 36%, 56%, and 35%, respectively, and the same statistical indexes decrease by 13%, 15%, and 14%, respectively, when scaling from annual to daily steps; (2) the time weight function based on an exponential function improves the predictive skill of the GTWR model by 3% when compared to geographically weighted regression (GWR) using a monthly time step; and (3) the GTWRK has the highest accuracy, and improves the MAE, MRE and RMSE by 3%, 10% and 1% with respect to monthly precipitation predictions, respectively, and by 3%, 10% and 5% concerning annual precipitation predictions, respectively, compared with the GWR results.

For c-φ soil formation (cohesive soil) of limited width with ground surface overload behind a deep retaining structure, a modified active earth pressure calculation model is established in this study. And three key issues are addressed through improved soil arching effect. First, the soil-wall interaction mechanism is determined by considering the soil arching effect. The slip surface of a limited soil is proved to be a double-fold line passing through the retaining wall toe and intersecting the side wall of the existing underground structure until it reaches the ground surface along the existing side wall. Second, the limited width boundary is explicated. And third, the variation in the active earth pressure from parameters of limited c-φ soil is determined. The lateral active earth pressure coefficient is nonlinear distributed based on the improved soil arching effect of the symmetric catenary curve. Furthermore, the active earth pressure distribution, the tension crack at the top of the retaining wall and the resultant force and its action point were obtained. By comparing with the existing analytical methods, such as the Rankine method, it demonstrates that the model proposed in this study is much closer to the measured and numerical results. Ignoring the influence of soil cohesion and the limited width will exponentially reduce the overall stability of the retaining structure and increase the risk of accidents.

The mouse bitter taste receptors Tas2r143, Tas2r135, and Tas2r126 are encoded by genes that cluster on chromosome 6 and have been suggested to be expressed under common regulatory elements. Previous studies indicated that the Tas2r143/Tas2r135/Tas2r126 cluster is expressed in the heart, but other organs had not been systematically analyzed. In order to investigate the expression of this bitter taste receptor gene cluster in non-gustatory tissues, we generated a BAC (bacterial artificial chromosome) based transgenic mouse line, expressing CreERT2 under the control of the Tas2r143 promoter. After crossing this line with a mouse line expressing EGFP after Cre-mediated recombination, we were able to validate the Tas2r143-CreERT2 transgenic mouse line and monitor the expression of Tas2r143. EGFP-positive cells, indicating expression of members of the cluster, were found in about 47% of taste buds, and could also be found in several other organs. A population of EGFP-positive cells was identified in thymic epithelial cells, in the lamina propria of the intestine and in vascular smooth muscle cells of cardiac blood vessels. EGFP-positive cells were also identified in the epithelium of organs readily exposed to pathogens including lower airways, the gastrointestinal tract, urethra, vagina, and cervix. With respect to the function of cells expressing this bitter taste receptor cluster, RNA-seq analysis in EGFP-positive cells isolated from the epithelium of trachea and stomach showed expression of genes related to innate immunity. These data further support the concept that bitter taste receptors serve functions outside the gustatory system.

GPR116 (ADGRF5) and ELTD1 (ADGRL4) belong to different subfamilies of the adhesion G-protein-coupled receptor group but are both expressed in endothelial cells. We therefore analyzed their functions in mice lacking these receptors. While loss of GPR116 or ELTD1 alone had no obvious effect on cardiovascular or kidney function, mice lacking both, GPR116 and ELTD1, showed malformations of the aortic arch arteries and the cardiac outflow tract leading to perinatal lethality in about 50% of the mutants. In addition to cardiovascular malformations, surviving mice developed renal thrombotic microangiopathy as well as hemolysis and splenomegaly, and their lifespan was significantly reduced. Loss of GPR116 and ELTD1 specifically in endothelial cells or neural crest-derived cells did not recapitulate any of the phenotypes observed in GPR116-ELTD1 double deficient mice, indicating that loss of GPR116 and ELTD1 expressed by other cells accounts for the observed cardiovascular and renal defects.

Satellite precipitation products (SPPs) are critical data sources for hydrological prediction and extreme event monitoring, especially for ungauged basins. This study conducted a comprehensive hydrological evaluation of six mainstream SPPs (i.e., TMPA 3B42RT, CMORPH-RT, PERSIANN-RT, TMPA 3B42V7, CMORPH-CRT, and PERSIANN-CDR) over humid Xixian basin in central eastern China for a period of 14 years (2000–2013). The evaluation specifically focused on the performance of the six SSPs in capturing precipitation and streamflow extremes. Results show that the two post-real-time research products of TMPA 3B42V7 and CMORPH-CRT exhibit much better performance than that of their corresponding real-time SPPs for precipitation estimation at daily and monthly time scales. By contrast, the newly released post-real-time research product PERSIANN-CDR insignificantly improves precipitation estimates compared with the real-time PERSIANN-RT does at daily time scale. The daily streamflow simulation of TMPA 3B42V7 fits best with the observed streamflow series among those of the six SPPs. The three month-to-month gauge-adjusted post-real-time research products can simulate acceptable monthly runoff series. TMPA 3B42V7 and CMORPH-CRT present good performance in capturing precipitation and streamflow extremes, although they still exhibit non-ignorable deviation and occurrence time inconsistency problems compared with gauge-based results. Caution should be observed when using the current TMPA, CMORPH, and PERSIANN products for monitoring and predicting extreme precipitation and flood at such medium-sized basin. This work will be valuable for the utilization of SPPs in extreme precipitation monitoring, streamflow forecasting, and water resource management in other regions with similar climate and topography characteristics.

Adeno-associated virus (AAV) is a promising in vivo gene delivery platform showing advantages in delivering therapeutic molecules to difficult or undruggable cells. However, natural AAV serotypes have insufficient transduction specificity and efficiency in kidney cells. Here, we developed an evolution-directed selection protocol for renal glomeruli and identified what we believe to be a new vector termed AAV2-GEC that specifically and efficiently targets the glomerular endothelial cells (GEC) after systemic administration and maintains robust GEC tropism in healthy and diseased rodents. AAV2-GEC-mediated delivery of IdeS, a bacterial antibody-cleaving proteinase, provided sustained clearance of kidney-bound antibodies and successfully treated antiglomerular basement membrane glomerulonephritis in mice. Taken together, this study showcases the potential of AAV as a gene delivery platform for challenging cell types. The development of AAV2-GEC and its successful application in the treatment of antibody-mediated kidney disease represents a significant step forward and opens up promising avenues for kidney medicine. [ABSTRACT FROM AUTHOR]

The largemouth bass (LMB) is a significant aquaculture species widely cultivated in China. High-density culture has led to an increased susceptibility of LMB to infection by the opportunistic bacterium Aeromonas. This study investigates a case of natural co-infection with the Largemouth bass ranavirus (LMBV), Aeromonas veronii, and Aeromonas hydrophila in Sichuan Province, China. To identify the causative agents of the infection, two bacterial strains were isolated from diseased LMB specimens and identified through 16S rRNA sequencing as Aeromonas vickert and Aeromonas hydrophila, both of which are gram-negative bacteria. The infection of LMBV was confirmed through polymerase chain reaction (PCR) analysis of tissue samples from the infected fish. After two blind passes of the virus fluid, the typical cytopathological effect (CPE) can be observed. Phylogenetic analysis of the virus sequences showed the highest similarity with LMBV isolates (ON418985 and MW630113) from Guangdong Province, China. This study offers important insights into diagnosing mixed infections in LMB and provides a reference for future research. [ABSTRACT FROM AUTHOR]