LncRNAs in Immune and Stromal Cells Remodel Phenotype of Cancer Cell and Tumor Microenvironment.

Emerging studies suggest that long non-coding RNAs (lncRNAs) participate in the mutual regulation of cells in tumor microenvironment, thereby affecting the anti-tumor immune activity of immune cells. Additionally, the intracellular pathways mediated by lncRNAs can affect the expression of immune checkpoints or change the cell functions, including cytokines secretion, of immune and stromal cells in tumor microenvironment, which further influences cancer patients' prognosis and treatment response. With the in-depth research, lncRNAs have shown great potency as a new immunotherapy target and predict immunotherapy response. The research on lncRNAs provides us with a new insight into developing new immunotherapy drugs and predicting the outcome of immunotherapy. With development of RNA sequencing technology, amounts of lncRNAs were found to be dysregulated in immune and stromal cells rather than tumor cells. These lncRNAs function through ceRNA network or regulating transcript factor activity, thus leading abnormal differentiation and activation of immune and stromal cells. Here, we review the function of lncRNAs in the immune microenvironment and focus on the alteration of lncRNAs in immune and stromal cells, and discuss how these alterations affect tumor growth, metastasis and treatment response.

Advancement and Applications of Nanotherapy for Cancer Immune Microenvironment.

Cancer treatment has evolved rapidly due to major advances in tumor immunity research. However, due to the complexity, heterogeneity, and immunosuppressive microenvironment of tumors, the overall efficacy of immunotherapy is only 20%. In recent years, nanoparticles have attracted more attention in the field of cancer immunotherapy because of their remarkable advantages in biocompatibility, precise targeting, and controlled drug delivery. However, the clinical application of nanomedicine also faces many problems concerning biological safety, and the synergistic mechanism of nano-drugs with immunity remains to be elucidated. Our study summarizes the functional characteristics and regulatory mechanisms of nanoparticles in the cancer immune microenvironment and how nanoparticles activate and long-term stimulate innate immunity and adaptive immunity. Finally, the current problems and future development trends regarding the application of nanoparticles are fully discussed and prospected to promote the transformation and application of nanomedicine used in cancer treatment.

Proteomic characterization of extracellular vesicles derived from lactic acid bacteria.

Lactobacillus species confer health benefits by their metabolites, secreted molecules, and population numbers. Extracellular vesicles (EVs) are nano-sized particles released from cells and mediate intercellular communications. EVs-encapsulated cargos are a crucial key to decide involved biological function. However, little is known about the composition of EVs, leaving mechanisms by which Lactobacillus-derived EVs affect recipient cells remaining unresolved. This study examined the composition of EV proteins from Lactobacillus species by using liquid chromatography coupled with tandem mass spectrometry, including L. plantarum, L. fermentum, and L. gasseri. The major proteins of EVs are associated with biological processes such as catalytic activity, gluco-neogenesis, cell wall organization, and glycolytic processes. Motif enrichment analysis revealed that EVs from L. plantarum and L. fermentum contained proteins with serine-rich motif. This is the first study to report the composition and comparison of EV proteins from Lactobacillus species, providing important information of EVs in functional food products development.

Effect of polysaccharide derived from dehulled adlay on regulating gut microbiota and inhibiting Clostridioides difficile in an in vitro colonic fermentation model.

Human body can digest only a few sugars with a low degree of polymerization. The rest of the carbohydrates become food for gastrointestinal symbiotic bacteria, affecting gut microbiota composition and human health. Adlay is a medicinal and food homologous crop. The study aims to determine whether dehulled adlay-derived polysaccharide regulates gut microbiota and barrier function to against Clostridioides difficile infection. Major molecular weight of adlay polysaccharide is 27 kDa. The growth of next-generation probiotics were promoted by adlay polysaccharides. In colonic fermentation model, the ratio of C. difficile was decreased when adding the condition medium of adlay polysaccharides-treated fecal microbiota. In addition, adlay polysaccharide promoted the expression of tight junction proteins and mucin in intestinal cells. This study shows that adlay polysaccharide can be used as prebiotics to regulate microbiota and maintain barrier function, which has the potential to be developed as novel functional food ingredients to protect intestinal health.

Profiling antibody signature of schizophrenia by Escherichia coli proteome microarrays.

Schizophrenia (SZ) is influenced by genetic and environmental factors, and associated with chronic neuroinflammation. If the symptoms express after adolescence, environmental impacts are more substantial, and the disease is defined as adult-onset schizophrenia (AOS). Effects of environmental factors on antibody responses such as Escherichia coli (E. coli) to immunoglobulin G (IgG) and immunoglobulin M (IgM) might increase the severity of symptoms in SZ via the gut-brain axis. The purpose of this study is to reveal antibody profiles of SZ against bacterial protein antigens. We analyzed the IgG and IgM antibodies using E. coli proteome microarrays from 80 SZ patients and 40 healthy controls (HC). Using support vector machine to select panels of proteins differentiating between groups and conducted enrichment analysis for those proteins. We identified that the groL, pldA, yjjU, livG, and ftsE can classify IgGs in AOS vs HC achieved accuracy of 0.7. The protein yjjU, livG and ftsE can form the best combination panel to classify IgG in AOS vs HC with accuracy of 0.8. The enrichment results are highly related to ABC (ATP binding cassette) transporter in the protein domain and cellular component. We further found that the human ATP binding cassette subfamily b member 1 (ABCB1) autoantibody level in AOS is significantly higher than in HC. The findings suggest that AOS had different immunoglobulin production compared to early-onset schizophrenia (EOS) and HC. We also identified potential antibody biomarkers of AOS and found their antigens are enriched in ABC transporter related domains, including human ABCB1 protein.

Ultrathin covalent and cuprophilic interaction-assembled copper-sulfur monolayer in organic metal chalcogenide for oriented photoconductivity.

We report the thinnest copper sulfur atomic monolayer in an organic copper chalcogenide [Cu(CMP)]n (CMP = 5-chloro-2-mercaptopyridine). The layer features a new type of copper sulfur structure woven by both covalent bond and cuprophilic interaction and shows an intriguing oriented photoconductivity.

Metformin inhibits gastric cancer cell proliferation by regulation of a novel Loc100506691-CHAC1 axis.

Long noncoding RNAs (lncRNAs) are a group of nonprotein coding transcripts that play a critical role in cancer progression. However, the role of lncRNA in metformin-induced inhibition of cell growth and its biological function in gastric cancer remain largely unknown. In this study, we identified an oncogenic lncRNA, Loc100506691, the expression of which was decreased in gastric cancer cells with metformin treatment. Moreover, Loc100506691 was significantly overexpressed in gastric cancer compared with adjacent normal tissues (p < 0.001), and high Loc100506691 expression was significantly correlated with poor survival of patients with gastric cancer. Additionally, Loc100506691 knockdown could significantly suppress gastric cancer cell growth in vitro, and ectopic Loc100506691 expression accelerated tumor growth in an in vivo mouse model. Analysis of the cell cycle revealed that Loc100506691 knockdown induced cell cycle arrest at the G2/M phase by impairing cell entry from the G2/M to G1 phase. Loc100506691 negatively regulated CHAC1 expression by modulating miR-26a-5p/miR-330-5p expression, and CHAC1 knockdown markedly attenuated Loc100506691 knockdown-induced gastric cancer cell growth and motility suppression. We concluded that anti-proliferative effects of metformin in gastric cancer may be partially caused by suppression of the Loc100506691-miR-26a-5p/miR-330-5p-CHAC1 axis.

Applications of Lactobacillus acidophilus-Fermented Mango Protected Clostridioides difficile Infection and Developed as an Innovative Probiotic Jam.

Clostridioides difficile infection (CDI) is a large intestine disease caused by toxins produced by the spore-forming bacterium C. difficile, which belongs to Gram-positive bacillus. Using antibiotics treatment disturbances in the gut microbiota and toxins produced by C. difficile disrupt the intestinal barrier. Some evidence indicates fecal microbiota transplantation and probiotics may decrease the risk of CDI recurrence. This study aimed to evaluate the efficacy of fermented mango by using the lactic acid bacteria Lactobacillus acidophilus and develop innovative products in the form of fermented mango jam. L. acidophilus-fermented mango products inhibited the growth of C. difficile while promoting the growth of next-generation probiotic Faecalibacterium prausnitzii. Both supernatant and precipitate of mango-fermented products prevented cell death in gut enterocyte-like Caco-2 cells against C. difficile infection. Mango-fermented products also protected gut barrier function by elevating the expression of tight junction proteins. Moreover, L. acidophilus-fermented mango jam with high hydrostatic pressure treatment had favorable textural characteristics and sensory quality.

Long-term Effects of the COVID-19 Pandemic on Public Sentiments in Mainland China: Sentiment Analysis of Social Media Posts.

BACKGROUND: The COVID-19 outbreak has induced negative emotions among people. These emotions are expressed by the public on social media and are rapidly spread across the internet, which could cause high levels of panic among the public. Understanding the changes in public sentiment on social media during the pandemic can provide valuable information for developing appropriate policies to reduce the negative impact of the pandemic on the public. Previous studies have consistently shown that the COVID-19 outbreak has had a devastating negative impact on public sentiment. However, it remains unclear whether there has been a variation in the public sentiment during the recovery phase of the pandemic. OBJECTIVE: In this study, we aim to determine the impact of the COVID-19 pandemic in mainland China by continuously tracking public sentiment on social media throughout 2020. METHODS: We collected 64,723,242 posts from Sina Weibo, China's largest social media platform, and conducted a sentiment analysis based on natural language processing to analyze the emotions reflected in these posts. RESULTS: We found that the COVID-19 pandemic not only affected public sentiment on social media during the initial outbreak but also induced long-term negative effects even in the recovery period. These long-term negative effects were no longer correlated with the number of new confirmed COVID-19 cases both locally and nationwide during the recovery period, and they were not attributed to the postpandemic economic recession. CONCLUSIONS: The COVID-19 pandemic induced long-term negative effects on public sentiment in mainland China even as the country recovered from the pandemic. Our study findings remind public health and government administrators of the need to pay attention to public mental health even once the pandemic has concluded.

Systematic Analysis of Phosphatidylinositol-5-phosphate-Interacting Proteins Using Yeast Proteome Microarrays.

We used yeast proteome microarrays (∼5800 purified proteins) to conduct a high-throughput and systematic screening of PI5P-interacting proteins with PI5P-tagged fluorescent liposomal nanovesicles. Lissamine rhodamine B-dipalmitoyl phosphatidylethanol was incorporated into the liposome bilayer to provide the nanovesicles with fluorescence without any encapsulants, which not only made the liposome fabrication much easier without the need for purification but also improved the chip-probing quality. A special chip assay was washed very gently without the traditional spin-dry step. Forty-five PI5P-interacting proteins were identified in triplicate with this special chip assay. Subsequently, we used flow cytometry to validate these interactions, and a total of 41 PI5P-interacting proteins were confirmed. Enrichment analysis revealed that these proteins have significant functions associated with ribosome biogenesis, rRNA processing, ribosome binding, GTP binding, and hydrolase activity. Their component enrichment is located in the nucleolus. The InterPro domain analysis indicated that PI5P-interacting proteins are enriched in the P-loop containing nucleoside triphosphate hydrolases domain (P-loop). Additionally, using the MEME program, we identified a consensus motif (IVGPAGTGKSTLF) that contains the Walker A sequence, a well-known nucleotide-binding motif. Furthermore, using a quartz crystal microbalance, both the consensus motif and Walker A motif showed strong affinities to PI5P-containing liposomes but not to PI5P-deprived liposomes or PI-containing liposomes. Additionally, the glycine (G6) and lysine (K7) residues of the Walker A motif (-GPAGTG6K7S-) were found to be critical to the PI5P-binding ability. This study not only identified an additional set of PI5P-interacting proteins but also revealed the strong PI5P-binding affinity (Kd = 1.81 × 10-7 M) of the Walker A motif beyond the motif's nucleotide-binding characteristic.

Comprehensive identification of microRNA arm selection preference in lung cancer: miR-324-5p and -3p serve oncogenic functions in lung cancer.

MicroRNA (miRNA/miR) dysfunction is a hallmark of lung cancer, and results in the dysregulation of tumor suppressors and oncogenes during lung cancer progression. Selection of the 5p and 3p arms of miRNA is a mechanism that improves the modulation of miRNA biological functions and complicates the regulatory network in human types of cancer. However, the involvement of arm selection preference of miRNA in lung cancer remains unclear. In the present study, changes in miRNA arm selection preference were comprehensively identified in lung cancer and corresponding adjacent normal tissues by analyzing The Cancer Genome Atlas. Arm selection was revealed to be consistent in the majority of miRNAs in lung cancer. Only a few miRNAs had significantly altered arm selection preference in lung cancer. Among these, the biological functions of the individual arms of miR-324 were investigated further. The data revealed that miR-324-5p and -3p were significantly overexpressed in lung cancer cells. Ectopic expression of miR-324-5p significantly promoted cell proliferation and invasion in lung cancer cells, while miR-324-3p overexpression significantly increased cell proliferation but did not alter the invasion of lung cancer cells. In conclusion, the arm selection preference of miRNA may be an additional mechanism through which biological functions are modulated. The results of the present study provide a novel insight into the underlying mechanisms of lung cancer and may direct research into future therapies.

Linc00659, a long noncoding RNA, acts as novel oncogene in regulating cancer cell growth in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers and causes of cancer-related death worldwide. In patients with CRC, metastasis is a crucial problem that leads to treatment failure and is the primary cause of the lethality of colon cancer. Long noncoding RNAs (lncRNAs) have recently emerged as critical molecules in the development, cell growth, apoptosis, and metastasis of CRC. METHOD: We investigated the transcriptome profiles of human lncRNAs in the primary tumor tissues and in the corresponding normal mucosa of two patients with CRC by using a microarray approach. The expression levels of lncRNAs were verified in colon cancer by real-time PCR. Using bioinformatics approach to illustrate putative biological function of Linc00659 in colon cancer. The effects of Linc00659 on cell growth, proliferation, cell cycle and apoptosis were studies by in vitro assays. RESULTS: Our data revealed that compared with adjacent normal tissues, 201 lncRNAs were deregulated (fold change ≥ 4 or ≤ 0.25) in CRC tissues. Among them, the expression levels of Linc00659 were significantly increased in colon cancer, and high expression levels were correlated with poor survival in patients with CRC. Bioinformatics analysis results indicated that Linc00659 was significantly coexpressed with cycle-related genes in CRC. Linc00659 expression knockdown could significantly suppress colon cancer cell growth by impairing cell cycle progression. In addition, our results showed that Linc00659 expression knockdown could accelerate cell apoptosis in colon cancer cells treated with chemotherapy drugs. Meanwhile, our results also demonstrated that silencing of Linc00659 expression leads to cell growth inhibition and induced apoptosis, possibly by suppressing PI3K-AKT signaling in colon cancer. CONCLUSION: Linc00659 is a novel oncogenic lncRNA involved in colon cancer cell growth by modulating the cell cycle. Our findings give an insight into lncRNA regulation and provide an application for colon cancer therapy.

Clinical analysis of the treatment of patients with medium volume of supratentorial hypertensive cerebral hemorrhage in the elderly / 中国医师进修杂志

Objective To discuss the clinical features and treatment measures on patients with medium volume of supratentorial hypertensive cerebral hemorrhage in the elderly.Methods The clinical data of 57 patients with medium volume of supratentorial hypertensive cerebral hemorrhage aged ≥ 70 years were analyzed retrospectively.Results All of 57 patients,15 cases accepted medical treatment,42 cases were treated with minimally invasive operation for 1-26 (4.6 ± 6.5) h after onset.Three cases died in hospital,7 cases were transferred or gave up,6 cases lived as plant,8 cases were severely maimed,11 cases were moderately maimed,22 cases [38.6％(22/57)] recovered favorably.The main clinical characteristics of elderly patients:long history of hypertension,blood pressure fluctuation; atypical symptoms of increased intracranial pressure; more complications such as arrhythmia and pulmonary infection; most of family members of patients were pessimistic to treatment.Conclusions All factors should be thought over about the treatment of elderly patients with medium volume of hypertensive cerebral hemorrhage.Individual treatment is reasonable.Do not emphasize on early operation,minimally invasive operation can be helpful for patients.

Fe2O3 xerogel used as the anode material for lithium ion batteries with excellent electrochemical performance.

A new strategy was applied to synthesise a porous nanostructure of α-Fe(2)O(3) xerogel assembled from nanocrystalline particles (∼5 nm) with abundant mesopores (∼3 nm) using a hydrothermal method. The α-Fe(2)O(3) xerogel exhibits excellent cycling performance (up to 1000 cycles) and rate capability (reversible discharging capacity 280 mAh g(-1) at 10 C) as a potential anode for high power lithium-ion batteries.

Study on the correlation between the polymorphism of STATS gene and asthma / 中国医师杂志

Objective To investigate the correlation rs2272087 polymorphism of STATS gene and asthma.Methods The polymerase chain reaction PCR- SBT technique was used to determine rs2272087 polymorphism in asthma and control group.Results The genotype of AA,AG and GG of rs2272087 were 0.600,0.412 and 0.167 in asthma group,and 0.430,0.200,0.367 in control group,respectively.The frequency of allele A and G was 0.903 and 0.344 in asthma group,and 0.656,0.970 in control group,respectively.There was significant difference in two groups(x2 =9.40,P ＜0.01 ;x2 =11.58,P ＜0.01 ).Conclusions The rs2272087 polymorphism of STAT5 gene may be an important candidate gene for asthma.

Effect of hypertensive agent on regional cerebral blood flow in patients with hypertensive intracerebral hemorrhage / 中华急诊医学杂志

Objective To investigate effects of hypertensive agents on regional cerebral blood flow (rCBF)and prognosis in patients with hypertensive intracerebral hemorrhage (HICH). Method Thirty patients withFILCH were divided into group A,B and C according to mean arterial pressure(MAP) with various ranges of <10%, 10 ～ 20%, and > 20%, respectively. Patients of three groups were checked with single photon emissioncomputed tomography (SPECT),and computerized tomography of head successively, 24 hours, 3 ～ 5 days, and 12～ 15 days after admission for the assessment of therapeutic effects. The rtes of the decrease in rCBF compared be-twecn groups were analyzed with t test. Neurologic function defect scale, activities of living scale and number of re-bleeding compared between two groups were analyzed by X2 test, respectively. Results There were statisticallysignificant differences in the rate of the decrease in rCBF. The neurologic function defect scale and activities of liv-ing scale at 24 hours, 3 ～ 5 days, and 12 ～ 15 days after admission compared between group C and group A, andbetween group C and group B showed significant differences ( P < 0.05). There were statistically significant differ-enees in rebleeding during acute phase of HICH between group A and group B or group C (P < 0.05).Conclusions If the systolic blood pressure is above 185mmHg or diastolic blood pressure over 95mmHg,it is ra-tional and safe to lower the MAP by about 15% with hypotensive gents so as to minimize the impact on regionalcerebral blood flow.

Minimally Invasive Surgery Treatment with Small Incision on Hypertensive Intracerebral Hemorrhage / 中国医师杂志

Objective To explore the principle and methods of normative minimally invasive surgery treatment on hypertensive intracerebral hemorrhage. Methods 49 cases of hypertensive intracerebral hemorrhage were treated by microsurgery with small incision. Results 46 cases survived and 3 cases died after surgery. 42 cases were followed up. Adopting GOS, 19 cases were normal, 12 cases were disable and could care for self, 5 cases were severely disable, sober and could not care for self, 3 cases were vegetable survival, and 3 cases were dead. Conclusion Application of minimally invasive surgery idea and normative treatment according to the patients' condition can obviously improve the efficacy of patients with hypertensive intracerebral hemorrhage.