Chronic low-dose deltamethrin exposure induces colon injury and aggravates DSS-induced colitis via promoting cellular senescence.

OBJECTIVE: Deltamethrin (DLM) is a commonly used insecticide, which is harmful to many organs. Here, we explored the effects of chronic low-dose DLM residues on colon tissue and its potential mechanism. METHODS: The mice were given long-term low-dose DLM by intragastric administration, and the body weights and disease activity index (DAI) scores of the mice were regularly recorded. The colon tissues were then collected for hematoxylin-eosin, immunofluorescence and immunohistochemistry staining. Besides, the RNA sequencing was performed to explore the potential mechanism. RESULTS: Our results showed that long-term exposure to low-dose DLM could cause inflammation in mice colon tissue, manifested as weight loss, increased DAI score, increased apoptosis of colonic epithelial cells, and increased infiltration of inflammatory cells. However, we observed that after long-term exposure to DLM and withdrawal for a period of time, although apoptosis was restored, the recovery of colon inflammation was not ideal. Subsequently, we performed RNA sequencing and found that long-term DLM exposure could lead to the senescence of some cells in mice colon tissue. The results of staining of cellular senescence markers in colon tissue showed that the level of cellular senescence in the DLM group was significantly increased, and the p53 signalling related to senescence was also significantly activated, indicating that cellular senescence played a key role in DLM-induced colitis. We further treated mice with quercetin (QUE) after long-term DLM exposure, and found that QUE could indeed alleviate DLM-induced colitis. In addition, we observed that long-term accumulation of DLM could aggravate DSS-induced colitis in mice, and QUE treatment could reverse this scenario. CONCLUSION: Continuous intake of DLM caused chronic colitis in mice, and the inflammation persisted even after discontinuation of DLM intake. This was attributed to the induction of cellular senescence in colon tissue. Treatment with QUE alleviated DLM-induced colitis by reducing cellular senescence. Long-term DLM exposure also aggravated DSS-induced colitis, which could be mitigated by QUE treatment.

LncRNA-BC069792 suppresses tumor progression by targeting KCNQ4 in breast cancer.

BACKGROUND: Breast cancer is the most common malignant tumor that threatens women's health. Attention has been paid on the study of long- non-coding RNA (lncRNA) in breast cancer. However, the specific mechanism remains not clear. METHODS: In this study, we explored the role of lncRNA BC069792 in breast cancer. In vitro and in vivo functional experiments were carried out in cell culture and mouse models. High-throughput next-generation sequencing technology and real-time fluorescence quantitative PCR technology were used to evaluate differentially expressed genes and mRNA expression, Western blot and immunohistochemical staining were used to detect protein expression. RNA immunoprecipitation assay and dual-luciferase activity assay were used to evaluate the competing endogenous RNAs (ceRNA), and rescue and mutation experiments were used for verification. RESULTS: We found that lncRNA BC069792 was expressed at a low level in breast cancer tissues, and significantly decreased in breast cancer with high pathological grade, lymph node metastasis and high Ki-67 index groups. Moreover, BC069792 inhibited the proliferation, invasion and metastasis of breast cancer cells in vitro and in vivo. Mechanically, BC069792 acts as a molecular sponge to adsorb hsa-miR-658 and hsa-miR-4739, to up-regulate the protein expression of Potassium Voltage-Gated Channel Q4 (KCNQ4), inhibits the activities of JAK2 and p-AKT, and plays a role in inhibiting breast cancer growth. CONCLUSIONS: LncRNA BC069792 plays the role of tumor suppressor gene in breast cancer and is a new diagnostic index and therapeutic target in breast cancer.

A nomogram based on platelet-to-lymphocyte ratio for predicting pathological complete response of breast cancer after neoadjuvant chemotherapy.

OBJECTIVE: To investigate the role of platelet-to-lymphocyte ratio (PLR) in complete pathological response (pCR) of breast cancer (BC) patients after neoadjuvant chemotherapy (NAC), as well as to establish and validate a nomogram for predicting pCR. METHODS: BC patients diagnosed and treated in the First Affiliated Hospital of Xi'an Jiaotong University from January 2019 to June 2022 were included. The correlation between pCR and clinicopathological characteristics was analyzed by Chi-square test. Logistic regression analysis was performed to evaluate the factors that might affect pCR. Based on the results of regression analysis, a nomogram for predicting pCR was established and validated. RESULTS: A total of 112 BC patients were included in this study. 50.89% of the patients acquired pCR after NAC. Chi-square test showed that PLR was significantly correlated with pCR (X2 = 18.878, P < 0.001). And the PLR before NAC in pCR group was lower than that in Non-pCR group (t = 3.290, P = 0.001). Logistic regression analysis suggested that white blood cell (WBC) [odds ratio (OR): 0.19, 95% confidence interval (CI): 0.04-0.85, P = 0.030)], platelet (PLT) (OR: 0.19, 95%CI: 0.04-0.85, P = 0.030), PLR (OR: 0.18, 95%CI: 0.04-0.90, P = 0.036) and tumor grade (OR: 9.24, 95%CI: 1.89-45.07, P = 0.006) were independent predictors of pCR after NAC. A nomogram prediction model based on WBC, PLR, PLR and tumor grade showed a good predictive ability. CONCLUSION: PLR, PLT, WBC and tumor grade were independent predictors of pCR in BC patients after NAC. The nomogram based on the above positive factors showed a good predictive ability.

Knockdown of RSPH14 inhibits proliferation, migration, and invasion and promotes apoptosis of hepatocellular carcinoma via RelA.

BACKGROUND: High RSPH14 expression appears to be related to poor prognosis of hepatocellular carcinoma (HCC). This study aimed to investigate the possible roles of RSPH14 in the proliferation, apoptosis, and invasion of HCC cells. METHODS: The UALCAN database and Kaplan-Meier Plotter were used to evaluate the expression level and prognostic role of RSPH14 in HCC. Lentiviral vectors containing shRNA against RSPH14 were constructed to transfect the BEL-7404 and SMMC-7721 HCC cell lines. Cell proliferation was investigated by BrdU, MTT, and colony-formation assays. Apoptosis was detected using flow cytometry. Cell migration and invasion were evaluated using the scratch wound-healing and Transwell assays. Immunohistochemistry and western blot were used to determine the expression levels of the proteins. The function of RSPH14 in vivo was evaluated using a xenograft mouse model. RESULTS: The expression of RSPH14 was higher in HCC tumor tissues than in adjacent normal tissues and was closely related to unfavorable prognostic factors and poorer survival (all P < 0.05). Knockdown of RSPH14 inhibited the cell proliferation, migration, and invasion of HCC cells and promoted apoptosis (all P < 0.05). Knockdown of RSPH14 inhibited tumor growth in vivo (P < 0.05). RSPH14 knockdown led to decreased expression of RelA (NF-κBp65), CDH2, and AKT1, thereby affecting the functions of the HCC cells (all P < 0.05). RelA overexpression could abate the inhibitory effect of BEL-7404 cell proliferation caused by RSPH14 depletion. CONCLUSION: Knockdown of RSPH14 could decrease cell proliferation, migration, and invasion and increase apoptosis of HCC cells by inhibiting RelA expression. RSPH14 could be a new treatment target for HCC.

Downregulation of the FBXO43 gene inhibits tumor growth in human breast cancer by limiting its interaction with PCNA.

BACKGROUND: The function and regulatory mechanism of FBXO43 in breast cancer (BC) are still unclear. Here, we intended to determine the role and mechanism of FBXO43 in BC. METHODS: FBXO43 expression in BC was evaluated by analysis of The Cancer Genome Atlas (TCGA). RT-qPCR and western blotting were utilized to detect FBXO43 expression in BC cell lines. Lentivirus was applied to downregulate FBXO43 in human BC cells. Proliferation assays were performed to evaluate the proliferative ability of BC cells. The apoptosis and cell cycle analysis of BC cells were analyzed by flow cytometry. Cell migration and invasion were investigated via Transwell assays. The function of FBXO43 in vivo was evaluated by constructing a xenograft mouse model. The proteins that might interact with FBXO43 in BC were identified by mass spectrometry, bioinformatics analysis, and co-immunoprecipitation (Co-IP) assays. Finally, rescue experiments were conducted to validate the recovery effects of the proteins interacting with FBXO43. RESULTS: FBXO43 was highly expressed in BC and was significantly downregulated after FBXO43 knockdown. The proliferation, migration, and invasion of BC cells were inhibited, and cell apoptosis was induced by FBXO43 knockdown. In addition, an in vivo experiment indicated that FBXO43 knockdown could inhibit the cell growth of BC. The results of the Co-IP assay showed that FBXO43 interacted with PCNA. Further rescue experiments confirmed that overexpression of PCNA significantly reversed the effects of FBXO43 knockdown on BC cells. CONCLUSION: Downregulation of FBXO43 inhibits the tumor growth of BC by limiting its interaction with PCNA. FBXO43 might be a new potential oncogene and a therapeutic target for BC.

Postoperative oxaliplatin-based hyperthermic intraperitoneal chemotherapy: an effective and safe palliative treatment option for colorectal cancer with peritoneal metastasis.

BACKGROUND: The prognosis of patients with colorectal cancer and peritoneal metastasis (CRC-PM) after incomplete cytoreductive surgery (CRS) or palliative surgery is poor. Novel and effective therapies are urgently needed. This study aimed to assess the effects of palliative postoperative hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with CRC-PM. METHODS: This retrospective study included patients with CRC-PM at the First Affiliated Hospital of Xi'an Jiaotong University in 05/2014-05/2019. Observation indicators included overall survival (OS), ascites-free survival, peritoneal cancer index (PCI), and completeness of cytoreduction (CC). Kaplan-Meier survival curves and multivariable Cox regression models were used to determine the factors associated with OS and ascites-free survival. The ascites-specific quality of life (QoL) was measured using the Functional Assessment of Chronic Illness Therapy-Ascites Index (FACIT-AI). RESULTS: Eighty-two patients were included, including 37 and 45 in the HIPEC and non-HIPEC groups, respectively. Mean OS was 10.3±3.7 (95% CI 9.5-11.2) months. Multivariable Cox proportional hazard regression suggested that PCI (HR=6.086, 95% CI 3.187-11.620, P < 0.0001) was independently associated with OS. The degree of ascites (HR=2.059, 95% CI 1.412-3.005, P < 0.0001), PCI (HR=6.504, 95% CI 2.844-14.875, P < 0.0001), and HIPEC (HR=0.328, 95% CI 0.191-0.562, P < 0.0001) were independently associated with ascites-free survival. In patients with survival >6 months, postoperative ascites-specific QoL was significantly improved after HIPEC compared with the non-HIPEC group (P < 0.001). Oxaliplatin-based HIPEC significantly increased the rates of neutropenia and peripheral neurotoxicity (both P < 0.05). CONCLUSION: These data indicate that postoperative oxaliplatin-based HIPEC might help increase ascites-free survival in CRC-PM patients after incomplete CRS or palliative surgery, with improved QoL after 6 months of follow-up.

Prevalence and Prognostic Significance of HPV in Laryngeal Squamous Cell Carcinoma in Northeast China.

BACKGROUND/AIMS: Human papillomavirus (HPV) is an etiological risk factor for a subset of head and neck squamous cell carcinomas. HPV has been proven to be a powerful prognostic biomarker for oropharyngeal cancer, but its role in the larynx has not been explored in depth. Here, we sought to evaluate the prevalence and genotype distribution of HPV in patients with laryngeal squamous cell carcinoma (LSCC) in northeast China. METHODS: HPV DNA in specimens from 211 patients diagnosed with LSCC was analyzed by the polymerase chain reaction and in situ hybridization, and p16 overexpression was evaluated by immunohistochemistry. p16 expression was scored positive if strong and diffuse nuclear and cytoplasmic staining was present in > 75% of tumor cells. RESULTS: In this study, infection with HPV and p16 expression were not absolutely consistent. Among all patients, 132 (62.6%) were positive for HPV DNA (HPV+), while 23 (10.9%) were inconsistent for HPV and p16. Multivariate analysis indicated that HPV, but not p16, is an independent prognostic factor for overall survival in LSCC. Overall survival was significantly improved in HPV+ LSCC patients compared with the HPV-negative group (hazard ratio, 0.395; 95% confidence interval, 0.185-0.843; p = 0.016). Among the 132 HPV+ patients, 28 (21.2%) were HPV-16 single infection. CONCLUSION: This study indicates that HPV DNA is a more reliable surrogate marker than p16 for the prediction of survival in patients with LSCC.

Clinicopathological and Prognostic Significance of Expression of B-Cell-Specific Moloney Murine Leukemia Virus Insertion Site 1 (BMI-1) Gene and Protein in Gastrointestinal Stromal Tumors.

BACKGROUND Gastrointestinal stromal tumor (GIST) is an uncommon visceral sarcoma that arises predominantly in the gastrointestinal tract. Since GISTs are encountered infrequently and inflexible to traditional therapy, the aim of the present study was to explore the correlation of B-cell-specific Moloney murine leukemia virus insertion site 1 (BMI-1) mRNA and BMI-1 protein levels with the clinicopathological characteristics and prognosis significance of GISTs. MATERIAL AND METHODS GIST tissues and normal tissues were collected from 156 patients who had undergone surgical treatment. RT-qPCR and immunohistochemistry were used to measure the BMI-1 mRNA and protein levels in GIST tissues and normal tissues. Univariate survival analysis was used for determination of the factors that affect prognosis of GIST patients. Cox proportional hazards model was plotted to determine the independent risk factors for prognosis of GIST patients. RESULTS The BMI-1 mRNA and protein levels in GIST tissues were higher than those in normal tissues. BMI-1 mRNA and positive protein levels were correlated with the National Institutes of Health (NIH) risk grade, tumor diameter and infiltration, and metastasis. There was a short survival period for the patients with a positive protein level and a high mRNA level of BMI-1. The site of primary tumor, tumor diameter, NIH risk grade, infiltration, and metastasis, as well as BMI-1 mRNA and protein levels were independent risk factors for prognosis of GIST patients. CONCLUSIONS Taken together, these findings suggest there might be a relationship between BMI-1 mRNA and protein levels, and clinicopathological characteristics, including NIH risk grade, tumor size as well as infiltration and metastasis, of GIST patients. In addition, BMI-1 mRNA and protein levels were identified as independent risk factors for prognosis of GIST patients.

Evidence of correlation between TGFBR2 gene expression mediated by NF-κb signaling pathways and Kawasaki disease in children.

BACKGROUND: We explored the correlation between the TGFBR2 gene that is mediated by NF-κb signaling pathways and the pathogenesis of Kawasaki disease in children. METHODS: In this study, 43 children with Kawasaki disease from April 2014 to January 2016 at our hospital were selected as the observation group, and 42 healthy children were selected as the control group. The mRNA expression levels of NF-κb gene and TGFBR2 gene in different groups were detected using fluorescence quantitative PCR. The protein expression levels of the NF-κb and TGFBR2 were detected using enzyme-linked immunosorbent assay (ELISA) in different groups. The expression levels of NF-κb and TGFBR2 in the observation group and the control group were detected using immunohistochemistry. RESULTS: Compared to the control group, the mRNA expression levels of NF-κb and TGFBR2 were 12.3 times and 27.5 times as high as those in the control group respectively and there were significant differences between the two groups (P<0.05). ELISA results showed that there were significant differences between the protein expression levels of NF-κb and TGFBR2 in the control group (0.87±0.12, 1.25±0.18 µg/L) and those in the observation group (3.27±0.17, 8.16±0.22 µg/L) (P<0.05). Western-blotting results showed that the expression levels of the NF-κB and TGFBR2 in children with Kawasaki disease were significantly higher than those in healthy subjects (P<0.05). Immunohistochemistry results showed that the positive cell rate of TGFBR2 (89.7%) was significantly higher in children with Kawasaki disease than that in healthy children (4.5%); there was significant difference between the two groups (P<0.05). CONCLUSIONS: The TGFBR2 may be involved in the pathogenesis of Kawasaki disease in children through NF-κb signaling pathways.

Stigmasterol exhibits potent antitumor effects in human gastric cancer cells mediated via inhibition of cell migration, cell cycle arrest, mitochondrial mediated apoptosis and inhibition of JAK/STAT signalling pathway.

PURPOSE: To investigate the anticancer effects of stigmasterol on the human gastric cancer cell line SNU-1, GES-1 normal cell line and to also investigate the effects on cancer cell migration, cell cycle phase distribution, apoptosis and JAK/STAT signalling pathway. METHODS: Growth inhibitory effects were evaluated by MTT assay. Apoptosis was detected by DAPI and annexin V/PI (PI) staining. Inverted phase contrast microscopy and fluorescence microscopy were used to study the effects on cell morphology. Protein expression analysis was performed by western blotting. RESULTS: The results showed that stigmasterol inhibited the growth of gastric cancer cells as observed by MTT and colony formation assay. The antiproliferative effects were due to induction of mitochondrial-mediated apoptosis as indicated by DAPI and annexin V/PI staining. This was further confirmed by Bax and Bcl-2 expression. Stigmasterol also inhibited cancer cell migration and induced G2/M cell cycle arrest in a dose-dependent manner. Furthermore, stigmasterol could also inhibit the JAK/STAT signalling pathway. Coclusion: The results of this study indicate that stigmasterol could prove beneficial in the treatment of gastric cancer and therefore further in vivo studies are required to confirm its efficacy within biosystems.

MicroRNA-125b in peripheral blood: a potential biomarker for severity and prognosis of children with viral encephalitis.

This study aims to evaluate the effect of peripheral blood miR-125b expression on severity and prognosis in children with viral encephalitis (VE). Children with VE (severe and mild groups) were grouped into VE group, and 40 healthy children as control group. Plasma RNA was extracted, and real-time quantitative PCR was conducted to detect miR-125b relative expression. Associations of miR-125b expression with clinical characteristics and prognosis of VE children were analyzed. Area under ROC curve (AUC) was calculated to evaluate the accuracy of the prognostic value of miR-125b. Univariate analysis and logistic regression analysis were performed to analyze risk factors of the prognoses of VE children. The plasma miR-125b expression was higher in the VE group than in the control group and higher in the severe group than the mild group. MiR-125b expression was associated with status convulsion, hemiplegia, multiple organ injuries, and stress hyperglycemia in VE children. Patients with poor prognosis exhibited higher miR-125b expression than those with good prognosis, and the rate of high miR-125b expression of the patients with poor prognosis (64.10%, 25/39) was higher than that in those with good prognosis (28.92%, 24/83). The AUC of miR-125b expression to predict prognosis of VE children was 0.833. When the cutoff value was 1.715, the diagnostic sensitivity (87.2%), specificity (71.1%), and accuracy (76.2%) were the highest. Status convulsion, stress hyperglycemia, and miR-125b were considered as risk factors for poor prognosis in VE children. Peripheral blood miR-125b expression may be correlated with the severity and prognosis of VE in children.

[Small-cell neuroendocrine carcinoma of the stomach: a clinical and prognostic analysis of 21 cases].

OBJECTIVE: To investigate and improve the diagnosis and management of small-cell neuroendocrine carcinoma of the stomach (SCNECS). METHODS: The clinicopathological information and survival data of 21 cases of SCNECS treated in our hospital from January 2003 to December 2012 were analyzed retrospectively. RESULTS: The median survival time of the 21 cases was (12.1±1.6) months. The 1-year overall survival rate of the patients was 33.3%. Univariate analysis showed that the risk factors of survival were tumor size, lymph node status, tumor stage, treatment and radical operation or not (P<0.05 for all). Multivariate analysis indicated that independent risk factors were tumor size ≥4.6 cm, lymph node metastasis and tumor stage III/IV (P<0.05 for all). Radical operation and comprehensive treatment (surgery + postoperative chemotherapy) were independent protective factors (all P<0.05). CONCLUSIONS: SCNECS is a rare malignant tumor with early metastasis and poor prognosis. Tumor size, stage, lymph node status, and treatment have potential impact on the prognosis. Comprehensive treatment based on radical operation may improve the survival of SCNECS patients.

Small RNAs as important regulators for the hybrid vigour of super-hybrid rice.

Heterosis is an important biological phenomenon; however, the role of small RNA (sRNA) in heterosis of hybrid rice remains poorly described. Here, we performed sRNA profiling of F1 super-hybrid rice LYP9 and its parents using high-throughput sequencing technology, and identified 355 distinct mature microRNAs and trans-acting small interfering RNAs, 69 of which were differentially expressed sRNAs (DES) between the hybrid and the mid-parental value. Among these, 34 DES were predicted to target 176 transcripts, of which 112 encoded 94 transcription factors. Further analysis showed that 67.6% of DES expression levels were negatively correlated with their target mRNAs either in flag leaves or panicles. The target genes of DES were significantly enriched in some important biological processes, including the auxin signalling pathway, in which existed a regulatory network mediated by DES and their targets, closely associated with plant growth and development. Overall, 20.8% of DES and their target genes were significantly enriched in quantitative trait loci of small intervals related to important rice agronomic traits including growth vigour, grain yield, and plant architecture, suggesting that the interaction between sRNAs and their targets contributes to the heterotic phenotypes of hybrid rice. Our findings revealed that sRNAs might play important roles in hybrid vigour of super-hybrid rice by regulating their target genes, especially in controlling the auxin signalling pathway. The above finding provides a novel insight into the molecular mechanism of heterosis.

The preoperative neutrophil-lymphocyte ratio predicts recurrence and survival among patients undergoing R0 resections of adenocarcinomas of the esophagogastric junction.

BACKGROUND AND OBJECTIVES: Elevated preoperative neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) predict survival rates among patients with several types of cancer. The current study sought to clarify whether NLR and PLR are clinically useful independent prognostic indicators of adenocarcinomas of the esophagogastric junction (AEG) among patients undergoing curative resections (i.e., R0 resections). METHODS: A total of 327 patients who underwent R0 resections for AEG were enrolled in the study. Data concerning demographic parameters, laboratory analyses, histopathology, and survival time were collected and analyzed. RESULTS: A total of 123 patients (37.6%) had elevated preoperative NLR (≥ 5). The median follow-up duration was 24.7 months (range = 2-39 months). NLR was significantly related to histology (P = 0.035), pTNM stage (P < 0.0001) and tumor recurrence (P = 0.022). Univariate analyses revealed that NLR were significantly associated with disease-free survival (DFS) and overall survival (OS; both P < 0.0001). Multivariable analyses revealed that elevated NLR independently predicted poorer DFS (hazard ratio [HR] = 2.551, P < 0.0001) and OS (HR = 2.743, P < 0.0001). However, PLR did not significantly predict DFS or OS. CONCLUSION: The present study indicates that elevated preoperative NLR (≥ 5) is a useful marker of tumor recurrence and independently predicts poorer disease-free and overall survival among patients with AEG undergoing R0 resections.

Clinical observation of hypofibrinogenemia induced by the treatment of tocilizumab in rheumatic diseases and exploration of risk factor for hypofibrinogenemia.

OBJECTIVE: The objective of this study was to analyze the changes in plasma fibrinogen (FIB) levels during tocilizumab (TCZ) treatment in patients with rheumatic diseases, to clarify the incidence of hypofibrinogenemia and its possible risk factors, and to establish a nomogram model for predicting the probability of hypofibrinogenemia in rheumatoid arthritis (RA) patients treated with TCZ. METHODS: Clinical data of patients treated with TCZ at the Department of Rheumatology and Immunology, the First Affiliated Hospital of Xi'an Jiaotong University from January 2014 to October 2021 were retrospectively analyzed to observe the incidence of hypofibrinogenemia in several rheumatic diseases at different time points. The risk factor of hypofibrinogenemia in RA patients treated with TCZ was determined by using Cox regression analysis. Based on the results of Cox regression analysis, a nomogram for predicting the probability of hypofibrinogenemia in rheumatoid arthritis (RA) patients treated with TCZ was established and validated through RStudio software. RESULTS: A total of 83 TCZ-treated patients were enrolled in this study, and 32 (38.55%) patients developed hypofibrinogenemia during TCZ treatment. There were 8 males and 24 females in the FIB-reduced group, with an average age of 44.88 ± 18.39 years. Hypofibrinogenemia was most common in TCZ-treated patients with takayasu arteritis (TA) and RA. Hypofibrinogenemia typically occured within 3 months after TCZ treatment. In RA patients treated with TCZ, platelet distribution width, parathyroid hormone, bone mineral density, tender joint count, and swollen joint count were independent risk factors for the occurrence of hypofibrinogenemia. The nomogram based on the above risk factors could effectively predict the probability of hypofibrinogenemia in RA patients receiving TCZ. CONCLUSION: Although bleeding symptoms were not observed in this study, the incidence of hypofibrinogenemia remained high after TCZ treatment, usually occurring within 3 months of treatment. Therefore, it is necessary to monitor FIB levels during TCZ treatment. In addition, clinicians can use the nomogram model developed from this study to predict the incidence of hypofibrinogenemia after TCZ treatment in RA patients. Key Points • Hypofibrinogenemia often occurs during TCZ treatment for rheumatic diseases. • PDW, PTH, BMD, tender joint count, and swollen joint count are risk factors for the occurrence of hypofibrinogenemia. • It is necessary to monitor FIB levels during TCZ treatment to avoid bleeding tendency.

Electron stochastic acceleration in laboratory-produced kinetic turbulent plasmas.

The origin of energetic charged particles in universe remains an unresolved issue. Astronomical observations combined with simulations have provided insights into particle acceleration mechanisms, including magnetic reconnection acceleration, shock acceleration, and stochastic acceleration. Recent experiments have also confirmed that electrons can be accelerated through processes such as magnetic reconnection and collisionless shock formation. However, laboratory identifying stochastic acceleration as a feasible mechanism is still a challenge, particularly in the creation of collision-free turbulent plasmas. Here, we present experimental results demonstrating kinetic turbulence with a typical spectrum k-2.9 originating from Weibel instability. Energetic electrons exhibiting a power-law distribution are clearly observed. Simulations further reveal that thermal electrons undergo stochastic acceleration through collisions with multiple magnetic islands-like structures within the turbulent region. This study sheds light on a critical transition period during supernova explosion, where kinetic turbulences originating from Weibel instability emerge prior to collisionless shock formation. Our results suggest that electrons undergo stochastic acceleration during this transition phase.

Efficient energy transport throughout conical implosions.

The double-cone ignition (DCI) scheme has been proposed as one of the alternative approaches to inertial confinement fusion, based on direct-drive and fast-ignition, in order to reduce the requirement for the driver energy. To evaluate the conical implosion energetics from the laser beams to the plasma flows, a series of experiments have been systematically conducted. The results indicate that 89%-96% of the laser energy was absorbed by the target, with moderate stimulated Raman scatterings. Here 2%-6% of the laser energy was coupled into the plasma jets ejected from the cone tips, which was mainly restricted by the mass reductions during the implosions inside the cones. The supersonic dense jets with a Mach number of 4 were obtained, which is favorable for forming a high-density, nondegenerated plasma core after the head-on collisions. These findings show encouraging results in terms of energy transport of the conical implosions in the DCI scheme.

Production of antibodies and antibody fragments containing non-natural amino acids in Escherichia coli.

Therapeutic bioconjugates are emerging as an essential tool to combat human disease. Site-specific conjugation technologies are widely recognized as the optimal approach for producing homogeneous drug products. Non-natural amino acid (nnAA) incorporation allows the introduction of bioconjugation handles at genetically defined locations. Escherichia coli (E. coli) is a facile host for therapeutic nnAA protein synthesis because it can stably replicate plasmids encoding genes for product and nnAA incorporation. Here, we demonstrate that by engineering E. coli to incorporate high levels of nnAAs, it is feasible to produce nnAA-containing antibody fragments and full-length immunoglobulin Gs (IgGs) in the cytoplasm of E. coli. Using high-density fermentation, it was possible to produce both of these types of molecules with site-specifically incorporated nnAAs at titers > 1 g/L. We anticipate this strategy will help simplify the production and manufacture of promising antibody therapeutics.

Expression of KIAA0101 protein is associated with poor survival of esophageal cancer patients and resistance to cisplatin treatment in vitro.

The KIAA0101 protein is overexpressed in various human cancers, including esophageal cancer (EC). This study assessed the association of KIAA0101 protein with prognosis and resistance to chemotherapy in EC patients and then explored the role of KIAA0101 in EC cells in vitro. A total of 228 EC patients participated in the study. Tissue samples were collected for immunohistochemical analysis of KIAA0101 expression in tumor and normal tissues for association with clinicopathological and survival data. KIAA0101 cDNA or shRNA were transfected into EC cells for assessment of tumor cell viability, sensitivity to cisplatin treatment, and gene expression. Array-based comparative genomic hybridization (aCGH) was used to detect the changed copy-number alterations in cell lines expressing different levels of KIAA0101. Expression of KIAA0101 protein was upregulated in EC tissues, which was associated with pTNM stage, resistance to chemotherapy, tumor recurrence, and poor survival of EC patients. In vitro experiments showed that expression of KIAA0101 enhanced cell proliferation and upregulated cyclins A and B expression, leading to a reduced G1 phase of the cell cycle. KIAA0101 also induced resistance of EC Eca-109 and TE-1 cell lines to cisplatin treatment through a decrease in apoptosis. The aCGH data showed that levels of KIAA0101 expression altered chromosome stability, affecting genes that are associated with cancer progression. In conclusion, upregulated KIAA0101 expression is associated with EC progression, resistance to chemotherapy, and poor survival of the patients.

Elevated KIAA0101 expression is a marker of recurrence in human gastric cancer.

Gastric cancer (GC) is one of the most common malignant tumors with a high rate of recurrence, which results in surgery being unsuccessful. Therefore, it is important to find the reason for the surgery failing. The purpose of the present study was to investigate a factor related to recurrence. Expression of KIAA0101 was assessed in 61 paired human primary GC and non-cancerous gastric tissue using immunohistochemistry. After surgery, all 61 patients were followed regularly for more than 24 months or until death to analyze the 2-year survival rate and recurrence. After suppressing KIAA0101 by RNA interference in human GC cell lines, the cell viability was detected using MTT. We are first to find that KIAA0101 was elevated in GC tissues compared with paired non-cancerous gastric tissues. Immunohistochemical staining also revealed the predominant nuclear localization of KIAA0101 protein. Despite these findings, GC patients with elevated KIAA0101 expression levels exhibited a high recurrence and subsequently poor prognosis in the survival study. Also, cell viability was significantly inhibited after suppressing KIAA0101 in GC cells, suggesting that KIAA0101 might promote cancer cell proliferation. KIAA0101 is increased in human GC and is a marker of recurrence.