SPINK4 modulates inhibition of glycolysis against colorectal cancer progression.

Dysregulation of glycolysis is frequently linked to aggressive tumor activity in colorectal cancer (CRC). Although serine peptidase inhibitor, Kazal type 4 (SPINK4) has been linked to CRC, its exact linkage to glycolytic processes and gene expression remains unclear. Differentially expressed genes (DEGs) were screened from two CRC-related datasets (GSE32323 and GSE141174), followed by expression and prognostic analysis of SPINK4. In vitro techniques such as flow cytometry, western blotting, transwell assay, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to assess SPINK4 expression in CRC cells. Its effects on apoptosis, glycolysis, and the cell cycle were also investigated. Finally, the impact of SPINK4 overexpression on tumor development was assessed using a xenograft model, while histological and immunohistochemical analyses characterized SPINK4 expression patterns in CRC tissues. SPINK4 expression was downregulated in CRC, correlating with poor patient prognosis. In vitro assays confirmed that overexpression of SPINK4 reduced CRC cell proliferation, invasion, and migration, while its knockdown promoted these processes and caused G1 arrest. SPINK4 also regulated apoptosis by altering caspase activation and Bcl-2 expression. Besides, SPINK4 overexpression altered glycolytic activity, reduced 2-Deoxy-D-glucose (2-DG) absorption, and controlled critical glycolytic enzymes, resulting in alterations in metabolic pathways, whereas SPINK4 knockdown reversed this effect. SPINK4 overexpression significantly reduced tumor volume in vivo, indicating its inhibitory role in carcinogenesis. Moreover, high expression of SPINK4, hexokinase 2 (HK2), glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), and pyruvate kinase M2 (PKM2) was observed in CRC tissues. As a key inhibitor of glycolytic metabolism in CRC, SPINK4 promises metabolic intervention in CRC therapy due to its impact on tumor growth and cell proliferation.

Nano-energy interference: A novel strategy for blunting tumor adaptation and metastasis.

Blunting the tumor's stress-sensing ability is an effective strategy for controlling tumor adaptive survival and metastasis. Here, we have designed a cyclically amplified nano-energy interference device based on lipid nanoparticles (LNP), focused on altering cellular energy metabolism. This innovative nano device efficiently targets and monitors the tumor's status while simultaneously inhibiting mitochondrial respiration, biogenesis and ribosome production. To this end, we first identified azelaic acid (AA), a binary acid capable of disrupting the mitochondrial respiratory chain. Upon encapsulation in LNP and linkage to mitochondrial-targeting molecules, this disruptive effect is further augmented. Consequently, tumors exhibit a substantial upregulation of the glycolytic pathway, intensifying their glucose demand and worsening the tumor's energy-deprived microenvironment. Then, the glucose analog, 2-Deoxy-D-glucose (2-DG), linked to the LNP, efficiently targets tumors and competitively inhibits the tumor's normal glucose uptake. The synergetic results of combining AA with 2-DG induce comprehensive energy deficiency within tumors, blocking the generation of energy-sensitive ribosomes. Ultimately, the disruption of both mitochondria and ribosomes depletes energy supply and new protein-generating capacity, weakening tumor's ability to adapt to environmental stress and thereby inhibiting growth and metastasis. Comprehensively, this nano-energy interference device, by controlling the tumor's stress-sensing ability, provides a novel therapeutic strategy for refractory tumors.

Quantitative microbiological risk assessments for Salmonella spp. contaminated taiwanese salty chicken in the taiwanese population.

The aim of the study is to develop Salmonella spp. Quantitative microbial risk assessments (QMRA) and to evaluate the risk of Salmonellosis illness in the Taiwanese population after consumption of Taiwanese salty chicken (TSC). We assume that Salmonella spp. May contaminate the fresh raw chicken used in TSC. After transport to the diner, fresh raw chicken is received, cleaned, and surface-washed by diner staff. The TSC is then cooked and sold to consumers. We set four different cross-contamination scenarios to evaluate the contamination level of Salmonella spp. In TSC. We used a Monte Carlo simulation method, a probabilistic analysis method, and exceedance risk to evaluate the risk of Salmonellosis illness. When the exceedance risk was 5 %, and taking the Taiwanese population above 19 years old as an example, the rate of contracting Salmonellosis from the consumption of TSC will be 2.94 % (2.94 million per 100 million people) if the chef does not clean their hands, knives, or cutting boards. However, if the chef washes their hands, knives, and cutting boards with cold water and soap, the illness rate of Salmonellosis from consuming TSC will be 1.93E-04 % (193 per 100 million people). Sensitivity analysis indicates that the most important risk factor in the QMRAs of TSC is the temperature of the fresh raw chicken during transportation, following which were the Salmonella spp. Residual. If the staff of the diner separates the cooking tools used for raw ingredients and those for cooked food, the illness risk of Salmonellosis will be very low.

Feasibility and safety of 1-min sit-to-stand test in acute decompensated heart failure confirmed by lung ultrasound.

Aim: This study innovatively proposed the 1-min sit-to-stand test (1-min STST) as an assessment tool for functional capacity in acute decompensated heart failure (ADHF), in which its feasibility and safety were investigated. Methods: This was a prospective, single-center cohort study. The 1-min STST was performed after the first 48 h of admission when vital signs and Borg score were collected. Lung ultrasound was used to measure pulmonary edema by B-lines before and after the test. Results: Seventy-five patients were enrolled in the study, of whom 40% were in functional class IV on admission. The mean age was 58.3 ± 15.7 years and 40% of the patients were male. 95% patients accomplished the test and the average number of repetitions was 18 ± 7. No adverse event was recorded during or after the 1-min STST. Blood pressure, heart rate, and degree of dyspnea were increased after the test (all p < 0.001), while oxygen saturation was slightly decreased (97.0 ± 1.6 vs. 96.3 ± 2.0%, p = 0.003). The degree of pulmonary edema (χ2 = 8.300, p = 0.081) was not significantly changed, while there was a reduction in the absolute number of B-lines [9 (3, 16) vs. 7 (3, 13), p = 0.008]. Conclusion: The application of the 1-min STST in early stage of ADHF appeared to be safe and feasible, which induce neither adverse event nor pulmonary edema. It may serve as a new tool of functional capacity assessment, as well as a reference of exercise rehabilitation.

Clinical cancer immunotherapy: Current progress and prospects.

Immune checkpoint therapy via PD-1 antibodies has shown exciting clinical value and robust therapeutic potential in clinical practice. It can significantly improve progression-free survival and overall survival. Following surgery, radiotherapy, chemotherapy, and targeted therapy, cancer treatment has now entered the age of immunotherapy. Although cancer immunotherapy has shown remarkable efficacy, it also suffers from limitations such as irAEs, cytokine storm, low response rate, etc. In this review, we discuss the basic classification, research progress, and limitations of cancer immunotherapy. Besides, by combining cancer immunotherapy resistance mechanism with analysis of combination therapy, we give our insights into the development of new anticancer immunotherapy strategies.

Efficacy and safety of digital therapeutics-based cardiac rehabilitation in heart failure patients: a systematic review.

During the coronavirus disease 2019 (COVID-19) pandemic, it has become difficult to provide centre-based cardiac rehabilitation for heart failure patients. Digital therapeutics is a novel concept proposed in recent years that refers to the use of evidence-based therapeutic interventions driven by high-quality software programs to treat, manage, or prevent a medical condition. However, little is known about the use of this technology in heart failure patients. This study aims to explore the safety and efficacy of digital therapeutics-based cardiac rehabilitation in heart failure patients and to provide new insights into a new cardiac rehabilitation model during the COVID-19 era. To identify technologies related to digital therapeutics, such as the use of medical applications, wearable devices, and the Internet, all relevant studies published on PubMed, EMBASE, Cochrane database, and China National Knowledge Internet were searched from the time the database was established until October 2021. The PEDro was used to assess the quality of included studies. We ultimately identified five studies, which included 1119 patients. The mean age was 66.37, the mean BMI was 25.9, and the NYHA classification ranged from I to III (I = 232, II = 157, III = 209). The mean 6-min walk distance was 397.7 m. The PEDro scores included in the study ranged from 4 to 8, with a mean of 5.8. Exercise training was performed in four studies, and psychological interventions were conducted in three studies. No death or serious adverse events were observed. Adherence was reported in three studies, and all exceeded 85%. The results of most studies showed that digital therapeutics-based cardiac rehabilitation significantly increases exercise capacity and quality of life in heart failure patients. Overall, although this study suggests that digital therapeutics-based cardiac rehabilitation may be a viable intervention for heart failure patients during the COVID-19 era, the efficacy of this new model in routine clinical practice needs to be further validated in a large clinical trial.

Perioperative respiratory muscle training improves respiratory muscle strength and physical activity of patients receiving lung surgery: A meta-analysis.

BACKGROUND: The clinical role of perioperative respiratory muscle training (RMT), including inspiratory muscle training (IMT) and expiratory muscle training (EMT) in patients undergoing pulmonary surgery remains unclear up to now. AIM: To evaluate whether perioperative RMT is effective in improving postoperative outcomes such as the respiratory muscle strength and physical activity level of patients receiving lung surgery. METHODS: The PubMed, EMBASE (via OVID), Web of Science, Cochrane Library and Physiotherapy Evidence Database (PEDro) were systematically searched to obtain eligible randomized controlled trials (RCTs). Primary outcome was postoperative respiratory muscle strength expressed as the maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP). Secondary outcomes were physical activity, exercise capacity, including the 6-min walking distance and peak oxygen consumption during the cardio-pulmonary exercise test, pulmonary function and the quality of life. RESULTS: Seven studies involving 240 participants were included in this systematic review and meta-analysis. Among them, four studies focused on IMT and the other three studies focused on RMT, one of which included IMT, EMT and also combined RMT (IMT-EMT-RMT). Three studies applied the intervention postoperative, one study preoperative and the other three studies included both pre- and postoperative training. For primary outcomes, the pooled results indicated that perioperative RMT improved the postoperative MIP (mean = 8.13 cmH2O, 95%CI: 1.31 to 14.95, P = 0.02) and tended to increase MEP (mean = 13.51 cmH2O, 95%CI: -4.47 to 31.48, P = 0.14). For secondary outcomes, perioperative RMT enhanced postoperative physical activity significantly (P = 0.006) and a trend of improved postoperative pulmonary function was observed. CONCLUSION: Perioperative RMT enhanced postoperative respiratory muscle strength and physical activity level of patients receiving lung surgery. However, RCTs with large samples are needed to evaluate effects of perioperative RMT on postoperative outcomes in patients undergoing lung surgery.

Predictive value of prognostic nutritional index on infection after radical gastrectomy: a retrospective study.

Background: The prognostic nutritional index (PNI) is a useful tool to evaluate nutritional status, which is associated with postoperative complications and prognosis of patients with cancer. Recent studies have shown that PNI has important predictive value for postoperative infection in cancer patients. However, the role and clinical value of PNI in infection after radical gastrectomy remains unclear. This study investigated the relationship between PNI and infection after radical surgery for gastric cancer (GC), focusing on the predictive value of PNI. Methods: A total of 1,111 patients with primary gastric cancer who underwent radical surgery in our hospital from December 2010 to December 2020 were included in this retrospective study. The demographic and clinicopathological data of all patients were acquired through hospital information system (HIS). Preoperative serum albumin (ALB) level and peripheral blood lymphocyte count were obtained for PNI calculation. We selected 812 patients by propensity score matching to reduce biases due to the different distributions of co-variables among the comparable groups. The factors influencing postoperative infection in the matched patients were explored using univariate and multivariate analyses. Results: Baseline characteristics significantly differed among patients with different PNI scores. After one-to-one matching, the clinicopathological data of the 2 groups were comparable, and 812 patients were included for further analysis. Among these patients, 101 developed infections, with an infection rate of 12.4%, which were mainly caused by gram-negative bacteria. The incidence of infection was significantly higher in the low PNI group than in the high PNI group. Univariate and multivariate analyses identified body mass index (BMI) ≥25 kg/m2 [odds ratio (OR) =2.314, P=0.004], diabetes mellitus (OR =1.827, P=0.042), PNI score <45 (OR =2.138, P=0.037), combined multi-organ resection (OR =2.946, P<0.001), operation time ≥240 minutes (OR =2.744, P=0.023), and perioperative blood transfusion (OR =2.595, P=0.025) as risk factors for infection after radical surgery for GC. Conclusions: Infection is the most common complication after radical gastrectomy for GC, and a low preoperative PNI score is a risk factor for postoperative infection.

Downregulation of PDGF-D Inhibits Proliferation and Invasion in Breast Cancer MDA-MB-231 Cells.

BACKGROUND: The platelet derived growth factor-D (PDGF-D) plays an important role in breast tumor aggressiveness. However, limited study has investigated the effect of silencing PDGF-D on the biological function of breast cancer. The purpose of this study is to clarify the potential value of PDGF-D as a target for breast cancer treatment. METHODS: Reverse transcription-polymerase chain reaction and western blot were used to detect PDGF-D expression in 5 different breast cancer cells. The lentiviral vector was usd to silence PDGF-D in MDA-MB-231 cells. Then, Methyl Thiazolyl Tetrazolium was used to detect cell viability, 5-Ethynyl-2'- deoxyuridine and a soft agar assay were used to detect cell proliferation and clonality. Additionally, cell apoptosis after PDGF-D knockdown was measured by Annexin V/ Prodium Iodide staining, and cell migration was detected by trans-well assay. Survival rate and tumor size were measured by nude mice transplantation. RESULTS: The MDA-MB-231 and SK-BR-3 cell lines showed higher PDGF-D expression than the MCF7 cell lines (P<.05). After the PDGF-D gene was silenced, the growth and colony forming abilitys ignificantly decreased (P<.05) together with the induction of apoptosis in MDA-MB-231 cells (P<.05). Moreover, MDA-MB-231 cells with PDGF-D silencing showed significantly diminished aggressive migration and invasion potential compared to other cells (P<.05). In vivo experiments also indicated that PDGF-D silencing inhibited tumor growth and improved the survival rate of tumor-bearing mice. CONCLUSION: Downregulation of PDGF-D had dramatic effects on breast cancer cell proliferation, apoptosis and migration, which indicates that it plays an important role in breast cancer development and progression.

ceRNAs in Cancer: Mechanism and Functions in a Comprehensive Regulatory Network.

Noncoding RNAs have been shown with powerful ability in post-transcriptional regulation, enabling intertwined RNA crosstalk and global molecular interaction in a large amount of dysfunctional conditions including cancer. Competing endogenous RNAs (ceRNAs) are those competitively binding with shared microRNAs (miRNAs), freeing their counterparts from miRNA-induced degradation, thus actively influencing and connecting with each other. Constantly updated analytical approaches boost outstanding advancement achieved in this burgeoning hotspot in multilayered intracellular communication, providing new insights into pathogenesis and clinical treatment. Here, we summarize the mechanisms and correlated factors under this RNA interplay and deregulated transcription profile in neoplasm and tumor progression, underscoring the great significance of ceRNAs for diagnostic values, monitoring biomarkers, and prognosis evaluation in cancer.

Inhibition of BCL9 Modulates the Cellular Landscape of Tumor-Associated Macrophages in the Tumor Immune Microenvironment of Colorectal Cancer.

Tumor-associated macrophages (TAMs) are an indispensable part of the tumor microenvironment (TME), and they likely play a negative rather than positive role in cancer treatment. However, the cellular landscape and transcriptional profile regulation of TAMs in the case of tumor gene inactivation or chemical interference remains unclear. The B-cell lymphoma 9/B-cell lymphoma 9-like (BCL9/BCL9L) is a critical transcription co-factor of ß-catenin. Suppression of Bcl9 inhibits tumor growth in mouse models of colorectal cancer (CRC). Here, we studied the TAMs of CRC by single-cell sequencing. Bcl9 depletion caused macrophage polarization inhibition from M0 to M2 and changed the CRC TME, which further interferes with the inflammation of M0 and M1. The transcription factor regulating these processes may be related to the Wnt signaling pathway from multiple levels. Furthermore, we also found that the cells delineated from monocyte to NK-like non-functioning cells were significantly different in the BCL9-deprived population. Combining these data, we proposed a TAM-to-NK score to evaluate the dynamic balance in TME of monocyte/TAM cells and NK-like non-functioning cells in The Cancer Genome Atlas (TCGA) clinical samples to verify the clinical significance. We demonstrated that the cell type balance and transcription differences of TAMs regulated by BCL9-driven Wnt signaling affected immune surveillance and inflammation of cancer, ultimately affecting patients' prognosis. We thereby highlighted the potential of targeting Wnt signaling pathway through cancer immunotherapy.

Pharmacological Inhibition and Genetic Knockdown of BCL9 Modulate the Cellular Landscape of Cancer-Associated Fibroblasts in the Tumor-Immune Microenvironment of Colorectal Cancer.

Cancer-associated fibroblasts (CAFs) exert a key role in cancer progression and liver metastasis. They are activated in the tumor microenvironment (TME), but their prometastatic mechanisms are not defined. CAFs are abundant in colorectal cancer (CRC). However, it is not clear whether they are raised from local tissue-resident fibroblasts or pericryptal fibroblasts and distant fibroblast precursors, and whether they may stimulate metastasis-promoting communication. B-cell lymphoma 9/B-cell lymphoma 9-like (BCL9/BCL9L) is the key transcription cofactor of ß-catenin. We studied the TME of CRC with single-cell sequencing and consequently found that Bcl9 depletion caused a pro-tumor effect of CAFs, while inhibition of abnormal activation of Wnt/ß-catenin signal through Bcl9 depletion benefited T-cell-mediated antitumor immune responses. We also identified and evaluated four types of CAFs in CRC with liver metastasis. In summary, we demonstrate cell type landscape and transcription difference upon BCL9 suppression in CAFs, as well as how CAF affects cancer associated immune surveillance by inhibition of Wnt signaling. Targeting the Wnt signaling pathway via modulating CAF may be a potential therapeutic approach.

BCL9/BCL9L promotes tumorigenicity through immune-dependent and independent mechanisms in triple negative breast cancer.

Treatment of patients with triple-negative breast cancer (TNBC) has been challenging due to a lack of well-defined molecular targets. The Wnt/ß-catenin pathway is known to be activated in many TNBC patients and BCL9 and BCL9L are important transcriptional co-activators of ß-catenin, but whether inhibition of BCL9/BCL9L can suppress TNBC growth and the underlying mechanism are not fully understood. Here we demonstrate that the expression of BCL9 and BCL9L is directly correlated with malignancy in TNBC patient tumors and that BCL9 and BCL9L promote tumor cell growth, cell migration and metastasis in TNBC models. Mechanistically, we found that BCL9/BCL9L promotes tumorigenicity through both the Wnt and TGF-ß pathways. Besides, BCL9/BCL9L expression inversely correlates with CD8+ T cell infiltration in TNBC and BCL9/BCL9L inhibits the infiltration of CD8+ T cells in the tumor microenvironment. hsBCL9CT-24, an inhibitor of BCL9/ß-catenin peptides, promotes intratumoral infiltration of cytotoxic T cells, reducing regulatory T cells (Treg) and increasing dendritic cells (DCs). Inhibition of BCL9/BCL9L and TGF-ß suppresses activity of Treg. TGF-ß signaling increases tumor infiltration of cytotoxic CD8+ T cells. In accordance, genetic or pharmacological inhibition of BCL9/BCL9L synergizes with PD-1/L1 antibodies to inhibit tumor growth. In summary, these results suggest that targeting BCL9/BCL9L has a direct anti-tumor effect and also unleashes an anti-cancer immune response through inhibition of both Wnt and TGF-ß signaling, suggesting a viable therapeutic approach for TNBC treatment.

Fabrication of fish gelatin / sodium alginate double network gels for encapsulation of probiotics.

BACKGROUND: To improve the environmental resistance of probiotics, and particularly their survival in the gastrointestinal environment, a fish gelatin (FG) / sodium alginate (SA) double network gelation (FSDN) was developed to encapsulate them. Thermal treatment and calcium ion inducement were adopted to fabricate fish gelatin and sodium alginate gels. It was feasible to scale up this process. The effects of FG concentration (0-60 g/L) on FSDN properties, including morphology, water-holding capacity, and encapsulation efficiency were evaluated. RESULTS: The results indicated that the addition of FG could improve the transparency, rehydration, and water-holding capacity of FSDN. Scanning electronic microscope (SEM) images revealed that FSDN had a denser and more complete structure than SA. Encapsulation efficiency improved from 15.85% to 91.91% as the FG concentration ranged from 0 to 50 g/L. Bifidobacterium longum embedded by FSDN showed better thermal stability than when it was free. Compared with bare probiotics (1.7%), the encapsulated ones exhibited higher viability (above 15%) in simulated gastric fluid. CONCLUSION: In conclusion, interpenetrating FSDN is an effective barrier constituent and could achieve the targeted delivery of probiotics. It is a potential new delivery carrier for the oral administration of probiotics. © 2021 Society of Chemical Industry.

Physical Therapist Management of COVID-19 in the Intensive Care Unit: The West China Hospital Experience.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has dominated the attention of health care systems globally since January 2020. Various health disciplines, including physical therapists, are still exploring the best way to manage this new disease. The role and involvement of physical therapists in the management of COVID-19 are not yet well defined and are limited in many hospitals. This article reports a physical therapy service specially commissioned by the Health Commission of Sichuan Province to manage COVID-19 during patients' stay in the intensive care unit (ICU) at the Public Health Clinical Center of Chengdu in China. METHODS: Patients diagnosed with COVID-19 were classified into 4 categories under a directive from the National Health Commission of the People's Republic of China. Patients in the "severe" and "critical" categories were admitted to the ICU irrespective of mechanical ventilation was required. Between January 31, 2020, and March 8, 2020, a cohort of 16 patients was admitted to the ICU at the Public Health Clinical Center of Chengdu. The median (minimum to maximum) hospital and ICU stays for these patients were 27 (11-46) and 15 (6-38) days, respectively. Medical management included antiviral, immunoregulation, and supportive treatment of associated comorbidities. Physical therapist interventions included body positioning, airway clearance techniques, oscillatory positive end-expiratory pressure, inspiratory muscle training, and mobility exercises. All patients had at least 1 comorbidity. Three of the 16 patients required mechanical ventilation and were excluded for outcome measures that required understanding of verbal instructions. In the remaining 13 patients, respiratory outcomes-including the Borg Dyspnea Scale, peak expiratory flow rate, Pao2/Fio2 ratio, maximal inspiratory pressure, strength outcomes, Medical Research Council Sum Score, and functional outcomes (including the Physical Function in Intensive Care Test score, De Morton Mobility Index, and Modified Barthel Index)-were measured on the first day the patient received the physical therapist intervention and at discharge. RESULTS: At discharge from the ICU, while most outcome measures were near normal for the majority of the patients, 61% and 31% of these patients had peak expiratory flow rate and maximal inspiratory pressure, respectively, below 80% of the predicted value and 46% had De Morton Mobility Index values below the normative value. CONCLUSION: The respiratory and physical functions of some patients remained poor at ICU discharge, suggesting that long-term rehabilitation may be required for these patients. IMPACT: Our experience in the management of patients with COVID-19 has revealed that physical therapist intervention is safe and appears to be associated with an improvement in respiratory and physical function in patients with COVID-19 in the ICU.

T-cell-based immunotherapy in colorectal cancer.

Colorectal cancer (CRC) is the leading cause of cancer death worldwide. CRC therapeutic strategies include surgical resection, chemotherapy, radiotherapy, and other approaches. However, patients with metastatic CRC have worse prognoses. In recent years, T-cell-based immunotherapy has elicited promising responses in B-cell malignancies, melanoma, and lung cancer, but most CRC patients are resistant to immunotherapy, chemotherapy, and targeted therapy. Immune checkpoint inhibitors have shown encouraging results in non-small cell lung cancer, melanoma, and other cancers, but immune checkpoint blockade is only effective for CRC subset with microsatellite instability. Other immunotherapies, such as cytokines, cancer vaccines, small molecules, oncolytic viruses, and chimeric antigen-receptor therapy, are currently in use against CRC. This review analyzes recent developments in immunotherapy for CRC treatment as well as the challenges in overcoming resistance.

Microbial Risk Assessment of Escherichia coli O157:H7 in Beef Imported from the United States of America to Taiwan.

Outbreaks of foodborne illness caused by pathogenic Escherichia coli (E. coli) O157:H7, which are attributable to the consumption of undercooked beef, have occurred in many countries. In Taiwan, the production of domestic beef accounts for only 5% of the total amount of beef sold. Therefore, we applied different contextual assumptions to develop a quantitative microbial risk assessment of E. coli O157:H7 and evaluated the risk of illness in the Taiwanese population consuming beef imported from the United States of America. The probability distribution showed that, in males aged 19-65 years in the Taiwanese population, for example, when rare beef was consumed 100 servings, there was a 90% probability of randomly intaking seven colony forming units of E. coli O157:H7. When medium beef was consumed 10,000 servings, there was a 90% probability of randomly intaking two colony forming units of E. coli O157:H7. When the exceedance risk was 5%, the rate of foodborne illnesses caused by consuming rare beef contaminated with E. coli O157:H7 was 10-28 cases per 1 million individuals. For medium beef, this rate was 6-13 per 100 million individuals. Sensitivity analyses indicated that the amount of E. coli O157:H7 remaining in beef products after cooking was the most important risk factor, followed by the amount of beef products consumed. Proper cooking of imported beef consumed by the Taiwanese public reduces the incidence of foodborne disease to almost zero, without risk of harm to health.

Single-cell transcriptome analysis reveals tumor immune microenvironment heterogenicity and granulocytes enrichment in colorectal cancer liver metastases.

Colorectal cancer (CRC) is among the top 3 leading causes of cancer-related deaths, and tumor malignant progression and metastases contribute to the high mortality of advanced CRC. Immune components in the tumor microenvironment can modulate tumor progression and are attractive therapeutic targets. Recently, intra-tumor mutational diversification of colorectal cancer cells at the single cell level was conducted. However, single cell transcriptome analysis of the microenvironment composition and characteristics in CRC liver metastases has yet to be performed. In this study, samples of liver metastasis cancer tissue and adjacent tissue from CRC patients were examined by single cell RNA sequencing. A total of 12 clusters corresponding to 6 cell types, including cancer cells, T cells, myeloid cells, endothelial cells, fibroblasts and B cells, were identified. Expression clustering of 445 cell cluster deregulated genes (CCDGs) identified 6 gene modules and functional enrichment was conducted to analyse the pathways in cancer cell and T cell populations. Next, the clinical significance of the expression of 93 cell cluster specifically deregulated genes (CCSDGs) in tumor-infiltrating immune cells and the correlation of the expression of these genes with patients' survival rates were investigated with the TCGA dataset. Then, the mechanisms for increased proportion of granulocytes in the cancer sample were explored, and abnormal ferroptosis-mediated granulocyte cell death was proposed. Finally, the Wnt signalling pathway was found to be activated and promote granulocytes migration. This single cell RNA sequencing study may shed light on the tumor microenvironment composition and pave the way for CRC liver metastasis therapy.

Overexpression of gelsolin reduces the proliferation and invasion of colon carcinoma cells.

The enhanced motility of cancer cells via the remodeling of the actin cytoskeleton is crucial in the process of cancer cell invasion and metastasis. It was previously demonstrated that gelsolin (GSN) may be involved as a tumor or a metastasis suppressor, depending on the cell lines and model systems used. In the present study, the effect of GSN on the growth and invasion of human colon carcinoma (CC) cells was investigated using reverse transcription quantitative polymerase chain reaction and western blotting. It was observed that upregulation of the expression of GSN in human CC cells significantly reduced the invasiveness of these cells. The expression levels of GSN were observed to be reduced in CC cells, and the reduced expression level of GSN was often associated with a poorer metastasis­free survival rate in patients with CC (P=0.04). In addition, the overexpression of GSN inhibited the invasion of CC cells in vitro. Furthermore, GSN was observed to inhibit signal transducer and activator of transcription (STAT) 3 signaling in CC cells. Together, these results suggested that GSN is critical in regulating cytoskeletal events and inhibits the invasive and/or metastatic potential of CC cells. The results obtained in the present study may improve understanding of the functional and mechanistic links between GSN as a possible tumor suppressor and the STAT3 signaling pathway, with respect to the aggressive nature of CC. In addition, the present study demonstrated the importance of GSN in regulating the invasion and metastasis of CC cells at the molecular level, suggesting that GSN may be a potential predictor of prognosis and treatment success in CC.

Ubiquitin-conjugating enzyme UbcH10 promotes gastric cancer growth and is a potential biomarker for gastric cancer.

Gastric cancer is a fatal disease and the availability of early diagnostic methods is limited. There is an urgent need to identify effective targets for early diagnosis and therapeutics. UbcH10 is a ubiquitin-conjugating enzyme with high expression in various types of cancers. In the present study, several gastric tumor cell lines with high or low expression of UbcH10 were exploited to study the role of UbcH10 in gastric cancer. Knockdown of UbcH10 expression using siRNA in gastric cancer cell lines with high expression of UbcH10 resulted in reduced proliferation, increased cisplatin-induced apoptosis and reduced serum-induced ERK, Akt and p38 phosphorylation signaling. In agreement, overexpression of UbcH10 in gastric cancer cell lines with low expression of UbcH10 led to enhanced cell proliferation and resistance to cisplatin-induced apoptosis. Most importantly, IHC analyses showed that the UbcH10 protein was expressed at a high level in most patient gastric cancer tissues, but was absent in adjacent mesenchyme tissues. These data suggest that UbcH10 may promote gastric cancer growth and can serve as a biomarker for diagnosis or as a target for novel therapeutics in gastric cancer.