SYT7 (synaptotagmin 7) promotes cervical squamous cell carcinoma.

Cervical squamous cell carcinoma (CESC) ranks among the primary contributors to global cancer-associated mortality. However, the role mediated by synaptotagmin 7 (SYT7) in CESC remains unclear. Our study employed immunohistochemistry to assess the level of SYT7 expression in the tissue microarray. Furthermore, lentiviral shRNA transduction was utilized to establish SYT7 knockdown cell line models based on HeLa and SiHa cell lines. The functional impacts of silencing SYT7 expression in vitro were evaluated. A subcutaneous xenograft model was employed to examine the tumorigenic potential of cells with or without SYT7. The content of SYT7 in CESC tissues was significantly elevated compared to adjacent normal tissues. Functionally, silencing SYT7 in HeLa and SiHa cells suppressed cell proliferation, colony formation ability, and apoptosis enhancement. Additionally, cells with suppressed SYT7 also exhibited inhibited cell migration and invasion. In vivo experiments demonstrated the loss of tumorigenic ability in SYT7 knockdown cells and suppressed tumor growth. Quantitative PCR PrimeView PathArray and apoptosis antibody array analyses revealed that upon elimination of SYT7, there was a significant upregulation observed in Caspase 8, TNF-R1 (TNF receptor superfamily member 1A), and HSPA5 (heat shock protein family A [Hsp70] member 5), while TGFBI (transforming growth factor beta-induced), RPL31 (ribosomal protein L31), LUM (lumican), HSDL2 (hydroxysteroid dehydrogenase-like 2), ITGB5 (integrin subunit beta 5), and Smad2 (SMAD family member2) were downregulated. Overall, we have demonstrated the tumor-promoting functions of SYT7 in CESC.

Erastin induces ferroptosis in cervical cancer cells via Nrf2/HO-1 signaling pathway.

OBJECTIVE: Our research aims to assess the influence of erastin, a ferroptosis-inducing agent, on cervical cancer cells. INTRODUCTION: Cervical cancer is a prevalent malignancy in females. Dysregulation of ferroptosis, a form of cell demise reliant on iron, is implicated in several cancers. METHODS: The effect of erastin on HeLa and SiHa was detected by transwell assay, scratch test, and colony formation assay, while cell apoptosis was detected using flow cytometry. Cellular reactive oxygen species (ROS) generation was detected using the dichloro-dihydro-fluorescein diacetate assay. Sequencing analysis identified differentially expressed genes (DEGs), and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Enrichment analyses were employed to identify the target gene. Subsequently, the utilization of small interfering RNA (siRNA) was employed to suppress the targeted gene expression in HeLa cells, thereby effectively mitigating the impact of erastin on various cellular processes including invasion, colony formation, migration, and ROS generation. RESULTS: The findings indicate that erastin attenuates the viability of both HeLa cells (IC50 = 30.88 µM) and SiHa cells (IC50 = 29.40 µM). Treatment with erastin at 10 µM inhibits the invasion, colony formation, and migration of both HeLa and SiHa cells within 24 h. Ferrostatin-1 (1 µM) notably alleviates the inhibitory effects of erastin of HeLa and SiHa cells. Upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target, heme oxygenase-1 (HO-1), was found in erastin-treated cells compared to the control group. When knocked down HO-1 in HeLa cells, effectively counteracting the effects of erastin on the invasion, colony formation, migration, and ROS production in HeLa cells. CONCLUSION: Our research demonstrates that erastin induces ferroptosis and the accumulation of ROS in cervical cancer cells by activating the Nrf2/HO-1 pathway, significantly reducing cell proliferation and motility. These findings propose a potential molecular mechanism of erastin-mediated cervical cancer development.

Femtosecond laser-scribed superhydrophilic/superhydrophobic self-splitting patterns for one droplet multi-detection.

Superwettable patterned composite surfaces are being recognized as essential components in the field of precise droplet manipulation. However, developing simple and effective methods for manufacturing such surfaces remains a challenge especially for multi-detection surfaces. Here we present a femtosecond laser-based method to create a superhydrophobic/superhydrophilic (SHB/SHL) self-splitting pattern on a polyimide film to achieve droplet multi-detection. The mechanism behind droplet self-splitting on the SHB/SHL pattern surface is related to the dynamic behaviors of liquid recoiling and spreading. This behavior was affected by two main factors, including the width of the SHB stripe, and the radius of the SHL pattern. When the characteristic width is larger than 0.2, droplets are able to fully self-split. Furthermore, the SHB/SHL pattern can be utilized for alcohol detection and multiple biological tests performed using a single drop of biological fluid. This work provides a facile strategy for precise separation and distribution of microdroplets, and potentially could be applied in fluid recognition, biological screening, and combinatorial analysis.

One Droplet toward Efficient Alcohol Detection Using Femtosecond Laser Textured Micro/Nanostructured Surface with Superwettability.

Alcohol with different concentrations is commonly used in food, industry, and medicine fields all over the world. However, current methods for detecting alcohol concentration are restricted to large sample consumption, additional senergy consuming, or complex operations. Here, inspired by superwettability of lotus leaves, a superhydrophobic and superorganophilic surface is designed on the polydimethylsiloxane (PDMS) for one droplet efficient alcohol detection, which is prepared via femtosecond laser direct writing technology. Meanwhile, the contact angles of droplets with various alcohol concentrations on the laser-treated PDMS (LTP) surface are different. Based on the above characteristic, alcohol concentration through contact angle measurement without any external energy is directly detected, which is simple and efficient. Furthermore, it is worth noting that the LTP surface remains stable wettability after 1000 water-ethanol cycles and 300 days tests in air, indicating strong surface repeatability and stability. Significantly, the LTP surface has a broad potential application in one droplet detecting alcohol concentration, fake or genuine wine, and alcohol molecules. This work provides a new strategy to fabricate a superwetting surface for efficient one droplet alcohol detection.

MTFR2 shapes a barrier of immune microenvironment in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in the world. Mitochondrial fission regulator 2 (MTFR2) is involved in the development of various cancers. However, the roles of MTFR2 in HCC remain unknown. In this study, we conducted a comprehensive analysis of MTFR2 in HCC, which was generated from integrative MTFR2 analyses of eight HCC cell lines, and three datasets (public dataset, real-world dataset, and immunotherapy dataset) derived from bulk HCC tissues, survival, and immunotherapy data. We demonstrated that the expression level of MTFR2 is upregulated in HCC, leading to poor prognosis. MTFR2 is positively correlated with the level of immune cell infiltration, multiple immune checkpoints and immunotherapy response prediction pathways, and acts as an important role in cancer-immunity cycle. In conclusion, our work indicates that MTFR2 can shape a barrier of immune microenvironment and result in poor prognosis in hepatocellular carcinoma, but the immune barrier may be broken by immunotherapy.

Hsa_Circ_0066351 Acts as a Prognostic and Immunotherapeutic Biomarker in Colorectal Cancer.

Circular RNA (circRNA), a novel class of non-coding RNA, has been reported in various diseases, especially in tumors. However, the key signatures of circRNA-competitive endogenous RNA (ceRNA) network are largely unclear in colorectal cancer (CRC). We first characterized circRNAs profile by using circRNA-seq analysis from real-word dataset. The expression level of hsa_circ_0066351 in CRC tissues and cell lines was detected by quantitative real-time PCR. Then, cell proliferation assay was used to confirm the proliferation function of hsa_circ_0066351. Next, Cytoscape was used to construct circRNA-miRNA-mRNA networks. Last but not least, the landscape of hsa_circ_0066351-miRNA-mRNA in CRC had been investigated in the bulk tissue RNA-Seq level and single-cell Seq level. We proved that hsa_circ_0066351 was significantly downregulated in CRC cell lines and tissues (P < 0.001), and was negatively associated with distant metastasis (P < 0.01). Significantly, the expression of hsa_circ_0066351 was associated with better survival in patients with CRC. Function assays showed that hsa_circ_0066351 could inhibit CRC cells proliferation. In addition, a ceRNA network, including hsa_circ_0066351, two miRNAs, and ten mRNAs, was constructed. Our analyses showed that these ten mRNAs were consistently downregulated in pan-cancer and enriched in tumor suppressive function. A risk score model constructed by these ten downstream genes also indicated that they were related to the prognosis and immune response in CRC. In conclusion, we demonstrated that a novel circRNA (hsa_circ_0066351) inhibited CRC proliferation, and revealed a potential prognostic and immunotherapeutic biomarker in CRC.

Wetting Ridge-Guided Directional Water Self-Transport.

Directional water self-transport plays a crucial role in diverse applications such as biosensing and water harvesting. Despite extensive progress, current strategies for directional water self-transport are restricted to a short self-driving distance, single function, and complicated fabrication methods. Here, a lubricant-infused heterogeneous superwettability surface (LIHSS) for directional water self-transport is proposed on polyimide (PI) film through femtosecond laser direct writing and lubricant infusion. By tuning the parameters of the femtosecond laser, the wettability of PI film can be transformed into superhydrophobic or superhydrophilic. After trapping water droplets on the superhydrophilic surface and depositing excess lubricant, the asymmetrical wetting ridge drives water droplets by an attractive capillary force on the LIHSS. Notably, the maximum droplet self-driving distance can approach ≈3 mm, which is nearly twice as long as the previously reported strategies for direction water self-transport. Significantly, it is demonstrated that this strategy makes it possible to achieve water self-transport, anti-gravity pumping, and chemical microreaction on a tilted LIHSS. This work provides an efficient method to fabricate a promising platform for realizing directional water self-transport.

Prognostic stratification based on m5C regulators acts as a novel biomarker for immunotherapy in hepatocellular carcinoma.

Background: Immunotherapy is a promising anti-cancer strategy in hepatocellular carcinoma (HCC). However, a limited number of patients can benefit from it. There are currently no reliable biomarkers available to find the potential beneficiaries. Methylcytosine (m5C) is crucial in HCC, but its role in forecasting clinical responses to immunotherapy has not been fully clarified. Methods: In this study, we analyzed 371 HCC patients from The Cancer Genome Atlas (TCGA) database and investigated the expression of 18 m5C regulators. We selected 6 differentially expressed genes (DEGs) to construct a prognostic risk model as well as 2 m5C-related diagnostic models. Results: The 1-, 3-, and 5-year area under the curve (AUC) of m5C scores for the overall survival (OS) was 0.781/0.762/0.711, indicating the m5C score system had an ideal distinction of prognostic prediction for HCC. The survival analysis showed that patients with high-risk scores present a worse prognosis than the patients with low-risk scores (p< 0.0001). We got consistent results in 6 public cohorts and validated them in Xiangya real-world cohort by quantitative real-time PCR and immunohistochemical (IHC) assays. The high-m5C score group was predicted to be in an immune evasion state and showed low sensitivity to immunotherapy, but high sensitivity to chemotherapy and potential targeted drugs and agents, such as sepantronium bromide (YM-155), axitinib, vinblastine and docetaxel. Meanwhile, we also constructed two diagnostic models to distinguish HCC tumors from normal liver tissues or liver cirrhosis. Conclusion: In conclusion, our study helps to early screen HCC patients and select patients who can benefit from immunotherapy. Step forwardly, for the less likely beneficiaries, this study provides them with new potential targeted drugs and agents for choice to improve their prognosis.

Femtosecond Laser Thermal Accumulation-Triggered Micro-/Nanostructures with Patternable and Controllable Wettability Towards Liquid Manipulating.

Versatile liquid manipulating surfaces combining patternable and controllable wettability have recently motivated considerable attention owing to their significant advantages in droplet-solid impacting behaviors, microdroplet self-removal, and liquid-liquid interface reaction applications. However, developing a facile and efficient method to fabricate these versatile surfaces remains an enormous challenge. In this paper, a strategy for the fabrication of liquid manipulating surfaces with patternable and controllable wettability on Polyimide (PI) film based on femtosecond laser thermal accumulation engineering is proposed. Because of its controllable micro-/nanostructures and chemical composition through adjusting the local thermal accumulation, the wettability of PI film can be tuned from superhydrophilicity (~ 3.6°) to superhydrophobicity (~ 151.6°). Furthermore, three diverse surfaces with patternable and heterogeneous wettability were constructed and various applications were successfully realized, including water transport, droplet arrays, and liquid wells. This work may provide a facile strategy for achieving patternable and controllable wettability efficiently and developing multifunctional liquid steering surfaces.

Identification of tumour immune infiltration-associated snoRNAs (TIIsno) for predicting prognosis and immune landscape in patients with colon cancer via a TIIsno score model.

BACKGROUND: Colon cancer (CC) is the leading cause of tumour-related death worldwide. SnoRNA plays a critical role in the tumour microenvironment. The tumour microenvironment can be shaped by tumour-infiltrating immune cells, which control the destiny of immunotherapy efficacy. This study uniquely focused on snoRNAs derived from immune cells to identify new biomarkers for immune landscape. METHODS: A novel computational framework was initiated for identifying tumour immune infiltration-associated snoRNAs (TIIsno) signatures and developed a TIIsno score model from integrative snoRNA profiling analysis of 21 purified immune cell lines, 43 colon cancer cell lines, and three datasets (training, test, real-world validation set). FINDINGS: Our study found that a high TIIsno score was associated with poor CC prognosis. TIIsno scores were seen to be negatively correlated with (I) the infiltration level of most immune cells, (II) the inhibitory immune checkpoints expression level, and (III) the immune score. These findings, taken together with the observation that TIIsno score is lower in MSI-H patients, suggests that patients with a low TIIsno score may have a better response to immunotherapy. INTERPRETATION: In conclusion, we successfully identified TIIsno and constructed a TIIsno score model, a new potential biomarker of immunotherapy response, which can effectively predict the prognosis of CC patients as well. FUNDING: National Key R & D Program of China, National Natural Science Foundation of China, key projects from the Nature Science Foundation of Hunan Province, projects from Beijing CSCO Clinical Oncology Research Foundation, Fundamental Research Funds for the Central Universities of Central South University.

tRF3008A suppresses the progression and metastasis of colorectal cancer by destabilizing FOXK1 in an AGO-dependent manner.

BACKGROUND: tRNA-derived fragments (tRFs) have been shown to have critical regulatory roles in cancer biology. However, the contributions of tRFs to colorectal cancer (CRC) remain largely unknown. METHODS: tRF3008A (a tRFRNA derived from tRNAVal) was identified by RNA sequencing and validated by quantitative reverse transcription PCR. The role of tRF3008A in CRC progression was assessed both in vitro and in vivo, and its downstream target genes were identified and validated in CRC cells. RNA pull-down with mass spectrometry and AGO-RIP were used to confirm the interaction of tRF3008A and AGO proteins. The clinical implications of tRF3008A were assessed in CRC tissues and blood samples. RESULTS: The expression of tRF3008A was reduced in colorectal cancer, and its reduction was significantly correlated with advanced and metastatic disease in CRC. Patients with low tRF3008A expression showed significantly shorter DFS, and multivariate analysis identified tRF3008A as an independent prognostic biomarker in CRC. Functionally, tRF3008A inhibits the proliferation and migration of CRC in vivo and in vitro by repressing endogenous FOXK1, a positive regulator of the Wnt/ß-catenin pathway. Mechanistically, tRF3008A binds to AGO proteins as a guide to destabilize oncogenic FOXK1 transcript. CONCLUSIONS: tRF3008A suppresses the metastasis and progression of colorectal cancer by destabilizing FOXK1 in an AGO-dependent manner.

Separation and characterization of two series of unknown degradation impurities caused by light irradiation and autoclaving in xinfujunsu injection using liquid chromatography tandem mass spectrometry.

RATIONALE: A series of photodegradation impurities and a series of degradation impurities produced in autoclaving in xinfujunsu injection were discovered, and these unknown impurities were separated and characterized thoroughly using liquid chromatography tandem quadrupole time-of-flight mass spectrometry. METHODS: The column was a Platisil 5 µm ODS (4.6 × 250 mm, 5 µm). For the analysis of degradation impurities caused by light irradiation and autoclaving, the mobile phase was composed of 0.01 M ammonium formate aqueous solution and acetonitrile/isopropanol (90:10, V/V). Full scan LC-MS and LC-MS2 was carried out to obtain as much structural information as possible. The fragmentation behavior of actinomycin D, actinomycin S3 , and its impurities was studied and used to obtain information about the structures of these impurities. RESULTS: Based on MS2 spectral data and exact mass measurements, the chemical structures of two series of degradation impurities were characterized, among which five unknown impurities were photodegradation impurities and seven unknown impurities were degradation impurities produced in autoclaving of xinfujunsu injection. CONCLUSIONS: Based on characterization of impurities, this study also revealed the cause of impurity production and provided guidance for enterprises to improve the process and drug packaging material to reduce impurity content. Furthermore, this study also provided scientific basis for further improvement of official monographs in pharmacopoeias.

Shift in competitive ability mediated by soil biota in an invasive plant.

Understanding the shifts in competitive ability and its driving forces is key to predict the future of plant invasion. Changes in the competition environment and soil biota are two selective forces that impose remarkable influences on competitive ability. By far, evidence of the interactive effects of competition environment and soil biota on competitive ability of invasive species is rare. Here, we investigated their interactive effects using an invasive perennial vine, Mikania micrantha. The competitive performance of seven M. micrantha populations varying in their conspecific and heterospecific abundance were monitored in a greenhouse experiment, by manipulating soil biota (live and sterilized) and competition conditions (competition-free, intraspecific, and interspecific competition). Our results showed that with increasing conspecific abundance and decreasing heterospecific abundance, (1) M. micrantha increased intraspecific competition tolerance and intra- vs. interspecific competitive ability but decreased interspecific competition tolerance; (2) M. micrantha increased tolerance of the negative soil biota effect; and (3) interspecific competition tolerance of M. micrantha was increasingly suppressed by the presence of soil biota, but intraspecific competition tolerance was less affected. These results highlight the importance of the soil biota effect on the evolution of competitive ability during the invasion process. To better control M. micrantha invasion, our results imply that introduction of competition-tolerant native plants that align with conservation priorities may be effective where M. micrantha populations are long-established and inferior in inter- vs. intraspecific competitive ability, whereas eradication may be effective where populations are newly invaded and fast-growing.

RASA4 inhibits the HIFα signaling pathway to suppress proliferation of cervical cancer cells.

RAS p21 protein activator 4 (RASA4) has been recognized as a Ca2+-promoted Ras-MAPK pathway suppressor that inhibits tumor growth. However, the role of RASA4 in cervical squamous cell carcinoma (CESC) remains unclear. The mRNA levels of RASA4 were analyzed using the GEO and GEPIA databases. Kaplan-Meier analysis and ROC analyses were conducted to determine the prognostic and diagnostic values for patients from the TCGA-CSCE cohort. The CCK8 and colony assays were performed to assess the impact of RASA4 ectopic expression and gene inactivation on tumor cell proliferation. In vivo experiments were performed. Luciferase reporter assays and LW6 (a HIFα inhibitor) were employed to verify the regulatory relationship between RASA4 and the HIFa signaling pathway. The GEPIA and GEO database analysis demonstrated poorly expressed RASA4 in the CESC tissues relative to that in the noncancerous tissues. Based on the TCGA database, poorly expressed RASA4 signified high prognostic and diagnostic values. Ectopically expressed RASA4 weakened the proliferative potential of HeLa cells, whereas RASA4 genetic inactivation produced the opposite impact in the HeLa and C-33A cells. The promoting effect of RASA4 deficiency on tumourigenesis was also recorded in vivo. Subsequently, RASA4 negatively regulated the HIFα-driven luciferase activities and weakened the expression of survivin. Meanwhile, LW6 treatment abrogated the increased proliferation of HeLa cells, as well as the increased expression of survivin by RASA4 depletion. Our findings indicated that RASA4 can inhibit the proliferation of cervical cancer cells by inactivating the HIFα signaling pathway, suggesting novel prospects for targeted therapy against CESC.

The profile analysis of circular RNAs in cervical cancer.

ABSTRACT: Cervical cancer (CC) is the third most common cancer among women and has a high mortality rate at the advanced stage. The mechanisms underlying the development and progression of CC are still elusive. Circular RNAs (circRNAs) play an important role in various physiological and pathological processes. The aim of this study was to identify the circRNAs significantly associated with cervical squamous cell carcinoma (CSCC), in order to discover novel diagnostic markers and elucidate their mechanistic basis.The circRNA expression profiles of CSCC and paired para-cancerous cervical tissues was downloaded from the Gene Expression Omnibus. Bioinformatics analysis were used to screen for the differentially expressed circRNAs (DECRs). The expression levels of hsa_circ_0000745, hsa_circ_0084927, hsa_circ_0002762, hsa_circ_0075341, hsa_circ_0007905, hsa_circ_0031027, hsa_circ_0065898, hsa_circ_0070190, and hsa_circ_0078383 were verified in CC and normal cervical tissues by quantitative real-time PCR.A total of 197 DECRs were identified between the CSCC and normal tissues, including 87 upregulated and 110 downregulated circRNAs. In addition, 37 miRNAs were predicted for the upregulated circRNAs and 39 for the downregulated circRNAs. Functional analysis showed that the DECRs were associated with positive regulation of substrate adhesion-dependent cell spreading, metabolism, positive regulation of GTPase activity, protein regulation, and intercellular adhesion. The MAPK signaling pathway that plays a significant role in the progression of CC, was also enriched. Consistent with the in-silico analysis, hsa_circ_0000745, hsa_circ_0084927, hsa_circ_0002762, hsa_circ_0007905 were upregulated and hsa_circ_0078383 was downregulated in CC tissues (P < .001), whereas hsa_circ_0075341 (P < .001) and hsa_circ_0031027 (P = .001) showed opposite trends.We identified novel diagnostic and therapeutic biomarkers of CSCC along with the mechanistic basis.

Development and Psychometric Testing of the Supportive Care Needs Scale for Patients with Tuberculosis (SCN-TB).

PURPOSE: Patients affected by tuberculosis have diverse unmet supportive care needs (SCN) that may seriously affect their treatment adherence. Accurately assessing patients' SCN is important for providing efficient patient-centred care, but few instruments are suitable for use in clinical practice. Therefore, the purpose of this study was to develop an SCN scale for patients with tuberculosis (SCN-TB) and to evaluate its psychometrical properties. PATIENTS AND METHODS: Based on the SCN framework, the SCN-TB was designed via a literature review, Delphi consultation and pilot study. Then, 550 patients from four tuberculosis specialist hospitals in Shaanxi Province were enrolled by convenience sampling to further test the validity and reliability of the SCN-TB. RESULTS: A total of 518 patients completed the survey. The final scale encompasses 25 items in five domains: physical, practical, psycho-emotional, social, and informational. The content validity for the scale was 0.93, with that for each item ranging from 0.80 to 1.00. Five factors that explained 80.38% of the variance were identified in exploratory factor analysis. A five-factor model was then confirmed with confirmatory factor analysis using maximum likelihood estimation with bootstrapping. The model fit indices were χ 2/df=1.062 (Bollen-Stine χ 2=281.382, df=265, p<0.001), CFI=0.997, RMSEA=0.016, SRMR=0.053, NFI=0.951, and GFI=0.929. All factors had acceptable convergent and discriminant validity. The Cronbach's α, split-half, and test-retest reliability coefficients of the scale were 0.884, 0.883, and 0.854, respectively. CONCLUSION: The SCN-TB is a valid and reliable theory based tool for assessing the needs of patients with tuberculosis and can be applied in both clinical practice and research.

A comprehensive analysis of the efficacy and safety of COVID-19 vaccines.

The numbers of cases and deaths from coronavirus disease 2019 (COVID-19) are continuously increasing. Many people are concerned about the efficacy and safety of the COVID-19 vaccines. We performed a comprehensive analysis of the published trials of COVID-19 vaccines and the real-world data from the Vaccine Adverse Event Reporting System. Globally, our research found that the efficacy of all vaccines exceeded 70%, and RNA-based vaccines had the highest efficacy of 94.29%; moreover, Black or African American people, young people, and males may experience greater vaccine efficacy. The spectrum of vaccine-related adverse drug reactions (ADRs) is extremely broad, and the most frequent ADRs are pain, fatigue, and headache. Most ADRs are tolerable and are mainly grade 1 or 2 in severity. Some severe ADRs have been identified (thromboembolic events, 21-75 cases per million doses; myocarditis/pericarditis, 2-3 cases per million doses). In summary, vaccines are a powerful tool that can be used to control the COVID-19 pandemic, with high efficacy and tolerable ADRs. In addition, the spectrum of ADRs associated with the vaccines is broad, and most of the reactions appear within a week, although some may be delayed. Therefore, ADRs after vaccination need to be identified and addressed in a timely manner.

M6A "Writer" Gene METTL14: A Favorable Prognostic Biomarker and Correlated With Immune Infiltrates in Rectal Cancer.

Rectal cancer (RC) is the leading cause of tumor-related death among both men and women. The efficacy of immunotherapy for rectal cancer is closely related to the immune infiltration level. The N6-methyladenosine (m6A) modification may play a pivotal role in tumor-immune interactions. However, the roles of m6A-related genes in tumor-immune interactions of rectal cancer remain largely unknown. After an evaluation on the expression levels of m6A-related genes and their correlations with the prognosis of rectal cancer patients, we found that METTL14 was the only gene to be significantly correlated with prognosis in rectal cancer patients. Therefore, we further observed the impact of METTL14 expression and m6A modification on the immune infiltration in rectal cancer. Our study indicates that low expression of the m6A "writer" gene METTL14 in rectal cancer may lead to the downregulation of m6A RNA modification, thus reducing the level of immune cell infiltration and resulting in poor prognosis. METTL14 expression level is an independent prognostic factor in rectal cancer and is positively correlated with the immune infiltration level. Our study identified METTL14 as a potential target for enhancing immunotherapy efficacy in rectal cancer.

The effects of plant-soil feedback on invasion resistance are soil context dependent.

There is growing interest in understanding the role that plant-soil feedbacks (PSFs) may play in invasion resistance. However, recent studies have shown that there is great uncertainty in explaining community patterns by PSF studies regarding invasions. This uncertainty may be partly because soils used for PSF studies are usually collected from open areas rather than natural communities, thus ignoring the effects of community contexts that may specifically influence the soil feedbacks of community residents to invaders. We performed a two-phase pot experiment to study the soil feedback initiated by ten co-occurring native and exotic species to a forest invader, Phytolacca americana, and the experiments were performed in forest soil and open area soil. The context-dependent mechanisms were further explored by studying different components of PSF. The results showed that natives and exotics had positive and negative effects on P. americana in the open area soil, respectively, but both had negative effects in the forest soil. Nutrient limitation was more important for the PSF in open area soil, whereas biotic factors were likely the primary mechanisms explaining the PSF in forest soil. Additionally, the litter-mediated allelopathy of dominant Quercus acutissima caused the strongest inhibition of the invader. These results suggest that native species can effectively resist invasion by producing negative PSF depending on the community context. Evidence that exotic species promote invasion through positive PSFs was not obtained. This study provided preliminary insights into the possibility of bridging PSF studies and community patterns.

Low expression of NLRP1 is associated with a poor prognosis and immune infiltration in lung adenocarcinoma patients.

NLRP1 (NLR family, pyrin domain containing 1), the first NLR protein, described to form an inflammasome, plays critical roles in innate immunity and inflammation. However, NLRP1 has not been reported to be linked to LUAD (lung adenocarcinoma) risk, prognosis, immunotherapy or any other treatments. This research aimed to explore the prognostic value and mechanism of NLRP1 in LUAD. We performed bioinformatics analysis on LUAD data downloaded from TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus), and jointly analyzed with online databases such as TCGAportal, LinkedOmics, TIMER, ESTIMATE and TISIDB. NLRP1 expression of LUAD tissue was considerably lower than that in normal lung tissue. Decreased NLRP1 expression of LUAD was associated with relatively high pathological, T and N stages. Kaplan-Meier survival analysis indicated that patients with low NLRP1 expression had a worse prognosis than those with high expression. Multivariate Cox analysis further showed that NLRP1 expression level was an independent prognostic factor of LUAD. Moreover, the level of NLRP1 expression was positively linked to the degree of infiltration of various TIICs (tumor-infiltrating immune cells). Our findings confirmed that reduced expression of NLRP1 was significantly related to poor prognosis and low degree of immune cell infiltration in LUAD patients.