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OBJECTIVE To clarify whether systemic lymph node dissection (LND) influences the safety of surgery and the survival of patients with locally advanced esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemoradiotherapy (nCRT). SUMMARY BACKGROUND DATA Prognostic impact of systemic lymphadenectomy during surgery after nCRT for ESCC is still uncertain and requires clarification. METHODS This is a secondary analysis of NEOCRTEC5010 trial which compared nCRT followed by surgery versus surgery alone for locally advanced ESCC. Relationship between number of LND and perioperative, recurrence and survival outcomes were analyzed in the nCRT group. RESULTS Three-year overall survival was significantly better in the nCRT group than the S group (75.2% vs 61.5%; P=0.011). In the nCRT group, greater number of LND was associated with significantly better overall survival (HR, 0.358; P < 0.001) and disease-free survival (HR, 0.415; P=0.001), but without any negative impact on postoperative complications. Less LND (< 20 vs ≥ 20) was significantly associated with increased local recurrence (18.8% vs 5.2%, P=0.004) and total recurrence rates (41.2% vs 25.8%, P=0.027). Compared to patients with persistent nodal disease, significantly better survival was seen in patients with complete response and with LND ≥ 20, but not in those with LND < 20. CONCLUSIONS Systemic lymph node dissection does not increase surgical risks after nCRT in ESCC patients. And it is associated with better survival and local disease control. Therefore, systemic lymphadenectomy should still be considered as an integrated part of surgery after nCRT for ESCC.

Graphical abstract, Introduction The COVID-19 global pandemic is far from ending. There is an urgent need to identify applicable biomarkers for early predicting the outcome of COVID-19. Growing evidences have revealed that SARS-CoV-2 specific antibodies evolved with disease progression and severity in COIVD-19 patients. Objectives We assumed that antibodies may serve as biomarkers for predicting the clinical outcome of hospitalized COVID-19 patients on admission. Methods By taking advantage of a newly developed SARS-CoV-2 proteome microarray, we surveyed IgG responses against 20 proteins of SARS-CoV-2 in 1,034 hospitalized COVID-19 patients on admission and followed till 66 days. The microarray results were further correlated with clinical information, laboratory test results and patient outcomes. Cox proportional hazards model was used to explore the association between SARS-CoV-2 specific antibodies and COVID-19 mortality. Results Nonsurvivors (n=955) induced higher levels of IgG responses against most of non-structural proteins than survivors (n=79) on admission. In particular, the magnitude of IgG antibodies against 8 non-structural proteins (NSP1, NSP4, NSP7, NSP8, NSP9, NSP10, RdRp, and NSP14) and 2 accessory proteins (ORF3b and ORF9b) possessed significant predictive power for patient death, even after further adjustments for demographics, comorbidities, and common laboratory biomarkers for disease severity (all with p trend < 0.05). Additionally, IgG responses to all of these 10 non-structural/accessory proteins were also associated with the severity of disease, and differential kinetics and serum positive rate of these IgG responses were confirmed in COVID-19 patients of varying severities within 20 days after symptoms onset. The area under curves (AUCs) for these IgG responses, determined by computational cross-validations, were between 0.62 and 0.71. Conclusions Our findings might have important implications for improving clinical management of COVID-19 patients.

MicroRNA-1290 (miR-1290) has been reported to be involved in many diseases and play a key role during the development process. However, the role of miR-1290 in atherosclerosis (AS) is still unclear. The current study showed that the expressions of miR-1290 were high in serum of patients with hyperlipidemia. The functional role of miR-1290 were then investigated in human umbilical vein endothelial cells (HUVECs). Here, we found that miR-1290 expressions were notably enhanced in HUVECs mediated by IL-8. miR-1290 inhibitor repressed monocytic THP-1 cells adhesion to HUVECs by regulating ICAM-1 and VCAM-1, inhibited proliferation through regulating cyclinD1 and PCNA, and inhibited inflammatory response by regulating IL-1β. Mechanistically, we verified that miR-1290 mimic was able to directly target the 3′-UTR of GSK-3β mRNA using luciferase reporter assay. Knockdown of GSK-3β (si-GSK-3β) promoted HUVECs adhesion and the expression of IL-1β, and partially restore the depression effect of miR-1290 inhibitor on HUVECs adhesion and inflammation. In contrast, si-GSK-3β inhibited the proliferation of HUVECs and the expression of cyclinD1 and PCNA. In summary, our study revealed that miR-1290 promotes IL-8-mediated the adhesion of HUVECs by targeting GSK-3β. However, GSK-3β is not the target protein for miR-1290 to regulate the proliferation of HUVECs. Our findings may provide potential target in atherosclerosis treatment.

Solute carrier organic anion transporter family member 4A1 (SLCO4A1-AS1), a newly discovered lncRNA, may exert effects in tumors. Since its role in gastric cancer remains obscure, we sought to explore the mechanism of SLCO4A1-AS1 in gastric cancer. The relationship among SLCO4A1-AS1, miR-149-5p, and STAT3 was detected by bioinformatics, dual luciferase analysis, and Pearson’s test, and the expressions of these genes were determined by quantitative real-time PCR and Western blot. Moreover, CCK-8, flow cytometry, wound healing assay, and Transwell analysis were performed to verify the function of SLCO4A1-AS1 in gastric cancer. Rescue experiments were used to detect the role of miR-149-5p. The expressions of SLCO4A1-AS1 and STAT3 were increased, while the expression of miR-149-5p was suppressed in gastric cancer tissues and cell lines. In addition, STAT3 expression was negatively correlated with miR-149-5p expression but was positively correlated with SLCO4A1-AS1 expression. Overexpression of SLCO4A1-AS1 promoted cell viability, migration, invasion, and STAT3 expression but suppressed apoptosis, while knockdown of SLCO4A1-AS1 had the opposite effect. SLCO4A1-AS1 bound to miR-149-5p and targeted STAT3. Moreover, miR-149-5p mimic inhibited the malignant development of gastric cancer cells and obviously reversed the function of SLCO4A1-AS1 overexpression. Our research reveals that abnormally increased SLCO4A1-AS1 expression may be an important molecular mechanism in the development of gastric cancer.

Circular RNAs (circRNAs) are crucial elements of non-coding RNA, that regulate various biological processes. To date, expression patterns and functional roles of circRNAs during osteogenic differentiation of human umbilical cord mesenchymal stromal cells (hUCMSCs) remain unknown. In this study, we analyzed RNA-sequence data to reveal expression profiles of circRNAs during osteogenesis of hUCMSCs, then elucidated the underlying mechanisms of action. We identified a total of 5457 circRNAs in hUCMSCs, of which 34 and 33 were upregulated and downregulated, respectively. We applied Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses to determine functions and related pathways of differentially expressed circRNAs. Moreover, we applied bioinformatics tools to construct competing endogenous RNA networks, comprising 10 circRNAs, 46 micro RNAs and 413 mRNAs. Furthermore, we predicted protein-coding potential of the upregulated circRNAs then constructed a co-expression network comprising the top 5 upregulated circRNAs and 75 RNA-binding proteins. Next, we validated 6 differentially-expressed circRNAs and found that overexpressing circ‐CTTN could promote osteogenesis of hUCMSCs. Overall, our findings indicate that clusters of circRNAs are aberrantly expressed in hUCMSCs during osteogenic differentiation, hence lay a foundation for future research into promoting hUCMSCs osteogenic differentiation and bone regeneration.

Myocardin‐related transcription factor‐A/serum response factor (MRTF‐A/SRF), a well‐known transcriptional programme, has been proposed to play crucial roles in skeletal muscle development and function. However, whether MRTF‐A participates in muscle regeneration and the molecular mechanisms are not completely understood. Here, we show that MRTF‐A levels are highly correlated with myogenic genes using a RNA‐seq assay, which reveal that MRTF‐A knockdown in C2C12 cells significantly reduces PAX7 expression. Subsequent in vitro and in vivo data show that MRTF‐A and PAX7 present identical expression patterns during myoblast differentiation and CTX‐induced muscle injury and repair. Remarkably, MRTF‐A overexpression promotes myoblast proliferation, while inhibiting cell differentiation and the expression of MyoD and MyoG. MRTF‐A loss of function produces the opposite effect. Moreover, mice with lentivirus (MRTF‐A) injection possesses more PAX7+ satellite cells, but less differentiating MyoD+ and MyoG+ cells, leading subsequently to diminished muscle regeneration. Our mechanistic results reveal that MRTF‐A contributes to PAX7‐mediated myoblast self‐renewal, proliferation, and differentiation by binding to its distal CArG box. Overall, we propose that MRTF‐A functions as a novel PAX7 regulator upon myoblast commitment to differentiation, which could provide pathways for dictating muscle stem cell fate and open new avenues to explore stem cell‐based therapy for muscle degenerative diseases.

Fibrosis is a pathological process characterized by abnormal activation of fibroblasts with increased synthesis of extracellular matrix components, including collagens. It may lead to loss of proper tissue architecture and organ function in clinical diseases such as systemic sclerosis and liver fibrosis. Excess accumulation of collagens is considered the primary indicator of fibrosis. Notch signaling has been reported to be involved in the fibrosis of many different organs, including the liver. Our previous study showed that the uterine-specific over-activation of canonical Notch1 signaling in the mouse uterus (Pgrcre/+ Rosa26N1ICD/+ , OEx) results in complete infertility as a consequence of multiple developmental and physiological defects, together with increased collagen accumulation evidenced by Masson's staining. In this study, we further detected expressions of all 44 collagen genes in these Notch1 gain-of-function transgenic mice and found that 18 collagens have been largely affected. In another aspect, using an intrauterine adhesion model (IUA), we mimicked fibrosis in the mouse uterine. The results suggested that Notch receptors were upregulated only 3 days after induction, and most of the fibril-forming collagen began to upregulate 6 days after the surgery. Furthermore, when induced IUA in the N1ICD-OEx mice, the expression of collagens and fibrosis levels were significantly enhanced. At last, as a Notch signaling inhibitor, the γ-secretase inhibitor N-[N-(3,5-difl uorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) pretreatment could alleviate the expression of collagens and the symptoms of fibrosis. These results demonstrate that Notch signaling may play a role in upregulating collagens expression in endometrial fibrosis and might be a potential target of fibrosis therapy in the endometrium.

Objectives Previous literature has shown that chronic diseases and psychological distress are correlated. However, the mediating and moderating mechanisms underlying this relationship have not been sufficiently studied. The purpose of this study was to explore the role played by activities of daily living (ADL) and perceived social support. Method Face-to-face questionnaire-based surveys were conducted with 3250 valid participants (age ≥60 years). Participants were assessed using the Barthel Index, Perceived Social Support Scale, and Depression Anxiety Stress Scale-21. Results 1) Chronic diseases had a significant direct effect on psychological distress in older adults; 2) the relationship between chronic diseases and psychological distress was partially mediated by ADL; and 3) the impact of chronic diseases on psychological distress was significantly moderated by perceived social support. More importantly, perceived social support was a protective factor that could effectively alleviate the adverse effects of chronic diseases on psychological distress. Conclusion The results add to the existing literature by uncovering the underlying mechanisms between chronic diseases and mental health. These findings have implications for early intervention and prevention of mental health problems in older adults.

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are serious neurodegenerative diseases. Although their pathogenesis is unclear, the abnormal accumulation of TAR DNA-binding protein of 43 kDa (TDP-43) is a pathological feature that exists in almost all patients. Thus far, there is no drug that can cure ALS/FTLD. Tetramethylpyrazine nitrone (TBN) is a derivative of tetramethylapyrazine, derived from the traditional Chinese medicine Ligusticum chuanxiong, which has been widely proven to have therapeutic effects on models of various neurodegenerative diseases. TBN is currently under clinical investigation for several indications including a Phase II trial of ALS. Here, we explored the therapeutic effect of TBN in an ALS/FTLD mouse model. We injected the TDP-43 M337V virus into the striatum of mice unilaterally and bilaterally, and then administered 30 mg/kg TBN intragastrically to observe changes in behavior and survival rate of mice. The results showed that in mice with unilateral injection of TDP-43M337V into the striatum, TBN improved motor deficits and cognitive impairment in the early stages of disease progression. In mice with bilateral injection of TDP-43M337V into the striatum, TBN not only improved motor function but also prolonged survival rate. Moreover, we show that its therapeutic effect may be through activation of the Akt/mTOR/GSK-3β and AMPK/PGC-1α/Nrf2 signaling pathways. In summary, TBN is a promising agent for the treatment of ALS/FTLD.

Depression is the most frequent psychiatric disorder among the older adults, the purpose of this study is to explore the mediation effect of health promoting lifestyle on the relationship between Socioeconomic Status (SES) and depression, so as to provide practical reference for effectively preventing and alleviating depression of the older adults.A multi-stage random sampling method was conducted in Shanxi Province. A total 8526 older adults were included in the analysis. Regression analysis was used to explore the relationship between the socioeconomic status, health promoting lifestyle and depression, and the mediation effect test process was used to verify the mediating mechanism of health promoting lifestyle on this relationship.62.1% of the older adults had depression symptoms in this study, and there were significant differences in depression scores among the older adults with gender, age, residence, marital status, endowment pattern, self-care ability, exercise frequency, physical examination frequency, daily diet rules(P0.05). The results of mediating effect analysis showed that health promoting lifestyle as mediation effect between social economic status and depression was established, and the mediating effect was accounted for (a*b/c) 63.1%.Given the cross-sectional study, it is not possible to make causal inferences.There were different degrees of depression in the older adults. The lower the SES is, the higher the risk of depression is. This result once again confirms the social causation theory. Combined with the theory of health risk behavior, the study further confirmed the applicability of lifestyle mechanism in the intermediate mechanism of the relationship between SES and depression in the elderly. Thus, in addition to providing material support and financial assistance, helping the elderly develop a healthy lifestyle is also effective measure to improve their depression.

Obesity is epidemiologically linked to 13 forms of cancer. The local and systemic obese environment is complex and likely affect tumors through multiple avenues. This includes modulation of cancer cell phenotypes and the composition of the tumor microenvironment. A molecular understanding of how obesity links to cancer holds promise for identifying candidate genes for targeted therapy for obese cancer patient. Herein, we review both the cell-autonomous and non-cell-autonomous mechanisms linking obesity and cancer as well as provide an overview of the mouse model systems applied to study this.

Objective This study was aimed at exploring whether miR-30a enhanced sensitivity of non-small-cell lung cancer (NSCLC) cells against neoadjuvant chemotherapy through an autophagy-dependent way. Methods We totally recruited 304 NSCLC patients who have underwent chemotherapy, as well as 185 NSCLC patients who did not receive chemotherapy. NSCLC cell lines (i.e. H1299 and H460) were also purchased, and they were transfected by miR-30a mimic/inhibitor. Furthermore, cisplatin (DDP)/pemetrexed (PEM) resistance of NSCLC cells was assessed utilizing MTT assay, and autophagic proteins isolated from NSCLC tissues and cells were quantitated by western blotting. Results Lowly expressed miR-30a was reflective of lymph node metastasis, advanced TNM stage and poor 5-year survival among NSCLC patients treated by neoadjuvant chemotherapy (i.e. combined treatment of DDP and PEM) (P Conclusions Intentionally elevating miR-30a expression was conducive to improving NSCLC prognosis after neoadjuvant chemotherapy, for its depressing drug-caused autophagy and resistance.

Background The aim of the present study was to analyze the association of programmed cell death-ligand 1 (PD-L1) and vascular endothelial growth factor receptor 2 (VEGFR2) expression levels with clinicopathological characteristics and survival to provide a treatment strategy for rectal cancer. Methods Immunohistochemical staining of VEGFR2 and PD-L1 was carried out, and the association of PD-L1 and VEGFR2 expression levels with clinicopathological characteristics and survival were investigated in 77 pair-matched rectal cancer patients. Results PD-L1 and VEGFR2 expression levels in surgical tumor tissues were higher than those in paired adjacent normal tissues, respectively (both P

Type 2 diabetes (T2D) is a chronic endocrine disorder with rapidly increasing prevalence worldwide. Genetic instability leading to metabolic dysfunction plays an important role in T2D susceptibility and progression. Structural alteration in genome, that is, copy number variation (CNV) is emerging as the inherent marker for disease identification. Previous genomic CNV array revealed that protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene was overlapped with a CNV region, however, whether this CNV affected T2D risk remains to be further elucidated. In this study, we first identified divergent distributions of the PTPN22 copy number (CN) between T2D patients and healthy controls in Chinese population (p < 0.01). Risk assessment analysis revealed that the CN gain (OR = 3.28, p < 0.001) was the promising risk factor for T2D. Also, significantly positive correlations of the PTPN22 CNV with fasting plasma glucose and glycated hemoglobin were demonstrated in T2D patients. Statistical association analysis investigated that the T2D individuals carrying CN gain showed higher plasma glucose and lower insulin levels than those carrying CN normal and loss at 60 min/120 min/180 min during an OGTT test. In addition, the PTPN22 CNV had an effect on total cholesterol, and the CN gain presented higher values than the other two CN types. These results suggested that the CN gain types of the PTPN22 gene accompany with the glycometabolism dysregulation, and finally predispose their carriers to T2D; therefore, the PTPN22 CNV may be a promising biomarker for predicting T2D risk, or a clinical target for T2D diagnosis and therapy.

In vitro cultures of primary cortical neurons are widely used to investigate neuronal function. However, it has yet to be fully investigated whether there are significant differences in development and function between cultured rodent and primate cortical neurons, and whether these differences influence the utilization of cultured cortical neurons to model pathological conditions. Using in vitro culture techniques combined with immunofluorescence and electrophysiological methods, our study found that the development and maturation of primary cerebral cortical neurons from cynomolgus monkeys were slower than those from mice. We used a microelectrode array technique to compare the electrophysiological differences in cortical neurons, and found that primary cortical neurons from the mouse brain began to show electrical activity earlier than those from the cynomolgus monkey. Although cultured monkey cortical neurons developed slowly in vitro, they exhibited typical pathological features-revealed by immunofluorescent staining-when infected with adeno-associated viral vectors expressing mutant huntingtin (HTT), the Huntington's disease protein. A quantitative analysis of the cultured monkey cortical neurons also confirmed that mutant HTT significantly reduced the length of neurites. Therefore, compared with the primary cortical neurons of mice, cultured monkey cortical neurons have longer developmental and survival times and greater sustained physiological activity, such as electrophysiological activity. Our findings also suggest that primary cynomolgus monkey neurons cultured in vitro can simulate a cell model of human neurodegenerative disease, and may be useful for investigating time-dependent neuronal death as well as treatment via neuronal regeneration. All mouse experiments and protocols were approved by the Animal Care and Use Committee of Jinan University of China (IACUC Approval No. 20200512-04) on May 12, 2020. All monkey experiments were approved by the IACUC protocol (IACUC Approval No. LDACU 20190820-01) on August 23, 2019 for animal management and use.

Accompanying with diabetes mellitus-induced osteoporosis (DM-OS), diabetic patients show poor peri-implant osteogenesis after implantation for dentition defect. Berberine (BBR), a candidate oral hypoglycemic agent, is a promising agent for treating DM-OS. In this study, BBR was applied on DM rats and high-glucose-cultured bone mesenchymal stem cells (BMSCs) to investigate its therapeutic mechanism on DM-OS, thus laying a theoretical basis for the future application of BBR in implant restoration. Phenotypes were assessed in the DM rats after 4 w of gavage with BBR. Furthermore, BMSCs were cultured with high glucose and BBR. Cell Counting Kit-8, 2',7'-dichlorofluorescin diacetate (H2 DCF-DA), quantitative real-time PCR (qRT-PCR), and western blot were performed to estimate the cell proliferation, oxidative stress, and osteogenic differentiation. Moreover, the DM rats treated with BBR and insulin receptor substrate-1 anti-sense oligonucleotide (IRS-1-ASO) underwent a 4-w implant-healing period and then micro computed tomography (Micro-CT) and histology were performed to verify the mechanism. Results showed that the 4-w administration of BBR markedly improved the glucose metabolism and bone metabolism in the DM rats. in vitro experiments revealed that BBR alleviated high-glucose-inhibited osteogenesis of the BMSCs by upregulating reactive oxygen species (ROS)-mediated IRS-1 signaling. Besides, injection of IRS-1-ASO abolished the BBR promotion of implant osseointegration in the DM rats. In conclusion, targeting ROS-mediated IRS-1 signaling, BBR acted as an efficient agent to advance osseointegration in DM, which indicated that BBR use is a good strategy for future implants restoration in diabetic patients.

The histone H3 lysine 36 methyltransferase SET-domain-containing 2 (SETD2) has been reported to be frequently mutated or deleted in many types of human cancer. However, the role of SETD2 in lung adenocarcinoma (LUAD) has not been well documented. In the present study, we found that SETD2 was significantly down-regulated both in LUAD tissues and cell lines. Functionally, the increased expression of SETD2 significantly attenuated the proliferation of cancer cells by affecting the cell cycle, whereas SETD2 deficiency dramatically improved these proliferative abilities of cancer cells. Through conjoint analysis of RNA-seq and ChIP data, we identified a functional target gene of SETD2, CXCL1, and its expression was negatively correlated with that of SETD2. Moreover, SETD2 deletion stimulated cell cycle-related proteins to promote LUAD. Further mechanistic studies demonstrated that histone H3 lysine 36 trimethylation (H3K36me3) catalyzed by SETD2 interacted with the promoter of CXCL1 to regulate its transcription and downstream signaling pathways, contributing to tumorigenesis in vitro and in vivo. Our findings suggested that SETD2 inhibited tumor growth via suppressing CXCL1-mediated activation of cell cycle, indicating that the regulation of H3K36me3 level by targeting SETD2 and/or the administration of downstream CXCL1 might represent a potential therapeutic way for new treatment in LUAD.

Hepatitis C virus (HCV) infection is the cause of severe liver disease in many people. The restricted species tropism of HCV hinders the research and development of drugs and vaccines. The Chinese tree shrew (Tupaia belangeri chinensis) is a close relative of primates and can be infected by HCV, but the underlying mechanisms are unknown. In this study, we have characterized the functions of tree shrew MAVS (tMAVS) in response to HCV infection and defined the capacity of HCV replication. HCV was shown to be colocalized with tMAVS in primary tree shrew hepatocytes and cleaved tMAVS at site Cys508 via its NS3/4A protease, with a modulating effect by site Glu506 of tMAVS. The tMAVS cleavage by HCV NS3/4A impaired the IRF3-mediated induction of IFN-β but maintained the activated NF-κB signaling in the tree shrew primary cells. Activation of the tMAVS-dependent NF-κB signaling inversely inhibited HCV replication and might limit the establishment of persistent infection. Overall, our study has revealed an elegant example of the balance between the host defenses and HCV infection via the MAVS-mediated antiviral signaling and has provided an insight into the mechanisms underpinning HCV infection in the Chinese tree shrew.

A poly (acrylic acid-co-N-methylol acrylamide-co-butyl acrylate) copolymer grafted-carboxymethyl cellulose (PA-PN-PBA-g-CMC) binder is synthesized via a free radical copolymerization for Si-based anodes in lithium ion batteries. In this multifunctional polymer binder system, carboxyl-rich poly (acrylic acid) and carboxymethyl cellulose can bond with Si particles and copper current collectors. Additionally, a robust cross-linking network can be obtained through the condensation reaction between hydroxyl and hydroxymethyl groups which are present in carboxymethyl cellulose and N-methylol acrylamide segments, respectively. This network structure helps to keep the integrity of the Si electrode, and thereby significantly improves the cycling performance of the Si anodes (capacity retention rate after 200 cycles is above 90%). The butyl groups in poly (butyl acrylate) segments provide the nonpolar sections in the binder, which help the electrolytes easily wet the electrodes, allowing Li ions to diffuse rapidly in the Si anodes. With this multi-functional binder, the Si-based LIBs perform well in both cycle performance and rate performance.

Gastric cancer is one of the leading causes of cancer-related death due to late diagnosis with high metastatic frequency. In this study, the impact of tumor secreted exosomes on immune function in the tumor environment was investigated using exosomes isolated from gastric cancer cell lines MKN-28, MKN-45, and SGC-7901. Results show that exosomes derived from all of these cell lines changed the gene expression and cytokine secretion levels of CD8+ T cells. They also block cell cycle progression, induced apoptosis in CD8+ T cells. Image analysis of fluorescent labeled exosomes derived from three cell lines injected systemically into C57BL/6 mice revealed these exosomes primarily localize to the lungs. We further showed exosomes were mainly taken up by natural killer cells and macrophages in the lung. After long-term exposure to inject exosomes from MKN-45 cells, mice developed an immunosuppressive tumor microenvironment in the lung with increased frequency of effector memory CD4+ T and MDSC, decreased CD8+ T cell and NK frequency. This immune suppressive environment promotes gastric cancer lung metastasis. Lung metastasis sites developed after mice were exposed to exosomes isolated from all three gastric cancer cell lines when the mice were injected with MFC cells. Results suggest that exosomes derived from gastric cancer cells (especially MKN-45 and MKN-28) changed CD8+ T cell gene expression and cytokine secretion patterns to create an immunosuppressive condition for metastatic niche formation in the lung. Overall, this study provides new insights into how gastric cancer derived exosomes modulate the immune response to promote lung tumor metastasis.

Lung cancer (LC), is the most common and lethal cancer worldwide. It affects both sexes and in its early stages is clinically silent, until it reaches a more advanced stage, when it becomes highly incurable. In order to improve the high mortality associated with LC there has been an urgent need for screening high risk patients by low dose CT scan (LDCT) for the early detection of small resectable malignant tumors. However, while highly sensitive to detect small lung nodules, LDCT is non-specific, resulting in a compelling need for a complementary diagnostic tool. For example, a non-invasive blood test or liquid biopsy, (LB), could prove quite useful to confirm a diagnosis of malignancy prior to definitive therapy. With the advent of LB becoming increasingly clinically accepted in the diagnosis and management of LC, there has been an explosion of publications highlighting new technologies for the isolation of and detection of circulating tumor cells (CTCs) and cell free tumor DNA (cfDNA). The enormous potential for LB to play an important role in the diagnosis and management of LC to obtain valuable diagnostic information via an approach that may yield equivalent information to a surgical biopsy, regarding the presence of cancer and its molecular landscape is described.

Colorectal cancer (CRC) has the second highest mortality rate among all cancers worldwide. Surgery, chemotherapy, radiotherapy, molecular targeting and other treatment methods have significantly prolonged the survival of patients with CRC. Recently, the emergence of tumor immunotherapy represented by immune checkpoint inhibitors (ICIs) has brought new immunotherapy options for the treatment of advanced CRC. As the efficacy of ICIs is closely related to the tumor immune microenvironment (TME), it is necessary to clarify the relationship between the immune microenvironment of CRC and the efficacy of immunotherapy to ensure that the appropriate drugs are selected. We herein review the latest research progress in the immune microenvironment and strategies related to immunotherapy for CRC. We hope that this review helps in the selection of appropriate treatment strategies for CRC patients.

Silicon is a promising anode material for lithium-ion batteries because of its high theoretical capacity, but Si particles are faced with huge volume change during charge/discharge process, causing a rapid capacity degradation. Among various methods designed to improve the performance of lithium-ion batteries, employing flexible binders is an effective way to sustain the bending of electrodes and the volume change of Si particles. Herein, we develop a polymer binder composed of carboxymethyl cellulose and polydopamine. This polymer composite binder is instrumental in moderating mechanical fracture of the Si anode during cycling, showing excellent adhesion force (10.8 N) and high stretchability (128.7%). The electrochemical properties (80% capacity retention after 150 cycles with an initial capacity of 2303 mAh g−1) of the Si anode show obviously improvement.

The presence of tumor infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) in tumor tissues are of great prognostic significance in several types of human cancer. The present study investigated the density of TILs and TLSs in gastric cancer (GC) tissues and their association with pathological parameters. Moreover, the clinical significance of follicular CD8+ cytotoxic T cells present within the germinal centers of the tumor-associated TLSs was investigated. Immunohistochemistry and H&E staining were used to examine the infiltration and distribution patterns of TILs, TLSs and germinal center (gc) CD8+ TILs in tumor tissues obtained from 63 patients with GC. The number of TILs, TLSs, combination of TILs and TLSs (TILs-TLSs) and gcCD8+ TILs were used to define tumoral immune parameters, and the prognostic value of these parameters was assessed. The analysis revealed that patients with GC with increased levels of TILs, TLSs, or gcCD8+ TILs exhibited improved overall survival. In addition, gcCD8+ TILs levels were significantly associated with patient age, histological grade and pTN stage. Increased levels of TILs-TLSs were positively associated with nerve invasion, tumor thrombus, nodal metastasis and histological grade. Multivariate Cox regression analysis revealed that TILs-TLSs and gcCD8+ TILs were independent prognostic factors. The data obtained in the present study demonstrated that high levels of tumoral immune parameters are important independent prognostic predictors for human GC. The results also suggested a possible role of gcCD8+ TILs in tumor immune surveillance.

Three configurations that incorporate a negative stiffness element and an inerter in parallel connection into the conventional isolator are considered to investigate their vibration characteristics from the point of view of resonance frequencies and displacement transmissibility. Analytical and numerical results are evaluated and compared with each other. It is illustrated that for the configuration of the inerter and an additional viscous damper in series connection which are then connected with the negative stiffness element in parallel, the isolator shows a better vibration isolation performance.

Background Gallbladder torsion is a rare acute abdominal condition that requires emergency surgery. It occurs more commonly in elderly people and in women in the adult population. Diagnosis is a challenge as non-specific symptoms and signs have been reported on ultrasonography, computed tomography and magnetic resonance imaging. Prompt cholecystectomy can decrease the mortality and morbidity of perforation due to gallbladder torsion. Case summary An 82-year-old woman with upper-right quadrant pain and associated nausea and vomiting was diagnosed with ectopic acute calculus cholecystitis. Magnetic resonance cholangiopancreatography (MRCP) showed a V-shaped distortion of the extrahepatic bile ducts and a particularly extended twisted cystic duct, which indicated the presence of gallbladder torsion. Emergency laparoscopic cholecystectomy confirmed the diagnosis and the patient recovered without incident. Conclusion Gallbladder torsion can be diagnosed pre-operatively by MRCP. The specific signs are a V-shaped distortion of the extrahepatic bile ducts and a particularly extended twisted cystic duct which can be called twisting signs.