Proteome trait regulation of marine Synechococcus elemental stoichiometry under global change.

Recent studies have demonstrated regional differences in marine ecosystem C:N:P with implications for carbon and nutrient cycles. Due to strong co-variance, temperature and nutrient stress explain variability in C:N:P equally well. A reductionistic approach can link changes in individual environmental drivers with changes in biochemical traits and cell C:N:P. Thus, we quantified effects of temperature and nutrient stress on Synechococcus chemistry using laboratory chemostats, chemical analyses, and data-independent acquisition mass spectrometry proteomics. Nutrient supply accounted for most C:N:Pcell variability and induced tradeoffs between nutrient acquisition and ribosomal proteins. High temperature prompted heat-shock, whereas thermal effects via the "translation-compensation hypothesis" were only seen under P-stress. A Nonparametric Bayesian Local Clustering algorithm suggested that changes in lipopolysaccharides, peptidoglycans, and C-rich compatible solutes may also contribute to C:N:P regulation. Physiological responses match field-based trends in ecosystem stoichiometry and suggest a hierarchical environmental regulation of current and future ocean C:N:P.

GINS2 promotes the progression of human HNSCC by altering RRM2 expression.

INTRODUCTION: GINS2 exerts a carcinogenic effect in multiple human malignancies, while it is still unclear that the potential roles and underlying mechanisms of GINS2 in HNSCC. METHODS: TCGA database was used to screen out genes with significant differences in expression in HNSCC. Immunohistochemistry and qRT-PCR were used to measure the expression of GINS2 in HNSCC tissues and cells. GINS2 was detected by qRT-PCR or western blot after knockdown or overexpression. Celigo cell counting, MTT, colony formation, and flow cytometric assay were used to check the ability of proliferation and apoptosis. Bioinformatics and microarray were used to screen out the downstream genes of GINS2. RESULTS: GINS2 in HNSCC tissues and cells was up-regulated, which was correlated with poor prognosis. GINS2 gene expression was successfully inhibited and overexpressed in HNSCC cells. Knockdown of GINS2 could inhibit proliferation and increase apoptosis of cells. Meanwhile, overexpression of GINS2 could enhance cell proliferation and colony formation. Knockdown of RRM2 may inhibit HNSCC cell proliferation, while overexpression of RRM2 rescued the effect of reducing GINS2 expression. CONCLUSION: Our study reported the role of GINS2 in HNSCC for the first time. The results demonstrated that in HNSCC cells, GINS2 promoted proliferation and inhibited apoptosis via altering RRM2 expression. Therefore, GINS2 might play a carcinogen in HNSCC, and become a specific promising therapeutic target.

Sp1 Regulates the M1 Polarization of Microglia Through the HuR/NF-κB Axis after Spinal Cord Injury.

The M1 polarization of microglia, followed by the production of pro-inflammatory mediators, hinders functional recovery after spinal cord injury (SCI). Our previous study has illuminated that specificity protein 1 (Sp1) expression is increased following SCI, whereas the function and regulatory mechanism of Sp1 during M1 polarization of microglia following SCI remain unknown. RNA binding protein, HuR, has been shown to be up-regulated in the injured spinal cord through analysis of the GEO database. Further investigation using Chip-Atlas data suggests a binding between Sp1 and HuR. Emerging evidence indicates that HuR plays a pivotal role in neuroinflammation after SCI. In this research, Sp1 and HuR levels in mice with SCI and BV2 cells treated with lipopolysaccharide (LPS) was determined by using quantitative real-time polymerase chain reaction and Western blotting techniques. A series of in vitro assays were performed to investigate the function of Sp1 during M1 polarization of microglia. The association between Sp1 and its target gene HuR was confirmed through gene transfection and luciferase reporter assay. Enhanced expression of HuR was observed in both SCI mice and LPS-treated BV2 cells, while Sp1 knockdown restrained M1 polarization of microglia and its associated inflammation by inhibiting the NF-κB signaling pathway. Silencing Sp1 also suppressed microglia activation and its mediated inflammatory response, which could be reversed by overexpression of HuR. In conclusion, silencing Sp1 restrains M1 polarization of microglia through the HuR/NF-κB axis, leading to neuroprotection, and thus promotes functional restoration following SCI.

A Novel CNN-BiLSTM Ensemble Model With Attention Mechanism for Sit-to-Stand Phase Identification Using Wearable Inertial Sensors.

Sit-to-stand transition phase identification is vital in the control of a wearable exoskeleton robot for assisting patients to stand stably. In this study, we aim to propose a method for segmenting and identifying the sit-to-stand phase using two inertial sensors. First, we defined the sit-to-stand transition into five phases, namely, the initial sitting phase, the flexion momentum phase, the momentum transfer phase, the extension phase, and the stable standing phase based on the preprocessed acceleration and angular velocity data. We then employed a threshold method to recognize the initial sitting and the stable standing phases. Finally, we designed a novel CNN-BiLSTM-Attention algorithm to identify the three transition phases, namely, the flexion momentum phase, the momentum transfer phase, and the extension phase. Fifteen subjects were recruited to perform sit-to-stand transition experiments under a specific paradigm. A combination of the acceleration and angular velocity data features for the sit-to-stand transition phase identification were validated for the model performance improvements. The integration of the CNN, Bi-LSTM, and Attention modules demonstrated the reasonableness of the proposed algorithms. The experimental results showed that the proposed CNN-BiLSTM-Attention algorithm achieved the highest average classification accuracy of 99.5% for all five phases when compared to both traditional machine learning algorithms and deep learning algorithms on our customized dataset (STS-PD). The proposed sit-to-stand phase recognition algorithm could serve as a foundation for the control of wearable exoskeletons and is important for the further development of intelligent wearable exoskeleton rehabilitation robots.

Mining the candidate genes of rice panicle traits via a genome-wide association study.

Panicle traits are important for improving the panicle architecture and grain yield of rice. Therefore, we performed a genome-wide association study (GWAS) to analyze and determine the genetic determinants of five panicle traits. A total of 1.29 million single nucleotide polymorphism (SNP) loci were detected in 162 rice materials. We carried out a GWAS of panicle length (PL), total grain number per panicle (TGP), filled grain number per panicle (FGP), seed setting rate (SSR) and grain weight per panicle (GWP) in 2019, 2020 and 2021. Four quantitative trait loci (QTLs) for PL were detected on chromosomes 1, 6, and 9; one QTL for TGP, FGP, and GWP was detected on chromosome 4; two QTLs for FGP were detected on chromosomes 4 and 7; and one QTL for SSR was detected on chromosome 1. These QTLs were detected via a general linear model (GLM) and mixed linear model (MLM) in both years of the study period. In this study, the genomic best linear unbiased prediction (BLUP) method was used to verify the accuracy of the GWAS results. There are nine QTLs were both detected by the multi-environment GWAS method and the BLUP method. Moreover, further analysis revealed that three candidate genes, LOC_Os01g43700, LOC_Os09g25784, and LOC_Os04g47890, may be significantly related to panicle traits of rice. Haplotype analysis indicated that LOC_Os01g43700 and LOC_Os09g25784 are highly associated with PL and that LOC_Os04g47890 is highly associated with TGP, FGP, and GWP. Our results offer essential genetic information for the molecular improvement of panicle traits. The identified candidate genes and elite haplotypes could be used in marker-assisted selection to improve rice yield through pyramid breeding.

Diagnosis of atrial fibrillation based on unsupervised domain adaptation.

In recent years, the proportion of the elderly in the society is continuously increasing. Cardiovascular disease is a big problem that puzzles the health of the elderly. Among them, atrial fibrillation is one of the most common arrhythmia diseases in recent years, which poses a great threat to human life safety. At the same time, deep learning has become a powerful tool for medical and healthcare applications due to its high accuracy and fast detection speed. The diagnosis of atrial fibrillation is based on electrocardiogram, ECG) timing signals. At present, the scale of the open ECG data set is limited, and a large amount of labeled ECG data is needed to build a high-precision diagnostic model. In this study, a two-channel network model and a feature queue technique are proposed. A high-quality classification diagnosis model of atrial fibrillation is obtained by unsupervised domain adaptive technique, which uses a small amount of labeled data and a large amount of unlabeled data for training. The research content of this paper includes the following aspects: 1) Build a dual-channel network model, which can analyze ECG signals from different feature dimensions. At the same time, the dual-channel output also improves the reliability of the model's pseudo-label in the adaptive training stage and the accuracy of the output in the testing stage. 2) Innovative feature queue technology including global centroid is proposed to participate in the process of domain discrepancy metric calculation, which can use a small amount of labeled data and a large amount of unlabeled data to achieve a more stable and rapid update of the network. 3) Improved and innovated the domain discrepancy metric function, and introduced an evaluation formula for the credibility of false labels to improve the learning efficiency of unlabeled data. Finally, the experimental results show that the proposed two-channel network model and the feature queue technique with global centroid can achieve a high generalization and high precision depth network model by training with a small amount of labeled data and a large amount of unlabeled data. 4) The proposed model achieved a precision of 95.12%, a recall of 95.36%, an accuracy of 98.05%, and an F1 score of 95.23% in the MIT-BIH Arrhythmia Database. In the MIT-BIH Atrial Fibrillation Database, the model achieved a precision of 98.9%, a recall of 99.03%, an accuracy of 99.13%, and an F1 score of 99.08%.

LAX1, functioning with MADS-box genes, determines normal palea development in rice.

Normal floral organ development in rice is necessary for grain formation. Many MADS-box family genes that belong to ABCDE model have been widely implicated in rice flower development. The LAX1 allele encodes a plant-specific basic helix-loop-helix (bHLH) transcription factor, which is the main regulator of axillary meristem formation in rice. However, the molecular mechanisms of LAX1 allele together with MADS-box family genes underlying palea development have not been reported. We found a short palea mutant plant in a population of indica rice variety 9311 treated with cobalt 60. We report the map-based cloning and characterization of lax1-7, identified as a new mutant allele of the LAX1 locus, and the role of its wild-type allele LAX1 in rice palea development. Through complementary experiments, combined with genetic and molecular biological analyses, the function of the LAX1 allele was determined. We showed that LAX1 allele is expressed specifically in young spikelets and encodes a nucleus-localized protein. In vitro and in vivo experiments revealed that the LAX1 protein physically interacts with OsMADS1, OsMADS6 and OsMADS7. The LAX1 allele is pleiotropic for the maintenance of rice palea identity via cooperation with MADS-box genes and other traits, including axillary meristem initiation, days to heading, plant height, panicle length and spikelet fertility.

Mining Salt Tolerance SNP Loci and Prediction of Candidate Genes in the Rice Bud Stage by Genome-Wide Association Analysis.

Mining salt tolerance genes is significant for breeding high-quality salt-tolerant rice varieties in order to improve the utilization of saline-alkaline land. In this study, 173 rice accessions were measured for their germination potential (GP), germination rate (GR), seedling length (SL), root length (RL), germination potential relative to salt damage rate (GPR), germination rate relative to salt damage rate (GRR), seedling length relative to salt damage rate (SLR), relative salt damage rate at the germination stage (RSD) and comprehensive relative salt damage rate in the early seedling stage (CRS) under normal and salt stress conditions. Genome-wide association analysis was performed with 1,322,884 high-quality SNPs obtained by resequencing. Eight quantitative trait loci (QTLs) related to salt tolerance traits at the germination stage were detected in 2020 and 2021. They were related to the GPR (qGPR2) and SLR (qSLR9), which were newly discovered in this study. Three genes were predicted as salt tolerance candidate genes: LOC_Os02g40664, LOC_Os02g40810, and LOC_Os09g28310. At present, marker-assisted selection (MAS) and gene-edited breeding are becoming more widespread. Our discovery of candidate genes provides a reference for research in this field. The elite alleles identified in this study may provide a molecular basis for cultivating salt-tolerant rice varieties.

LINC01376 promotes nasopharyngeal carcinoma tumorigenesis by competitively binding to the SP1/miR-4757/IGF1 axis.

The long non-coding RNA (lncRNA)-microRNA (miRNA) interaction network plays a crucial part in the pathogenesis of nasopharyngeal carcinoma (NPC). Here, we discovered a relationship between LINC01376 and miR-4757 in NPC tumor development. First, LINC01376 was abnormally overexpressed in NPC tissues and cells, and its elevated expression was associated with advanced clinical stage and shorter distant metastasis-free survival time. Moreover, biological experiments showed that LINC01376 facilitated the proliferative, invasive, and migratory abilities of NPC cells in vitro and in vivo. Mechanistically, bioinformatics and RT-qPCR assays revealed that LINC01376 knockdown upregulated the expression level of downstream miR-4757, including miR-4757 primary transcript (pri-miR-4757) and mature miR-4757. Furthermore, LINC01376 competitively sponged the transcription factor SP1 and reduced its enrichment in the upstream promoter region of miR-4757 to repress miR-4757 expression. Finally, insulin-like growth factor 1(IGF1) was identified as the target of miR-4757. Rescue experiments indicated that LINC01376 accelerated NPC cell proliferation, migration, and invasion through the miR-4757-5p/IGF1 axis. In conclusion, the SP1/miR-4757/IGF1 axis, which is regulated by LINC01376 in NPC deterioration and metastasis, is expected to provide new insights into the molecular mechanism of NPC carcinogenesis.

Nitric oxide releasing poly(vinyl alcohol)/S-nitrosated keratin film as a potential vascular graft.

Nitric oxide (NO) releasing vascular graft is promising due to its merits of thromboembolism reduction and endothelialization promotion. In this study, keratin-based NO donor of S-nitrosated keratin (KSNO) was blended with poly(vinyl alcohol) (PVA) and further crosslinked with sodium trimetaphosphate (STMP) to afford PVA/KSNO biocomposite films. These films could release NO sustainably for up to 10 days, resulting in the promotion of HUVECs growth and the inhibition of HUASMCs growth. In addition, these films displayed good blood compatibility and antibacterial activity. Taken together, these films have potential applications in vascular grafts.

Tannic Acid-Assisted Immobilization of Copper(II), Carboxybetaine, and Argatroban on Poly(ethylene terephthalate) Mats for Synergistic Improvement of Blood Compatibility and Endothelialization.

Due to thrombosis and intimal hyperplasia, small-diameter vascular grafts have poor long-term patency. A combination strategy based on nitric oxide (NO) and anticoagulants has the potential to address those issues. In this study, poly(ethylene terephthalate) (PET) mats were prepared by electrospinning and coated with tannic acid (TA)/copper ion complexes. The chelated copper ions endowed the mats with sustained NO generation by catalytic decomposition of endogenous S-nitrosothiol. Subsequently, zwitterionic carboxybetaine acrylate (CBA) and argatroban (AG) were immobilized on the mats. The introduced AG and CBA had synergistic effects on the improvement of blood compatibility, resulting in reduced platelet adhesion and prolonged blood clotting time. The biocomposite mats selectively promoted the proliferation and migration of human umbilical vein endothelial cells while inhibiting the proliferation and migration of human umbilical arterial smooth muscle cells under physiological conditions. In addition, the prepared mats exhibited antibacterial activity against Escherichia coli and Staphylococcus aureus. Collectively, the prepared mats hold great promise as artificial small-diameter vascular grafts.

Neoadjuvant sintilimab and chemotherapy in patients with resectable esophageal squamous cell carcinoma: A prospective, single-arm, phase 2 trial.

Background: Immunotherapy (Programmed cell death 1 blockade) has entered the ranks of advanced esophageal cancer first-line treatment; however, little is known about the efficacy of PD-1 inhibitor as neoadjuvant therapy in resectable esophageal squamous cell carcinoma (ESCC). We aim to evaluate the activity and safety of the neoadjuvant sintilimab combined with chemotherapy in the treatment of resectable thoracic ESCC. Methods: The enrolled patients with resectable (clinical stage II to IVA) ESCC received neoadjuvant sintilimab injection (200 mg/time, day 1), paclitaxel liposomes (135 mg/m2, day 1), and carboplatin (area under curve of 5 mg/mL/min, day 1) every 21 days for 2 cycles, and esophagectomy was performed within 3-6 weeks after the 2 cycles of treatment. The primary endpoint of the study was the pathological complete response (PCR) rate. Results: From July 2019 to March 2021, a total of 47 patients were enrolled, of which 33 patients (70.2%) had clinical stage III disease. All patients completed the full two-cycle treatment and forty-five patients received radical surgery, including 44 (97.8%) R0 resections. Ten (22.2%) of 45 patients had a PCR, and the major pathological response (MPR) rate was 44.4% (20/45). The grade 3-4 treatment-related adverse events (TRAEs) were mainly neutropenia (6 of 47,12.8%) and leucopenia (8 of 47,17.0%). One (2.1%) patient occurred postoperative immune-associated encephalitis. No delays in surgery were observed. Conclusions: sintilimab combined with paclitaxel liposome and carboplatin, as demonstrated in this phase II trial to exhibit a relatively high PCR rate and acceptable safety, warrants additional investigation in resectable ESCC. Trial Registration: http://www.chictr.org.cn/, ChiCTR1900026593.

Postoperative Concurrent Chemoradiotherapy for Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma: A Phase II Clinical Trial.

Background: This study aims to investigate the efficacy and safety of postoperative intensity-modulated radiotherapy (IMRT) covering partial regional lymph node areas combined with chemotherapy for locally advanced thoracic esophageal squamous cell carcinoma patients. Methods: This was a single-center, single-arm phase II clinical trial that began in 2014. Patients who underwent radical transthoracic resection within 3 months and were histologically confirmed esophageal squamous cell carcinoma (pT3-4 or N+, M0 determined according to AJCC Guidelines, Edition 7) were recruited. Postoperative radiotherapy was performed with a total dose of 50.4Gy in 28 fractions using IMRT. Clinical target volumes (CTVs) included tumor bed, anastomosis, bilateral supraclavicular region, and superior mediastinal lymph nodes. Synchronous chemotherapy for 2 cycles (paclitaxel 150mg/m2, day1; Cisplatin 25mg/m2, day1-3; every 4 weeks), followed by 2 cycles of consolidation chemotherapy with the same regimen. The primary endpoint was the 2-year local control rate, and the secondary endpoints were overall survival (OS) and adverse events (AEs). Results: A total of 75 eligible patients were included from 2014 to 2017. The 2-year LRFS rate, as the primary endpoint, was 73.3%. The 1-year and 3-year OS rates were 88.0% and 68.0%, respectively. Local recurrence occurred in 13/75 (17.4%) patients, of which 2.7% (2/75) were extra-target lymph nodes. Grade 4 adverse events reported in this study included 10 cases (13.3%) of neutropenia, 1 case (1.3%) of anemia, and 2 cases (2.7%) of thrombocytopenia, without toxic-related deaths. Almost all (96%) patients completed the entire postoperative radiotherapy course, and 62 (82.7%) patients completed at least 2 cycles of chemotherapy. Conclusion: Postoperative IMRT (clinical target volume including tumor bed, anastomosis, bilateral supraclavicular region, and superior mediastinal lymph nodes) combined with synchronous chemotherapy in patients with locally advanced thoracic esophageal squamous cell carcinoma was well tolerated, with a high local control rate and a low probability of recurrence outside the irradiation field. Clinical Trial Registration: https://clinicaltrials.gov/ChiCTR1900022689.

The lncRNA ZNF667-AS1 Inhibits Propagation, Invasion, and Angiogenesis of Gastric Cancer by Silencing the Expression of N-Cadherin and VEGFA.

Purpose: Gastric cancer is one of the most common malignancies with high mortality worldwide. It is known that long noncoding RNAs (lncRNAs) play important roles in the pathogenesis of gastric cancer. This study investigates the role of lncRNA ZNF667-AS1 in gastric cancer cells. Methods: We have applied real-time quantitative PCR (qPCR) to study the levels of ZNF667-AS1 in gastric cancer biopsies and cell lines. The effects of ZNF667-AS1 on the propagation, clonogenicity, metastasis, and angiogenesis of gastric cancer cells were evaluated by calorimetry, colony formation, cell migration, and angiogenesis assays. Western blotting was used to identify the levels of proteins involved in cancer invasion and angiogenesis signaling pathways. Result: It was found that lncRNA ZNF667-AS1 was downregulated in gastric cancer biopsies. Overexpression of ZNF667-AS1 reduced the propagation, migration, and angiogenesis of gastric cancer cells. Molecular mechanism studies displayed that the high level of lncRNA ZNF667-AS1 promoted the expression of E-cadherin and inhibited the expression of N-cadherin and VEGFA, leading to the inhibition of the proliferation, migration, and angiogenesis of gastric cancer cells. Conclusion: As a tumor suppressor gene, lncRNA ZNF667-AS1 significantly hinders the propagation, metastasis, and angiogenesis of gastric cancer cells by promoting the expression of E-cadherin and inhibiting the expression of N-cadherin and VEGFA. Therefore, lncRNA ZNF667-AS1 could play a synergistic therapeutic role by targeting tumor cells and vascular endothelial cells, which represents a new therapeutic scheme for novel therapeutics of gastric cancer.

Paclitaxel and cisplatin combined with concurrent involved-field irradiation in definitive chemoradiotherapy for locally advanced esophageal squamous cell carcinoma: a phase II clinical trial.

PURPOSE: This trial aims to explore the efficacy and safety of involved-field irradiation (IFI) combined with paclitaxel plus cisplatin as concurrent chemoradiotherapy for locally advanced esophageal squamous cell carcinoma (ESCC), under the premise of intensity-modulated radiotherapy (IMRT). METHODS: Enrolled patients with locally advanced ESCC were treated with definitive concurrent chemoradiotherapy. IFI was administered adopting IMRT and the total dose was 61.2 Gy delivered in 34 fractions. On the first day of radiotherapy, the patients were treated with paclitaxel and cisplatin one cycle per month for 2 cycles followed by the same regimen in consolidation chemotherapy for two cycles. The primary endpoint of the study was the 2-year locoregional recurrence-free survival (LRFS) rate, and secondary endpoints included overall survival (OS), progression-free survival (PFS), and safety. RESULTS: Between January 2018 and September 2020, 108 patients participated in the trial. 78.7% (85/108) of patients completed all 4 cycles of chemotherapy. The median follow-up of the surviving patients was 33.9 months (interquartile range, 29.2-41.1). The 2-year LRFS rate, as the primary endpoint, was 64.2%. In addition, the median PFS was 39.2 months, and 1-year and 3-year OS rates of 88.0% and 63.3%, respectively. Among the patients, out-of-field regional failure was seen in only 7 (6.5%) patients. Neutropenia grade 3 and 4 occurred in 21.3% and 37.0% of the patients, respectively. CONCLUSIONS: IFI using IMRT combined with paclitaxel and cisplatin concurrent chemotherapy for locally advanced ESCC yields encouraging local control and overall survival, but high hematological toxicity. Trial registration Clinical Trials ChiCTR1800017039.

CircFOXM1 acts as a ceRNA to upregulate SMAD2 and promote the progression of nasopharyngeal carcinoma.

BACKGROUND: In recent years, the development of high-throughput sequencing technology has promoted the rapid development of circRNA-related research. Studies have found that circRNA plays a key role in a variety of tumors, but few people study the role of circRNA in nasopharyngeal carcinoma. Under comprehensive treatments, the 5-year survival rate can reach about 70%, but some patients still have distant metastases or recurrences after treatment. Therefore, it is very important to study the molecular mechanisms of the proliferation and invasion of nasopharyngeal carcinoma. METHODS: QRT-PCR was applied to detect the relative expression level of circFOXM1 in NPC and nasopharyngeal epithelial cell lines. We knocked down circFOXM1 and studied the influence of circFOXM1 on NPC cells. Nuclear and cytoplasmic RNA isolation experiments, fluorescence in situ hybridization (FISH), bioinformatics analysis, the dual-luciferase reporter experiment, Western Blot, and other experiments were conducted to verify the relationships among circFOXM1, miR-136-5p, and SMAD2. We collected clinical NPC samples to prove the effect of circFOXM1 on the prognosis and treatment of NPC. RESULTS: In this study, we found that circFOXM1 is highly expressed in nasopharyngeal carcinoma tissue cells compared with adjacent normal tissues and is related to the staging of nasopharyngeal carcinoma. High expression of circFOXM1 indicates a poor prognosis for nasopharyngeal carcinoma. Knockdown of CircFOXM1 inhibited the proliferation and invasion of nasopharyngeal carcinoma cells. CONCLUSION: CircFOXM1 promotes the malignant proliferation of nasopharyngeal carcinoma cells by regulating the miR-136-5p-SMAD2 axis.

MYC-activated RNA N6-methyladenosine reader IGF2BP3 promotes cell proliferation and metastasis in nasopharyngeal carcinoma.

N6-Methyladenosine (m6A) modification is the most abundant RNA modification in eukaryotic cells. IGF2BP3, a well-known m6A reader, is deregulated in many cancers, but its role in nasopharyngeal carcinoma (NPC) remains unclear. In this work, IGF2BP3 was upregulated in NPC tissues and cells. The high level of IGF2BP3 was positively related to late clinical stages, node metastasis, and poor outcomes. Moreover, IGF2BP3 accelerated NPC cell tumor progression and metastasis in vitro and vivo. Upstream mechanism analyses indicated that the high expression of IGF2BP3 in head and neck tumors was mainly due to mRNA level amplification. Luciferase assay and chromatin immunoprecipitation assay (CHIP) depicted that MYC was effectively bound to the promoter of IGF2BP3, thereby improving its transcriptional activity. Results also showed that IGF2BP3 was not only positively correlated with KPNA2 expression but also modulated the expression of KPNA2. m6A RNA immunoprecipitation (MeRIP) and RNA stability experiments verified that silencing IGF2BP3 significantly inhibited the m6A modification level of KPNA2, thereby stabilizing the mRNA stability of KPNA2. Rescue experiments proved that the effect of inhibiting or overexpressing IGF2BP3 on NPC cells was partly reversed by KPNA2. Collectively, MYC-activated IGF2BP3 promoted NPC cell proliferation and metastasis by influencing the stability of m6A-modified KPNA2. Our findings offer new insights that IGF2BP3 may serve as a new molecular marker and potential therapeutic target for NPC treatment.

Comparison of 3 Paclitaxel-Based Chemoradiotherapy Regimens for Patients With Locally Advanced Esophageal Squamous Cell Cancer: A Randomized Clinical Trial.

Importance: Multiple paclitaxel-based regimens are widely used in chemoradiation therapy against esophageal cancer, including regimens combining paclitaxel with fluorouracil, cisplatin, and carboplatin. However, which among these 3 regimens provides the best prognosis with minimum adverse events is still unknown. Objective: To compare the efficacy and adverse events of fluorouracil, cisplatin, and carboplatin in definitive chemoradiotherapy in patients with esophageal squamous cell carcinoma (ESCC). Design, Setting, and Participants: This randomized clinical trial of patients with ESCC was conducted in 11 treatment centers in China. Eligible patients were aged 18 to 75 years and had histologically confirmed ESCC stages IIa to IVa with no prior treatment, Eastern Cooperative Oncology Group performance status of 2 or lower, and adequate organ functions. The study was conducted between July 2015 and February 2018, and the cutoff date for data analysis was August 31, 2020. Interventions: Patients with locally advanced ESCC were randomly assigned (1:1:1) to groups combining paclitaxel treatment with fluorouracil, cisplatin, or carboplatin. Patients in the cisplatin group were treated with 2 cycles of concurrent chemoradiotherapy followed by 2 cycles of consolidation chemotherapy with monthly paclitaxel plus cisplatin. For the fluorouracil group, patients were administered 6 cycles of weekly paclitaxel plus fluorouracil in concurrent chemoradiotherapy followed by 2 cycles of monthly paclitaxel plus fluorouracil in consolidation chemotherapy. Patients in the carboplatin group were treated with 6 cycles of weekly paclitaxel plus carboplatin in concurrent chemoradiotherapy followed by 2 cycles of monthly paclitaxel plus carboplatin in consolidation chemotherapy. All patients received radiotherapy of 61.2 Gy delivered in 34 fractions. Main Outcomes and Measures: The primary end point was overall survival (OS). The secondary end points were progression-free survival and adverse events. Results: Overall, 321 patients (median [IQR] age, 64 years [59-69 years]; 248 [77.3%] men) with ESCC from 11 centers were randomized into fluorouracil, cisplatin, or carboplatin groups between July 2015 and February 2018. Over a median (IQR) follow-up time of surviving patients of 46.0 months (36.6-53.0 months), the 3-year OS rates were 57.2% in the fluorouracil group, 60.1% in the cisplatin group, and 56.5% in the carboplatin group, respectively (fluorouracil vs cisplatin: HR, 1.06; 95% CI, 0.71-1.60; P = .77; fluorouracil vs carboplatin: HR, 0.94; 95% CI, 0.63-1.40; P = .77). The cisplatin group had significantly higher incidences of acute grade 3 or 4 neutropenia (69 events [60.8%] vs 19 [17.8%] for fluorouracil and 37 [34.6%] carboplatin; P < .001), thrombocytopenia (14 events [13.1%] vs 4 [3.7%] for fluorouracil and 5 [4.7%] for carboplatin; P = .01), anemia (50 events above grade 2 [46.7%] vs 25 [23.4%] for fluorouracil and 37 [34.6%] for carboplatin; P = .35), fatigue (11 events [10.3%] vs 2 [1.9%] for fluorouracil and 1 [0.9%] carboplatin; P = .007), and vomiting (17 events above grade 2 [15.9%] vs 3 [2.8%] for fluorouracil and 5 [4.7%] for carboplatin; P < .001) than the other 2 groups. Conclusions and Relevance: In this randomized clinical trial, paclitaxel plus fluorouracil did not show OS superiority over paclitaxel plus cisplatin or paclitaxel plus carboplatin regimens in definitive chemoradiation in patients with locally advanced ESCC. Higher rates of hematologic and gastrointestinal toxic effects were reported in the cisplatin group compared with those in the fluorouracil or carboplatin groups. Trial Registration: ClinicalTrials.gov Identifier: NCT02459457.

A comparative analysis of eleven neural networks architectures for small datasets of lung images of COVID-19 patients toward improved clinical decisions.

The 2019 novel severe acute respiratory syndrome coronavirus 2-SARS-CoV2, commonly known as COVID-19, is a highly infectious disease that has endangered the health of many people around the world. COVID-19, which infects the lungs, is often diagnosed and managed using X-ray or computed tomography (CT) images. For such images, rapid and accurate classification and diagnosis can be performed using deep learning methods that are trained using existing neural network models. However, at present, there is no standardized method or uniform evaluation metric for image classification, which makes it difficult to compare the strengths and weaknesses of different neural network models. This paper used eleven well-known convolutional neural networks, including VGG-16, ResNet-18, ResNet-50, DenseNet-121, DenseNet-169, Inception-v3, Inception-v4, SqueezeNet, MobileNet, ShuffeNet, and EfficientNet-b0, to classify and distinguish COVID-19 and non-COVID-19 lung images. These eleven models were applied to different batch sizes and epoch cases, and their overall performance was compared and discussed. The results of this study can provide decision support in guiding research on processing and analyzing small medical datasets to understand which model choices can yield better outcomes in lung image classification, diagnosis, disease management and patient care.

Impact of childbirth policy changes on obstetric workload over a 13-year period in a regional referral center in China - implications on service provision planning.

BACKGROUND: We aimed to appraise the impact of the changing national childbirth policy since 2002, currently allowing two children per family, on obstetric workload in a regional referral center in China. METHODS: In a retrospective cohort study, temporal changes were examined in relation with maternal demographics, incidence of women with high risk pregnancies and resource statistics in our hospital in managing singleton viable pregnancies (birth from 28 weeks gestational age onwards) for the period 2005-2017. RESULTS: During this 13-year period, the number of singleton livebirths from 28 weeks gestational age onwards was 49,479. Annual numbers of births increased from 1,941 to 2005 to 5,777 in 2017. There were concomitant and significant increases in the incidence of multiparous women (10.6-50.8 %), of age ≥35 years (6.5-24.3 %), with prior caesarean Sec. (2.6-23.6 %), with ≥3 previous pregnancy terminations (1.0-4.9 %), with pre-gestational diabetes (0.2-0.9 %), and with chronic hypertension (0.2-1.2 %). There were associated increases in beds and staff complement and reduced average hospital stay. Nevertheless, while the workload of medical staff remained stable with increasing staff complement, that of midwives increased significantly as reflected by the total births: midwife ratio which increased from 194.1:1 to 320.9:1 (p < 0.001). CONCLUSIONS: In our hospital, progressively increasing numbers of annual births in combination with an increased incidence of women with high risk pregnancies took place following the revised national childbirth policy. Only the increase in medical and nursing, but not midwifery, staff was commensurate with workload. Remedial measures are urgently required before the anticipated progressive increase in care demand would overwhelm maternity care with potentially disastrous consequences.