Naturally occurring substitution of an amino acid in a plant virus gene-silencing suppressor enhances viral adaptation to increasing thermal stress.

Cereal yellow dwarf virus (CYDV-RPV) encodes a P0 protein that functions as a viral suppressor of RNA silencing (VSR). The strength of silencing suppression is highly variable among CYDV-RPV isolates. In this study, comparison of the P0 sequences of CYDV-RPV isolates and mutational analysis identified a single C-terminal amino acid that influenced P0 RNA-silencing suppressor activity. A serine at position 247 was associated with strong suppressor activity, whereas a proline at position 247 was associated with weak suppressor activity. Amino acid changes at position 247 did not affect the interaction of P0 with SKP1 proteins from Hordeum vulgare (barley) or Nicotiana benthamiana. Subsequent studies found P0 proteins containing a P247 residue were less stable than the P0 proteins containing an S247 residue. Higher temperatures contributed to the lower stability and in planta and the P247 P0 proteins were subject to degradation via the autophagy-mediated pathway. A P247S amino acid residue substitution in P0 increased CYDV-RPV replication after expression in agroinfiltrated plant leaves and increased viral pathogenicity of P0 generated from the heterologous Potato virus X expression vector system. Moreover, an S247 CYDV-RPV could outcompete the P247 CYDV-RPV in a mixed infection in natural host at higher temperature. These traits contributed to increased transmission by aphid vectors and could play a significant role in virus competition in warming climates. Our findings underscore the capacity of a plant RNA virus to adapt to climate warming through minor genetic changes in gene-silencing suppressor, resulting in the potential for disease persistence and prevalence.

Functional analysis of polymorphism haplotypes of MGMT in residents of high background radiation area.

To investigate the distribution of polymorphisms and their frequent haplotypes in the regulatory region of MGMT in residents of high background radiation area (HBRA) and their impacts on transcriptional activity, we collected DNA samples from 83 healthy Chinese residents in HBRA and searched for genetic polymorphisms in the regulatory region of MGMT. Haplotypes were characterized by Haploview analysis. Transcriptional activities of different polymorphism haplotypes were detected by using a dual-luciferase reporter assay. Six genetic polymorphisms were identified within the regulatory region (1024 bp) of MGMT. Linkage disequilibrium (LD) patterns and haplotype profiles were analyzed using the identified genetic polymorphisms. These polymorphisms we found to be in high LD, with a D' of 0.928 (r2 = 0.581) for -808 T>C and -19 C>T, 0.928 (r2 = 0.581) for -797 G>A and -19 C>T in Han Chinese HBRA residents. Complete LD with a D' of 1.0 (r2 = 1.0) was observed between -808 T>C and -797 G>A. Haploview analysis revealed the existence of three polymorphism haplotypes in the core region of regulatory region of MGMT. Using serially truncated regulatory region of human MGMT luciferase reporter gene constructs, we found a 1002 bp (-637 nt to +365 nt) fragment in the MGMT gene was the core region. Dual-luciferase reporter assays showed that different polymorphism haplotypes bearing different variant alleles exhibit distinct transcriptional activities, especially the polymorphism haplotype carrying -19 T has the strongest transcriptional activity. In summary, the present study obtained genetic characteristics of the six polymorphisms in the regulatory region of the MGMT gene in HBRA residents, and the results suggest that different polymorphism haplotypes have significant effects on the transcriptional activity of the MGMT and that the -19 C>T polymorphism may be a functional variant involved in the transcriptional regulation of the MGMT gene.

Syntheses of functionalized benzocoumarins by photoredox catalysis.

Direct functionalization of inert C(sp3)-H bonds is an attractive synthetic technology for the preparation of pharmaceutically significant compounds in modern synthetic organic chemistry. In this work, we report a new method for the synthesis of functionalized benzocoumarins through the strategy of activation of multiple C-H bonds on 2-aryl toluenes under visible-light-enabled photoredox conditions. This method has the advantages of high functional group compatibility, mild reaction conditions, and effectively avoiding the use of strong oxidants and precious metal catalysts. Detailed mechanistic investigations, including spectroscopic and electrochemical studies, support the reaction's mechanistic course.

Milrinone for the treatment of heart failure caused by severe Pneumonia in children with congenital heart disease: a meta-analysis.

BACKGROUND: Children with congenital heart disease (CHD) are easily complicated by severe pneumonia and heart failure. We aimed to conduct a meta-analysis to evaluate the effects and safety of milrinone for the treatment of heart failure caused by severe pneumonia in children with CHD to provide evidence for the clinical CHD treatment. METHODS: Two authors searched MEDLINE, PubMed, Embase, Science Direct, Cochrane Central Register of Controlled Trials, the Cochrane Library, Wanfang database, Chinese Biomedical Literature Database, China National Knowledge Infrastructure (CNKI) for randomized controlled trials (RCTs) about the application of milrinone in the treatment of heart failure caused by severe pneumonia in children with CHD in children up to December 10, 2022. Two evaluators independently selected the literature, extracted data and evaluated the methodological quality, meta-analysis was carried out with RevMan 5.3 software. RESULTS: Eight RCTs involving 680 CHD children complicated by severe pneumonia and heart failure were included in this meta-analysis. Meta-analysis indicated that total effective rate of the milrinone group was higher than that of control group (RR = 1.25, 95%CI: 1.17 ~ 1.34, P < 0.001), the time to stable heart rate of the milrinone group was less than that of control group (RR=-0.88, 95%CI: -1.09~ -0.67, P < 0.001). The time to stable respiration of the milrinone group was less than that of control group (RR=-0.98, 95%CI: -1.17~ -0.78, P < 0.001). The LVEF of the milrinone group was higher than that of control group (RR = 6.46, 95%CI: 5.30 ~ 7.62, P < 0.001). There was no significant difference in the incidence of adverse reactions between the milrinone group and control group (RR = 0.85, 95%CI: 0.47 ~ 1.56, P = 0.061). Funnel plots and Egger regression test results indicated that there were no statistical publication bias amongst the synthesized outcomes (all P > 0.05). CONCLUSIONS: Milrinone is beneficial to improve clinical symptoms and cardiac function and increase the therapeutic effect and safety in children with CHD complicated by severe pneumonia and heart failure. However, more RCTs with large samples and rigorous design are needed to verify this finding.

MicroRNA-382-5p Promotes Oral Squamous Cell Carcinoma Development and Progression by Negatively Regulating PTEN Expression.

PURPOSE: Oral squamous cell carcinoma (OSCC) local recurrence and distant metastasis remain a poorly understood clinical challenge. The objective of this study was to investigate how dysregulation of miR-382-5p impacts invasion and dissemination of OSCC. METHODS: Tissue samples were collected from 20 subjects with OSCC. Expression levels of miR-382-5p were determined by quantitative real-time polymerase chain reaction (qRT-PCR), and correlations with clinical characteristics were investigated. qRT-PCR was used to determine the miR-382-5p and peptidyl-prolyl cis/trans isomerase (PTEN) expression in tumor tissues, adjacent normal tissues, normal human oral keratinocyte line, and OSCC line (SCC-9). Cell proliferation, invasion, and migration of knock-in and knock-down miR-382-5p transfectants were assessed using cell counting kit-8 and Transwell assays. PTEN was confirmed to be a downstream target using a TargetScan prediction, dual-luciferase reporter assays, and western blot analysis. Statistical analysis of experimental data was performed with SPSS 22.0 software. RESULTS: We found high expression of miR-382-5p and significant downregulation of PTEN in tumor tissues and SCC-9 cells from OSCC patients (P < .05). miR-382-5p expression was lower in early stage (I + II) than in late stage (III + IV), while PTEN exhibited higher expression in early stage (I + II) instead of in late stage (III + IV) (P < .05). In addition, overexpression of miR-382-5p promoted the proliferation, invasion, and migration of OSCC cells. However, the proliferation, invasion, and migration of OSCC cells were inhibited after suppression of miR-382-5p. Finally, PTEN is downregulated by miR-382-5p. CONCLUSION: MiR-382-5p supports proliferation, invasion, and migration of OSCC cells through the PTEN pathway. Further investigation may improve our understanding of OSCC local recurrence and distant metastasis.

Neurobrucellosis with ischemic stroke and spinal cord involvement: a case report.

BACKGROUND: Brucellosis is a common zoonotic disease that may have a variety of clinical manifestations when it affects the nervous system. Ischemic stroke is a rare clinical symptom, but if it is not diagnosed and treated early, it may cause more severe consequences. CASE PRESENTATION: We report a 38-year-old man presenting with hearing impairment for four years and sudden weakness of the right limb for two years, recurrent aphasia, and gradual weakness of bilateral lower limbs for nine months. He had bilateral positive Babinski's sign. Cerebrospinal fluid (CSF) showed raised protein and pleocytosis. Magnetic resonance imaging (MRI) showed ischemic infarcts in the pons and extensive enhancement of spinal meninges combined with spinal cord atrophy and ischemia. The tests revealed Brucella Rose Bengal positive in serum and CSF. Brucella culture in CSF was also positive. Next-generation sequencing (NGS) of CSF revealed positive for Brucella with 105 species were detected. He showed significant improvement with antibiotics at five months follow-up. CONCLUSIONS: Neurobrucellosis may mimic stroke and transverse myelitis like syndromes. NB is a treatable infectious condition and should always be considered in the differentials, especially if there are risk factors, as in our case.

A novel previously undescribed fusarivirus from the phytopathogenic fungus Setosphaeria turcica.

A putative mycovirus belonging to the proposed family "Fusariviridae" was discovered in Setosphaeria turcica by sequencing a double-stranded RNA extracted from this phytopathogenic fungus. The virus was tentatively named "Setosphaeria turcica fusarivirus 1" (StFV1). StFV1 has a genome comprising 6685 nucleotides. The genome contains three open reading frames (ORF). The largest ORF, ORF1, is preceded by an untranslated region (UTR) of 16 nucleotides and separated from ORF2 by an intergenic region of 63 nucleotides. The smallest ORF, ORF3, overlaps ORF2 by 16 nucleotides and is followed by a 3'-UTR of 82 nucleotides. The protein encoded by ORF1 is 71.8%, 67.4% and 68.1% identical to the RNA-dependent RNA polymerases (RdRps) of Pleospora typhicola fusarivirus 1 (PtFV1), Plasmopara viticola lesion-associated fusarivirus 1 (PvlaFV1), and Plasmopara viticola lesion-associated fusarivirus 3 (PvlaFV3), respectively, but has less than 47% amino acid sequence identity to the RdRps of other fusariviruses. To our knowledge, this is the first fusarivirus discovered in S. turcica and the first virus to be identified in this fungus using conventional cloning methods.

Effects of different preoperative enteral nutrition feeding routes on the duration of gastrointestinal decompression after definitive surgery for small intestinal fistula.

PURPOSE: The purpose of this study is to investigate the effects of different preoperative enteral nutrition feeding routes on the duration of gastrointestinal decompression after definitive surgery for small intestinal fistula. METHODS: From January 2015 to June 2019, patients with small intestinal fistula and receiving a definitive surgery were enrolled. According to the feeding route, patients were divided into a nasointestinal tube group and a nasogastric tube group. Clinical characteristics of the two groups were analyzed, and the influence of the two route on the recovery of gastrointestinal function was evaluated. RESULT: A total of 151 patients were enrolled in our study. There were 49 patients in the nasogastric tube group, and 102 patients in the nasointestinal tube group. Enteral nutrition via nasogastric feeding route had a positive effect on shortening the duration of gastrointestinal decompression (adjusted HR = 2.488, 95% CI: 1.692-3.659, P < 0.001). After propensity matching (PM), 44 patients were enrolled (22 vs 22). EN via nasogastric tube was a positive factor for getting rid of gastrointestinal decompression (adjusted HR = 3.563, 95% CI: 1.639-7.746, P = 0.001). CONCLUSION: Preoperative enteral nutrition via nasogastric route can reduce the duration of gastrointestinal decompression after definitive surgery for small intestinal fistula.

Geosynchronous Satellite GF-4 Observations of Chlorophyll-a Distribution Details in the Bohai Sea, China.

We analyzed the distribution of chlorophyll-a (Chla) in the Bohai Sea area based on data from the geosynchronous orbit optical satellite Gaofen-4 (GF-4), which was launched in 2015, carrying a panchromatic multispectral sensor (PMS). This is the first time the geosynchronous orbit optical satellite GF-4 remote-sensing data has been used in China to detect the Chla change details in the Bohai Sea. A new GF-4 retrieved model was established based on the relationship between in situ Chla value and the reflectance combination of 2 and 4 bands, with the R2 of 0.9685 and the total average relative error of 37.42%. Twenty PMS images obtained from 2017 to 2019 were applied to analyze Chla in Bohai sea. The results show that: (1) the new built Chla inversion model PMS-1 for the GF-4 PMS sensor can extract Chla distribution details in the Bohai Sea well. The high Chla content in the Bohai Sea is mainly located in coastal areas, such as the top of Laizhou Bay, Bohai Bay and Liaodong Bay, with the value being around 13 µg/L. The concentration of Chla in the Bohai Strait and northern Yellow Sea is relatively low with the value being around 5 µg/L. (2). Taking full advantage of the continuous observation of geostationary orbit satellite, GF-4 with a high-resolution sensor PMS of 50 m can effectively detect short-term change (changes within 10 min) in Chla concentration. The changes mainly appear at the southwest and northeast costal area as well as in the center of Bohai Sea with the change value of around 3 µg/L. (3) The change of Chla concentration in the Bohai sea is related to the environmental factors such as seawater temperature, salinity, illumination and nutrient salts, as well as the dynamic factors such as wind, flow field and tidal current.

Complete sequence of a novel alphaendornavirus from the phytopathogenic fungus Arthrocladiella mougeotii.

A novel double-stranded RNA (dsRNA) virus, which was provisionally named Arthrocladiella mougeotii endornavirus (AmEV), was isolated from Arthrocladiella mougeotii, the phytopathogenic fungus infecting Lycium chinense in Beijing, China. The genome of AmEV is 11,683 nucleotides in length with a 5' and 3' non-coding region of 16 and 50 nt, respectively, as well as a single 11,617-nt long open reading frame potentially encoding a putative protein of 3,871 amino acids with conserved Helicase and RNA-dependent RNA polymerase (RdRp) domains. Phylogenetic analysis based on the the amino acid sequence of the RdRp showed that AmEV is most closely related to Erysiphe cichoracearum endornavirus (EcEV).

The complete genomic sequence of a novel botybirnavirus isolated from a phytopathogenic Bipolaris maydis.

Bipolaris maydis is the causal agent of corn southern leaf blight. Here, we report a novel double-stranded RNA (dsRNA) mycovirus designated Bipolaris maydis botybirnavirus 1 (BmBRV1) from B. maydis strain JZ11 in Jingzhou, Hubei province of China. BmBRV1 has a genome consisting of two dsRNAs (dsRNA1 and dsRNA2) with a size of 6435 and 5987 bp, respectively, each of which contains a single open reading frame (ORF). The two polyproteins encoded by dsRNA1 and dsRNA2 share the highest amino acid identities of 81.8 and 75.3%, respectively, with the RdRp and coat protein of Sclerotinia sclerotiorum botybirnavirus 1 (SsBRV1), a tentative species of the genus Botybirnavirus. Phylogenetic analysis based on the amino acid sequences of RdRp indicated that BmBRV1 belongs to a distinct species of the newly proposed family Botybirnaviridae.

Association of Genetic Variants Related to Gluteofemoral vs Abdominal Fat Distribution With Type 2 Diabetes, Coronary Disease, and Cardiovascular Risk Factors.

Importance: Body fat distribution, usually measured using waist-to-hip ratio (WHR), is an important contributor to cardiometabolic disease independent of body mass index (BMI). Whether mechanisms that increase WHR via lower gluteofemoral (hip) or via higher abdominal (waist) fat distribution affect cardiometabolic risk is unknown. Objective: To identify genetic variants associated with higher WHR specifically via lower gluteofemoral or higher abdominal fat distribution and estimate their association with cardiometabolic risk. Design, Setting, and Participants: Genome-wide association studies (GWAS) for WHR combined data from the UK Biobank cohort and summary statistics from previous GWAS (data collection: 2006-2018). Specific polygenic scores for higher WHR via lower gluteofemoral or via higher abdominal fat distribution were derived using WHR-associated genetic variants showing specific association with hip or waist circumference. Associations of polygenic scores with outcomes were estimated in 3 population-based cohorts, a case-cohort study, and summary statistics from 6 GWAS (data collection: 1991-2018). Exposures: More than 2.4 million common genetic variants (GWAS); polygenic scores for higher WHR (follow-up analyses). Main Outcomes and Measures: BMI-adjusted WHR and unadjusted WHR (GWAS); compartmental fat mass measured by dual-energy x-ray absorptiometry, systolic and diastolic blood pressure, low-density lipoprotein cholesterol, triglycerides, fasting glucose, fasting insulin, type 2 diabetes, and coronary disease risk (follow-up analyses). Results: Among 452 302 UK Biobank participants of European ancestry, the mean (SD) age was 57 (8) years and the mean (SD) WHR was 0.87 (0.09). In genome-wide analyses, 202 independent genetic variants were associated with higher BMI-adjusted WHR (n = 660 648) and unadjusted WHR (n = 663 598). In dual-energy x-ray absorptiometry analyses (n = 18 330), the hip- and waist-specific polygenic scores for higher WHR were specifically associated with lower gluteofemoral and higher abdominal fat, respectively. In follow-up analyses (n = 636 607), both polygenic scores were associated with higher blood pressure and triglyceride levels and higher risk of diabetes (waist-specific score: odds ratio [OR], 1.57 [95% CI, 1.34-1.83], absolute risk increase per 1000 participant-years [ARI], 4.4 [95% CI, 2.7-6.5], P < .001; hip-specific score: OR, 2.54 [95% CI, 2.17-2.96], ARI, 12.0 [95% CI, 9.1-15.3], P < .001) and coronary disease (waist-specific score: OR, 1.60 [95% CI, 1.39-1.84], ARI, 2.3 [95% CI, 1.5-3.3], P < .001; hip-specific score: OR, 1.76 [95% CI, 1.53-2.02], ARI, 3.0 [95% CI, 2.1-4.0], P < .001), per 1-SD increase in BMI-adjusted WHR. Conclusions and Relevance: Distinct genetic mechanisms may be linked to gluteofemoral and abdominal fat distribution that are the basis for the calculation of the WHR. These findings may improve risk assessment and treatment of diabetes and coronary disease.

Functional identification of MSMEG_6402 protein from Mycobacterium smegmatis in decaprenylphosphoryl-D-arabinose biosynthesis.

The arabinogalactan (AG) of the mycobacterial cell wall consists of an arabinan region, a galactan region and a disaccharide linker. Decaprenylphosphoryl-D-arabinose (DPA) is the donor for arabinofuran residues, which are formed from phosphoribose diphosphate (PRPP) and decaprenyl phosphate (DP). DP is sequentially catalyzed by a three-step process that involves a transferase, a phosphatase and an epimerase. Rv3807c is a putative phospholipid phosphatase that might generate the intermediate product of decaprenyl-phosphoryl-ribose (DPR) in DPA biosynthesis. Mycobacterium smegmatis MSMEG_6402 is a homolog gene of Mycobacterium tuberculosis Rv3807c and was substituted for the functional identification of Rv3807c. Previously, we generated a conditional MSMEG_6402 gene knockout strain (M. sm-ΔM_6402) that exhibited significantly affected cell wall structure. To understand the function of MSMEG_6402 in DPA biosynthesis, this gene was amplified and expressed, and the resulting protein was identified and purified using a His-tagged approach. A MSMEG_6402 enzymatic reaction system with PRPP and DP as substrates was utilized, and the reaction products were separated using thin layer chromatography (TLC). The results revealed a specific lipid-linked sugar band that appeared in the reaction with the addition of MSMEG_6402. Furthermore, ESI-MS detection was utilized in this study, and the results revealed that the enzymatic reaction products involving MSMEG_6402 included DPPR and a sodium ion adduct of DPR. Additionally, the phosphatase activity of MSMEG_6402 was also determined through phosphate group detection using the colorimetric method. Based on our results together with the results of previous studies, including the functional identification and bioinformatics analysis of M. tuberculosis Rv3807c, we propose that MSMEG_6402, as a phosphatase, has an intimate relationship with DPA biosynthesis.

Prokaryotic Expression, Identification and Bioinformatics Analysis of the Mycobacterium tuberculosis Rv3807c Gene Encoding the Putative Enzyme Committed to Decaprenylphosphoryl-d-arabinose Synthesis.

Decaprenylphosphoryl-d-arabinofuranosyl (DPA), the immediate donor for the polymerized d-Araf residues of mycobacterial arabinan, is synthesized from 5-phosphoribose-1-diphosphate (PRPP) in three-step reactions. (i) PRPP is transferred to decaprenyl-phosphate (DP) to form decaprenylphosphoryl-d-5-phosphoribose (DPPR). (ii) DPPR is dephosphorylated to form decaprenylphosphoryl-d-ribose (DPR). (iii) DPR is formed to DPA by the epimerase. Mycobacterium tuberculosis Rv3806c and heteromeric Rv3790/Rv3791 have been identified as the PRPP: decaprenyl-phosphate 5-phosphoribosyltransferase and the epimerase respectively. Rv3807c, however, as the candidate of phospholipid phosphatase, catalyzing the biosynthesis of decapreny-l-phosphoryl-ribose (DPR) from decaprenylphosphoryl-ß-d-5-phosphoribose by dephosphorylating, has no direct experimental evidence of its essentiality in any species of mycobacterium. In this study, Rv3807c gene was amplified from the genome of M. tuberculosis H37Rv by PCR, and was successfully expressed in Escherichia coli BL21 (DE3) via the recombinant plasmid pColdII-Rv3807c. The resulting protein with the 6× His-tag was identified by SDS-PAGE and Western blotting. The protein was predicted through bioinformatics to contain three transmembrane domains, the N-terminal peptide, and a core structure with phosphatidic acid phosphatase type2/haloperoxidase. This study provides biochemical and bioinformatics evidence for the importance of Rv3807c in mycobacteria, and further functional studies will be conducted for validating Rv3807c as a promising phospholipid phosphatase in the synthetic pathway of DPA.

Visible-Light-Enabled Catalytic Approach to N,O-Spirocycles through Amidyl Radical Addition/Cyclization.

A rational combination of photoredox catalyst anthraquinone and hydrogen atom transfer (HAT) catalyst methyl thioglycolate allows for the rapid and straightforward conversion of a range of 2-amidated acetylenic alcohols to multifunctional N,O-spirocycles under visible light irradiation. With oxygen as the sole terminal oxidant, these reactions can be carried out efficiently at room temperature without the involvement of transition metals or strong oxidants. The successful application of this mild catalytic strategy in the late-stage functionalization of bioactive skeletons further highlights its practical value.

Using medical university websites for health education about COVID-19; an effective solution for public education during a pandemic.

BACKGROUND: Medical universities use their websites to teach, research, and promote a culture of health. Therefore, this study aimed to evaluate the performance of medical universities in terms of health information and education regarding COVID-19 by surveying the website of Iranian medical universities. METHODS: This descriptive-analytical study was conducted in June to August 2020 on the websites of medical universities in three categories of universities (type 1, type 2 and type 3). The information of this study was collected from medical universities located in the east, west, north, south and center of Iran. Data were collected according to a checklist. The checklist contained 3 sections; the first part with 8 components regarding general information of the university websites, the second part with 11 components regarding the information and news related to the coronavirus and the third part with 12 components regarding the content of personal health education and environmental health for the prevention of coronavirus. To determine the status of each website in the two areas of health information and education, websites were divided into three categories based on scores (poor, average and good). Data were analyzed by chi-square. RESULTS: In this study, 1118 web pages related to 48 Iranian universities of medical sciences were reviewed, where 19 were type 1 universities, 21 type 2 universities, and 8 type 3 universities. The mean scores of the websites regarding the information and news related to the coronavirus (8.54 ± 1.750) and the mean scores of the websites regarding the personal and environmental health education related to coronavirus (10.96 ± 1.148) were in a favorable and positive condition. The ranking of medical universities by type showed that the scores in the two areas of health information and education about the coronavirus were in good condition and none of the universities were in bad condition. Chi-square showed that the information status and news related to the coronavirus had a significantly positive relationship with the type of medical universities (χ2 = 10.343, p = 0.006). CONCLUSIONS: The results of this study showed that type1 and type 2 and 62.5% of type 3 medical universities were in good condition in terms of total scores in the two areas of health information and education about coronavirus and none of the universities were in a bad situation. It is suggested that the website of medical universities can serve as a reliable and appropriate source of information not only for academics and students but also for the general public.

Ultrasound image segmentation based on Transformer and U-Net with joint loss.

Background: Ultrasound image segmentation is challenging due to the low signal-to-noise ratio and poor quality of ultrasound images. With deep learning advancements, convolutional neural networks (CNNs) have been widely used for ultrasound image segmentation. However, due to the intrinsic locality of convolutional operations and the varying shapes of segmentation objects, segmentation methods based on CNNs still face challenges with accuracy and generalization. In addition, Transformer is a network architecture with self-attention mechanisms that performs well in the field of computer vision. Based on the characteristics of Transformer and CNNs, we propose a hybrid architecture based on Transformer and U-Net with joint loss for ultrasound image segmentation, referred to as TU-Net. Methods: TU-Net is based on the encoder-decoder architecture and includes encoder, parallel attention mechanism and decoder modules. The encoder module is responsible for reducing dimensions and capturing different levels of feature information from ultrasound images; the parallel attention mechanism is responsible for capturing global and multiscale local feature information; and the decoder module is responsible for gradually recovering dimensions and delineating the boundaries of the segmentation target. Additionally, we adopt joint loss to optimize learning and improve segmentation accuracy. We use experiments on datasets of two types of ultrasound images to verify the proposed architecture. We use the Dice scores, precision, recall, Hausdorff distance (HD) and average symmetric surface distance (ASD) as evaluation metrics for segmentation performance. Results: For the brachia plexus and fetal head ultrasound image datasets, TU-Net achieves mean Dice scores of 79.59% and 97.94%; precisions of 81.25% and 98.18%; recalls of 80.19% and 97.72%; HDs (mm) of 12.44 and 6.93; and ASDs (mm) of 4.29 and 2.97, respectively. Compared with those of the other six segmentation algorithms, the mean values of TU-Net increased by approximately 3.41%, 2.62%, 3.74%, 36.40% and 31.96% for the Dice score, precision, recall, HD and ASD, respectively.

Heterogeneity of cancer-associated fibroblasts in head and neck squamous cell carcinoma.

Cancer-associated fibroblasts (CAFs) consist of heterogeneous cellular populations that contribute critical roles in head and neck squamous cell carcinoma (HNSCC). A series of computer-aided analyses were performed to determine various aspects of CAFs in HNSCC, including their cellular heterogeneity, prognostic value, relationship with immune suppression and immunotherapeutic response, intercellular communication, and metabolic activity. The prognostic significance of CKS2+ CAFs was verified using immunohistochemistry. Our findings revealed that fibroblasts group demonstrated prognostic significance, with the CKS2+ subset of inflammatory CAFs (iCAFs) exhibiting a significant correlation with unfavorable prognosis and being localized in close proximity to cancer cells. Patients with a high infiltration of CKS2+ CAFs had a poor overall survival rate. There is a negative correlation between CKS2+ iCAFs and cytotoxic CD8+ T cells and natural killer (NK) cells, while a positive correlation was found with exhausted CD8+ T cells. Additionally, patients in Cluster 3, characterized by a high proportion of CKS2+ iCAFs, and patients in Cluster 2, characterized by a high proportion of CKS2- iCAFs and CENPF-/MYLPF- myofibroblastic CAFs (myCAFs), did not exhibit significant immunotherapeutic responses. Moreover, close interactions was confirmed to exist between cancer cells and CKS2+ iCAFs/ CENPF+ myCAFs. Furthermore, CKS2+ iCAFs demonstrated the highest level of metabolic activity. In summary, our study enhances the understanding of the heterogeneity of CAFs and provided insights into improving the efficacy of immunotherapies and prognostic accuracy for HNSCC patients.

Causal associations between cardiorespiratory fitness and type 2 diabetes.

Higher cardiorespiratory fitness is associated with lower risk of type 2 diabetes. However, the causality of this relationship and the biological mechanisms that underlie it are unclear. Here, we examine genetic determinants of cardiorespiratory fitness in 450k European-ancestry individuals in UK Biobank, by leveraging the genetic overlap between fitness measured by an exercise test and resting heart rate. We identified 160 fitness-associated loci which we validated in an independent cohort, the Fenland study. Gene-based analyses prioritised candidate genes, such as CACNA1C, SCN10A, MYH11 and MYH6, that are enriched in biological processes related to cardiac muscle development and muscle contractility. In a Mendelian Randomisation framework, we demonstrate that higher genetically predicted fitness is causally associated with lower risk of type 2 diabetes independent of adiposity. Integration with proteomic data identified N-terminal pro B-type natriuretic peptide, hepatocyte growth factor-like protein and sex hormone-binding globulin as potential mediators of this relationship. Collectively, our findings provide insights into the biological mechanisms underpinning cardiorespiratory fitness and highlight the importance of improving fitness for diabetes prevention.

Cerebellar infarction caused by vertebral artery dissection: A case report.

RATIONALE: Vertebral artery dissection is an important cause of posterior circulation ischemic stroke in young and middle-aged people. We reported a young man with cerebellar infarction caused by dissection of the right vertebral artery. PATIENT CONCERNS: A 34-year-old man presented with intermittent dizziness, blurred vision, nausea, and transient tinnitus 10 days before admission. All these symptoms were gradually aggravated and followed by vomiting and unfavorable movement of the right limbs. All these symptoms gradually aggravated. DIAGNOSIS: Neurological examination on admission showed ataxia of the right limbs. Magnetic resonance imaging of the head revealed a right cerebellar infarction. High-resolution vessel wall magnetic resonance imaging showed dissection of the right vertebral artery. Whole-brain CT digital subtraction angiography revealed occlusion of the third segment (V3) of the right vertebral artery. This supports the diagnosis of vertebral artery dissection. INTERVENTIONS: The patient received anticoagulant treatment with warfarin. OUTCOMES: After 2 weeks of treatment, the patient showed remarkably alleviated dizziness and unfavorable movement of the right limbs. After 3 months of treatment, the modified Rankin Scale score was 0. MRI of the head revealed that the original right cerebellar focus was softened, and there were no newly formed infarct foci. LESSONS: When young and middle-aged patients without atherosclerotic risk factors encounter sudden dizziness, tinnitus, and unfavorable limb movement, vertebral artery dissection may be considered. Careful inquiry into the medical history may help make a final diagnosis. Further high-resolution vessel wall magnetic resonance imaging is an effective means to find arterial dissection. Early diagnosis and treatment for vertebral artery dissection has a favorable prognosis.