Stratification and prognostic evaluation of breast cancer subtypes defined by obesity-associated genes.

OBJECTIVE: Breast cancer was the most common type of cancer among women worldwide, significantly impacting their quality of life and survival rates. And obesity has been widely accepted as an important risk factor for breast cancer. However, the specific mechanisms by which obesity affects breast cancer were still unclear. Therefore, studying the impact mechanisms of obesity as a risk factor for breast cancer was of utmost importance. METHODS: This study was based on TCGA breast cancer RNA transcriptomic data and the GeneCard obesity gene set. Through single and multiple factor Cox analysis and LASSO coefficient screening, seven hub genes were identified. The independent mechanisms of these seven hub genes were evaluated from various aspects, including survival data, genetic mutation data, single-cell sequencing data, and immune cell data. Additionally, the risk prognosis model and the neural network diagnostic model were established to further investigate these seven hub genes. In order to achieve precision treatment for breast cancer (BRCA), based on the RNA transcriptomic data of the seven genes, 1226 BRCA patients were divided into two subtypes: BRCA subtype 1 and BRCA subtype 2. By studying and comparing the immune microenvironment, investigating the mechanisms of differential gene expression, and exploring the mechanisms of subnetworks, we aim to explore the clinical differences in the presentation of BRCA subtypes and achieve precision treatment for BRCA. Finally, qRT-PCR experiments were conducted to validate the conclusions of the bioinformatics analysis. RESULTS: The 7 hub genes showed good diagnostic independence and can serve as excellent biomarkers for molecular diagnosis. However, they do not perform well as independent prognostic molecular markers for BRCA patients. When predicting the survival of BRCA patients, their AUC values at 1 year, 3 years, and 5 years are mostly below 0.5. Nevertheless, through the establishment of the risk prognosis model considering the combined effect of the seven hub genes, it was found that the survival prediction of BRCA patients can be significantly improved. The risk prognosis model, compared to the independent use of the seven hub genes as prognostic markers, achieved higher timeROC AUC values at 1 year, 3 years, and 5 years, with values of 0.651, 0.669, and 0.641 respectively. Additionally, the neural network diagnostic model constructed from the 7 genes performs well in diagnosing BRCA, with an AUC value of 0.94, accurately identifying BRCA patients. The two subtypes identified by the seven hub genes exhibited significant differences in survival period, with subtype 1 having a poor prognosis. The differential mechanisms between the two subtypes mainly originate from regulatory differences in the immune microenvironment. Finally, the results of this study's bioinformatics analysis were validated through qRT-PCR experiments. CONCLUSION: 7 hub genes serve as excellent independent biomarkers for molecular diagnosis, and the neural network diagnostic model can accurately distinguish BRCA patients. In addition, based on the expression levels of these seven genes in BRCA patients, two subtypes can be reliably identified: BRCA subtype 1 and BRCA subtype 2, and these two subtypes showed significant differences in BRCA patient survival prognosis, proportion of immune cells, and expression levels of immune cells. Among them, patients with subtype 1 of BRCA had a poor prognosis.

Mechanistic Investigation of Calcium Channel Regulation-Associated Genes in Pulmonary Arterial Hypertension and Signatures for Diagnosis.

Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary disorder with complex causes. Calcium channel blockers have long been used in its treatment. Our study aimed to validate experimental results showing increased calcium ion concentration in PAH patients. We investigated the impact of genes related to calcium channel regulation on PAH development and developed an accurate diagnostic model. Clinical trial data from serum of 18 healthy individuals and 18 patients with PAH were retrospectively analyzed. Concentrations of calcium and potassium ions were determined and compared. Datasets were retrieved, selecting genes associated with calcium ion release. R packages processed the datasets, filtering 174 common genes, and conducting Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Six hub genes were identified, and nomogram and logistic regression prediction models were constructed. Random forest filtered cross genes, and a diagnostic model was developed and validated using an artificial neural network. The 174 intersection genes related to calcium ions showed significant correlations with biological processes, cellular components, and molecular functions. Six key genes were obtained by constructing a protein-protein interaction network. A diagnostic model with high accuracy (> 90%) and diagnostic capability (AUC = 0.98) was established using a neural network algorithm. This study validated the experimental results, identified key genes associated with calcium ions, and developed a highly accurate diagnostic model using a neural network algorithm. These findings provide insights into the role of calcium release genes in PAH and demonstrate the potential of the diagnostic model for clinical application. However, due to limitations in sample size and a lack of prognosis data, the regulatory mechanisms of calcium ions in PAH patients and their impact on the clinical prognosis of PAH patients still need further exploration in the future.

Mushroom Poisoning Outbreaks - China, 2023.

What is already known about this topic?: Mushroom poisoning poses a significant food safety concern in China, with a total of 196 species identified in poisoning incidents by the end of 2022. What is added by this report?: In 2023, the China CDC conducted an investigation into 505 cases of mushroom poisoning spanning 24 provincial-level administrative divisions. This investigation resulted in 1,303 patients and 16 deaths, yielding a case fatality rate of 1.23%. A total of 97 mushrooms were identified as the cause of 6 distinct clinical disease types, with 12 species newly documented as poisonous mushrooms in China. What are the implications for public health practice?: Close collaboration among CDC staff, physicians, and mycologists remains crucial for the control and prevention of mushroom poisoning in the future.

SEA-NET: medical image segmentation network based on spiral squeeze-and-excitation and attention modules.

BACKGROUND: Medical image segmentation is an important processing step in most of medical image analysis. Thus, high accuracy and robustness are required for them. The current deep neural network based medical segmentation methods have good effect on image with balanced foreground and background, but it will loss the characteristics of small targets on image with imbalanced foreground and background after multiple convolutions. METHODS: In order to retain the features of small targets in the deep network, we proposed a new medical image segmentation model based on the U-Net with squeeze-and-excitation and attention modules which form a spiral closed path,callled as Spiral Squeeze-and-Excitation and Attention NET (SEA-NET) in this paper. The segmentation model used squeeze-and-extraction modules to adjust the channel information to enhance the useful information and used attention modules to adjust the spatial information of the feature map to highlight the target area for small target segmentation when up-sampling. The deep semantic information is integrated into the shallow feature map by the attention model. Therefore, the deep semantic information cannot be scattered by continuous up-sampling. We used cross entropy loss + Tversky loss function for fast convergence and well processing the imbalanced data sets. Our proposed SEA-NET was tested on the brain MRI dataset LPBA40 and peripheral blood smear images. CONCLUSIONS: On brain MRI data, the average value of the Dice coefficient we obtained reached 98.1[Formula: see text]. On the peripheral blood smear dataset, our proposed model has a good segmentation effect on adhesion cells. RESULTS: The experimental results proved that the proposed SEA-Net performed better than U-Net, U-Net++, etc. in medical image segmentation.

Motor control differs for increasing and decreasing force production during ankle Isometric exercises in children.

BACKGROUND: Performance of the central nervous system (CNS) in increased and decreasing muscle force around the ankle joint is essential for upright tasks of daily living. Previous studies have shown altered CNS control when they decrease force compared with when they increase force in young and older adults. But whether such alteration exists during childhood with incomplete maturation of CNS systems remain unclear. Therefore, this study aimed to evaluate the disparities in intramuscular EMG-EMG coherence, which serve as indicators of corticospinal drive to muscles during ankle isometric increasing and decreasing force generation in children. METHODS: We measured intramuscular EMG-EMG coherence activity of the tibialis anterior (TA) and the associated ability to perform isometric efforts at the ankle in 12 typically developing children (mean ± SD age = 5.91±1.37 years) and 12 healthy young adults (mean ± SD age = 23.16±1.52 years). The participants maintained isometric contractions at 20% of their maximal voluntary contractions (MVC) during ankle dorsiflexion to match a triangle trajectory for 7 s, including ramping up in 3.5 s (increasing force phase) and then linearly ramping down to rest in 3.5 s (decreasing force phase). The variability of force control was characterized by the coefficient of variance (CoV) of force output. Intramuscular EMG-EMG coherence from TA in two frequency bands, the beta band (15-30 Hz) and gamma band (30-45) that could reflect the corticospinal drive, were calculated for the comparison. A repeated measures ANOVA with the within-subjects factor of force generation phase (increasing force vs. decreasing force)x between-subjects factor of the group (children and young adults) was used for statistical analysis. RESULTS: Regarding the within-subjects difference, our results exhibited significantly higher CoV of force (p < 0.01) and lower EMG-EMG coherence of TA when they decrease force compared with when they increase force in both children and young adult groups. Regarding the between-subjects difference, the CoV of force was significantly higher (p < 0.01) in children compared to young adults, while the EMG-EMG coherence in children showed a significantly lower (p < 0.01) coherence compared with young adults. Furthermore, the EMG-EMG coherence measures were negatively correlated with the CoV of force. CONCLUSIONS: The findings suggest that the age-related development would increase the corticospinal drive to TA muscle to deal with ankle isometric dorsiflexion during childhood, which could be also modulated with the force production phases, including increasing and decreasing force.

Gait asymmetry in children with Duchenne muscular dystrophy: evaluated through kinematic synergies and muscle synergies of lower limbs.

BACKGROUND: Gait is a complex, whole-body movement that requires the coordinated action of multiple joints and muscles of our musculoskeletal system. In the context of Duchenne muscular dystrophy (DMD), a disease characterized by progressive muscle weakness and joint contractures, previous studies have generally assumed symmetrical behavior of the lower limbs during gait. However, such a symmetric gait pattern of DMD was controversial. One aspect of this is criticized, because most of these studies have primarily focused on univariate variables, rather than on the coordination of multiple body segments and even less investigate gait symmetry under a motor synergy of view. METHODS: We investigated the gait pattern of 20 patients with DMD, compared to 18 typical developing children (TD) through 3D Gait Analysis. Kinematic and muscle synergies were extracted with principal component analysis (PCA) and non-negative matrix factorization (NNMF), respectively. The synergies extracted from the left and right sides were compared with each other to obtain a symmetry value. In addition, bilateral spatiotemporal variables of gait, such as stride length, percentage of stance and swing phase, step length, and percentage of double support phase, were used for calculating the symmetry index (SI) to evaluate gait symmetry as well. RESULTS: Compared with the TD group, the DMD group walked with decreased gait velocity (both p < 0.01), stride length (both p < 0.01), and step length (both p < 0.001). No significant difference was found between groups in SI of all spatiotemporal parameters extracted between the left and right lower limbs. In addition, the DMD group exhibited lower kinematic synergy symmetry values compared to the TD group (p < 0.001), while no such significant group difference was observed in symmetry values of muscle synergy. CONCLUSIONS: The findings of this study suggest that DMD influences, to some extent, the symmetry of synergistic movement of multiple segments of lower limbs, and thus kinematic synergy appears capable of discriminating gait asymmetry in children with DMD when conventional spatiotemporal parameters are unchanged.

Longitudinal change of circulating tumour cell count and its relation to prognosis in advanced intrahepatic cholangiocarcinoma patients.

Circulating tumour cells (CTCs) are related to poor prognosis in hepatobiliary cancers, including hepatocellular carcinoma and gallbladder carcinoma, but their value in intrahepatic cholangiocarcinoma (ICC) is obscure. This study aimed to investigate the change in CTCs during chemotherapy and its correlation with clinical features, treatment response and survival profile in advanced ICC patients. Fifty-one unresectable, advanced ICC patients who underwent chemotherapy were consecutively enrolled. Peripheral blood samples were collected at diagnosis and 2 months (M2) after chemotherapy initiation for CTC detection via the ISET method. The mean and median CTC counts at diagnosis were 7.4 ± 12.2 and 4.0 (range: 0.0-68.0), respectively, with 92.2% of patients having more than one CTC. A higher CTC count at diagnosis was correlated with elevated lymph node metastasis (p = 0.005), distant metastasis (p = 0.005) and TNM stage (p = 0.001) but no other characteristics. In addition, the CTC count at diagnosis was higher in nonobjective-response patients than in objective-response patients (p = 0.002), and a CTC count at diagnosis above 3 correlated with worse progression-free survival (PFS) (p = 0.007) and overall survival (OS) (p = 0.036). At M2, the CTC count was greatly decreased (p < 0.001). CTC count at M2 also correlated with lower treatment response (p < 0.001), and CTC counts above 3 were associated with poor PFS (p = 0.003) and OS (p = 0.017). After multivariate Cox analyses, CTC counts at diagnosis above 3 and CTC count increase from diagnosis to M2 independently predicted PFS and OS (p < 0.05). Detection of CTCs before and during chemotherapy is useful for prognostication in advanced ICC patients.

Mushroom Poisoning Outbreaks - China, 2022.

What is already known about this topic?: Mushroom poisoning is one of the most serious food safety issues in China. By the end of 2021, over 520 poisonous mushrooms had been discovered in China. The Southwest region of China was the most severely affected. Mushroom poisonings mainly concentrated in the summer and autumn months. What is added by this report?: In 2022, China CDC conducted an investigation of 482 incidents of mushroom poisoning across 21 provincial-level administrative divisions (PLADs). This resulted in 1,332 patients and 28 deaths, with a total case fatality rate of 2.1%. A total of 98 mushrooms were identified, causing 7 different clinical types of diseases. Three provisional new species (Collybia humida nom. prov., Spodocybe venenata nom. prov., and Omphalotus yunnanensis nom. prov.) were newly recorded as poisonous mushrooms in China, in addition to 10 other species. What are the implications for public health practice?: In view of the extensive impact and harm of poisonous mushrooms on public health, it is necessary to promote prevention and improve the ability of professionals to identify, diagnose, and treat mushroom poisoning.

Association of chromosome 2 open reading frame 71 in colorectal cancer susceptibility.

BACKGROUND: Colorectal cancer (CRC) is a serious threat to human physical and mental health. Due to the novelty of the open reading frame (ORF), ORF has shown a wide range of new genetic associations in cancer. The purpose of this study was to explore the association between the C2orf71 SNPs and CRC susceptibility. METHODS: We recruited 1419 participants to perform an association analysis between C2orf71 SNPs and CRC risk through SNPStats online solftware. Genotyping was completed by the AgenaMassARRAY. In addition, we used false-positive report probability analysis to detect whether the positive findings were noteworthy observations. We also used Haploview 4.2 software and SNPStats online software to conduct the haplotype analysis and analysis of linkage disequilibrium (LD). Finally, the interaction of SNP-SNP in CRC risk was evaluated by multi-factor dimensionality reduction (MDR). RESULTS: The overall analysis showed thatC2orf71-rs17744093, -rs10200693, and -rs13385188 were significantly associated with the CRC susceptibility. C2orf71-rs17744093 was associated with CRC risk under dominant model (OR = 1.25, p = 0.048). -rs10200693 was associated with CRC risk under allele (OR = 1.17, p = 0.041) and log-additive model (OR = 1.16, p = 0.045). -rs13385188 had significant association with CRC risk under multiple genetic models (allele: OR = 1.19, p = 0.023; log-additive: OR = 1.18, p = 0.026). Multiple stratified analyses showed that except for the three candidate SNPS mentioned above, -rs10166913 (age < 60 years and drinking) and -RS17007544 (< 60 years) were associated with increased CRC risk. CONCLUSION: C2orf71-rs17744093, -rs10200693, -rs10166913, -rs17007544, and -rs13385188 were associated with CRC susceptibility.

Elucidating common pathogenic transcriptional networks in infective endocarditis and sepsis: integrated insights from biomarker discovery and single-cell RNA sequencing.

Background: Infective Endocarditis (IE) and Sepsis are two closely related infectious diseases, yet their shared pathogenic mechanisms at the transcriptional level remain unclear. This research gap poses a barrier to the development of refined therapeutic strategies and drug innovation. Methods: This study employed a collaborative approach using both microarray data and single-cell RNA sequencing (scRNA-seq) data to identify biomarkers for IE and Sepsis. It also offered an in-depth analysis of the roles and regulatory patterns of immune cells in these diseases. Results: We successfully identified four key biomarkers correlated with IE and Sepsis, namely CD177, IRAK3, RNASE2, and S100A12. Further investigation revealed the central role of Th1 cells, B cells, T cells, and IL-10, among other immune cells and cytokines, in the pathogenesis of these conditions. Notably, the small molecule drug Matrine exhibited potential therapeutic effects by targeting IL-10. Additionally, we discovered two Sepsis subgroups with distinct inflammatory responses and therapeutic strategies, where CD177 demonstrated significant classification value. The reliability of CD177 as a biomarker was further validated through qRT-PCR experiments. Conclusion: This research not only paves the way for early diagnosis and treatment of IE and Sepsis but also underscores the importance of identifying shared pathogenic mechanisms and novel therapeutic targets at the transcriptional level. Despite limitations in data volume and experimental validation, these preliminary findings add new perspectives to our understanding of these complex diseases.

Age-related differences in gait symmetry obtained from kinematic synergies and muscle synergies of lower limbs during childhood.

The age-related changes of gait symmetry in healthy children concerning individual joint and muscle activation data have previously been widely studied. Extending beyond individual joints or muscles, identifying age-related changes in the coordination of multiple joints or muscles (i.e., muscle synergies and kinematic synergies) could capture more closely the underlying mechanisms responsible for gait symmetry development. To evaluate the effect of age on the symmetry of the coordination of multiple joints or muscles during childhood, we measured gait symmetry by kinematic and EMG data in 39 healthy children from 2 years old to 14 years old, divided into three equal age groups: preschool children (G1; 2.0-5.9 years), children (G2; 6.0-9.9 years), pubertal children (G3; 10.0-13.9 years). Participants walked barefoot at a self-selected walking speed during three-dimensional gait analysis (3DGA). Kinematic synergies and muscle synergies were extracted with principal component analysis (PCA) and non-negative matrix factorization (NNMF), respectively. The synergies extracted from the left and right sides were compared with each other to obtain a symmetry value. Statistical analysis was performed to examine intergroup differences. The results showed that the effect of age was significant on the symmetry values extracted by kinematic synergies, while older children exhibited higher kinematic synergy symmetry values compared to the younger group. However, no significant age-related changes in symmetry values of muscle synergy were observed. It is suggested that kinematic synergy of lower joints can be asymmetric at the onset of independent walking and showed improving symmetry with increasing age, whereas the age-related effect on the symmetry of muscle synergies was not demonstrated. These data provide an age-related framework and normative dataset to distinguish age-related differences from pathology in children with neuromotor disorders.

hsa_circ_0067514 suppresses gastric cancer progression and glycolysis via miR-654-3p/LATS2 axis.

Gastric cancer is the third most frequent cancer with high prevalence and mortality globally. Circular RNAs (circRNAs) play a key role in cancer regulation, including gastric cancer. Nevertheless, only a few circRNAs have been well elucidated in gastric cancer. Hence, we investigated the action of circ_0067514 on gastric cancer and clarified the underlying mechanism. Here, we found that circ_0067514 was decreased in gastric cancer patients and cancer cells. The circ_0067514 expression was correlated with gastric cancer overall survival, lymph node metastasis, tumor, node, metastasis (TNM) stage, and histological differentiation. Overexpression of circ_0067514 blocked proliferation, invasion, and glycolysis of gastric cancer cells. Besides, circ_0067514 regulated large tumor suppressor kinase 2 (LATS2) expression by absorbing microRNA (miR)-654-3p. Furthermore, circ_0067514 modulated gastric cancer aggressive behaviors and glycolysis via miR-654-3p/LATS2 axis. Moreover, circ_0067514 constrained tumor growth in vivo. Together, this study showed that circ_0067514 suppressed gastric cancer aggressive development and glycolysis via miR-654-3p/LATS2 axis, making circ_0067514 a valuable target for preventing gastric cancer progression.

Comprehensive analysis of TCR repertoire of COVID-19 patients in different infected stage.

BACKGROUND: The current pandemic of coronavirus disease 2019 (COVID-19), transmitted person-to-person by the severe acute respiratory syndrome of coronavirus 2 (SARS-CoV-2), poses a threat to global public health. OBJECTIVE: In this study, we performed the comprehensive analysis of the T cell receptor (TCR) repertoire may contribute to a more in-depth understanding of the pathogenesis of COVID-19. METHODS: A comprehensive immunological analysis was performed to explore the features of the TCR repertoire and identified TCR sequences correlated with SARS-CoV-2 viral antigens. RESULTS: we analyzed the COVID-19 patients' TCR repertoires in peripheral blood mononuclear cells (PBMC) which obtained before (baseline), during (acute), and after rehabilitation (convalescent) by ImmunoSEQ-technology, and found that repertoire features of TCRß-chain (TCRß) complementary-determining region 3 (CDR3) in COVID-19 patients were remarkable difference, including decreased TCR diversity, abnormal CDR3 length, difference of TRBV/J gene usage and higher TCR sequence overlap. Besides, we identified some COVID-19 disease-associated TCRß clones, and the abundance of them changed with the progression of the disease. Importantly, these disease-associated TCRß clones could be used to distinguish COVID-19 patients from healthy controls with high accuracy. CONCLUSIONS: We provide a clear understanding of the TCR repertoire of COVID-19 patients, which lays the foundation for better diagnosis and treatment of COVID-19 patients.

Mushroom Poisoning Outbreaks - China, 2021.

What is already known about this topic?: Mushroom poisoning is one of the most serious food safety issues in China. Most poisoning incidents resulted from eating mushrooms causing gastroenteritis and psycho-neurological disorder from which patients usually could fully recover. Most deaths resulted from species causing acute liver failure and rhabdomyolysis, and the remaining deaths were attributed to acute renal failure and hemolysis. What is added by this report?: In 2021, the total number of investigations was 327 from 25 provincial-level administrative divisions, involving 923 patients and 20 deaths, and the overall mortality was 2.17%. Overall, 74 poisonous mushrooms causing 6 different clinical syndromes were successfully identified, 15 of which were newly recorded in China as poisonous mushrooms. What are the implications for public health practice?: Considering the potential huge risks for collecting and eating wild mushrooms, we strongly advise not collecting and eating unfamiliar wild mushrooms. Promoting knowledge about poisonous mushrooms is essential and urgent to reduce mushroom poisonings. Precise species identification timely after mushroom poisoning is important for appropriate diagnosis and treatment. Many deaths were ascribed to delayed hospitalization.

COVID-19 Outbreak Caused by Contaminated Packaging of Imported Cold-Chain Products - Liaoning Province, China, July 2020.

What is known about this topic? Few major outbreaks of coronavirus disease 2019 (COVID-19) have occurred in China after major non-pharmaceutical interventions and vaccines have been deployed and implemented. However, sporadic outbreaks that had high possibility to be linked to cold chain products were reported in several cities of China.. What is added by this report? In July 2020, a COVID-19 outbreak occurred in Dalian, China. The investigations of this outbreak strongly suggested that the infection source was from COVID-19 virus-contaminated packaging of frozen seafood during inbound unloading personnel contact. What are the implications for public health practice? Virus contaminated paper surfaces could maintain infectivity for at least 17-24 days at -25 ℃. Exposure to COVID-19 virus-contaminated surfaces is a potential route for introducing the virus to a susceptible population. Countries with no domestic transmission of COVID-19 should consider introducing prevention strategies for both inbound travellers and imported goods. Several measures to prevent the introduction of the virus via cold-chain goods can be implemented.

Mushroom Poisoning Outbreaks - China, 2020.

SUMMARY: What is already known about this topic? Acute liver failure, rhabdomyolysis, acute renal failure, and hemolysis caused by poisonous mushrooms are the most important mushroom poisoning threats to the Chinese population. The most notorious lethal mushrooms are the species from genera Amanita, Lepiota, and Galerina that cause acute liver failure, and Russula subnigricans that leads to rhabdomyolysis.What is added by this report? In 2020, the total number of investigations reached 676, involving an estimated 102 species of poisonous mushrooms, 24 of which were newly recorded in China. Gyromitra venenata was newly discovered in incidents in Yunnan and Guizhou provinces and were the first reported poisonings due to gyromitrins in China since 2000. The rare poisoning Shiitake mushroom dermatitis was recorded in China. Hemolysis poisoning caused by Paxillus involutus was recorded for the second time since the beginning of the new century, resulting in one death in Inner Mongolia Autonomous Region.What are the implications for public health practice? Promoting knowledge about safe consumption of mushrooms is essential to reduce mushroom poisonings. It is not wise to collect and eat wild mushrooms. For southwestern provinces such as Yunnan, especially, caution must be exercised with unfamiliar mushroom species.

Long Distance Transmission of SARS-CoV-2 from Contaminated Cold Chain Products to Humans - Qingdao City, Shandong Province, China, September 2020.

What is already known about this topic? Though coronavirus disease 2019 (COVID-19) has largely been controlled in China, several outbreaks of COVID-19 have occurred from importation of cases or of suspected virus-contaminated products. Though several outbreaks have been traced to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolated on the outer packaging of cold chain products, live virus has not been obtained. What is added by this report? In September 2020, two dock workers were detected as having asymptomatic SARS-CoV-2 infection using throat swabs during routine screening in Qingdao, China. Epidemiological information showed that the two dock workers were infected after contact with contaminated outer packaging, which was confirmed by genomic sequencing. Compared to the Wuhan reference strain, the sequences from the dock workers and the package materials differed by 12-14 nucleotides. Furthermore, infectious virus from the cold chain products was isolated by cell culture, and typical SARS-CoV-2 particles were observed under electron microscopy. What are the implications for public health practice? The international community should pay close attention to SARS-CoV-2 transmission mode through cold chain, build international cooperative efforts in response, share relevant data, and call on all countries to take effective prevention and control measures to prevent virus contamination in cold-chain food production, marine fishing and processing, transportation, and other operations.

T-cell receptor repertoires as potential diagnostic markers for patients with COVID-19.

OBJECTIVE: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing global health emergency. T-cell receptors (TCRs) are crucial mediators of antiviral adaptive immunity. This study sought to comprehensively characterize the TCR repertoire changes in patients with COVID-19. METHODS: A large sample size multi-center randomized controlled trial was implemented to study the features of the TCR repertoire and identify COVID-19 disease-related TCR sequences. RESULTS: It was found that some T-cell receptor beta chain (TCRß) features differed markedly between COVID-19 patients and healthy controls, including decreased repertoire diversity, longer complementarity-determining region 3 (CDR3) length, skewed utilization of the TCRß variable gene/joining gene (TRBV/J), and a high degree of TCRß sharing in COVID-19 patients. Moreover, this analysis showed that TCR repertoire diversity declines with aging, which may be a cause of the higher infection and mortality rates in elderly patients. Importantly, a set of TCRß clones that can distinguish COVID-19 patients from healthy controls with high accuracy was identified. Notably, this diagnostic model demonstrates 100% specificity and 82.68% sensitivity at 0-3 days post diagnosis. CONCLUSIONS: This study lays the foundation for immunodiagnosis and the development of medicines and vaccines for COVID-19 patients.

The chloroplast genome of Archontophoenix alexandrae (Arecaceae): an important landscape tree for the subtropics.

Archontophoenix alexandrae, known as king palm, is an important landscape tree for the subtropics and potential sources of dietary fiber. In this study, the complete chloroplast genome of A. alexandrae was determined through Illumina sequencing method. The chloroplast genome was 159,196 bp in length and contained a small single-copy region (17,763 bp), a large single-copy region (87,055 bp) and a pair of IR regions (27,189 bp). 135 genes were determined in the A. alexandrae chloroplast genome, including 86 CDS, 39 tRNA genes, and 8 rRNA genes. Archontophoenix alexandrae showed the closest relationship with Veitchia arecina in the phylogenetic analysis.

The Role and Mechanism of S1PR5 in Colon Cancer.

PURPOSE: To investigate the role and mechanism of S1PR5 in colon cancer. MATERIALS AND METHODS: Lentiviral infection and drug screening helped to establish colon cancer cell lines with stable overexpression and knockdown of S1PR5. Effects of S1PR5 expression on cell growth, proliferation, migration, and invasion were analyzed using a subcutaneous xenograft model in nude mice. Western blot (WB) was used to detect the effects of S1PR5 expression on p-AKT, STAT3, NF-κB, and p-JNK. The distribution of p65 was evaluated in nuclear and cytoplasmic fractions using WB. CCK-8, Transwell migration, and Transwell invasion assays analyzed cell growth, proliferation, migration, and invasion. qRT-PCR analysis revealed that S1PR5 expression was associated with altered expression levels of NF-κB downstream target genes, such as IL-6, TNF-α, and indoleamine 2, 3-dioxygenase 1 (IDO1). RESULTS: qRT-PCR and WB analysis showed that the S1PR5 level in colon cancer cell lines-SW480, SW620, HCT116, and LoVo-was significantly higher than in NCM460, a healthy colonic epithelial cell line. SW620 and SW480, with high and low expression of S1PR5, respectively, were selected as model cell lines. S1PR5 knockdown in SW620 caused the growth rate, proliferation, migration, invasion, and subcutaneous tumor formation rate to decrease in mice, whereas S1PR5 overexpression in SW480 caused all of these parameters to increase. WB analysis showed an increase in phospho-p65 and its nuclear translocation. S1PR5 knockdown caused a decrease in phospho-p65 levels and its nuclear import, thereby inhibiting its activity. In S1PR5 knockdown and overexpressing cells, p65 was overexpressed and knocked down, respectively. qRT-PCR and WB showed that S1PR5 over-expression up-regulates IDO1, and S1PR5 knockdown inhibits IDO1. CCK-8 and Transwell assays showed that p65 and IDO1 overexpression antagonizes the antitumor effect of S1PR5 knockdown, and that p65 and IDO1 knockdown antagonizes the tumorigenic effect of S1PR5 overexpression. CONCLUSION: S1PR5 overexpression promotes the growth, migration, and invasion of cancer by activating the NF-κB/IDO1 signaling pathway.