Transarterial chemoembolization with 125I seed insertion for multifocal hepatocellular carcinoma.

Background: A common treatment strategy for individuals with multifocal hepatocellular carcinoma (HCC) who are not candidates for surgical resection is transarterial chemoembolization (TACE). Combining TACE with 125I seed insertion (ISI) may offer a means of enhancing therapeutic efficacy. The purpose of this study was to compare the therapeutic efficacy of TACE administered with and without ISI for the treatment of multifocal HCC. Methods: The data from the two centers were analyzed retrospectively. The present study involved 85 consecutive patients with multifocal HCC who underwent TACE between January 2018 and December 2021. Of these patients, 43 were in the combined group, receiving TACE with ISI, and 42 were in the TACE-only group, receiving TACE without ISI. Comparisons of treatment outcomes were made between these groups. Results: No significant differences in baseline data were observed between these groups of patients. Higher rates of complete (60.5% vs. 33.3%, P = 0.016) and total (93.0% vs. 61.9%, P = 0.001) responses were evident in the combined group compared to the TACE-only group. Median progression-free survival (PFS, 13 vs. 10 months, P = 0.014) and overall survival (OS, 22 vs. 17 months, P = 0.035) were also significantly longer in the combined group than in the TACE-only group. Using a Cox regression analysis, risk variables associated with shorter PFS and OS included Child-Pugh B status (P = 0.027 and 0.004) and only TACE treatment (P = 0.011 and 0.022). Conclusion: In summary, these findings suggest that, as compared to TACE alone, combining TACE and ISI can enhance HCC patients' treatment outcomes and survival.

Genetically Predicted Apolipoprotein E Levels with the Risk of Panvascular Diseases: A Mendelian Randomization Study.

The aim of this study was to comprehensively assess the causal relationship between the overall genetic effect of circulating ApoE levels and panvascular lesions using newer genome-wide association data and two-sample bidirectional Mendelian randomization (MR) analysis. Two-way MR using single-nucleotide polymorphisms of circulating ApoE as instrumental variables was performed using the highest-priority Genome-wide association study (GWAS) data, with factor-adjusted and data-corrected statistics, to estimate causal associations between circulating ApoE levels and 10 pan-vascular diseases in > 500,000 UK Biobank participants, > 400,000 participants of Finnish ancestry, and numerous participants in a consortium of predominantly European ancestry. Meta-analysis was conducted to assess positive results. After correcting for statistical results, elevated circulating ApoE levels were shown to have a significant protective effect against Cerebral ischemia (CI) [IVW odds ratio (OR) 0.888, 95% Confidence Interval (CI): 0.823-0.958, p = 2.3 × 10-3], Coronary heart disease [IVW OR 0.950,95% CI: 0.924-0.976, p = 2.0 × 10-4] had a significant protective effect and potentially suggestive protective causality against Angina pectoris [IVW odds ratio (OR) 0.961, 95%CI: 0.931-0.991, p = 1.1 × 10-2]. There was a potential causal effect for increased risk of Heart failure (HF) [IVW ratio (OR) 1.040, 95%CI: 1.006-1.060, p = 1.8 × 10-2]. (Bonferroni threshold p < 0.0026, PFDR < 0.05) Reverse MR analysis did not reveal significant evidence of a causal effect of PVD on changes in circulating ApoE levels. Meta-analysis increases reliability of results. Elevated circulating ApoE levels were particularly associated with an increased risk of heart failure. Elevated ApoE levels reduce the risk of cerebral ischemia, coronary heart disease, and angina pectoris, reflecting a protective effect. The possible pathophysiological role of circulating ApoE levels in the development of panvascular disease is emphasized.

Effects of Solitaire AB stent thrombectomy with tirofiban and butylphthalide on neurological function and inflammatory factors in acute cerebral infarction patients.

BACKGROUND: Acute cerebral infarction profoundly affects patients' neurological function and quality of life. This study explores the impact of Solitaire AB stent thrombectomy, combined with tirofiban and butylphthalide, on neurological function and inflammatory factors in patients with acute cerebral infarction. METHODS: Seventy-three eligible patients treated between 2021 and 2023 were divided into a control group (Solitaire AB stent thrombectomy) and a treatment group (Solitaire AB stent thrombectomy with tirofiban and butylphthalide). Postoperative neurological function scores and inflammatory factor levels were analyzed. RESULTS: The treatment group demonstrated a higher clinical effective rate, lower National Institutes of Health Stroke Scale scores at one day and seven days and higher Mini-Mental State Examination and Montreal Cognitive Assessment scores post-treatment. Inflammatory factor levels (Neuron Specific Enolase (NSE), S100-ß, TNF-α and IL-6) were lower in the treatment group. No significant differences in adverse outcomes were observed. CONCLUSION: Solitaire AB stent thrombectomy with tirofiban and butylphthalide shows superior efficacy, improving neurological function and inflammatory factors without increasing adverse outcomes. This offers valuable insights for clinical treatment of acute cerebral infarction.

A Planar Multi-Inertial Navigation Strategy for Autonomous Systems for Signal-Variable Environments.

The challenge of precise dynamic positioning for mobile robots is addressed through the development of a multi-inertial navigation system (M-INSs). The inherent cumulative sensor errors prevalent in traditional single inertial navigation systems (INSs) under dynamic conditions are mitigated by a novel algorithm, integrating multiple INS units in a predefined planar configuration, utilizing fixed distances between the units as invariant constraints. An extended Kalman filter (EKF) is employed to significantly enhance the positioning accuracy. Dynamic experimental validation of the proposed 3INS EKF algorithm reveals a marked improvement over individual INS units, with the positioning errors reduced and stability increased, resulting in an average accuracy enhancement rate exceeding 60%. This advancement is particularly critical for mobile robot applications that demand high precision, such as autonomous driving and disaster search and rescue. The findings from this study not only demonstrate the potential of M-INSs to improve dynamic positioning accuracy but also to provide a new research direction for future advancements in robotic navigation systems.

Morphological, phytochemical and genetic characterization of Centella asiatica accessions collected throughout Vietnam and Laos.

Pennywort (Centella asiatica L.) is commonly grown in the tropical world for its nutritional and medicinal values. Valuable saponins in pennywort are extensively investigated for their anti-tumour activities. The diversity in morphology, phytochemical contents and genetics among pennywort accessions has been extensively studied to identify elite landraces for large-scale production. While pennywort is widely consumed in Vietnam, a systematic characterization of their diverse morphology, secondary metabolites and genetics is lacking. In this work, 26 pennywort accessions were collected across Vietnam and Laos. Their morphological features and yields were characterized under uniform agro-climatic conditions at Hue city in central Vietnam. The highest yield was obtained with HUIB_CA20 (478 g per tray), compared to the lowest yield in HUIB_CA19 (107 g per tray). Furthermore, a range of phytochemical markers, including vitamin C, reducing sugar, carotenoid, tannin, phenolic, flavonoid and saponin contents, were determined. Based on yield, phenolic and flavonoid contents, HUIB_CA20 and HUIB_CA27 were determined to be elite cultivars in this germplasm. Finally, microsatellite analysis was performed to explore the genetic diversity within the germplasm. Using fourteen SSR primer pairs, a total of 47 alleles were identified with 45 alleles (96 %) being polymorphic. These results will be useful for breeding programs aiming to create elite pennywort cultivars with enhanced properties.

A Correlated Network Scale-up Model: Finding the Connection Between Subpopulations.

Aggregated relational data (ARD), formed from "How many X's do you know?" questions, is a powerful tool for learning important network characteristics with incomplete network data. Compared to traditional survey methods, ARD is attractive as it does not require a sample from the target population and does not ask respondents to self-reveal their own status. This is helpful for studying hard-to-reach populations like female sex workers who may be hesitant to reveal their status. From December 2008 to February 2009, the Kiev International Institute of Sociology (KIIS) collected ARD from 10,866 respondents to estimate the size of HIV-related groups in Ukraine. To analyze this data, we propose a new ARD model which incorporates respondent and group covariates in a regression framework and includes a bias term that is correlated between groups. We also introduce a new scaling procedure utilizing the correlation structure to further reduce biases. The resulting size estimates of those most-at-risk of HIV infection can improve the HIV response efficiency in Ukraine. Additionally, the proposed model allows us to better understand two network features without the full network data: 1. What characteristics affect who respondents know, and 2. How is knowing someone from one group related to knowing people from other groups. These features can allow researchers to better recruit marginalized individuals into the prevention and treatment programs. Our proposed model and several existing NSUM models are implemented in the networkscaleup R package.

Probabilistic HIV recency classification-a logistic regression without labeled individual level training data.

Accurate HIV incidence estimation based on individual recent infection status (recent vs long-term infection) is important for monitoring the epidemic, targeting interventions to those at greatest risk of new infection, and evaluating existing programs of prevention and treatment. Starting from 2015, the Population-based HIV Impact Assessment (PHIA) individual-level surveys are implemented in the most-affected countries in sub-Saharan Africa. PHIA is a nationally-representative HIV-focused survey that combines household visits with key questions and cutting-edge technologies such as biomarker tests for HIV antibody and HIV viral load which offer the unique opportunity of distinguishing between recent infection and long-term infection, and providing relevant HIV information by age, gender, and location. In this article, we propose a semi-supervised logistic regression model for estimating individual level HIV recency status. It incorporates information from multiple data sources - the PHIA survey where the true HIV recency status is unknown, and the cohort studies provided in the literature where the relationship between HIV recency status and the covariates are presented in the form of a contingency table. It also utilizes the national level HIV incidence estimates from the epidemiology model. Applying the proposed model to Malawi PHIA data, we demonstrate that our approach is more accurate for the individual level estimation and more appropriate for estimating HIV recency rates at aggregated levels than the current practice - the binary classification tree (BCT).

Stability Constant and Potentiometric Sensitivity of Heavy Metal-Organic Fluorescent Compound Complexes: QSPR Models for Prediction and Design of Novel Coumarin-like Ligands.

Industrial wastewater often consists of toxic chemicals and pollutants, which are extremely harmful to the environment. Heavy metals are toxic chemicals and considered one of the major hazards to the aquatic ecosystem. Analytical techniques, such as potentiometric methods, are some of the methods to detect heavy metals in wastewaters. In this work, the quantitative structure-property relationship (QSPR) was applied using a range of machine learning techniques to predict the stability constant (logßML) and potentiometric sensitivity (PSML) of 200 ligands in complexes with the heavy metal ions Cu2+, Cd2+, and Pb2+. In result, the logßML models developed for four ions showed good performance with square correlation coefficients (R2) ranging from 0.80 to 1.00 for the training and 0.72 to 0.85 for the test sets. Likewise, the PSML displayed acceptable performance with an R2 of 0.87 to 1.00 for the training and 0.73 to 0.95 for the test sets. By screening a virtual database of coumarin-like structures, several new ligands bearing the coumarin moiety were identified. Three of them, namely NEW02, NEW03, and NEW07, showed very good sensitivity and stability in the metal complexes. Subsequent quantum-chemical calculations, as well as physicochemical/toxicological profiling were performed to investigate their metal-binding ability and developability of the designed sensors. Finally, synthesis schemes are proposed to obtain these three ligands with major efficiency from simple resources. The three coumarins designed clearly demonstrated capability to be suitable as good florescent chemosensors towards heavy metals. Overall, the computational methods applied in this study showed a very good performance as useful tools for designing novel fluorescent probes and assessing their sensing abilities.

Prevalence and Factors Affecting Appropriate Inhaler Use in Elderly Patients with Chronic Obstructive Pulmonary Disease: A Prospective Study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) mainly affects individuals aged 60 and older. The proper use of inhalers is crucial for managing COPD. This study aimed to evaluate the prevalence and factors affecting the appropriate use of inhalers among elderly patients with COPD. METHODS: We enrolled 91 elderly patients with COPD admitted to the Department of Respiratory, University Medical Center HCMC between October 2020 and May 2021. Patients who were capable of using the inhaler would have their inhaler usage recorded through video footage. Two respiratory experts carefully analyzed 133 video-recorded demonstrations for evaluation purposes. RESULTS: 18.7% of the patients demonstrated the correct inhaler technique. Pressurized metered dose inhaler (pMDI) and Turbuhaler had the lowest documented correct usage rates (11.9% and 10.0%, respectively). Two critical steps, namely "holding breath for about five seconds or as long as comfortable" and "breathing out gently," were commonly performed incorrectly when using pMDI, Respimat, Breezhaler, or Turbuhaler. Multivariable logistic regression analysis showed that lower mMRC scores (AOR = 5.3, CI 1.1-25.5, p = 0.037) and receiving inhaler instruction within the past three months (AOR = 5.2, CI 1.3-20.1, p = 0.017) were associated with increased odds of using the inhaler correctly. CONCLUSIONS: Our study found that less than 20% of elderly patients with COPD use inhalers correctly. Common errors include inadequate breath-holding and gentle exhalation. mMRC scores and recent inhaler instruction were predictors of proper use. These findings can aid clinicians in improving inhaler management for elderly patients with COPD.

Development of Activity Rules and Chemical Fragment Design for In Silico Discovery of AChE and BACE1 Dual Inhibitors against Alzheimer's Disease.

Multi-target drug development has become an attractive strategy in the discovery of drugs to treat of Alzheimer's disease (AzD). In this study, for the first time, a rule-based machine learning (ML) approach with classification trees (CT) was applied for the rational design of novel dual-target acetylcholinesterase (AChE) and ß-site amyloid-protein precursor cleaving enzyme 1 (BACE1) inhibitors. Updated data from 3524 compounds with AChE and BACE1 measurements were curated from the ChEMBL database. The best global accuracies of training/external validation for AChE and BACE1 were 0.85/0.80 and 0.83/0.81, respectively. The rules were then applied to screen dual inhibitors from the original databases. Based on the best rules obtained from each classification tree, a set of potential AChE and BACE1 inhibitors were identified, and active fragments were extracted using Murcko-type decomposition analysis. More than 250 novel inhibitors were designed in silico based on active fragments and predicted AChE and BACE1 inhibitory activity using consensus QSAR models and docking validations. The rule-based and ML approach applied in this study may be useful for the in silico design and screening of new AChE and BACE1 dual inhibitors against AzD.

Secondary metabolites as potential drug candidates against Zika virus, an emerging looming human threat: Current landscape, molecular mechanism and challenges ahead.

Nature has given us yet another wild card in the form of Zika virus (ZIKV). It was found in 1947, but has only recently become an important public health risk, predominantly to pregnant women and their unborn offspring. Currently, no specific therapeutic agent exists for ZIKV and treatment is mainly supportive. Natural products (NPs) can serve as a major source of potent antiviral drugs. To create this review, a comprehensive search was conducted from different databases (PubMed, ScienceDirect, Google scholar). A statistical analysis on the number of publications related to NPs and ZIKV was conducted to analyse the trend in research covering the period 1980-2020. From the data collated in this review, a number of NPs have been found to be inhibitive towards different stages of the ZIKV lifecycle in in vitro studies. For instance, baicalin, (-)-epigallocatechin gallate, curcumin, nanchangmycin, gossypol, cephaeline, emetine, resveratrol, berberine, amongst others, can prevent viral entry by attacking ZIKV E protein. Compounds luteolin, myricetin, astragalin, rutin, (-)-epigallocatechin gallate, carnosine, pedalitin, amongst others, inhibited NS2B-NS3 protease activity which consequently hamper replication. Interestingly, a few NPs had the ability to arrest both viral entry and replication, namely baicalin, (-)-epigallocatechin gallate, curcumin, cephaeline, emetine, and resveratrol. To the best of our knowledge, we obtained only one in vivo study conducted on emetine and results showed that it decreased the levels of circulating ZIKV by approximately 10-fold. Our understanding on NPs exhibiting anti-ZIKV effects in in vivo testing as well as clinical trials is limited. Our trend analysis showed that interest in searching for a cure or prevention against Zika in NPs is negligible and there are no publications yet covering the clinical evaluation. NPs with anti-ZIKV property can a winning strategy in controlling the bio-burden of an epidemic or pandemic. We therefore opine that in the future, more research should be devoted to ZIKV. This review attempts to provide baseline data and roadmap to pursuit detailed investigations for developing potent and novel therapeutic agents to prevent and cure ZIKV infection.

A Theoretical Study of Interband Absorption Spectra of Spherical Sector Quantum Dots under the Effect of a Powerful Resonant Laser.

We explore the variation of interband absorption spectra of GaAs spherical sector quantum dots (QDs) in response to a strong resonant laser, using the renormalized wave function method. Even though a spherical sector QD appears identical to a section cut from a spherical QD, it contains a controllable additional spatial parameter, the apical angle, which results in radically different wave functions and energy levels of particles, and is anticipated to exhibit novel optical properties. The obtained findings reveal that the apical angle of the dot has a considerable effect on the interband absorption spectrum. With the increase in the dot apical angle, a significant redshift of the interband absorption peaks has been identified. Increasing the pump laser detuning and dot radius yields similar results. Especially when a powerful resonant laser with tiny detuning is utilized, a dynamical coupling between electron levels arises, resulting in the formation of new interband absorption peaks. These new peaks and the former ones were similarly influenced by the aforementioned parameters. Furthermore, it is thought that the new peaks, when stimulated by a suitable laser, will produce the entangled states necessary for quantum information.

Dearomatization-Rearomatization Reaction of Metal-Polarized Aza-ortho-Quinone Methides.

Metal-polarized aza-ortho-quinone methides (aza-o-QMs) are a unique and efficient handle for azaheterocycle synthesis. Despite great achievements, the potential of these reactive intermediates has not yet been fully exploited, especially the new reaction modes. Herein, we disclosed an unprecedented dearomatization process of metal-polarized aza-o-QMs, affording transient dearomatized spiroaziridine intermediates. Based on this serendipity, we accomplished three sequential dearomatization-rearomatization reactions of benzimidazolines with aza-sulfur ylides, enabling the divergent synthesis of bis-nitrogen heterocycles with high efficiency and flexibility. Moreover, experimental and theoretical studies were performed to explain the proposed mechanisms and observed selectivity. Further cellular evaluation of the dibenzodiazepine products identified a hit compound for new antitumor drugs.

Mapping the number of female sex workers in countries across sub-Saharan Africa.

Female sex workers (FSW) are affected by individual, network, and structural risks, making them vulnerable to poor health and well-being. HIV prevention strategies and local community-based programs can rely on estimates of the number of FSW to plan and implement differentiated HIV prevention and treatment services. However, there are limited systematic assessments of the number of FSW in countries across sub-Saharan Africa to facilitate the identification of prevention and treatment gaps. Here we provide estimated population sizes of FSW and the corresponding uncertainties for almost all sub-national areas in sub-Saharan Africa. We first performed a literature review of FSW size estimates and then developed a Bayesian hierarchical model to synthesize these size estimates, resolving competing size estimates in the same area and producing estimates in areas without any data. We estimated that there are 2.5 million (95% uncertainty interval 1.9 to 3.1) FSW aged 15 to 49 in sub-Saharan Africa. This represents a proportion as percent of all women of childbearing age of 1.1% (95% uncertainty interval 0.8 to 1.3%). The analyses further revealed substantial differences between the proportions of FSW among adult females at the sub-national level and studied the relationship between these heterogeneities and many predictors. Ultimately, achieving the vision of no new HIV infections by 2030 necessitates dramatic improvements in our delivery of evidence-based services for sex workers across sub-Saharan Africa.

Pemigatinib in previously treated Chinese patients with locally advanced or metastatic cholangiocarcinoma carrying FGFR2 fusions or rearrangements: A phase II study.

OBJECTIVE: This study evaluated the antitumor activity and safety of pemigatinib in previously treated Chinese patients with advanced cholangiocarcinoma and fibroblast growth factor receptor 2 (FGFR2) fusions or rearrangements. BACKGROUND: Pemigatinib provided clinical benefits for previously treated patients with cholangiocarcinoma carrying FGFR2 fusions or rearrangements and was approved for this indication in multiple countries. METHODS: In this ongoing, multicenter, single-arm, phase II study, adult patients with locally advanced or metastatic cholangiocarcinoma carrying centrally confirmed FGFR2 fusions or rearrangements who had progressed on ≥1 systemic therapy received 13.5 mg oral pemigatinib once daily (3-week cycle; 2 weeks on, 1 week off) until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was objective response rate (ORR) assessed by an independent radiology review committee. RESULTS: As of January 29, 2021, 31 patients were enrolled. The median follow-up was 5.1 months (range, 1.5-9.3). Among 30 patients with FGFR2 fusions or rearrangements evaluated for efficacy, 15 patients achieved partial response (ORR, 50.0%; 95% confidence interval [CI], 31.3-68.7); 15 achieved stable disease, contributing to a disease control rate of 100% (95% CI, 88.4-100). The median time to response was 1.4 months (95% CI, 1.3-1.4), the median duration of response was not reached, and the median progression-free survival was 6.3 months (95% CI, 4.9-not estimable [NE]). Eight (25.8%) of 31 patients had ≥grade 3 treatment-emergent adverse events. Hyperphosphatemia, hypophosphatasemia, nail toxicities, and ocular disorders were mostly

Transarterial chemoembolization with insertion of radioactive seeds for hepatocellular carcinoma.

Introduction: For patients diagnosed with hepatocellular carcinoma (HCC) not eligible for surgical tumor resection, transarterial chemoembolization (TACE) is commonly employed as a therapeutic strategy. After TACE is complete, a variety of other therapeutic approaches can be employed to improve patient overall survival (OS) and progression-free survival (PFS). Aim: This study was developed with the goal of comparing the relative clinical efficacy and long-term outcomes observed in HCC patients who underwent combination TACE and radioactive seed insertion (RSI) treatment to those of patients who only underwent TACE treatment. Material and methods: This retrospective analysis included a total of 80 patients with HCC who underwent treatment via TACE with (n = 39) or without (n = 41) RSI. Treatment responses and long-term outcomes in these two groups were compared with one another. Results: The baseline characteristics of both groups were comparable. None of the patients experienced adverse complications related to treatment. Individuals in the combination treatment group experienced complete response (59.0% vs. 22.0%, p = 0.001) and total response (92.3% vs. 58.5%, p = 0.001) rates that were significantly better than those of patients that underwent TACE alone. Combination treatment was also associated with significant prolongation of patient PFS (13 vs. 7 months, p = 0.019) and OS (23 vs. 15 months, p = 0.005), with Cox regression analyses identifying combination treatment as a predictor of prolonged PFS and OS. Conclusions: These data suggest that a combination of TACE and RSI can contribute to significant improvements in HCC patient therapeutic response rates, OS, and PFS relative to TACE alone.

In Vitro and In Silico Pharmacological and Cosmeceutical Potential of Ten Essential Oils from Aromatic Medicinal Plants from the Mascarene Islands.

In this study, 10 essential oils (EOs), from nine plants (Cinnamomum camphora, Curcuma longa, Citrus aurantium, Morinda citrifolia, Petroselinum crispum, Plectranthus amboinicus, Pittosporum senacia, Syzygium coriaceum, and Syzygium samarangense) were assessed for their antimicrobial, antiaging and antiproliferative properties. While only S. coriaceum, P. amboinicus (MIC: 0.50 mg/mL) and M. citrifolia (MIC: 2 mg/mL) EOs showed activity against Cutibacterium acnes, all EOs except S. samarangense EO demonstrated activity against Mycobacterium smegmatis (MIC: 0.125-0.50 mg/mL). The EOs were either fungistatic or fungicidal against one or both tested Candida species with minimum inhibitory/fungicidal concentrations of 0.016-32 mg/mL. The EOs also inhibited one or both key enzymes involved in skin aging, elastase and collagenase (IC50: 89.22-459.2 µg/mL; 0.17-0.18 mg/mL, respectively). Turmerone, previously identified in the C. longa EO, showed the highest binding affinity with the enzymes (binding energy: -5.11 and -6.64 kcal/mol). Only C. aurantium leaf, C. longa, P. amboinicus, P. senacia, S. coriaceum, and S. samarangense EOs were cytotoxic to the human malignant melanoma cells, UCT-MEL1 (IC50: 88.91-277.25 µg/mL). All the EOs, except M. citrifolia EO, were also cytotoxic to the human keratinocytes non-tumorigenic cells, HaCat (IC50: 33.73-250.90 µg/mL). Altogether, some interesting therapeutic properties of the EOs of pharmacological/cosmeceutical interests were observed, which warrants further investigations.

Effects of Laser Forming on the Mechanical Properties and Microstructure of DP980 Steel.

Due to its high strength and good plasticity, dual-phase (DP) steel is widely used for manufacturing the structural and reinforcement components of automobiles. Therefore, it is urgent to investigate the mechanical properties and microstructure variation in DP steel after deformation, especially those subjected to hot-forming processes. In this study, the mechanical properties and microstructure of laser-formed DP980 steel plates under different laser parameters were investigated by means of monotonic tensile tests, microhardness tests, and metallographic tests. The results showed that both yield strength and tensile strength increased with increasing laser line energy in the range of 5~19 J/mm due to the increasing volume content of martensite laths. Elongation was slightly improved after the laser-forming process due to the existence of residual austenite. The average microhardness of the heat-affected zone also increased with an increase in laser line energy and reached a maximum of 412.8 HV0.2-an improvement of 23.5% compared to that of the parent material.

MIR99AHG inhibits EMT in pulmonary fibrosis via the miR-136-5p/USP4/ACE2 axis.

BACKGROUND: Long non-coding RNAs (lncRNAs) are closely related to the occurrence and development of cancer. Abnormally expressed lncRNA can be used as a diagnostic marker for cancer. In this study, we aim to investigate the clinical significance of MIR99AHG expression in lung adenocarcinoma (LUAD), and its biological roles in LUAD progression. METHODS: The relative expression of MIR99AHG in LUAD tissues and cell lines was analyzed using public databases and RT-qPCR. The biological functions of MIR99AHG were investigated using a loss-of-function approach. The effect of MIR99AHG on lung fibrosis was assessed by scratch assay, invasion assay and lung fibrosis rat model. FISH, luciferase reporter assay and immunofluorescence were performed to elucidate the underlying molecular mechanisms. RESULTS: LncRNA MIR99AHG expression level was downregulated in LUAD tissues and cell lines. Low MIR99AHG levels were associated with poorer patient overall survival. Functional analysis showed that MIR99AHG is associated with the LUAD malignant phenotype in vitro and in vivo. Further mechanistic studies showed that, MIR99AHG functions as a competitive endogenous RNA (ceRNA) to antagonize miR-136-5p-mediated ubiquitin specific protease 4 (USP4) degradation, thereby unregulated the expression of angiotensin-converting enzyme 2 (ACE2), a downstream target gene of USP4, which in turn affected alveolar type II epithelial cell fibrosis and epithelial-mesenchymal transition (EMT). In summary, the MIR99AHG/miR-136-5p/USP4/ACE2 signalling axis regulates lung fibrosis and EMT, thus inhibiting LUAD progression. CONCLUSION: This study showed that downregulated MIR99AHG leads to the development of pulmonary fibrosis. Therefore, overexpression of MIR99AHG may provide a new approach to preventing LUAD progression.

What we can learn from the exported cases in detecting disease outbreaks - a case study of the COVID-19 epidemic.

PURPOSE: Early warning in the travel origins is crucial to prevent disease spreading. When travel origins have delays in reporting disease outbreaks, the exported cases could be used to estimate the epidemic. METHODS: We developed a Bayesian model to jointly estimate the epidemic prevalence and detection delay using the exported cases and their arrival and detection dates. We used simulation studies to discuss potential biases generated by the exported cases. We proposed a hypothesis testing framework to determine the epidemic severity. RESULTS: We applied the method to the early phase of the COVID-19 epidemic of Wuhan, United States, Italy, and Iran and found that the indicators estimated from the exported cases were consistent with the domestic data under certain scenarios. The exported cases could generate various biases if not modeled properly. We presented the required number of exported cases for determining different severity levels of the outbreak. CONCLUSIONS: The exported case data is a good addition to the domestic data but also has its drawbacks. Utilizing the diagnosis resources from all countries, we advocate that countries work collaboratively to strengthen the global infectious disease surveillance system.