Application of optimized LSTM in prediction of the cumulative confirmed cases of COVID-19.

This paper proposes an optimized Long Short-Term Memory (LSTM+) model for predicting cumulative confirmed cases of COVID-19 in Germany, the UK, Italy, and Japan. The LSTM+ model incorporates two key optimizations: (1) fine-adjustment of parameters and (2) a 're-prediction' process that utilizes the latest prediction results from the previous iteration. The performance of the LSTM+ model is evaluated and compared with that of Backpropagation (BP) and traditional LSTM models. The results demonstrate that the LSTM+ model significantly outperforms both BP and LSTM models, achieving a Mean Absolute Percentage Error (MAPE) of less than 0.6%. Additionally, two illustrative examples employing the LSTM+ model further validate its general applicability and practical performance for predicting cumulative confirmed COVID-19 cases.

Actin filaments altered distribution in wheat (Triticum aestivum) "Bending Root" to respond to enhanced Ultraviolet-B radiation / Distribuição alterada dos filamentos de actina no trigo (Triticum aestivum) "Raiz dobrada" para responder à radiação ultravioleta B aprimorada

Abstract Plants adjust their shoot growth to acclimate to changing environmental factors, such as to enhanced Ultraviolet-B (UV-B) radiation. However, people have ignored that plant roots can also respond to UV-B light. Here, we find the morphology curled wheat roots under UV-B radiation, that we call, "bending roots." The curly region is the transition zone of the root after observed at the cellular level. After exposed to enhanced UV-B radiation for 2 d (10.08 KJ/m2/d), cell size decreased and actin filaments gathered in wheat roots. We also find that H2O2 production increased and that content of the indole-3-acetic acid (IAA) increased remarkably. The pharmacological experiment revealed that actin filaments gathered and polymerized into bundles in the wheat root cells after irrigated H2O2 and IAA. These results indicated that actin filaments changed their distribution and formed the "bending root," which was related to H2O2 production and increase in IAA. Overall, actin filaments in wheat root cells could be a subcellular target of UV-B radiation, and its disruption determines root morphology.

Resumo As plantas ajustam o crescimento da parte aérea para se adaptarem a fatores ambientais variáveis, como o aumento da radiação ultravioleta B (UVB). No entanto, as pessoas ignoram que as raízes das plantas também podem responder à luz UVB. Neste estudo, verificamos a morfologia das raízes enroladas de trigo sob radiação UVB, o que chamamos de "raízes dobradas". A região encaracolada é a zona de transição da raiz no nível celular. Depois de exposição à radiação UVB aprimorada por 2 dias (10,08 KJ/m2/d), o tamanho das células diminuiu, e os filamentos de actina se reuniram. Também constatamos que a produção de H2O2 aumentou e que o conteúdo do ácido indol-3-acético (IAA) aumentou notavelmente. O experimento farmacológico revelou que os filamentos de actina se reuniram e polimerizaram em feixes nas células da raiz de trigo após irrigação com H2O2 e IAA. Esses resultados indicam que os filamentos de actina alteraram sua distribuição e formaram a "raiz dobrada", relacionada à produção de H2O2 e ao aumento do IAA. No geral, os filamentos de actina nas células da raiz de trigo podem ser um alvo subcelular da radiação UVB, e sua interrupção determina a morfologia da raiz.

Actin filaments altered distribution in wheat (Triticum aestivum) "Bending Root" to respond to enhanced Ultraviolet-B radiation.

Plants adjust their shoot growth to acclimate to changing environmental factors, such as to enhanced Ultraviolet-B (UV-B) radiation. However, people have ignored that plant roots can also respond to UV-B light. Here, we find the morphology curled wheat roots under UV-B radiation, that we call, "bending roots." The curly region is the transition zone of the root after observed at the cellular level. After exposed to enhanced UV-B radiation for 2 d (10.08 KJ/m2/d), cell size decreased and actin filaments gathered in wheat roots. We also find that H2O2 production increased and that content of the indole-3-acetic acid (IAA) increased remarkably. The pharmacological experiment revealed that actin filaments gathered and polymerized into bundles in the wheat root cells after irrigated H2O2 and IAA. These results indicated that actin filaments changed their distribution and formed the "bending root," which was related to H2O2 production and increase in IAA. Overall, actin filaments in wheat root cells could be a subcellular target of UV-B radiation, and its disruption determines root morphology.

[Research progress of prognostic biomarkers in diffuse large B-cell lymphoma].

Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous malignancy. A variety of indicators have been identified to predict the prognosis of DLBCL. However, with the emerging new drugs and new therapeutic options in recent years, the prognostic value of these risk prediction models becomes limited, failing to accurately guide treatment. The rapid development of high throughput technologies has led to dramatic improvement in understanding of the biology of DLBCL. The emergence of various new biomarkers contributes to further understanding the pathogenesis, treatment optimization and prognostic stratification of this disease. This review summarizes the prognostic biomarkers related to DLBCL, which mainly covers the hematological, genetic and tumor microenvironment factors, aiming to provide some theoretical basis for the precision treatment of DLBCL.

[Four-steps surgery for infected pancreatic necrosis based on "Step-up" strategy: a retrospective study].

Objective: To examine the effect of the "four-steps" treatment on infectious pancreatic necrosis(IPN). Methods: The data of 207 patients who were diagnosed with IPN from January 2013 to December 2017 at Department of Pancreaticobiliary Surgery, the First Affiliated Hospital of Harbin Medical University were analyzed retrospectively. Among 207 patients, 132(63.8%) were males and 75(36.2%) were females. The median age was 45 years old (range: 19 to 80 years old). One hundred and fifty-eight patients(76.3%) suffered severe acute pancreatitis and 49 patients(23.7%) suffered moderately severe acute pancreatitis. Percutaneous catheter drainage(PCD) was performed on all the patients(Step 1). Patients received "four-steps" minimally invasive treatment strategy in step-up group(173 patients). The following steps after PCD were mini-incision access pancreatic necrosectomy(MIAPN) (Step 2), sinus tract endoscopic debridement and(or) PCD for residual infections(Step 3) and finally conventional open pancreatic necrosectomy(OPN) (Step 4). Patients(34 cases) received conventional open pancreatic necrosectomy after invalided PCD in OPN group. The perioperative parameters and prognosis were compared between Step-up group and OPN group. Normally distributed quantitative variables were analyzed by t-test, non-normally distributed quantitative variables were analyzed by Wilcoxon chi-square test and categorical variables were analyzed by χ(2) test or Fisher exact test, respectively. Results: The basic characteristics of the two groups of patients were similar, but the referral rate of patients and the rate of preoperative 3 days organ failure in the OPN group were significantly higher than those of step-up group patients(47.1% vs. 28.9%, χ(2)=4.313, P=0.038; 26.5% vs. 9.2%, χ(2)=2.819, P=0.011). The frequency of PCD and the number of PCD tube (root) were less than those in the step-up group(1(1) vs. 2(1), Z=-3.373, P=0.018; 2(1) vs. 3(2), Z=-2.208, P=0.027). Compared with the OPN group, the interval time from onset to surgery and the MIAPN operation time were significantly shorter in the step-up group(29(15) days vs. 36(17)days, Z=-0.567, P=0.008; 58(27)minutes vs. 90(56)minutes, Z=-3.908, P<0.01); postoperative mortality was lower(5.8% vs.17.6%, χ(2)=4.070, P=0.044); the overall incidence of postoperative complications was reduced(23.1% vs. 55.9%, χ(2)=14.960, P<0.01) and the incidence of new-onset organ failure was decreased after operation in the step-up group(37.5% vs.47.4%, χ(2)=7.133, P=0.007). The incidence of local abdominal complications (pancreatic fistula, intra-abdominal hemorrhage, gastrointestinal fistula) showed no significant difference between the two groups (P>0.05). Fewer patients required ICU treatment after operation in the step-up group compared with OPN group(22.0% vs. 44.1%, χ(2)=6.204, P=0.013). Patients in the Step-up group has shorter hospital stay than patients in OPN group (46(13) days vs. 52(13)days, Z=-1.993, P=0.046). Conclusions: The clinical effects of "four-steps" exhibited the superiority of minimally invasive treatment of IPN.And MIAPN is a simple, safe and effective procedure to remove pancreatic necrotic tissue and decrease complications.

[Research advances on the therapy of pancreatic fistula after pancreatic surgery].

Pancreatic fistula is a common and serious complication after pancreatic surgery. Pancreatic fistula, intra-abdominal infection and hemorrhage are known as the " lethal triad" after pancreatic surgery, which seriously affect the curative efficacy of operation. Although the incidence of pancreatic fistula has not been significantly reduced, there have been a large number of studies on the risk factors of pancreatic fistula and the means of prevention and therapy, which try to minimize the harm of pancreatic fistula. In this article we review the recent development of the latest definition, high risk factors and treatment of postoperative pancreatic fistula according to relevant literatures at home and abroad, aiming at summarizing the research advances on the therapy of pancreatic fistula after pancreatic surgery.

Identification and molecular mapping of indica high-tillering dwarf mutant htd4, a mild phenotype allelic mutant of D14 in rice (Oryza sativa L.).

Metabolism of strigolactones (SLs) can improve the efficiency of nutrient use by regulating the development of roots and shoots in crops, making them an important research focus for molecular breeding. However, as a very important plant hormone, the molecular mechanism of SL signal transduction still remains largely unknown. In this study, we isolated an indica high-tillering dwarf mutant 4 (htd4), a spontaneous mutant of rice, from the restorer line Gui99. Mapping and sequencing analysis showed that htd4 was a novel allelic mutant of D14, in which a single base substitution forms a premature termination codon. Quantitative RT-PCR analyses revealed that expression levels of the genes D10, D17, D27, D3 and D14 increased significantly, while expression of D53 decreased in htd4, compared with the wild type. A subcellular localisation assay showed that the mutant of D14 in htd4 did not disturb the normal localisation of D14 proteins. However, a BiFC assay suggested that the mutant-type D14 could not interact with D3. Additionally, compared with other D14 allelic mutants, htd4 was the first mutant of D14 discovered in indica, and the differences in many yield traits such as plant height, seed-setting rate and grain sizes between htd4 and the wild type were less than those between other D14 allelic mutants and the wild type. Therefore, htd4 is considered a mild phenotype allelic mutant of D14. We conclude that the absence of functional D14 caused the high-tillering dwarf phenotype of htd4. Our results may provide vital information for research on D14 function and the application of htd4 in molecular breeding.

Actin filaments altered distribution in wheat (Triticum aestivum) Bending Root to respond to enhanced Ultraviolet-B radiation

Abstract Plants adjust their shoot growth to acclimate to changing environmental factors, such as to enhanced Ultraviolet-B (UV-B) radiation. However, people have ignored that plant roots can also respond to UV-B light. Here, we find the morphology curled wheat roots under UV-B radiation, that we call, bending roots. The curly region is the transition zone of the root after observed at the cellular level. After exposed to enhanced UV-B radiation for 2 d (10.08 KJ/m2/d), cell size decreased and actin filaments gathered in wheat roots. We also find that H2O2 production increased and that content of the indole-3-acetic acid (IAA) increased remarkably. The pharmacological experiment revealed that actin filaments gathered and polymerized into bundles in the wheat root cells after irrigated H2O2 and IAA. These results indicated that actin filaments changed their distribution and formed the bending root, which was related to H2O2 production and increase in IAA. Overall, actin filaments in wheat root cells could be a subcellular target of UV-B radiation, and its disruption determines root morphology.

Resumo As plantas ajustam o crescimento da parte aérea para se adaptarem a fatores ambientais variáveis, como o aumento da radiação ultravioleta B (UVB). No entanto, as pessoas ignoram que as raízes das plantas também podem responder à luz UVB. Neste estudo, verificamos a morfologia das raízes enroladas de trigo sob radiação UVB, o que chamamos de raízes dobradas. A região encaracolada é a zona de transição da raiz no nível celular. Depois de exposição à radiação UVB aprimorada por 2 dias (10,08 KJ/m2/d), o tamanho das células diminuiu, e os filamentos de actina se reuniram. Também constatamos que a produção de H2O2 aumentou e que o conteúdo do ácido indol-3-acético (IAA) aumentou notavelmente. O experimento farmacológico revelou que os filamentos de actina se reuniram e polimerizaram em feixes nas células da raiz de trigo após irrigação com H2O2 e IAA. Esses resultados indicam que os filamentos de actina alteraram sua distribuição e formaram a raiz dobrada, relacionada à produção de H2O2 e ao aumento do IAA. No geral, os filamentos de actina nas células da raiz de trigo podem ser um alvo subcelular da radiação UVB, e sua interrupção determina a morfologia da raiz.

[Clinicopathological features of thyroid papillary microcarcinoma of which the maximum diameter is less than 5 mm: a series of 487 cases].

Objective: To analyze the clinical and pathological features of papillary thyroid microcarcinoma(PTMC) of which the maximum diameter is less than 5 mm. Methods: Clinical data of 487 PTMC (≤5 mm) patients who underwent primary surgery by the same team of doctors between March 2013 to March 2016 at Department of Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University were analyzed retrospectively. Female patients accounted for 77.4%(377/487). The age ranged from 22 to 80 years, with an average of (46±11) years.χ2 test and multivariate Logistic regression analysis were used to analyze risk factors. Results: There were 93.6% (456/487) of the patients with preoperative definite diagnosis. There were 92.6% (452/487) of the patients underwent unilateral thyroid lobectomy with isthmectomy and ipsilateral central lymph node dissection. Multifocal carcinoma accounted for 20.3% (99/487), Ⅲ to Ⅳ phase cases accounted for 12.3% (60/487), patients with low risk of recurrence accounted for 67.6% (329/487). The central lymph node metastasis rate was 34.9% (170/487). Male (OR=2.149, 95%CI: 1.367 to 3.381), age<45 years (OR=0.451, 95%CI: 0.303 to 0.672), multifocal carcinoma (OR=1.798, 95%CI: 1.116 to 2.898), and capsular invasion (OR=3.678, 95%CI: 1.406 to 9.622) were the independent risk factors for lymph node metastasis (P<0.05). Conclusion: Regardless of tumor size, PTMC still needs to be taken seriously, especially male, age < 45 years, capsular invasion, or multifocal carcinoma patients.

Computed tomography findings of hepatic veno-occlusive disease caused by Sedum aizoon with histopathological correlation

This study investigated the value of computed tomography (CT) in the diagnosis and treatment of hepatic veno-occlusive disease (HVOD) caused by Sedum aizoon (SA). The clinical manifestations, treatment results, imaging findings, and histological findings of the liver were analyzed in 39 patients with HVOD caused by SA. Hepatomegaly, liver dysfunction, abdominal effusion, and geographic density changes on liver CT scans were found in all 39 patients. The pathological findings of histological liver examination included swelling and point-like necrosis of liver cells, significant expansion and congestion of the sinuses, endothelial swelling, and wall thickening with incomplete lumen occlusion of small liver vessels. CT geographic density changes were confirmed by histological examination of the liver in 18 patients. Sixteen patients with small amounts of ascites that started within 4 weeks of treatment recovered completely or significantly improved after symptomatic and supportive treatment. However, only 43.75% of the patients with larger amounts of ascites improved following symptomatic and supportive treatment. In conclusion, liver CT examination is a valuable, safe, and noninvasive tool for the diagnosis of HVOD caused by SA. In selected cases, liver CT examination may replace liver biopsy and histological analysis.

Computed tomography findings of hepatic veno-occlusive disease caused by Sedum aizoon with histopathological correlation.

This study investigated the value of computed tomography (CT) in the diagnosis and treatment of hepatic veno-occlusive disease (HVOD) caused by Sedum aizoon (SA). The clinical manifestations, treatment results, imaging findings, and histological findings of the liver were analyzed in 39 patients with HVOD caused by SA. Hepatomegaly, liver dysfunction, abdominal effusion, and geographic density changes on liver CT scans were found in all 39 patients. The pathological findings of histological liver examination included swelling and point-like necrosis of liver cells, significant expansion and congestion of the sinuses, endothelial swelling, and wall thickening with incomplete lumen occlusion of small liver vessels. CT geographic density changes were confirmed by histological examination of the liver in 18 patients. Sixteen patients with small amounts of ascites that started within 4 weeks of treatment recovered completely or significantly improved after symptomatic and supportive treatment. However, only 43.75% of the patients with larger amounts of ascites improved following symptomatic and supportive treatment. In conclusion, liver CT examination is a valuable, safe, and noninvasive tool for the diagnosis of HVOD caused by SA. In selected cases, liver CT examination may replace liver biopsy and histological analysis.

Practising case-based learning in oral medicine for dental students in China.

INTRODUCTION: Teacher-centred education dominates dental education in China. Student-centred education has recently been introduced in the School of Stomatology, Wuhan University, and the effectiveness of such methods needs to be tested. The purpose of this study is to compare the learning outcomes of case-based learning (CBL) and lecture-based education (LBE) in an oral medicine curriculum. MATERIALS AND METHODS: We chose oral leukoplakia as the learning subject for dental students. Forty fourth-year dental students participated in the study. First, they were presented to basic knowledge of oral leukoplakia and related oral mucosal diseases. Then, they were divided into a CBL group (n=20) and an LBE group (n=20) by random numbers. The groups experienced the remaining course in separate groups. All students answered a questionnaire on their satisfaction with the education and the same standardised written test to analyse their learning outcomes. RESULTS: Both CBL and LBE courses were well accepted by students according to the satisfactory scores of the questionnaire. The test scores of the CBL group (90.00±6.69) were significantly higher (P<0.01) than those of the LBE group (83.00±6.77). The percentage of high test score (test score≥85) of the CBL group (85%) was also significantly higher (P<0.01) than that of the LBE group (45%). CONCLUSIONS: In this example, CBL was found to be more effective than LBE to teach dental students. These findings suggest that CBL should be added in our future oral medicine curriculum for dental students.

Up-regulation of KCa3.1 promotes human airway smooth muscle cell phenotypic modulation.

Airway smooth muscle (ASM) cell phenotype modulation, characterized by reversible switching between contractile and proliferative phenotypes, is considered to contribute to proliferative diseases such as allergic asthma and chronic obstructive pulmonary disease (COPD). KCa3.1 has been suggested to be involved in regulating ASM cell activation, proliferation, and migration. However, little is known regarding the exact role of KCa3.1 in ASM cell phenotypic modulation. To elucidate the role of KCa3.1 in regulating ASM cell phenotypic modulation, we investigated the effects of KCa3.1 channels on ASM contractile marker protein expression, proliferation and migration of primary human bronchial smooth muscle (BSM) cells. We found that PDGF increased KCa3.1 channel expression in BSM cells with a concomitant marked decrease in the expression of contractile phenotypic marker proteins including smooth muscle myosin heavy chain (SMMHC), smooth muscle α-actin (α-SMA), myocardin and KCa1.1. These changes were significantly attenuated by the KCa3.1 blocker, TRAM-34, or gene silencing of KCa3.1. Pharmacological blockade or gene silencing of KCa3.1 also suppressed PDGF-induced human BSM cell migration and proliferation accompanied by a decrease in intracellular free Ca(2+) levels as a consequence of membrane depolarization, resulting in a reduction in cyclin D1 level and cell cycle arrest at G0-G1 phase. Additionally, PDGF-induced up-regulation of KCa3.1 and down-regulation of BSM contractile marker proteins were regulated by the ERK inhibitor U0126 and the AKT inhibitor LY294002. These findings highlight a novel role for the KCa3.1 channel in human BSM cell phenotypic modulation and provide a potential target for therapeutic intervention for proliferative airway diseases.

Functional analysis of DNA methylation in lung cancer.

OBJECTIVES: We aimed to explore the DNA methylation difference between lung cancer samples and non-cancer lung samples, and to investigate the role of DNA methylation in the mechanism of lung cancer development. Besides, we analyzed the transcriptional regulation network of DNA methylation and the miRNAs regulated by DNA methylation. This study provides a framework for DNA methylation in other tumors or diseases. MATERIALS AND METHODS: DNA methylation and gene expression profiles used were obtained from Gene Expression Omnibus. Firstly, we identified differentially methylated genes (DMGs) by Student's t-test. Then we detected the biological processes and pathways changed in lung cancer by Gene Ontology (GO) and KEGG pathway enrichment analysis. The transcriptional factors in differential genes were identified and the microRNAs regulated by them were also obtained in TransmiR. RESULTS: We obtained 108 DMGs between lung cancer samples and non-cancer samples. Besides development related biological processes and pathways were dramatically disordered. For the DMGs, we identified 11 transcriptional factors regulating them. Moreover, we screened out 21 relationships between DMGs and their transcriptional targets. Five microRNAs are reported to be regulated by DNA methylation genes. Finally a regulation network of DNA methylation was constructed. CONCLUSIONS: DNA methylation participates in carcinogenesis at the transcriptional and post-transcriptional level. Aberrant DNA methylation will prevent its binding with the upstream regulatory proteins, inhibit the function of downstream target genes and regulate the expression of downstream miRNA, and consequently affect cell development, immunoresponse and apoptosis.

SIRT1 as a novel potential treatment target for vascular aging and age-related vascular diseases.

Aging is one of the greatest risk factors in vascular diseases (VDs). During aging, there are structural and functional changes in the vasculature, including dilated lumen, altered intimal-medial thickness (IMT), vascular stiffness, endothelial dysfunction, increased endothelial apoptosis, matrix metalloproteinase (MMP) dysregulation, increased expression of inflammatory molecules, aggravated oxidative stress and shortened telomere length. These changes leave the body more susceptible to primary hypertension, stroke and coronary artery disease. Molecules that suppress these age-related changes would provide an excellent medical intervention for VDs. Mammalian Sir2 (SIRT1, a NAD+-dependent deacetylase), previously shown to extend the lifespan of lower organisms, is a promising target molecule to influence some aspects of vascular aging. In this review, we summarized roles of SIRT1 in various pathophysiological processes of vascular aging and proposed that SIRT1 and its activators can become novel therapeutic targets for age-related VDs.

TNF-α-induced CXCL8 production by A549 cells: involvement of the non-neuronal cholinergic system.

It was recently suggested that the non-neuronal cholinergic system has a regulatory role in pulmonary inflammation. We investigated this system's involvement in the control of cytokine production by the A549 human alveolar epithelial cell line. CXCL8 and acetylcholine (ACh) concentrations were measured using ELISA and LC-MS/MS, respectively. The mRNA expression of muscarinic receptor (MR) subtypes was determined using RT-PCR. In A549 cells, TNF-α increased the release of CXCL8 and ACh and the expression of the subtype 3 MR (M3R). Furthermore, TNF-α-induced CXCL8 secretion was (i) inhibited by the MR antagonist tiotropium and the M3R antagonist 4-DAMP and (ii) enhanced by the M1/M3R agonist pilocarpine and the cholinesterase inhibitor physostigmine. Taken as a whole, these results suggest that ACh release by A549 cells enhances TNF-α-induced CXCL8 secretion through activation of the M3R. Western blot analysis revealed that pilocarpine and physostigmine enhanced the TNF-α-induced phosphorylation of ERK1/2 and p38 MAPK and the degradation of IκBα. Inhibition of these pathways with specific inhibitors abrogated the pilocarpine-induced CXCL8 release. Our results suggest that the TNF-α-induced secretion of CXCL8 in A549 cells is regulated by the release of ACh, the latter's binding to the M3R and the downstream activation of NF-κB and the ERK1/2 and p38 MAPK signaling pathways. Our findings suggest that MR antagonists may have anti-inflammatory effects by preventing pro-inflammatory events driven by endogenous, non-neuronal ACh.