Recurrence of macular edema in patients with branch retinal vein occlusion: a proteomic study.

BACKGROUND: Branch retinal vein occlusion (BRVO) is a common retinal vascular disease leading to severe vision loss and blindness. This study aimed to investigate and reveal the pathophysiological mechanisms underlying macular edema (ME) recurrence in patients with BRVO through a proteomic approach. METHODS: We detected proteins in the aqueous humor of 14 untreated, four refractory, and four post-operative patients with BRVO-ME and 12 age-matched cataract controls using four-dimensional label-free proteomic and bioinformatics analyses. RESULTS: In total, 84 proteins exhibited significant differential expression between the BRVO and control samples (fold change [FC] ≥ 1.2 and adjusted p-value < 0.05). Compared to the control group, 43 and 41 proteins were upregulated and downregulated, respectively, in the BRVO group. These proteins were involved in cell adhesion, visual perception, retina homeostasis, and platelet activation. Several significantly enriched signaling pathways included complement and coagulation cascades and platelet activation. In the protein-protein interaction networks generated using the search tool for retrieval of interacting genes (STRING), the fibrinogen alpha chain and fibrinogen beta chain constituted a tightly connected cluster. Many common protein expression trends, such as the fibrinogen alpha chain and fibrinogen beta chain, were observed in both the recurrent and refractory groups. Differentially expressed proteins in the two groups were involved in complement activation, acute-phase response, platelet activation, and platelet aggregation. Important signaling pathways include the complement and coagulation cascades, and platelet activation. Protein-protein interaction analysis suggested that the fibrinogen alpha chain and fibrinogen beta chain constituted a tightly connected cluster. The expression of some differentially expressed proteins shared by the BRVO and the recurrent and refractory groups was reversed in the post-operative group. CONCLUSIONS: Our study is the first to analyze the proteomics of recurrent, refractory, and post-operative groups treated for BRVO-ME, and may potentially provide novel therapeutic interventions for the recurrence of ME.

Prognosis and immunotherapy response prediction based on M2 macrophage-related genes in colon cancer.

BACKGROUND: M2 macrophage were revealed to play a crucial role in immune evasion and immunotherapies. This study aims to explore the potential significance of M2 macrophage-related genes in colon adenocarcinoma (COAD) by analysizing the transcriptome data in a comprehensive way. METHODS: We collected RNA-sequencing (RNA-seq) data of COAD from The Cancer Genome Atlas (TCGA) and Gene Expression Ominibus (GEO) databases. We calculated the immune infiltration scores of every sample using CIBERSORT algorithm. Through weighted gene co-expression network analysis (WGCNA), we picked out M2 macrophage-related genes. With these genes we screened out prognosis related genes which were utilized to construct a signature to assess the prognosis of patients. To extend the potential application of the signature, we also calculated the correlations with immune infiltration. Finally, we applied techniques such as quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunoblotting (Western Blotting) to validate the RNF32 gene in cellular in vitro assays. RESULTS: Seven M2 macrophage-related genes signature was constructed, which was an excellent prognostic predictor in two independent groups. The high-risk group showed lower immune infiltration and poorer response to immunotherapies than those of the low-risk group. The cell vitro experiments showed that the expression level of RNF32 was upregulated in colon cancer cell lines compared with normal cell lines. Moreover, we found that RNF32 may promote the proliferation, migration and invasion of cancer cells in vitro by inhibiting apoptosis. CONCLUSION: A novel M2 macrophage-related gene signature affects the prognosis and immune characteristics of colon cancer.

Bipolaris fujianensis sp. nov., an Emerging Pathogen of Sapling Shoot Blight on Chinese Fir, and Its Sensitivity to Fungicides.

Chinese fir is an extremely important economic tree species in southern China. In recent years, 74.5% of Chinese fir saplings suffered from shoot blight in Shunchang County, Nanping City, Fujian Province, China. Seventeen isolates were collected from rotten shoots, and their pathogenicity was confirmed following Koch's postulates. The five pathogenic isolates were identified as belonging to the genus Bipolaris based on morphological characteristics, including septate and geniculate conidiophores, smooth to slightly verruculose conidiogenous nodes, dematiaceous phragmospore conidia, oblong or fusiform conidia, and slightly protruding or truncate hilum on conidia, but the number of pseudosepta (3 to 11, mostly 5 to 8) and the size of conidia ([22.81 to 116.13] × [9.16 to 26.58] µm) are different from those of the known species of Bipolaris. A phylogenetic analysis based on ITS, GAPDH, and Tef1-α sequences determined that the five strains belong to a new species of Bipolaris, and the name Bipolaris fujianensis sp. nov. is proposed. The fungicide sensitivity of the pathogen strain Cfsb3 was further evaluated using eight fungicides. Flusilazole, difenoconazole, tebuconazole, and propiconazole exhibited high toxicity to Cfsb3, and the effective concentration inhibiting 50% (EC50) of mycelial growth was 0.08, 0.20, 0.34, and 0.36 µg/ml, respectively, for these four fungicides. Flusilazole, difenoconazole, and iprodione inhibited B. fujianensis by 100% on detached Chinese fir shoots at their recommended concentrations, but azoxystrobin and thiram were ineffective. In conclusion, this study reported an emerging pathogen of Chinese fir sapling shoot blight and proposed triazole and dicarboximide fungicides for disease control.

Advance nitrogen removal from anaerobic sludge digestion liquor using partial nitrification and denitrification coupled with simultaneous partial nitrification, anammox, and denitrification process.

A novel two-stage continuous-flow partial nitrification and denitrification coupled with simultaneous partial nitrification, anammox, and denitrification (PND-SNAD) process was developed to treat anaerobic sludge digestion liquor. During the stable phase, the total nitrogen and chemical oxygen demand (COD) removal efficiencies were 93 ± 3 % and 59 ± 7 %, respectively. Free ammonia suppression (26.2 ± 12.7 mg/L) and low dissolved oxygen (DO, 0.12 ± 0.07 mg/L) were key factors in the operation of the PND process, while the SNAD process was restricted successfully by limited oxygen (DO < 0.1 mg/L) and short solids retention time (9.7 d). The PND process was an important pretreatment process that could remove biodegradable dissolved COD by denitrification and supply ammonium-oxidizing bacteria (AOB) to the SNAD process. Nitrosomonas and Ca. Brocadia were the dominant AOB and anammox bacteria, respectively. Overall, this research presents a distinctive SNAD combined process for anaerobic sludge digestion liquor treatment.

Haplotypes at the sorghum ARG4 and ARG5 NLR loci confer resistance to anthracnose.

Sorghum anthracnose caused by the fungus Colletotrichum sublineola (Cs) is a damaging disease of the crop. Here, we describe the identification of ANTHRACNOSE RESISTANCE GENES (ARG4 and ARG5) encoding canonical nucleotide-binding leucine-rich repeat (NLR) receptors. ARG4 and ARG5 are dominant resistance genes identified in the sorghum lines SAP135 and P9830, respectively, that show broad-spectrum resistance to Cs. Independent genetic studies using populations generated by crossing SAP135 and P9830 with TAM428, fine mapping using molecular markers, comparative genomics and gene expression studies determined that ARG4 and ARG5 are resistance genes against Cs strains. Interestingly, ARG4 and ARG5 are both located within clusters of duplicate NLR genes at linked loci separated by ~1 Mb genomic region. SAP135 and P9830 each carry only one of the ARG genes while having the recessive allele at the second locus. Only two copies of the ARG5 candidate genes were present in the resistant P9830 line while five non-functional copies were identified in the susceptible line. The resistant parents and their recombinant inbred lines carrying either ARG4 or ARG5 are resistant to strains Csgl1 and Csgrg suggesting that these genes have overlapping specificities. The role of ARG4 and ARG5 in resistance was validated through sorghum lines carrying independent recessive alleles that show increased susceptibility. ARG4 and ARG5 are located within complex loci displaying interesting haplotype structures and copy number variation that may have resulted from duplication. Overall, the identification of anthracnose resistance genes with unique haplotype stucture provides a foundation for genetic studies and resistance breeding.

Large Stokes shift fluorescent RNAs for dual-emission fluorescence and bioluminescence imaging in live cells.

Fluorescent RNAs, aptamers that bind and activate small fluorogenic dyes, have provided a particularly attractive approach to visualizing RNAs in live cells. However, the simultaneous imaging of multiple RNAs remains challenging due to a lack of bright and stable fluorescent RNAs with bio-orthogonality and suitable spectral properties. Here, we develop the Clivias, a series of small, monomeric and stable orange-to-red fluorescent RNAs with large Stokes shifts of up to 108 nm, enabling the simple and robust imaging of RNA with minimal perturbation of the target RNA's localization and functionality. In combination with Pepper fluorescent RNAs, the Clivias enable the single-excitation two-emission dual-color imaging of cellular RNAs and genomic loci. Clivias can also be used to detect RNA-protein interactions by bioluminescent imaging both in live cells and in vivo. We believe that these large Stokes shift fluorescent RNAs will be useful tools for the tracking and quantification of multiple RNAs in diverse biological processes.

Integrated single-cell and bulk RNA sequencing analysis identifies a prognostic signature related to ferroptosis dependence in colorectal cancer.

Ferroptosis is an iron-dependent form of cell death induced by lipid oxidation with an essential role in diseases, including cancer. Since prognostic value of ferroptosis-dependent related genes (FDRGs) in colorectal cancer (CRC) remains unclear, we explored the significance of FDRGs in CRC through comprehensive single-cell analysis. We downloaded the GSE161277 dataset for single-cell analyses and calculated the ferroptosis-dependent gene score (FerrScore) for each cell type. According to each cell type-specific median FerrScore, we categorized the cells into low- and high-ferroptosis groups. By analyzing differentially-expressed genes across the two groups, we identified FDRGs. We further screened these prognosis-related genes used to develop a prognostic signature and calculated its correlation with immune infiltration. We also compared immune checkpoint gene efficacy among different risk groups, and qRT-PCR was performed in colorectal normal and cancer cell lines to explore whether the signature genes could be used as clinical prognostic indicators. In total, 523 FDRGs were identified. A prognostic signature including five signature genes was constructed, and patients were divided into two risk groups. The high-risk group had poor survival rates and displayed high levels of immune infiltration. Our newly developed ferroptosis-based prognostic signature possessed a high predictive ability for CRC.

SRSF3/AMOTL1 splicing axis promotes the tumorigenesis of nasopharyngeal carcinoma through regulating the nucleus translocation of YAP1.

Dysregulation of serine/arginine splicing factors (SRSFs) and abnormal alternative splicing (AS) have been widely implicated in various cancers but scarcely investigated in nasopharyngeal carcinoma (NPC). Here we examine the expression of 12 classical SRSFs between 87 NPC and 10 control samples, revealing a significant upregulation of SRSF3 and its association with worse prognosis in NPC. Functional assays demonstrate that SRSF3 exerts an oncogenic function in NPC progression. Transcriptome analysis reveals 1,934 SRSF3-regulated AS events in genes related to cell cycle and mRNA metabolism. Among these events, we verify the generation of a long isoform of AMOTL1 (AMOTL1-L) through a direct bond of the SRSF3 RRM domain with the exon 12 of AMOTL1 to promote exon inclusion. Functional studies also reveal that AMOTL1-L promotes the proliferation and migration of NPC cells, while AMOTL1-S does not. Furthermore, overexpression of AMOTL1-L, but not -S, significantly rescues the inhibitory effects of SRSF3 knockdown. Additionally, compared with AMOTL1-S, AMOTL1-L has a localization preference in the intracellular than the cell membrane, leading to a more robust interaction with YAP1 to promote nucleus translocation. Our findings identify SRSF3/AMOTL1 as a novel alternative splicing axis with pivotal roles in NPC development, which could serve as promising prognostic biomarkers and therapeutic targets for NPC.

Wnt3a-Loaded Hydroxyapatite Nanowire@Mesoporous Silica Core-Shell Nanocomposite Promotes the Regeneration of Dentin-Pulp Complex via Angiogenesis, Oxidative Stress Resistance, and Odontogenic Induction of Stem Cells.

Pulp exposure often leads to pulp necrosis, root fractures, and ultimate tooth loss. The repair of the exposure site with pulp capping treatment is of great significance to preserving pulp vitality, but its efficacy is impaired by the low bioactivity of capping materials and cell injuries from the local accumulation of oxidative stress. This study develops a Wnt3a-loaded hydroxyapatite nanowire@mesoporous silica (Wnt3a-HANW@MpSi) core-shell nanocomposite for pulp capping treatments. The ultralong and highly flexible hydroxyapatite nanowires provide the framework for the composites, and the mesoporous silica shell endows the composite with the capacity of efficiently loading/releasing Wnt3a and Si ions. Under in vitro investigation, Wnt3a-HANW@MpSi not only promotes the oxidative stress resistance of dental pulp stem cells (DPSCs), enhances their migration and odontogenic differentiation, but also exhibits superior properties of angiogenesis in vitro. Revealed by the transcriptome analysis, the underlying mechanisms of odontogenic enhancement by Wnt3a-HANW@MpSi are closely related to multiple biological processes and signaling pathways toward pulp/dentin regeneration. Furthermore, an animal model of subcutaneous transplantation demonstrates the significant reinforcement of the formation of dentin-pulp complex-like tissues and blood vessels by Wnt3a-HANW@MpSi in vivo. These results indicate the promising potential of Wnt3a-HANW@MpSi in treatments of dental pulp exposure.

The metabolic score for insulin resistance as a predictor of clinical outcome in stroke patients treated by intravenous thrombolysis.

BACKGROUND AND PURPOSE: Insulin resistance is associated with clinical outcomes among patients with ischemic stroke. We aimed to investigate the association between metabolic score for insulin resistance (METS-IR) and clinical outcomes in stroke patients treated by intravenous thrombolysis (IVT). METHODS: We recruited participants treated with IVT from a prospective registry including 3 stroke centers. Poor outcome was defined as a modified Rankin scale score ≥ 3 points at 90 days after the index stroke. We performed logistic regression models to investigate the association between METS-IR and the risk of poor outcome. We used the receiver operative characteristic to assess the discriminative ability and the restricted cubic spline to explore the relationship between METS-IR and the poor outcome. RESULTS: This study enrolled a total of 1074 patients (median age, 68; 63.8% male). Three hundred sixty (33.5%) patients had poor outcome after IVT. METS-IR was associated with the risk of the poor outcome with the increase of confounding factors in models (odds ratio [OR], 1.078; 95% confidence interval [CI], 1.058-1.099; P < 0.001). The area under the curve for METS-IR for predicting the poor outcome was 0.790 (95% CI, 0.761-0.819). The restricted cubic spline revealed an increasing and non-linear association between METS-IR and the poor outcome (P for non-linearity < 0.001). CONCLUSION: Our study found that METS-IR was associated with an increased risk of poor outcome after IVT. Further studies are warranted to investigate the efficacy of anti-diabetic agents regarding IR on clinical outcomes after IVT.

First Report of Leaf Tip Blight Caused by Epicoccum sorghinum on Phoebe bournei in Fujian, China.

Phoebe bournei, belonging to the family Lauraceae, is indigenous to China, where it is a protected species. In March 2022, ca. 90% of 20,000 P. bournei saplings suffered from leaf tip blight in a sapling nursery with an area of 200 m2 in Fuzhou, China. Initially, brown discoloration appeared on the tips of young leaves. The symptomatic tissue continued to expand as the leaf grew. To isolate the pathogen, 10 symptomatic leaves were randomly sampled from the nursery, and surface-sterilized in 75% alcohol for 30 s, followed by a 5% NaClO solution for 3 min, and then rinsed 3 times with sterile water. Twenty small pieces (0.3 x 0.3 cm) were excised from the margin of diseased and healthy tissue and transferred to five PDA plates amended with 50 µg/ml ampicillin. The plates were incubated at 25°C for 5 days. Finally, 17 isolates were obtained, and nine isolates with the highest isolation frequency shared the same morphological characteristics. On PDA, these colonies had aerial hyphae, white in the beginning, and became pale brown with the pigment production. Chlamydospores were observed after incubation for 7 days at 25°C, pale brown and nearly spherical, unicellular, or multicellular. Conidia were unicellular or bicellular, hyaline, and ellipsoidal, 5.15 to 9.89× 3.46 to 5.87 µm, n=50. The 9 fungi were identified as Epicoccum sp (Khoo et al. 2022a, b, c). Furthermore, strain MB3-1 was chosen randomly as the representative of the 9 isolates, and ITS, LSU, TUB sequences were amplified using the primers ITS1/ITS4, LR0R/LR5, Bt2a/Bt2b respectively (Raza et al. 2019). The sequences were submitted to NCBI and analyzed using BLAST. Results of BLAST showed that ITS (OP550308), LSU (OP550304), TUB (OP779213) sequences had 99.59% (490bp out of 492bp), 99.89% (870bp out of 871bp), 100% (321bp out of 321bp) identity to Epicoccum sorghinum sequences MH071389, MW800361, MW165323, respectively. ITS, LSU, TUB sequences were concatenated for phylogenetic analysis using the maximum likelihood method with 1000 bootstrap replicates in MEGA 7.0 software. The phylogenetic tree showed that MB3-1 was clustered together with E. sorghinum. Pathogenicity tests were performed on young leaves of healthy P. bournei saplings in vivo by inoculating with fungal conidia suspension. The conidia were eluted from the colony of MB3-1 and adjusted to 1×106 spores/ml. An amount of 20 µl conidia suspension (0.1% tween-80) was evenly sprayed on three leaves of one P. bournei sapling, 20 µl sterile water was sprayed on three other leaves of the same sapling as control, and three saplings were treated. All the treated saplings were kept at 25°C. MB3-1 caused leaf tip blight symptoms similar to those observed in nature at 6 days post inoculation (dpi). The pathogen was reisolated from inoculated leaves and identified as E. sorghinum. The experiment was repeated twice with the same results. Recently, E. sorghinum has been reported in Brazil (Gasparetto et al. 2017), Malaysia (Khoo et al. 2022a, b, c), and the United States (Imran et al. 2022). To our knowledge, this is the first report of E. sorghinum causing leaf tip blight on P. bournei. Wood from P. bournei is used to produce high-quality furniture due to its vertical grain and durability (Chen et al. 2020). And the demand for wood requires numerous saplings for afforestation. But this disease has the risk of causing insufficient saplings, which would affect the development of the P. bournei timber industry.

Structure-based investigations of the NAD+-II riboswitch.

Riboswitches are conserved non-coding domains in bacterial mRNA with gene regulation function that are essential for maintaining enzyme co-factor metabolism. Recently, the pnuC RNA motif was reported to selectively bind nicotinamide adenine dinucleotide (NAD+), defining a novel class of NAD+ riboswitches (NAD+-II) according to phylogenetic analysis. To reveal the three-dimensional architecture and the ligand-binding mode of this riboswitch, we solved the crystal structure of NAD+-II riboswitch in complex with NAD+. Strikingly and in contrast to class-I riboswitches that form a tight recognition pocket for the adenosine diphosphate (ADP) moiety of NAD+, the class-II riboswitches form a binding pocket for the nicotinamide mononucleotide (NMN) portion of NAD+ and display only unspecific interactions with the adenosine. We support this finding by an additional structure of the class-II RNA in complex with NMN alone. The structures define a novel RNA tertiary fold that was further confirmed by mutational analysis in combination with isothermal titration calorimetry (ITC), and 2-aminopurine-based fluorescence spectroscopic folding studies. Furthermore, we truncated the pnuC RNA motif to a short RNA helical scaffold with binding affinity comparable to the wild-type motif to allude to the potential of engineering the NAD+-II motif for biotechnological applications.

High-Quality Genome Resource of Bacillus subtilis N4, a Biological Control Agent Isolated from Phoebe bournei.

Bacillus subtilis strain N4, an endophyte isolated from the healthy leaves of Phoebe bournei, possesses an excellent biocontrol effect against stem canker of P. bournei caused by Lasiodiplodia theobromae. To understand its biocontrol mechanism, we assembled a high-quality genome of N4 using a combination of second- and third-generation sequencing methods. The N4 genome contained one circular DNA chromosome of 4,218,183 bp length with 43.5% GC content and 11 secondary metabolite biosynthesis gene clusters, including genes for subtilomycin synthesis. This high-quality genome assembly and gene annotation resource will provide better insights into the biocontrol potential of B. subtilis strain N4 against stem canker of P. bournei.

Structure-based insights into recognition and regulation of SAM-sensing riboswitches.

Riboswitches are highly conserved RNA elements that located in the 5'-UTR of mRNAs, which undergo real-time structure conformational change to achieve the regulation of downstream gene expression by sensing their cognate ligands. S-adenosylmethionine (SAM) is a ubiquitous methyl donor for transmethylation reactions in all living organisms. SAM riboswitch is one of the most abundant riboswitches that bind to SAM with high affinity and selectivity, serving as regulatory modules in multiple metabolic pathways. To date, seven SAM-specific riboswitch classes that belong to four families, one SAM/SAH riboswitch and one SAH riboswitch have been identified. Each SAM riboswitch family has a well-organized tertiary core scaffold to support their unique ligand-specific binding pocket. In this review, we summarize the current research progress on the distribution, structure, ligand recognition and gene regulation mechanism of these SAM-related riboswitch families, and further discuss their evolutionary prospects and potential applications.

Cross-sectional and longitudinal associations between body flexibility and sarcopenia.

BACKGROUND: The associations between body flexibility and sarcopenia were not well understood. This study aimed to explore the cross-sectional and longitudinal associations of flexibility with sarcopenia. METHODS: Our study selected participants aged 50-80 from the WELL-China cohort and the Lanxi cohort. Participants from the urban area of the Lanxi cohort were followed up 4 years later. Body flexibility was measured by the sit-and-reach test. Muscle mass was evaluated by dual-energy X-ray absorptiometry. Muscle strength was evaluated using handgrip strength. Sarcopenia was defined as having both low muscle mass and low muscle strength. We used multivariable logistic regressions to assess the cross-sectional associations of body flexibility with low muscle mass, low muscle strength and sarcopenia. We also used multivariable logistic regressions to explore the associations of baseline flexibility and 4-year changes in flexibility with incident low muscle mass, low muscle strength and sarcopenia. RESULTS: A total of 9453 participants were enrolled in the cross-sectional study, and 1233 participants were included in the longitudinal analyses. In the cross-sectional analyses, compared with low body flexibility, high body flexibility was inversely associated with low muscle mass (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.50-0.68; P < 0.001), low muscle strength (OR, 0.62; 95% CI, 0.55-0.69; P < 0.001) and sarcopenia (OR, 0.52; 95% CI, 0.41-0.65; P < 0.001), and these associations did not differ in different age groups, sex or physical activity levels. In the longitudinal analyses, compared with participants with low body flexibility, participants with high body flexibility had lower risk of the incident low muscle strength (OR, 0.53; 95% CI, 0.38-0.74; P < 0.001) and sarcopenia (OR, 0.36; 95% CI, 0.21-0.61; P < 0.001), but not incident low muscle mass (OR, 0.59; 95% CI, 0.33-1.06; P = 0.076). Every 1-cm increase in flexibility during 4 years was associated with reduced risk of incident low muscle mass (OR, 0.96; 95% CI, 0.93-1.00; P = 0.025), low muscle strength (OR, 0.96; 95% CI, 0.94-0.98; P = 0.002) and sarcopenia (OR, 0.96; 95% CI, 0.93-0.99; P = 0.007). CONCLUSIONS: High flexibility was associated with reduced risk of incident low muscle strength and sarcopenia. Increases in flexibility were associated with reduced risk of incident low muscle mass, low muscle strength and sarcopenia. Flexibility exercises and monitoring the dynamic change of flexibility might be helpful in preventing sarcopenia among adults aged 50 years or over.

Anaerobic ammonium oxidation driven by dissimilatory iron reduction in autotrophic Anammox consortia.

Feammox has been applied to wastewater biological nitrogen removal. However, few studies have reported that Fe(III)(hydr)oxides induced Anammox consortia to remove NH4+ via the Feammox pathway. In this study, Fe(OH)3 was added to Anammox systems to investigate its effect on nitrogen removal via Feammox. The specific Anammox activity increased by 39 % by Fe(OH)3. Ammonia oxidation was observed to occur along with Fe(III) reduction and Fe(II) generation, which was further confirmed by the isotope test with feeding 15NH4+-N to detect 30N2. The cyclic voltammetry test showed that electron-storage capacity of Anammox sludge increased with Fe(OH)3. In situ Fourier transform infrared spectroscopy suggested that Fe(OH)3 enhanced the polarization of functional groups of outer membrane cytochrome of Anammox consortia to benefit extracellular electron transfer. This study demonstrated that Fe(OH)3 could induce Anammox consortia to perform extracellular respiration to enhance NH4+-N removal in the Anammox sludge system.

Evaluating the Diagnostic Potentials of Circulating Tumor DNA against Melanoma: A Systematic Review and Meta-Analysis.

Background: The accurate detection of circulating tumor (ct) DNA is affected by multiple factors, and several controversies still persists regarding clinical applications. In order to assess the consistency of ctDNA gene mutation detection findings in matched melanoma tissue samples and peripheral blood, a meta-analysis was performed and provided evidence-based analysis for its clinical applications. Method: As of May 20, 2019, the database has been searched using the Embase, PubMed, and Cochrane Library search engines. The ctDNA investigations mentioned in this review may be used to directly or indirectly get the true positive (TP), true negative (TN), false positive (FP), and false negative (FN) values of melanoma patients. To be excluded from the study are duplicate publications, research that do not offer a full text, inadequate material or an inability to extract data, and animal trials. Results: Overall, the pooled specificity, sensitivity, NLR, PLR, and DOR were 0.94 (95% CI: 0.91-0.96), 0.73 (95% CI: 0.70-0.75), 0.32 (95% CI: 0.22-0.45), 8.21 (95% CI: 4.67-14.43), and 32.72 (95% CI: 14.81-72.30), respectively. Additionally, we calculated AUC by drawing the SROC curve, and the value of AUC is 0.9287, which indicates that the accuracy of ctDNA in diagnosing melanoma is 92.87% of the gold standard. Furthermore, we conducted a subgroup analysis for different countries, sample sources, and ctDNA detection methods. The pooled results showed that different countries, sample sources, and ctDNA detection methods showed significantly large differences in terms of sensitivity of ctDNA in diagnosing melanoma, while the specificity basically remained the same. Conclusion: We discovered that the diagnostic outcomes between matched tumor samples and ctDNA remained more reliable in melanoma patients. ctDNA has the advantages of low trauma, convenient dynamic monitoring, and simple operation. ctDNA is expected to become an auxiliary method for the diagnosis of melanoma gene mutations.

Predictability effects and parafoveal processing of compound words in natural Chinese reading.

We report a boundary paradigm eye movement experiment to investigate whether the predictability of the second character of a two-character compound word affects how it is processed prior to direct fixation during reading. The boundary was positioned immediately prior to the second character of the target word, which itself was either predictable or unpredictable. The preview was either a pseudocharacter (nonsense preview) or an identity preview. We obtained clear preview effects in all conditions, but more importantly, skipping probability for the second character of the target word and the whole target word from pretarget was greater when it was predictable than when it was not predictable from the preceding context. Interactive effects for later measures on the whole target word (gaze duration and go-past time) were also obtained. These results demonstrate that predictability information from preceding sentential context and information regarding the likely identity of upcoming characters are used concurrently to constrain the nature of lexical processing during natural Chinese reading.

Sarcopenia and sarcopenic obesity after cholecystectomy: A population-based study.

OBJECTIVE: The present study aimed to investigate the associations of cholecystectomy with low muscle mass, low muscle strength, sarcopenia, and sarcopenic obesity. METHODS: This population-based study included data from 4,909 participants aged 18 to 80 years. History of cholecystectomy was diagnosed using abdominal ultrasonography. Muscle mass was evaluated using a dual-energy x-ray absorptiometry scan, and muscle strength was evaluated using an electronic hand dynamometer. Sarcopenia was defined as the presence of both low muscle mass and low muscle strength. Sarcopenic obesity was defined as the presence of both sarcopenia and obesity. Multivariable logistic regression models were performed to investigate the associations of cholecystectomy with low muscle mass, low muscle strength, sarcopenia, and sarcopenic obesity. RESULTS: Participants with history of cholecystectomy were more likely than those without to have low muscle mass, low muscle strength, and sarcopenia. Furthermore, compared with cholecystectomy that occurred within 7 years (7 years is the median interval between cholecystectomy and the physical examination), participants with cholecystectomy that occurred more than 7 years ago had higher odds of sarcopenia. Finally, whether obesity was defined by BMI or body fat percentage, cholecystectomy was positively associated with sarcopenic obesity. CONCLUSIONS: Cholecystectomy is associated with low muscle mass, low muscle strength, sarcopenia, and sarcopenic obesity.