Search

Objective: Intrahepatic cholangiocarcinoma (ICC) is a silent liver malignancy with an increasing incidence. Gut mycobiota plays a crucial role in benign liver diseases; however, its correlation with ICC remains elusive. This study aimed to elucidate fungal differences in patients with ICC compared to healthy controls., Methods: The 40 fecal samples from 23 ICC patients and 17 healthy controls were collected and analyzed using ITS2 rDNA sequencing. Obtaining the OTUs and combining effective grouping, we carried out the biodiversity and composition of the fungi, as well as FUNGuild functional annotation., Results: Our results revealed the presence of intestinal fungal dysbiosis with significant enrichment of opportunistic pathogenic fungi such as Candida and C. albicans, and significant depletion of the beneficial fungus Saccharomyces cerevisiae in ICC patients compared with healthy controls. Alpha-diversity analysis demonstrated that patients with ICC showed decreased fungal diversity compared to healthy controls. Beta diversity analysis indicated that the two groups exhibited significant segregated clustering. Besides, C. albicans was found to be significantly more abundant in the ICC patients with TNM stage III-IV than those with stage I-II. The FUNGuild functional classification predicted that pathotrophs were the most abundant taxon in the ICC group, well above their abundance in healthy controls., Conclusion: This study indicates that dysbiosis of the fecal mycobiome might be involved in ICC development. Further research into gut fungi may contribute to new therapeutic options for ICC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Chen, Chai, Kuang, Deng and Wang.)

Transforming growth factor-β (TGF-β) plays a critical role in regulating cell growth and differentiation. Epithelial to mesenchymal transition (EMT) induced by TGF-β promotes cancer cell migration, invasion, and proliferation. Pirfenidone (5-methyl-1-phenyl-2(1 H)-pyridone, PFD), an approved drug for treating pulmonary and renal fibrosis, is a potent TGF-β inhibitor and found reduced incidence of lung cancer and alleviated renal function decline. However, whether PFD plays a role in controlling renal cancer progression is largely unknown. In the present study, we demonstrated that high TGF-β1 expression was negatively associated with ten-year overall survival of patients with renal cancer. Functionally, blockade of TGF-β signaling with PFD significantly suppressed the progression of renal cancer in a murine model. Mechanistically, we revealed that PFD significantly decreased the expression and secretion of TGF-β both in vitro and in vivo tumor mouse model, which further prevented TGF-β-induced EMT and thus cell proliferation, migration, and invasion. Importantly, the downregulation of TGF-β upon PFD treatment shaped the immunosuppressive tumor microenvironment by limiting the recruitment of tumor-infiltrating MDSCs. Therefore, our study demonstrated that PFD prevents renal cancer progression by inhibiting TGF-β production of cancer cells and downstream signaling pathway, which might be presented as a therapeutic adjuvant for renal cancer.

Albumin-bound paclitaxel (abPTX) has been widely used in cancer treatment. However, dose-related side effects, such as myelosuppression, restrict its clinical application. Cell-based targeting drug delivery is a promising way to mitigate systematic side-effects and improve antitumoral efficacy. In this study, we demonstrated that reassembled abPTX could be engulfed by neutrophils in vivo and delivered to tumor site, thus improving therapeutic efficacy and mitigating myelosuppression. First, in vitro analysis confirmed that reassembling of abPTX formed uniform and stable serum albumin nanoparticles (NP-abPTX) with size of 107.5 ± 2.29 nm and reserved the ability to kill tumor cells. Second, we found that NP-abPTX could be engulfed by activated neutrophil in vitro and in vivo but do not affect neutrophils' function, such as chemotaxis and activation. In a murine tumor model, we further proved that local radiotherapy (RT) induced inflammation activated peripheral neutrophils to capture venous infused NP-abPTX and carry them into tumor tissue. As compared to abPTX, infusion of NP-abPTX dramatically enhanced inhibition of tumor growth treated by local RT and mitigated hematotoxicity. Therefore, our study demonstrated a novel strategy to mitigate side-effects and to improve tumor killing efficacy of abPTX through neutrophil-mediated targeting drug delivery.

Mitochondrial plasticity including mitochondrial dynamics, metabolic flexibility, and mitochondrial quality control, impact tumor cells' progression and determine immune cells' fate. Complement C1q binding protein (C1QBP) plays an indispensable role through regulating mitochondrial morphology, metabolism, and autophagy. C1QBP promotes mitochondrial plasticity to impact tumor metastasis and their therapeutic response. At the same time, C1QBP is involved in regulating immune cells' maturation, differentiation, and effector function through the enhancement of mitochondrial function. In this regard, manipulation of C1QBP has been shown to adjust the competitive balance between tumor cells and immune cells. In the course of evolution, mitochondrial plasticity has endowed numerous advantages against the relentless microenvironment of tumors. In this current review, we summarize the current knowledge of the mechanism of C1QBP regulation of cancer and immunity. We explain this process in vision of potentially new anticancer therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Chai, Sobhani, Sun, Neeli, Zheng and Tian.)

Background: Prolyl 3-hydroxylase 1 (P3H1) is essential for human collagen synthesis. Here, we investigated its relevance to multiple cancers, especially hepatocellular carcinoma (LIHC)., Methods: We estimated the relationship of P3H1 with 33 cancers using publicly available databases. And immunohistochemistry was utilized to verify the P3H1 expression in liver, gastric, colon, pancreatic, and rectal cancer. Then, we attenuated P3H1 expression in BEL-7402 and HLF cells by lentivirus technology and assessed the effect of P3H1 on cell proliferation, migration, and invasion., Results: Bioinformatic analysis revealed a significantly higher expression of P3H1 in almost all tumors, which was consistent with the immunohistochemical findings in the liver, gastric, colon, pancreatic, and rectal cancers. P3H1 expression was associated with overall survival, progression-free interval, disease-specific survival, and disease-free interval in most cancers, particularly in LIHC. Besides, we also found that P3H1 expression was an independent prognostic factor for LIHC. And knockdown of P3H1 significantly reduced liver cancer cell proliferation, migration, and invasion in liver cancer cells. Interestingly, P3H1 expression levels showed a significant positive connection with Th2 infiltration through multiple immune infiltration algorithms. ICI treatment was less effective in LIHC patients with high P3H1 expression. Finally, we also identified an upstream regulatory mechanism of P3H1 in LIHC, namely, AL355488.1, HCG18, and THUMPD3-AS1/hsa-miR-29c-3p-P3H1 axis., Conclusion: We have systematically described for the first time that P3H1 is closely related to various tumors, particularly in LIHC, and interference with P3H1 may be a therapeutic target for patients with LIHC., Competing Interests: There are no conflicts of interest among authors., (Copyright © 2022 Chunlei Li et al.)

Esophageal squamous cell carcinoma (ESCC) is one of the most common and deadly cancers. Fbxo45, a substrate recognition subunit of E3 ligase, is critically involved in tumorigenesis and tumor progression. However, the function of Fbxo45 and the underlying mechanisms have not been elucidated in ESCC. We used cellular and molecular methods to explore the molecular basis of Fbxo45-mediated ESCC development. We found that ectopic overexpression of Fbxo45 promoted the growth of Kyse-150, Kyse30 and ECA-109 cells and inhibited the apoptosis. Moreover, overexpression of Fbxo45 promoted the migration and invasion of ESCC cells. Consistently, knockdown of Fbxo45 exhibited the opposite effects on ESCC cells. Mechanistically, we observed that Fbxo45 binds to GGNBP2 via its SPRY domain and targets GGNBP2 for ubiquitination and degradation. GGNBP2 overexpression exhibited anticancer activity in ESCC cells. Furthermore, Fbxo45 exerted its functions by regulating GGNBP2 stability in ESCC cells. Notably, overexpression of Fbxo45 facilitated tumor growth in mice. Strikingly, Fbxo45 was highly expressed in ESCC tissues, and GGNBP2 had a lower expression in ESCC specimens. High expression of Fbxo45 and low expression of GGNBP2 were associated with poor prognosis in ESCC patients. Fbxo45 was negatively correlated with GGNBP2 expression in ESCC tissues. Therefore, Fbxo45 serves as an oncoprotein to promote ESCC tumorigenesis by targeting the stability of the tumor suppressor GGNBP2 in ESCC., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: Immune checkpoint inhibitors (ICIs) have recently demonstrated promising performance in improving the prognosis of urological cancer patients. The goal of this meta-analysis was to determine the impact of PPI use on the clinical outcomes of urological cancer patients receiving ICI therapy. Methods: Before 6 May 2022, the eligible literature was searched using PubMed, EMBASE, Cochrane Library, and Google Scholar. The clinical outcomes were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Results: A total of six articles met the inclusion criteria, and of the 1980 patients with advanced or metastatic urothelial cancers (UC) included. The meta-analysis displayed that PPI use could increase the risk of progression by 50.7% (HR: 1.507, 95% CI: 1.327-1.711, p < 0.001) and death by 58.7% (HR: 1.587, 95% CI: 1.367-1.842, p < 0.001), and reduce the ORR (OR: 0.503, 95% CI: 0.360-0.703, p < 0.001) in UC patients receiving ICIs. No significant heterogeneity and publication bias existed. Sensitivity analysis proved that the results were stable and reliable. Conclusion: The meta-analysis indicated that concomitant PPI use was significantly associated with low clinical benefit in UC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Chen, Chai, Li, Kuang, Liu, Dong, Deng and Wang.)

In order to study the impact of food safety concerns and government regulation on Chinese urban residents’ organic food consumption willingness and behavior, an “online + offline” survey of 799 urban residents in Beijing has been conducted. Based on the theory of planned behavior, a structural equation model (SEM) was established and the government’s food production support regulation (GP) and sales guarantee regulation (GC) were incorporated separately into the SEM as moderator variables. The path influence coefficients of respondents’ food safety concerns, subjective norms, and perceived behavioral control on organic food consumption willingness were 0.065 (p < 0.05), 0.174 (p < 0.01) and 0.574 (p < 0.01), respectively. The influence of GP on organic food consumption willingness was 0.243 (p < 0.01), but its moderating effect on the promotion effect of food safety concerns and attitude to organic food consumption willingness was −0.001 (p < 0.01). The moderating effect of GC on the transformation from consumption willingness to behavior was 0.083 (p < 0.05). The results show that respondents attach the most importance to the comparison of costs and the benefits of organic food. Although the government’s food production regulation will weaken the driving effect of food safety concern and benefit perception of organic food consumption willingness, it will still promote organic food consumption willingness on the whole. The government’s supervision of food processing and sales is conducive to the occurrence of organic food consumption behavior.

Objective: To investigate the expression and clinical significance of sperm-associated antigen 6 and NM23 proteins in human osteosarcoma. Methods: The specimens of conventional osteosarcoma with follow-up from 42 Chinese patients were analyzed in this study, and 12 cases of osteochondroma were considered controls. The expression of SPAG6 and NM23 was inspected using immunohistochemical staining, qRT-PCR, and Western blotting methods. Results: The positive expression rate of SPAG6 protein (71.43%) in 42 cases of osteosarcoma tissue was significantly higher than that (33.33%) in 12 cases of osteochondroma tissues ( p < 0.05), while the positive rate of NM23 protein (35.71%) in osteosarcoma tissue was lower than that (58.33%) in osteochondroma tissue ( p < 0.05). The mRNA and protein levels of SPAG6 were significantly higher than those of the adjacent normal tissues, while the expression of NM23 was lower in osteosarcoma tissues than that in the controls ( p < 0.05 for all). There was a positive relationship between the expression of SPAG6 and pathological grade, metastasis, and Enneking stage ( p < 0.05 for all). The overall survival rate of osteosarcoma patients with SPAG6 positive expression was significantly lower than that with SPAG6 negative expression. The relationship between the expression of NM23 and pathological grade, metastasis, and Enneking stage was negative ( p < 0.05 for all). The overall survival rate of the osteosarcoma patients with NM23 positive expression was higher than that of the patients with NM23 negative expression ( p < 0.05). Conclusion: Overexpression of SPAG6 and low expression of NM23 are negatively related to pathological grade, metastasis, and Enneking stage and prognosis of osteosarcoma patients. This suggested that SPAG6 and NM23 should be considered candidate prognostic biomarkers for patients with osteosarcoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bao, Zhu, Fan, Ye, Li and Chai.)

Hepatocellular carcinoma (HCC) is one of the cancers with the highest morbidity and mortality in the world. However, clinical progress in the treatment of HCC has not shown a satisfactory therapeutic effect. Here, we have developed a novel strategy to treat HCC with an adenovirus (Ad)-based vaccine, which contains a specific antigen glypican-3 (GPC3) and an immunostimulatory cytokine IL-12. In the subcutaneous tumor model, Ad-IL-12/GPC3 vaccine was injected into muscles three times to evaluate its therapeutic effect. Compared with the control immunization group, the Ad-IL-12/GPC3 immunization group showed a significant tumor growth inhibition effect, which was confirmed by the reduced tumor volume and the increased tumor inhibition. Ad-IL-12/GPC3 co-immunization promoted the induction and maturation of CD11c + or CD8 + CD11c + DCs and increased the number of tumor-infiltrating CD8 + T cells. Furthermore, in the Ad-IL-12/GPC3 group, the proliferation of CD8 + T cells, the induction of multifunctional CD8 + T cells, and CTL activity were significantly increased. Interestingly, the deletion of CD8 + T cells abolished tumor growth inhibition by Ad-IL-12/GPC3 treatment, suggesting that CD8 + T cell immune responses were required to eliminate the tumor. Likewise, Ad-IL-12/GPC3 vaccine also effectively inhibited lung tumor growth or metastasis by enhancing CD8 + DCs-mediated multifunctional CD8 + T cell immune responses in the lung metastasis model. Therefore, these results indicate that IL-12 combined with Ad-GPC3 vaccine co-immunization might provide a promising therapeutic strategy for HCC patients.

Therapeutic vaccines are currently at the forefront of medical innovation. Various endeavors have been made to develop more consolidated approaches to producing nucleic acid-based vaccines, both DNA and mRNA vaccines. These innovations have continued to propel therapeutic platforms forward, especially for mRNA vaccines, after the successes that drove emergency FDA approval of two mRNA vaccines against SARS-CoV-2. These vaccines use modified mRNAs and lipid nanoparticles to improve stability, antigen translation, and delivery by evading innate immune activation. Simple alterations of mRNA structure- such as non-replicating, modified, or self-amplifying mRNAs- can provide flexibility for future vaccine development. For protein vaccines, the use of long synthetic peptides of tumor antigens instead of short peptides has further enhanced antigen delivery success and peptide stability. Efforts to identify and target neoantigens instead of antigens shared between tumor cells and normal cells have also improved protein-based vaccines. Other approaches use inactivated patient-derived tumor cells to elicit immune responses, or purified tumor antigens are given to patient-derived dendritic cells that are activated in vitro prior to reinjection. This review will discuss recent developments in therapeutic cancer vaccines such as, mode of action and engineering new types of anticancer vaccines, in order to summarize the latest preclinical and clinical data for further discussion of ongoing clinical endeavors in the field., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Endometriosis is a gynecological disorder affecting about 10% of women and can lead to invalidating painful symptoms and infertility. Since there is no current definitive cure for this disease, new therapeutic options are necessary. 17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) is involved in the production of estradiol (E2), the most potent estrogen in women, and of 5-androstene-3β,17β-diol (5-diol), a weaker estrogen than E2, but whose importance increases after menopause. 17β-HSD1 is therefore a pharmacological target of choice for the treatment of estrogen-dependent diseases such as endometriosis. We developed a targeted-covalent (irreversible) and non-estrogenic inhibitor of 17β-HSD1, a molecule named PBRM, and herein evaluated its efficiency for the treatment of endometriosis. In a cell-free assay containing estrone (E1), the natural substrate of 17β-HSD1, PBRM was able to block the formation of E2 in a collection of 50 human endometriosis lesions from a different clinical feature type, location, and phase. When given orally by gavage at 15 mg/kg to baboons, the resulting plasmatic concentration of PBRM was found to be sufficiently high (up to 125 ng/mL) for an efficacy study in a non-human primate (baboon) endometriosis model. After 2 months of treatment, the number of lesions/adhesions decreased in 60% of animals (3/5) in the PBRM-treated group, compared to the placebo group which showed an increase in the number of lesion/adhesions in 60% (3/5) of animals. Indeed, the total number of lesions/adhesions decreased in treated group (-6.5 or -19% when excluding one animal) while it increased in the control group receiving a placebo (+11%). Analysis of specific endometriotic lesions revealed that PBRM decreased the number of red lesions (-67%; 8/12) and white lesions (-35%; 11/31), but not of blue-black lesions. Similarly, PBRM decreased the surface area of dense adhesions and filmy adhesions, as compared to placebo. Also, PBRM treatment did not significantly affect the number of menstrual days. Finally, this targeted covalent inhibitor showed no adverse effects and no apparent toxicity for the duration of the treatment. These data indicate that 17β-HSD1 inhibitor PBRM is a promising candidate for therapy targeting endometriosis and supports the need of additional efforts toward clinical trials., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Therapeutic dendritic cell (DC) vaccines stimulate the elimination of tumor cells by the immune system. However, while antigen-specific T cell responses induced by DC vaccines are commonly observed, the clinical response rate is relatively poor, necessitating vaccine optimization. There is evidence that the suppression of DC function by immune checkpoints hinders the anti-tumor immune responses mediated by DC vaccines, ultimately leading to the immune escape of the tumor cells. The use of immune checkpoint inhibitors (ICIs) and immune checkpoint activators (ICAs) has extended the immunotherapeutic range. It is known that both inhibitory and stimulatory checkpoint molecules are expressed by most DC subsets and can thus be used to manipulate the effectiveness of DC vaccines. Such manipulation has been investigated using strategies such as chemotherapy, agonistic or antagonistic antibodies, siRNA, shRNA, CRISPR-Cas9, soluble antibodies, lentiviruses, and adenoviruses to maximize the efficacy of DC vaccines. Thus, a deeper understanding of immune checkpoints may assist in the development of improved DC vaccines. Here, we review the actions of various ICIs or ICAs shown by preclinical studies, as well as their potential application in DC vaccines. New therapeutic interventional strategies for blocking and stimulating immune checkpoint molecules in DCs are also described in detail., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Recently, immune checkpoint inhibitor (ICI) treatment has shown encouraging performance in improving the prognosis of hepatocellular carcinoma (HCC) patients. The gut microbiome plays a vital role in altering the efficacy of ICIs, which may be impacted by antibiotics. The aim of the meta-analysis is to estimate the influence of antibiotic use on the survival of HCC patients treated with ICIs., Methods: The literature review was conducted using databases like PubMed, EMBASE, Cochrane Library, CNKI, WANFANG DATA, VIP, Google Scholar, and ClinicalTrials.gov before May 15, 2022. The primary endpoints were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR)., Results: A total of six retrospective studies met the inclusion criteria. 1056 patients were included in the study, of which 352 (33.33%) received antibiotic treatment. The meta-analysis results revealed antibiotic use did not affect the OS (HR: 1.41, 95% CI: 0.96-2.08, P = 0.088) and PFS (HR: 1.21, 95% CI: 0.73-2.00, P = 0.459) in HCC patients treated with ICIs. Besides, the use of antibiotics did not reduce the ORR (OR: 1.06, 95% CI: 0.69-1.64, P = 0.784) and DCR (OR: 0.42, 95% CI: 0.09-2.06, P = 0.286) in HCC patients treated with ICIs., Conclusion: Current evidence reveals that antibiotic use does alter the therapeutic efficacy of ICIs in HCC patients., Systematic Review Registration: https://www.crd.york.ac.uk/, identifier CRD42022311948., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Chen, Chai, Li, Guan, Liu, Kuang, Deng and Wang.)

Backgrounds and Aims: Pain is the main reason for hysteroscopy failure. In day-surgical settings, hysteroscopy procedures are commonly performed with the patient under sedation. Hypoxia is the most common adverse event during sedation and can lead to severe adverse events. This study aimed to compare the incidence of hypoxia when using high-flow nasal oxygen (HFNO) with that when using regular nasal oxygen in patients undergoing hysteroscopy with sedation., Materials and Methods: In this single-center, prospective, randomized, single-blinded study, 960 female patients undergoing elective diagnostic or operative hysteroscopy were randomly enrolled into the following two groups: the regular nasal group [O 2 (3-6 L/min) covered by an HFNO] and the HFNO group [O 2 (30-60 L/min)] from September 2021 to December 2021. All women were sedated with propofol (1.5 mg/kg) and remifentanil (1.5 μg/kg) in the operating room. The primary outcome was the incidence of hypoxia (75% ≤ SpO 2 < 90%, < 60 s)., Results: HFNO decreased the incidence of hypoxia (75% ≤ SpO 2 < 90%, < 60 s), subclinical respiratory depression (90% ≤ SpO 2 < 95%) and severe hypoxia (SpO 2 < 75% for any duration or 75% ≤ SpO 2 < 90% for ≥ 60 s) from 24.38 to 0.83%, from 11.25 to 1.46% and from 3.75 to 0%, respectively ( P < 0.001)., Conclusion: In procedures conducted to treat female infertility, HFNO can reduce hypoxia during hysteroscopy in patients sedated with propofol, and it can prevent the occurrence of subclinical respiratory depression and severe hypoxia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tang, Huang, Chai, Zhang, Zhang, Chen, Su and Huang.)

In situ molecular transformation under hydrothermal conditions is a feasible method to introduce distinct organic ligands and suppress competitive reactions between different synthons. However, this strategy has not yet been explored for the preparation of polyoxometalate (POM)-encapsulated metal-organic frameworks (MOFs). In this work, we designed and prepared a new compound, [Co 2 (3,3'-bpy)(3,5'-bpp)(4,3'-bpy)](H 2 O) 3 [SiW 12 O 40 ] ( 1 ) (4,3'-bpy = 4,3'-dipyridine, 3,5'-bpp = 3,5'-bis(pyrid-4-yl)pyridine, and 3,3'-bpy = 3,3'-bis(pyrid-4-yl) dipyridine), via an in situ ligand synthesis route. The compound shows a novel POM-encapsulated MOF structure with two pairs of left- and right-handed double helixes. These left- and right-handed helical chains further lead to triangular and rhombus-like channels, respectively. Moreover, the as-synthesized title compound shows superior electrocatalytic activity toward the hydrogen evolution reaction (HER) in 1 M KOH aqueous solution with a low overpotential and Tafel slope of 92 mV and 92.1 mV dec -1 , respectively, under a current density of 10 cm -2 . Also, the compound exhibits a high activity for the photocatalytic degradation of the dye rhodamine B. The excellent performance of the compound may be attributed to the synergistic effect between W and Co elements and the presence of encapsulated POMs. The title compound proves that it is possible to prepare multifunctional MOFs with POMs and transition metals showing HER activity and dye degradation activity.

Numerous studies have demonstrated the importance of gut bacteria in the development of malignancy, while relatively little research has been done on gut mycobiota. As a part of the gut microbiome, the percentage of gut mycobiota is negligible compared to gut bacteria. However, the effect of gut fungi on human health and disease is significant. This review systematically summarizes the research progress on mycobiota, especially gut fungi, in patients with head and neck cancer (HNC), esophageal cancer (EC), gastric cancer (GC), colorectal cancer (CRC), hepatocellular carcinoma (HCC), pancreatic cancer, melanoma, breast cancer, and lung carcinoma-induced cachexia. Moreover, we also describe, for the first time in detail, the role of the fungal recognition receptors, C-type lectin receptors (CLRs) (Dectin-1, Dectin-2, Dectin-3, and Mincle) and their downstream effector caspase recruitment domain-containing protein 9 (CARD9), in tumors to provide a reference for further research on intestinal fungi in the diagnosis and treatment of malignant tumors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Chai, Chen, Li, Qiu, Kuang, Parveena, Dong, Yu, Deng and Wang.)

For decades since the central dogma, cancer biology research has been focusing on the involvement of genes encoding proteins. It has been not until more recent times that a new molecular class has been discovered, named non-coding RNA (ncRNA), which has been shown to play crucial roles in shaping the activity of cells. An extraordinary number of studies has shown that ncRNAs represent an extensive and prevalent group of RNAs, including both oncogenic or tumor suppressive molecules. Henceforth, various clinical trials involving ncRNAs as extraordinary biomarkers or therapies have started to emerge. In this review, we will focus on the prognostic and diagnostic role of ncRNAs for breast cancer.

Interferon-induced protein 35 (IFI35), is currently acknowledged to govern the virus-related immune inflammatory responses. However, the biological significance and function of IFI35 in renal cell cancer (RCC) is still not well understood. Here, IFI35 expression and function were investigated in RCC tissues, renal cancer cells, and animal models. The results showed that IFI35 expression was significantly increased in 200 specimens of RCC patients. We found that higher IFI35 levels were significantly correlated with poor RCC prognosis. In human cell lines, the knockdown of IFI35 suppressed the malignant behavior of renal cancer cells. Similarly, the IFI35 knockdown resulted in significant inhibition of tumor progression in the subcutaneous or lung metastasis mouse model. Furthermore, the knockdown of IFI35 promoted the induction of autophagy by enhancing the autophagy-related gene expression (LC3-II, Beclin-1, and ATG-5). Additionally, blockade of STAT1/STAT6 phosphorylation (pSTAT1/pSTAT6) abrogated the induced autophagy by IFI35 knockdown in renal cancer cells. The autophagy inhibitor 3-MA also abolished the prevention of tumor growth by deleting IFI35 in renal cancer models. The above results suggest that the knockdown of IFI35 suppressed tumor progression of renal cancer by pSTAT1/pSTAT6-dependent autophagy. Our research revealed that IFI35 may serve as a potential diagnosis and therapeutic target for RCC.

Background: Although several histological studies have documented airway inflammation and remodelling in the small airways of dust-exposed workers, little is known regarding the prevalence and risk factors of small airway dysfunction (SAD) in pneumoconiosis. The present study investigated the prevalence and characteristics of spirometry-defined SAD in pneumoconiosis and assessed the risk factors for associated with SAD., Methods: A total of 1255 patients with pneumoconiosis were invited to participate, of whom 1115 patients were eligible for final analysis. Spirometry was performed to assess SAD using the following three indicators: maximal mid-expiratory flow and forced expiratory flow 50% and 75%. SAD was defined as at least two of these three indicators being less than 65% of predicted value. Logistic regression analyses were used to analyse the relationships between clinical variables and SAD., Results: Overall, 66.3% of patients with pneumoconiosis had SAD, among never-smokers the prevalence of SAD was 66.7%. The proportion of SAD did not differ among the subtypes of pneumoconiosis. In addition, SAD was present across the patients with all stages of pneumoconiosis. Even among those with forced expiratory volume in 1 s (FEV 1 ) ≥ 80% and FEV 1 /forced vital capacity ratio ≥ 70%, 40.8% of patients had SAD. Patients with SAD were older than patients without SAD, more likely to be women and heavy smokers. Importantly, patients with SAD had more severe airflow obstruction, air trapping, and diffusion dysfunction. All patients with both pneumoconiosis and chronic obstructive pulmonary disease had SAD. Based on multivariate analysis, overall, aged 40 years and older, female sex, heavy smoking, body mass index ≥ 25.0 kg/m 2 and pneumoconiosis stage III were significantly associated with increased risk of SAD. Among the never smokers, risk factors for SAD included female sex, BMI ≥ 25.0 kg/m 2 , pneumoconiosis stage II and stage III CONCLUSION: Spirometry-defined SAD is one of the common functional abnormalities caused by occupational dust exposure and should be taken into account when monitoring respiratory health of workers to guide the early precautions and management in pneumoconiosis., (© 2022. The Author(s).)

Objective: To explore the effect of respiration training-assisted western medicine therapy on activity tolerance, pulmonary function, and quality of life (QOL) of chronic obstructive pulmonary disease (COPD) patients in the stable phase., Methods: The medical data of 90 COPD patients in the stable phase treated in the respiratory medicine of our hospital (November 2020-November 2021) were chosen for the retrospective analysis, and the patients were split into group A ( n  = 45, respiration training-assisted western medicine therapy) and group B ( n  = 45, western medicine therapy) according to the clinical reception order, so as to record and compare the activity tolerance, lung function, and QOL between the groups after intervention., Results: Compared with group B after intervention, group A showed greatly longer mean 6-min walking distance, significantly lower St. George's Respiratory Questionnaire (SGRQ) score, significantly higher specific airway conductance (sGAW) and level values of various lung function indicators, and significantly lower level values of airway resistance (RAW) and specific airway resistance (sRAW) ( p all<0.001); the total effective rate was significantly higher in group A ( p  < 0.05)., Conclusion: Respiration training-assisted western medicine therapy is a dependable way to improve the activity tolerance of COPD patients in the stable phase, and such strategy largely improves patients' lung function and QOL. Deeper studies will be helpful to establish a preferable solution for such patients., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Yaqi Tong et al.)

Aims: In garlic cultivation, long-time monoculture has resulted in continuous-cropping obstacles. However, the cause has not been studied to date., Methods: We analyzed soils from garlic fields in Pengzhou, China, to determine continuous-cropping obstacle related changes in soil physicochemical properties and enzyme activities, and in the diversity and composition of bacterial and fungal communities. Furthermore, we examined the relationships between soil properties and the bacterial and fungal communities., Results: The soil pH and the soil catalase, urease, invertase, and polyphenol oxidase activities were lower in the cropping obstacle soil than in the healthy control soil. The richness and diversity of the bacteria were lower in the cropping obstacle soil than in the control. The bacterial and fungal communities in the cropping obstacle soil were clearly different from those in the control soil. The differences in bacterial communities between the cropping obstacle soil and the control soil were associated with differences in pH and available potassium content. The taxa with higher relative abundances in the cropping obstacle soils included potential plant pathogens and the taxa with lower relative abundances included potential plant growth promoters., Conclusion: The enrichment of plant pathogens and the depletion of plant growth promoting fungi may have contributed to the poor growth of garlic in the cropping obstacle soil. The enzyme activity and microbial community differences were associated with acidification that was likely an important factor in the deterioration of the soil ecological environment and the garlic cropping obstacle. The results provide information to guide agricultural practices in cultivating garlic., Competing Interests: HL was employed by the CNPC Chuanqing Drilling Engineering Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yu, Liu, Wang, Huang, Chai, Gu, Zhao, Yu, Shuai, Liu, Zhang, Penttinen and Chen.)

Aim: The purpose of this study was to investigate the predicting value of platelet distribution width (PDW) and fibrinogen for in-stent restenosis (ISR) in patients with stable angina pectoris and type 2 diabetes mellitus (T2DM) after drug-eluting stent (DES) implantation., Methods: We enrolled 161 patients who were readmitted with recurrent chest pain and successfully reviewed for coronary angiography and were divided into the ISR and non-ISR groups. We compared the levels of PDW and fibrinogen between the two groups. Logistic regression was used for analyzing independent predictors of ISR. The receiver operating characteristic (ROC) curve analysis was used to determine the optimum cutoff points of PDW and fibrinogen to predict ISR. The Kaplan-Meier survival curves for target lesion failure (TLF) by levels of PDW and fibrinogen., Results: The multivariate logistic regression analysis showed that PDW and fibrinogen were independent predictors of ISR [odds ratio (OR) = 1.209, 95% CI: 1.024-1.427, p = 0.025; OR = 1.006, 95% CI: 1.002-1.011, p = 0.010, respectively]. The ROC analyses showed that PDW ≥ 13.15% and fibrinogen ≥ 333.5 mg/dl were predictive of ISR in patients with stable angina pectoris and T2DM after DES implantation. However, the Kaplan-Meier estimate for TLF showed no statistical significance., Conclusion: Higher levels of PDW and fibrinogen were associated with the incidence of ISR in patients with stable angina with T2DM after DES implantation, but were not independent predictors of TLF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chai, Yang, Wang, Lu, Dai and Zhou.)

Objective: To evaluate the effect of WeChat-based health preaching combined with an enhanced recovery after surgery (ERAS) model on perioperative limb motor function and complications in orthopaedic patients., Methods: By means of retrospective analysis, the medical data of 68 orthopaedic patients who received surgical treatment in our hospital (from 01, 2020-12, 2021) were collected, and the patients were equally divided into the study group (SG) and control group (CG) according to their admission order, with 34 cases each. From 7 d before surgery to the time of hospital discharge, WeChat-based health preaching combined with ERAS perioperative nursing was performed to patients in the SG, and routine orthopaedic perioperative nursing was performed to those in the CG. Before and after nursing, patients' Visual Analog Scale for Fatigue (VAS-F) scores, Houston Pain Outcome Instrument (HPOI) scores, and brief Fu-gI-Meyer (FMA) motor scores were investigated and the incidence rates of postoperative complications and nursing satisfaction of patients in the two groups were recorded., Results: After nursing, SG obtained a significantly better VAS-F score and HPOI score ( P  < 0.001), significantly higher postoperative 7 d and predischarge lower limb FMA scores (20.06 ± 2.13 vs 18.38 ± 2.36, 27.50 ± 1.90 vs 24.09 ± 2.25, P  < 0.05), and significantly lower annual incidence rate of complications compared with those of the CG ( P  < 0.05); and the nursing satisfaction scores of the SG and CG were 9.18 ± 0.82 points and 6.76 ± 0.91 points, respectively, indicating significantly higher nursing satisfaction in the SG than in the CG ( P  < 0.001)., Conclusion: The nursing model of WeChat-based health preaching combined with ERAS can effectively improve the knowledge level of orthopaedic patients, thereby improving their abilities of pain management and self-management, accelerating the recovery of their limb function, and reducing the incidence rate of postoperative complications. The patients are more satisfied with such nursing model, indicating its better promotion value., Competing Interests: The authors declare that they have no conflicts of interest, (Copyright © 2022 Zhijuan Pang et al.)

Background: Abnormal DNA methylation of tumor suppressor gene promoter has been found in breast cancer. Therefore, the current study set out to explore how DNA methyltransferase 1 (DNMT1) affects breast cancer through mediating miR-497/GPRC5A axis., Methods: After loss and gain-of-function approaches were conducted in MCF-7/ADR and MCF-7 cells, cell viability, IC50 value, invasion, migration and apoptosis were measured, respectively. In addition, drug resistance, metastasis and apoptosis-related protein expression were examined using immunoblotting. ChIP and dual-luciferase reporter gene assays were carried out to validate relationship among DNMT1, miR-497, and GPRC5RA. Subcutaneous xenograft tumor model in nude mice was established to detect effects of DNMT1 on growth and metastasis of breast cancer in vivo., Results: It was found that DNMT1 was notably increased, while miR-497 was poorly-expressed in breast cancer. Highly-expressed DNMT1 could promote chemotherapy resistance and metastasis of breast cancer. Meanwhile, DNMT1 modified methylation of CpG island in miR-497 promoter region, thereby repressing miR-497 level. In addition, miR-497 targeted GPRC5A expression to curb chemotherapy resistance and metastasis of breast cancer cells. Lastly, in vivo experiments showed that knockdown of DNMT1 could suppress breast cancer growth and metastasis., Conclusions: Collectively, our findings indicated that DNMT1 may inhibit miR-497 and boost the expression of GPRC5A through methylation, thus augmenting breast cancer chemotherapy resistance and metastasis, which provides novel mechanistic insight into the unrecognized roles of DNMT1 in breast cancer., (© 2022. The Author(s).)

Objectives: This study aimed to explore differences in clinical features and prognosis among patients with varied myeloperoxidase (MPO) antineutrophil cytoplasmic antibody-associated vasculitis (MPO-AAV) associated lung diseases., Methods: Patients with MPO-AAV-associated lung diseases were enrolled in this retrospective cohort study at a single center. Clinical features and laboratory data at the time of diagnosis were compared among patients with various lung disease patterns. Kaplan-Meier and Cox regression analyses were performed to analyze overall survival., Results: A total of 155 patients were finally included and categorized into five groups, as follows: 72 had a usual interstitial pneumonia (UIP) pattern, 40 had non-UIP interstitial pneumonia, 18 had bronchiectasis (BR), 13 had necrotizing granuloma (NG), and 12 had diffuse alveolar hemorrhage (DAH). Among the five groups, patients with DAH had higher dyspnea and hemoptysis frequencies, lower PaO 2 /FiO 2 levels, elevated C-reactive protein levels, and the poorest prognosis. The overall survival (OS) in the DAH group (median OS: 3.2 months) was significantly poorer than that in the NG group (median OS: not reached, log rank P < 0.001), the BR group (median OS: not reached, log rank P < 0.001), and the non-UIP IP group (median OS: 61.1 months, log rank P = 0.001). The UIP group had significantly more ex-smokers than the other groups (P < 0.001) and the second poorest survival (median OS: 39.1 months). The NG group tended to have female predominance, a higher incidence of ENT involvement, less severe renal involvement, and the best survival. After adjusting for multi-model Cox regression analysis, DAH and UIP (hazard ratio: 19.301 and 9.940, respectively, compared with NG) were independent predictors of all-cause mortality., Conclusions: Various patterns of lung disease-associated MPO-AAV may potentially predict patient survival. Key Point • The present study described the clinical and prognostic features of various lung diseases-associated MPO-AAV, indicating the potential prediction for the survival of MPO-AAV patients., (© 2021. International League of Associations for Rheumatology (ILAR).)

T cells survival, proliferation, and anti-tumor response are closely linked to their mitochondrial health. Complement C1q binding protein (C1QBP) promotes mitochondrial fitness through regulation of mitochondrial metabolism and morphology. However, whether C1QBP regulates T cell survival, proliferation, and anti-tumor immune function remains unclear. Our data demonstrated that C1QBP knockdown induced the accumulation of reactive oxygen species (ROS) and the loss of mitochondrial membrane potential to impair T cell mitochondrial fitness. At the same time, C1QBP insufficiency reduced the recruitment of the anti-apoptotic proteins, including Bcl-2 and Bcl-XL, and repressed caspase-3 activation and poly (ADP-ribose) polymerase cleavage, which consequently accelerated the T cell apoptotic process. In contrast, C1QBP knockdown rendered T cells with relatively weaker proliferation due to the inhibition of AKT/mTOR signaling pathway. To investigate the exact role of C1QBP in anti-tumor response, C1QBP +/- and C1QBP +/+ mice were given a subcutaneous injection of murine MC38 cells. We found that C1QBP deficiency attenuated T cell tumor infiltration and aggravated tumor-infiltrating T lymphocytes (TIL) exhaustion. Moreover, we further clarified the potential function of C1QBP in chimeric antigen receptor (CAR) T cell immunotherapy. Our data showed that C1QBP +/- CAR T cells exhibited relatively weaker anti-tumor response than the corresponding C1QBP +/+ CAR T cells. Given that C1QBP knockdown impairs T cells' anti-apoptotic capacity, proliferation as well as anti-tumor immune function, development of the strategy for potentiation of T cells' mitochondrial fitness through C1QBP could potentially optimize the efficacy of the related immunotherapy., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Chimeric antigen receptor (CAR) T cell is a T lymphocyte-based immunotherapy, which achieves great successes in treating blood malignancies and provides new hope to cue advanced cancer patients. Invariant natural killer T (iNKT) cells are a kind of special T lymphocytes characterized by expressing invariant TCR of Vα24Vβ11 to recognize CD1d-presented glycolipid antigens, which bridge innate and adaptive immune responses. iNKT cells themselves show strong anti-tumor effect in tumor models via CD1d-mediated killing of CD1d-positive tumor cells and immunosuppressive TAMs and MDSCs, and are closely related to the prognosis of cancer patients. iNKT cells are not restricted to polymorphic human leukocyte antigen (HLA) and can prevent Graft versus Host Disease (GvHD), which makes it to be an ideal CAR vector for allogeneic therapy. Although CAR-iNKT was developed and verified by several different teams and attracts more and more attentions, many obstacles are still needed to be resolved before obtaining CAR-iNKT therapeutics. In this review, we summarized the current status of clinical application of iNKT cells and the latest achievements of CAR-iNKT cells, which provides new insight in CAR-iNKT development and usages., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Accumulated evidence shows that the F-box protein 3 (FBXO3) has multiple biological functions, including regulation of immune pathologies, neuropathic diseases and antiviral response. In this review article, we focus on the role of FBXO3 in inflammatory disorders and human malignancies. We also describe the substrates of FBXO3, which contribute to inflammatory disorders and cancers. We highlight that the high expression of FBXO3 is frequently observed in rheumatoid arthritis, leukemia, pituitary adenoma, and oral squamous cell carcinoma. Moreover, we discuss the regulation of FBXO3 by both carcinogens and cancer preventive agents. Our review provides a comprehensive understanding of the role of FBXO3 in various biological systems and elucidates how FBXO3 regulates substrate ubiquitination and degradation during various physiological and pathological processes. Therefore, FBXO3 can be a novel target in the treatment of human diseases including carcinomas., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Bao, Gao, Yao, Wang and Chai.)

Background: In humans, riboflavin must be obtained through intestinal absorption because it cannot be synthesized by the body. SLC52A2 encodes a membrane protein belonging to the riboflavin transporter protein family and is associated with a variety of diseases. Here, we systematically explore its relevance to multiple human tumors., Methods: We analyzed the association of SLC52A2 with 33 tumors using publicly available databases such as TCGA and GEO. We verified the SLC52A2 expression in hepatocellular carcinoma, gastric cancer, colon cancer, and rectal cancer using immunohistochemistry., Results: We report that SLC52A2 was highly expressed in almost all tumors, and the immunohistochemical results in the hepatocellular, gastric, colon, and rectal cancers were consistent with the above. SLC52A2 expression was linked to patient overall survival, disease-specific survival, progression-free interval, diagnosis, mutations, tumor mutational burden, microsatellite instability, common immune checkpoint genes, and immune cells infiltration. Enrichment analysis showed that SLC52A2 was mainly enriched in oocyte meiosis, eukaryotic ribosome biogenesis, and cell cycle. In hepatocellular carcinoma, the SLC52A2 expression is an independent prognostic factor. The SNHG3 and THUMPD3-AS1/hsa-miR-139-5p-SLC52A2 axis were identified as potential regulatory pathways in hepatocellular carcinoma., Conclusion: In conclusion, we have systematically described for the first time that SLC52A2 is closely associated with a variety of tumors, especially hepatocellular carcinoma., (© 2022. The Author(s).)

Background: Serine/threonine protein kinase 25 (STK25) plays an important role in regulating glucose and insulin homeostasis and in ectopic lipid accumulation. It directly affects the progression and prognosis of nonalcoholic fatty liver disease (NAFLD). However, the effects of STK25 on lipid metabolism in hepatocellular carcinoma (HCC) remain unexplored. The aim of this study was to investigate the role of STK25 in HCC and to elucidate the underlying mechanisms., Methods: Immunohistochemistry was used to measure the expression of STK25 in hepatic tissues of HCC patients, and public datasets were used as supplementary material for predicting the expression of STK25 and the prognosis of patients with HCC. The interaction between STK25 and striatin (STRN) was determined by the STRING database, immunohistochemistry and western blot analyses. The involved signaling pathway was detected by the KEGG database and western blot. Moreover, the biological behaviors of the HCC cells were detected by wound healing assays, Transwell invasion assays and oil red O staining. Finally, it was verified again by xenograft model., Results: STK25 is highly expressed in HCC patients and is associated with poor prognosis. STK25 knockdown inhibited the HCC cell invasion and proliferation, promotes apoptosis. Consistently, STK25 knockdown inhibited tumor growth in xenograft mouse model. Besides, STK25 deficiency decreased lipid synthesis, energy reserve, epithelial-mesenchymal transition (EMT) by down-regulating lipid metabolism signaling pathway. STRN could reverse the change of lipid metabolism., Conclusions: Our results demonstrated that STK25 interacted with STRN to regulates the energy reserve and EMT via lipid metabolism reprogramming. Accordingly, high expression of STK25 may be associated with HCC patients and poor prognosis, which implicates STK25 could be a potential target for lipid metabolism in cancer therapy., (© 2021. The Author(s).)

We aimed to investigate prognostic factors of in-stent restenosis (ISR) within 3 years in older acute coronary syndrome (ACS) patients after drug-eluting stent (DES) implantation and establish a clinical model for predicting ISR. We retrospectively collected 215 older ACS patients who followed coronary angiography (CAG) after DES implantation, divided into ISR group and non in-stent restenosis (non-ISR) group according to the results of reviewed CAG. Logistic regression analysis was performed to screen independent predictors related to ISR and build the clinical predictive model, which clinical application was assessed by decision curve analysis (DCA) and clinical impact curve (CIC). Kaplan-Meier survival curves for ISR by independent predictors. In multivariate logistic regression analysis showed that the red cell distribution width (RDW) was higher in ISR group compared with non-ISR (odds ratio (OR) = 1.54, 95% confidence interval (CI): 1.14-2.08, p < 0.01). Instead, a negative correlation was observed between minimum stent diameter and ISR (OR = 0.28, 95%CI:0.09-0.86, p = 0.03). A novel nomogram composed of these significant features presented a concordance index (C-index) of 0.710, DCA and CIC suggested that the predictive nomogram had clinical utility. Schoenfeld residuals showed the model RDW ≥ 12.6% with minimum stent diameter <3 mm was consistent with the proportional risk assumption. The Kaplan-Meier estimate for ISR showed statistical significance. Higher levels of RDW and lower minimum stent diameter were associated with incidence of ISR within 3 years in older ACS patients after DES implantation.

Renal carcinoma progresses aggressively in patients with metastatic disease while curative strategies are limited. Here, we constructed a recombinant non-replicating adenovirus (Ad) vaccine encoding an immune activator, CD137L, and a tumor antigen, CAIX, for treating renal carcinoma. In a subcutaneous tumor model, tumor growth was significantly suppressed in the Ad-CD137L/CAIX vaccine group compared with the single vaccine group. The induction and maturity of CD11C + and CD8 + CD11C + dendritic cell (DC) subsets were promoted in Ad-CD137L/CAIX co-immunized mice. Furthermore, the Ad-CD137L/CAIX vaccine elicited stronger tumor-specific multifunctional CD8 + T cell immune responses as demonstrated by increased proliferation and cytolytic function of CD8 + T cells. Notably, depletion of CD8 + T cells greatly compromised the effective protection provided by Ad-CD137L/CAIX vaccine, suggesting an irreplaceable role of CD8 + T cells for the immunopotency of the vaccine. In both lung metastatic and orthotopic models, Ad-CD137L/CAIX vaccine treatment significantly decreased tumor metastasis and progression and increased the induction of tumor-specific multifunctional CD8 + T cells, in contrast to treatment with the Ad-CAIX vaccine alone. The Ad-CD137L/CAIX vaccine also augmented the tumor-specific multifunctional CD8 + T cell immune response in both orthotopic and metastatic models. These results indicated that Ad-CD137L/CAIX vaccine elicited a potent anti-tumor activity by inducing CD8 + DC-mediated multifunctional CD8 + T cell immune responses. The potential strategy of CD137L-based vaccine might be served as a novel treatment for renal carcinoma or other malignant tumors., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Chronic obstructive pulmonary disease (COPD) is a public health challenge globally. The burden of COPD is high in never-smokers but little is known about its causes. We aimed to find the prevalence and correlates of COPD in never-smokers, with a special focus on solid fuel exposure. Methods: We conducted a cross-sectional study in Western China. COPD was defined by FEV1/FVC < lower limits of normal (LLN). Descriptive statistics and multivariable logistic regression were used for analyses. Results: Six thousand two hundred and seventy one patients were enrolled between June 2015 and August 2016. The prevalence of COPD in never-smokers was 15.0% (95% confidence interval 14.1-15.9). The common independent predictors of COPD in never-smokers included age ≥60 years, exposure to solid fuel, living in a rural area and a history of tuberculosis. Participants with solid fuel exposure were 69% more likely to have COPD (adjusted odds ratio 1.69, 95% CI 1.41-2.04) than those without such exposure. In addition, we found a positive association between small airway dysfunction and solid fuel exposure (OR 1.35, 95% CI 1.18-1.53). Conclusions: This study confirmed the substantial burden of COPD among never-smokers and also defined the risk factors for COPD in never-smokers. Furthermore, we found a positive association between solid fuel exposure and COPD or small airway dysfunction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Long, Xing, Chai, Liu, Tong, Wang, Ma, Pan, Cui and Guo.)

Immunotherapy for cancer has attracted considerable attention. As one of the immunotherapeutics, tumor vaccines exert great potential for cancer immunotherapy. The most important components in tumor vaccines are antigens and adjuvants, which determine the therapeutic safety and efficacy, respectively. After decades of research, many types of adjuvants have been developed. Although these adjuvants can induce strong and long-lasting immune responses in tumor immunity, they also cause more severe toxic side effects and are therefore not suitable for use in humans. With the development of innate immunity research, pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) are receiving more attention in vaccine design. However, whether they have the potential to become new adjuvants remains to be elucidated. The purpose of this review is to provide newideas for the research and development of new adjuvants by discussing the mechanisms and related functions of PAMPs and DAMPs.

Objective: Clear cell carcinoma (CCC) of the endometrium is an uncommon yet aggressive tumor. Few cohort studies are reporting the overall survival time of CCC patients. This study aimed to retrospectively analyze the clinicopathologic features, molecular characteristics and survival data of 27 endometrial CCC patients to improve the understanding of CCC., Methods: The clinicopathologic features, molecular characteristics and survival data total of 27 CCC patients admitted to the BBMU affiliated hospital (Anhui, China) between January 2005 and December 2018 were retrospectively analyzed. Kaplan-Meier method was used to analyze the prognosis-related factors., Results: The median age of the patients was 60 years (range; 39 to 81 years). The average tumor size was 3.8 cm (range; 0.8 to 13.0cm). Myometrial infiltration greater than 50% was reported in 55.6% of the patients, while the Ki-67 index greater than 50% was reported in 70.4% of the patients. The patients' FIGO (2009) surgical stages were as follows: 18 I, 3 II, 4 III, and 2 IV. Besides, 7 (25.6%) patients had lymphovascular invasion, 3 (11.1%) patients with distant metastasis, including 1 patient with bone metastasis, and 2 with liver metastasis. Adjuvant treatment included 7 with chemotherapy alone, 9 with radiotherapy alone, and 9 with both radiotherapy and chemotherapy. The median overall survival time from the time of CCC diagnosis was 56 months. ER and PR showed negative expression and P16 showed patchy immunostaining. 18 (63%) cases showed Napsin A positive expression. Loss of MSH2, MSH6 and PTEN were seen in 5, 4 and 7 cases respectively. All cases showed HER-2/nue negative expression., Conclusion: CCC is a rare and invasive tumor. Age of diagnosis, FIGO stage, tumor size, myometrial infiltration, lymphovascular invasion, distant metastasis, Ki-67 index and P53 expression are important indicators to evaluate patient's prognosis (P = 0.048, P < 0.001, P = 0.016, P = 0.043, P = 0.001, P < 0.001, P = 0.026, and P = 0.007, respectively). CCC has a worse prognosis than endometrioid carcinoma (P = 0.002), and there is no significant difference when compared with uterine papillary serous carcinoma (P = 0.155)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Gao, Bao, Zeng, Yao, Chai and Li.)

Tumor DNA vaccine as an effective therapeutic approach can induce systemic immunity against malignant tumors, but its therapeutic effect is still not satisfactory in advanced renal cancer. Herein, a novel DNA vaccine containing dual antigens of fibrinogen-like protein 1 (FGL1) and carbonic anhydrase IX (CAIX) was developed and intramuscularly delivered by PLGA/PEI nanoparticles for renal cancer therapy. Compared with PLGA/PEI-pCAIX immunization, PLGA/PEI-pFGL1/pCAIX co-immunization significantly inhibited the subcutaneous tumor growth and promoted the differentiation and maturation of CD11c + DCs and CD11c + CD11b + DCs subset. Likewise, the increased capabilities of CD8 T cell proliferation, CTL responses, and multi-functional CD8 + T cell immune responses were observed in PLGA/PEI-pFGL1/pCAIX vaccine group. Interestingly, depletion of CD8 + T cells by using CD8 mAb resulted in a loss of anti-tumor function of PLGA/PEI-pFGL1/pCAIX vaccine, suggesting that the anti-tumor activity of the vaccine was dependent on CD8 + T cell immune responses. Furthermore, PLGA/PEI-pFGL1/pCAIX co-immunization also suppressed the lung metastasis of tumor mice by enhancing the multi-functional CD8 + T cell responses. Therefore, these results indicate that PLGA/PEI-pFGL1/pCAIX vaccine could provide an effective protective effect for renal cancer by enhanced DC-mediated multi-functional CD8 + T cell immune responses. This vaccine strategy offers a potential approach for solid or metastatic tumor treatment., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors.)

The carcinogenicity of radon has been convincingly documented through epidemiological studies of underground miners. However, there is a lack of early warning indicators for radon radiation damage. In this study, mixed serum samples of 3 groups were collected from 27 underground uranium miners and seven aboveground miners according to the radiation exposure dose. The differentially expressed proteins in the serum were identified using the isobaric tags for the relative and absolute quantitation (iTRAQ)-based method. Some differentially expressed proteins were validated by enzyme-linked immunosorbent assay (ELISA) in 84 underground and 32 aboveground miners. A total of 25 co-differentially expressed proteins in 2 underground miner groups were screened, of which 9 were downregulated and 13 were upregulated. Biological process analysis of these proteins using Metascape showed that 5 GO terms were enriched, such as negative regulation of very-low-density lipoprotein particle clearance, endocytosis, and regulated exocytosis. The results of the ELISA for the expression levels of GCN1, CIP2A, and IGHV1-24 in the serum of 116 miners' serum showed that the levels of GCN1 and CIP2A were consistent with the iTRAQ results. In conclusion, APOC1, APOC2, APOC3, ORM1, ORM2, ANTXR1, GCN1, and CIP2A may be potential early markers of radon radiation damage., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Metastatic renal carcinoma is a kind of tumor with high degree of malignancy, but there are no effective treatment methods and strategies at present. In this study, we designed a folate-grafted PEI600-CyD (H1) nanoparticle-mediated DNA vaccine containing an adjuvant of high mobility group box 1 protein (HMGB1) and a tumor-specific antigen of B7H3 (CD276) for renal carcinoma therapy. Mice bearing subcutaneous human B7H3 (hB7H3)-Renca tumor were immunized with H1-pHMGB1/pB7H3, H1-pB7H3, H1-pHMGB1, or Mock vaccine. Compared to other control groups, the growth of the tumor was significantly inhibited in H1-pHMGB1/pB7H3 vaccine group. The increased proportion and mature of CD11c + DCs were observed in the spleen of H1-pHMGB1/pB7H3 treated mice. Likewise, HMGB1 promoted B7H3 vaccine to induce tumor-specific CD8 + T cell proliferation and CTL responses. Beyond that, H1-pHMGB1/pB7H3 vaccine strengthened the induction of functional CD8 + T cells. With the depletion of CD8 + T cells, the anti-tumor effect of H1-pHMGB1/pB7H3 also disappeared, indicating that CD8 + T cells are the key factor of the anti-tumor activity of the vaccine. So, to sum up, H1-pHMGB1/pB7H3 vaccine could achieve the desired anti-tumor effect by enhancing the response of tumor-specific functional CD8 + T cell responses. H1 nanoparticle-based vaccines may have great potential and prospect in the treatment of primary solid tumors., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

5-Methylcytosine (m5C) is an important post-transcriptional modification that has been extensively found in multiple types of RNAs. Many studies have shown that m5C plays vital roles in many biological functions, such as RNA structure stability and metabolism. Computational approaches act as an efficient way to identify m5C sites from high-throughput RNA sequence data and help interpret the functional mechanism of this important modification. This study proposed a novel species-specific computational approach, Staem5, to accurately predict RNA m5C sites in Mus musculus and Arabidopsis thaliana . Staem5 was developed by employing feature fusion tactics to leverage informatic sequence profiles, and a stacking ensemble learning framework combined five popular machine learning algorithms. Extensive benchmarking tests demonstrated that Staem5 outperformed state-of-the-art approaches in both cross-validation and independent tests. We provide the source code of Staem5, which is publicly available at https://github.com/Cxd-626/Staem5.git., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a severe syndrome lacking efficient therapy and resulting in high morbidity and mortality. Although resveratrol (RES), a natural phytoalexin, has been reported to protect the ALI by suppressing the inflammatory response, the detailed mechanism of how RES affected the immune system is poorly studied. Pulmonary conventional dendritic cells (cDCs) are critically involved in the pathogenesis of inflammatory lung diseases including ALI. In this study, we aimed to investigate the protective role of RES via pulmonary cDCs in lipopolysaccharide (LPS)-induced ALI mice. Murine ALI model was established by intratracheally challenging with 5 mg/kg LPS. We found that RES pretreatment could mitigate LPS-induced ALI. Additionally, proinflammatory-skewed cytokines decreased whereas anti-inflammatory-related cytokines increased in bronchoalveolar lavage fluid by RES pretreatment. Mechanistically, RES regulated pulmonary cDCs' maturation and function, exhibiting lower level of CD80, CD86, major histocompatibility complex (MHC) II expression, and IL-10 secretion in ALI mice. Furthermore, RES modulated the balance between proinflammation and anti-inflammation of cDCs. Moreover, in vitro RES pretreatment regulated the maturation and function of bone marrow derived dendritic cells (BMDCs). Finally, the adoptive transfer of RES-pretreated BMDCs enhanced recovery of ALI. Thus, these data might further extend our understanding of a protective role of RES in regulating pulmonary cDCs against ALI., Competing Interests: Conflict of interest: The authors state no conflict of interest., (© 2021 Bingnan Guo et al., published by De Gruyter.)

MORF4-related gene-binding protein (MRGBP) is the subunit of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. Much of the research indicated an oncogenic role of MRGBP in the development of cancers. However, it is still unknown the role MRGBP plays in human cancers, which deserves further exploration. In this research, the expression profile, prognostic value of MRGBP, and the relationship between MRGBP and immune infiltration were explored in 33 types of cancer. The differences in MRGBP expression in tumor and normal tissues were explored using data from The Cancer Genome Atlas, Gene Expression Omnibus and ONCOMINE. Analysis of the association between MRGBP and prognosis using Kaplan-Meier survival curve and COX analysis. The data of Tumor mutational burden (TMB), microsatellite instability (MSI) from TCGA. The relationship Between MRGBP expression and immunity was analyzed using the ESTIMATE algorithm and CIBERSORT. Furthermore, we explored MRGBP expression and the relationship between MRGBP expression and macrophage infiltration using immunohistochemical analysis in lower grade glioma (LGG). Our results revealed that MRGBP was highly expressed in most cancer tissues compared with normal tissues. Tumors with increased MRGBP expression had a high clinicopathologic stage and poor prognosis. The expression of MRGBP was closely related to the TMB, MSI. We also found a significant negative correlation between MRGBP expression and stromal scores and immune scores in various types of cancer. Furthermore, MRGBP expression was associated with a variety of immune cells including B cells, NK cells, T cells, and macrophages. LGG and LIHC was selected as representative cancer types for further study, the results of immunohistochemistry indicated that the protein levels of MRGBP were significantly elevated in tumor tissues. Moreover, our LIHC data analysis showed that patients with high MRGBP expression were associated with short survival rates and MRGBP was a risk factor to determine OS. Immunohistochemistry also confirmed that M0 macrophage infiltration in the MRGBP-high group significantly increased. In conclusion, these results reveal that MRGBP can serve as a potential prognostic biomarker and it plays an important role in tumor immune infiltration in various tumors, especially in LGG and LIHC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chai, Zhang, Guan, Yuan, Li and Wang.)

Some individuals develop prediabetes and/or diabetes following acute pancreatitis (AP). AP-induced beta-cell injury and the limited regenerative capacity of beta cells might account for pancreatic endocrine insufficiency. Previously, we found that only a few pancreatic cytokeratin 5 positive (Krt5 + ) cells differentiated into beta cells in the murine AP model, which was insufficient to maintain glucose homeostasis. Notch signaling determines pancreatic progenitor differentiation in pancreas development. This study aimed to examine whether Notch signaling inhibition could promote pancreatic Krt5 + cell differentiation into beta cells and improve glucose homeostasis following AP. Pancreatic tissues from patients with acute necrotizing pancreatitis (ANP) were used to evaluate beta-cell injury, Krt5 + cell activation and differentiation, and Notch activity. The murine AP model was induced by cerulein, and the effect of Notch inhibition on Krt5 + cell differentiation was evaluated both in vivo and in vitro. The results demonstrated beta-cell loss in ANP patients and AP mice. Krt5 + cells were activated in ANP pancreases along with persistently elevated Notch activity, which resulted in the formation of massive duct-like structures. AP mice that received Notch inhibitor showed that impaired glucose tolerance was reversed 7 and 15 days following AP, and increased numbers of newborn small islets due to increased differentiation of Krt5 + cells to beta cells to some extent. In addition, Krt5 + cells isolated from AP mice showed increased differentiation to beta cells by Notch inhibition. Collectively, these findings suggest that beta-cell loss contributes to pancreatic endocrine insufficiency following AP, and inhibition of Notch activity promotes pancreatic Krt5 + cell differentiation to beta cells and improves glucose homeostasis. The findings from this study may shed light on the potential treatment of prediabetes/diabetes following AP., (© 2021. The Author(s).)

Renal carcinoma shows a high risk of invasion and metastasis without effective treatment. Herein, we developed a chitosan (CS) nanoparticle-mediated DNA vaccine containing an activated factor L-Myc and a tumor-specific antigen CAIX for renal carcinoma treatment. The subcutaneous tumor models were intramuscularly immunized with CS-pL-Myc/pCAIX or control vaccine, respectively. Compared with single immunization group, the tumor growth was significantly suppressed in CS-pL-Myc/pCAIX co-immunization group. The increased proportion and mature of CD11c + DCs, CD8 + CD11c + DCs and CD103 + CD11c + DCs were observed in the splenocytes from CS-pL-Myc/pCAIX co-immunized mice. Furthermore, the enhanced antigen-specific CD8 + T lymphocyte proliferation, cytotoxic T lymphocyte (CTL) responses, and multi-functional CD8 + T cell induction were detected in CS-pL-Myc/pCAIX co-immunization group compared with CS-pCAIX immunization group. Of note, the depletion of CD8 T cells resulted in the reduction of CD8 + T cells or CD8 + CD11c + DCs and the loss of anti-tumor efficacy induced by CS-pL-Myc/pCAIX vaccine, suggesting the therapeutic efficacy of the vaccine was required for CD8 + DCs and CD103 + DCs mediated CD8 + T cells responses. Likewise, CS-pL-Myc/pCAIX co-immunization also significantly inhibited the lung metastasis of renal carcinoma models accompanied with the increased induction of multi-functional CD8 + T cell responses. Therefore, these results indicated that CS-pL-Myc/pCAIX vaccine could effectively induce CD8 + DCs and CD103 + DCs mediated tumor-specific multi-functional CD8 + T cell responses and exert the anti-tumor efficacy. This vaccine strategy offers a potential and promising approach for solid or metastatic tumor treatment., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: The novel coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has quickly spread worldwide since its outbreak in December 2019. One of the primary measures for controlling the spread of SARS-CoV-2 infection is an accurate assay for its diagnosis. SARS-CoV-2 real-time PCR kits suffer from some limitations, including false-negative results in the clinic. Therefore, there is an urgent need for the development of a rapid antibody test kit for COVID-19 diagnosis., Methods: The nuclear capsid protein (N) and spike protein 1 (S1) fragments of SARS-CoV-2 were expressed in Escherichia coli, and rapid antibody-based tests for the diagnosis of SARS-CoV-2 infection were developed. To evaluate their clinical applications, the serum from COVID-19 patients, suspected COVID-19 patients, recovering COVID-19 patients, patients with general fever or pulmonary infection, doctors and nurses who worked at the fever clinic, and health professionals was analyzed by the rapid antibody test kits. The serum from patients infected with Mycoplasma pneumoniae and patients with respiratory tract infection was further analyzed to test its cross-reactivity with other respiratory pathogens., Results: A 47 kDa N protein and 67 kDa S1 fragment of SARS-CoV-2 were successfully expressed, purified, and renatured. The rapid antibody test with recombinant N protein showed higher positive rate than the rapid IgM antibody test with recombinant S1 protein. Clinical evaluation showed that the rapid antibody test kit with recombinant N protein had 88.56 % analytical sensitivity and 97.42 % specificity for COVID-19 patients, 53.48 % positive rate for suspected COVID-19 patients, 57.14 % positive rate for recovering COVID-19 patients, and 0.5-0.8 % cross-reactivity with other respiratory pathogens. The analytical sensitivity of the kit did not significantly differ in COVID-19 patients with different disease courses (p < 0.01)., Conclusions: The rapid antibody test kit with recombinant N protein has high specificity and analytical sensitivity, and can be used for the diagnosis of SARS-CoV-2 infection combined with RT-PCR., (© 2021. The Author(s).)

Importance: In the literature on opioid use disorder (OUD), opioid abstinence is used as an outcome measure for individuals receiving medication-assisted treatment (MAT), without consideration of patient-reported goals (PRGs)., Objectives: To identify common PRGs for youths receiving MAT for OUD and assess whether these patients achieve their stated goals., Design, Setting, and Participants: This prospective cohort study examined data from 152 individuals aged 16 to 25 years (noninclusive) recruited between May 22, 2018, and March 11, 2020, from 45 outpatient MAT clinics in the Pharmacogenetics of Opioid Substitution Treatment Response study. Youths receiving MAT for OUD were included and were followed up for 3 months., Exposures: Medication-assisted treatment for OUD., Main Outcomes and Measures: The frequency of each PRG; the success of goal attainment, compared between those who reported specific PRGs and those who did not; and associations between reporting certain goals and achieving them., Results: Among the 152 youths in the study, 82 were male (53.9%), and the mean (SD) age was 22.8 (1.8) years. Ten overarching goals were identified, with the most common being to taper the dose of or stop MAT (96 [63.2%]), avoid use of recreational substances (71 [46.7%]), manage OUD symptoms (25 [16.4%]), live a normal life (14 [9.2%]), improve mental health (11 [7.2%]), and gain employment (8 [5.3%]). Overall, individuals who reported PRGs had similar odds of achieving them as those who did not for the goals of taper dose of or stop MAT (OR, 1.98; 95% CI, 0.88-4.46; P = .10), avoid recreational substances (OR, 1.34; 95% CI, 0.65-2.74; P = .43), manage OUD symptoms (β coefficient, -0.93; 95% CI, -4.24 to 2.38; P = .58), and improve mental health (β coefficient, -0.76; 95% CI, -6.31 to 4.78; P = .79). Furthermore, multivariable logistic regression showed that goals to taper the dose of or stop MAT (odds ratio, 1.90; 95% CI, 0.78-4.63; P = .16) or avoid recreational substances (odds ratio, 1.27; 95% CI, 0.60-2.67; P = .53) were not associated with achieving these respective outcomes., Conclusions and Relevance: This study suggests that youths have highly variable PRGs regarding MAT for OUD and that reporting a goal may not mean one is at higher odds of achieving it. There is a need to develop treatment plans that effectively incorporate PRGs. In addition, the finding that most youths aim to minimize or stop their MAT dose warrants the creation of a tapering protocol to guide clinicians. Because a diagnosis of OUD has substantial psychosocial implications in this population, clinicians must ensure that these dimensions of care are part of routine clinical practice.

Classification of human actions is an ongoing research problem in computer vision. This review is aimed to scope current literature on data fusion and action recognition techniques and to identify gaps and future research direction. Success in producing cost-effective and portable vision-based sensors has dramatically increased the number and size of datasets. The increase in the number of action recognition datasets intersects with advances in deep learning architectures and computational support, both of which offer significant research opportunities. Naturally, each action-data modality-such as RGB, depth, skeleton, and infrared (IR)-has distinct characteristics; therefore, it is important to exploit the value of each modality for better action recognition. In this paper, we focus solely on data fusion and recognition techniques in the context of vision with an RGB-D perspective. We conclude by discussing research challenges, emerging trends, and possible future research directions.