Long survival after neoadjuvant and adjuvant camrelizumab plus chemotherapy and surgery in a patient with hepatoid adenocarcinoma of the lung: A case report.

Hepatoid adenocarcinoma of the lung (HAL) is a rare and aggressive subtype of lung cancer. The prognosis for patients with HAL is generally poor and currently, there are only limited treatment options. Here, we present a case of a 47-year-old male diagnosed with locally advanced-stage HAL who achieved a remarkably long disease-free survival after receiving neoadjuvant and adjuvant camrelizumab plus chemotherapy and surgery. This case highlights the potential of immunochemotherapy plus surgery in improving outcomes for patients with HAL.

Human Amniotic Membrane-Derived Mesenchymal Stem Cells Prevent Acute Graft-Versus-Host Disease in an Intestinal Microbiome-Dependent Manner.

Acute graft-versus-host disease (aGVHD) represents a fatal severe complication after allogeneic hematopoietic stem cell transplantation. As a promising cell therapeutic strategy of aGVHD, the mechanism of mesenchymal stem cells (MSC) to ameliorate aGVHD has not been fully clarified, especially in the field of intestinal homeostasis including the intestinal microbiome involved in the pathogenesis of aGVHD. The present study aimed to explore the effect of MSC on intestinal homeostasis including the intestinal barrier and intestinal microbiome and its metabolites, as well as the role of intestinal microbiome in the preventive process of hAMSCs ameliorating aGVHD. The preventive effects of human amniotic membrane-derived MSC (hAMSCs) was assessed in humanized aGVHD mouse models. Immunohistochemistry and RT-qPCR were used to evaluate intestinal barrier function. The 16S rRNA sequencing and targeted metabolomics assay were performed to observe the alternation of intestinal microbiome and the amounts of medium-chain fatty acids (MCFAs) and short-chain fatty acids (SCFAs), respectively. Flow cytometry was performed to analyze the frequencies of T immune cells. Through animal experiments, we found that hAMSCs had the potential to prevent aGVHD. HAMSCs could repair the damage of intestinal barrier structure and function, as well as improve the dysbiosis of intestinal microbiome induced by aGVHD, and meanwhile, upregulate the concentration of metabolites SCFAs, so as to reshape intestinal homeostasis. Gut microbiota depletion and fecal microbial transplantation confirmed the involvement of intestinal microbiome in the preventive process of hAMSCs on aGVHD. Our findings showed that hAMSCs prevented aGVHD in an intestinal microbiome-dependent manner, which might shed light on a new mechanism of hAMSCs inhibiting aGVHD and promote the development of new prophylaxis regimes for aGVHD prevention.

Exploring effective network design for monitoring soil pH and potentially toxic elements based on geochemical surveys in economically developed area.

Periodically visiting soil monitoring sites, i.e., sampling and analysis, is recognized as one of the most important ways to monitor soil quality. However, reconciling the monitoring costs with monitoring precision of the soil monitoring network (SMN) is a key technical problem to be solved. A statistically sound method, which depends on the spatial variation in monitoring indicators, was adopted to determine the number of monitoring sites and the monitoring interval as well as their ability to detect a particular change under an economically feasible scenario. The spatial variation in soil monitoring indicators was inquired from the "Multi-Purpose Regional Geochemical Survey in Zhejiang Province (MRGSZ)" project. Based on the data for soil pH and concentration of potentially toxic elements, the number of monitoring sites and the monitoring intervals that might be used for soil monitoring were determined with the administrative region as the monitoring unit. The results showed that there was great spatial variation in the MRGSZ region, which resulted in discrepancies in the minimum detectable changes (MDCs), monitoring site numbers, and temporal monitoring intervals for revisiting. Our research proposes a number of monitoring sites (nr) that could reconcile the monitoring costs, practicability and monitoring precision; thus, it was recommended for the design of SMNs. Under nr, the MDC values of each monitoring indicator were acceptable for all administrative regions, and the temporal monitoring intervals were practical with variations of 6.7-14.8 years.

Therapeutic Effects of HLA-G5 Overexpressing hAMSCs on aGVHD After Allo-HSCT: Involving in the Gut Microbiota at the Intestinal Barrier.

Background: Acute graft-versus-host disease (aGVHD) initiated by intestinal barrier dysfunction and gut microbiota dysbiosis, remains one of the main obstacles for patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) to achieve good prognosis. Studies have suggested that mesenchymal stem cells (MSCs) can suppress immune responses and reduce inflammation, and human leukocyte antigen-G5 (HLA-G5) plays an important role in the immunomodulatory effects of MSCs, but very little is known about the potential mechanisms in aGVHD. Thus, we explored the effect of HLA-G5 on the immunosuppressive properties of human amnion MSCs (hAMSCs) and demonstrated its mechanism related to the gut microbiota at the intestinal barrier in aGVHD. Methods: Patients undergoing allo-HSCT were enrolled to detect the levels of plasma-soluble HLA-G (sHLA-G) and regulatory T cells (Tregs). Humanized aGVHD mouse models were established and treated with hAMSCs or HLA-G5 overexpressing hAMSCs (ov-HLA-G5-hAMSCs) to explore the mechanism of HLA-G5 mediated immunosuppressive properties of hAMSCs and the effect of ov-HLA-G5-hAMSCs on the gut microbiota at the intestinal barrier in aGVHD. Results: The plasma levels of sHLA-G on day +30 after allo-HSCT in aGVHD patients were lower than those in patients without aGVHD, and the sHLA-G levels were positively correlated with Tregs percentages. ov-HLA-G5-hAMSCs had the potential to inhibit the expansion of CD3+CD4+ T and CD3+CD8+ T cells and promote Tregs differentiation, suppress proinflammatory cytokine secretion but promote anti-inflammatory cytokines release. Besides, ov-HLA-G5-hAMSCs also could reverse the intestinal barrier dysfunction and gut microbiota dysbiosis in aGVHD. Conclusion: We demonstrated that HLA-G might work with Tregs to create a regulatory network together to reduce the occurrence of aGVHD. HLA-G5 mediated hAMSCs to exert higher immunosuppressive properties in vivo and reverse the immune imbalance caused by T lymphocytes and cytokines. Furthermore, HLA-G5 overexpressing hAMSCs could restore gut microbiota and intestinal barriers, thereby ameliorating aGVHD.

Human Amniotic Mesenchymal Stem Cells Alleviate aGVHD after allo-HSCT by Regulating Interactions between Gut Microbiota and Intestinal Immunity.

Acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation poses one of the most vexing challenges. Gut microbiota dysbiosis can proceed aGVHD and mesenchymal stem cells (MSCs) have promising therapeutic potential for aGVHD. However, whether hAMSCs affect the gut microbiota during aGVHD mitigation remains unknown. Accordingly, we sought to define the effects and underlying mechanisms of human amniotic membrane-derived MSCs (hAMSCs) regulating the gut microbiota and intestinal immunity in aGVHD. By establishing humanized aGVHD mouse models and hAMSCs treatment, we found that hAMSCs significantly ameliorated aGVHD symptoms, reversed the immune imbalance of T cell subsets and cytokines, and restored intestinal barrier. Moreover, the diversity and composition of gut microbiota were improved upon treatment with hAMSCs. Spearman's correlation analysis showed that there was a correlation between the gut microbiota and tight junction proteins, immune cells as well as cytokines. Our research suggested that hAMSCs alleviated aGVHD by promoting gut microbiota normalization and regulating the interactions between the gut microbiota and intestinal barrier, immunity.

Solar-to-H2 O2 Energy Conversion by the Photothermal Effect of a Polymeric Photocatalyst via a Two-Channel Pathway.

With a view to using solar energy, the exploitation of near-infrared (NIR) light, which constitutes about 50 % of solar energy, in photocatalytic H2 O2 synthesis remains challenging. In this study, resorcinol-formaldehyde (RF), which has a relatively low bandgap and high conductivity, is introduced for photothermal catalytic generation of H2 O2 under ambient conditions. Owing to the promoted surface charge transfer rate under high temperature, the photosynthetic yield reaches roughly 2000 µm within 40 min under 400 mW cm-2 irradiation with a solar-to-chemical conversion (SCC) efficiency of up to 0.19 % at 338 K under ambient conditions, exceeding the rate of photocatalysis with a cooling system by a factor of about 2.5. Notably, the H2 O2 produced by RF during photothermal process was formed via a two-channel pathway, leading to the overall promotion of H2 O2 formation. The resultant H2 O2 can be applied in situ for pollutant removal. This work offers a sustainable and economical route for the efficient formation of H2 O2 .

Regular Tennis Exercise May Improve the Vascular Endothelial Function in Postmenopausal Women: The Influence of Hemodynamics.

Physical inactivity plays a role in the incidence of cardiovascular disease (CVD). Although the current guidelines for physical activity, such as the prescription of exercise, seek to combat CVD, attaining the recommended targets remains challenging. Tennis exercise has been proven to have a unique advantage in reducing the mortality of CVD, but little is known about the influence of playing tennis on impaired vascular endothelial function (VEF), which initiates CVD. Thus, this study aimed to investigate whether regular tennis participation could protect the VEF better than merely meeting the physical activity recommended by the current guidelines. A cross-sectional design was performed based on a sample of 38 healthy postmenopausal women who were matched for physical activity, of which 17 subjects had long-term tennis experience and 21 age-matched subjects regularly exercised but did not play tennis. The cardiovascular function and the body composition of all subjects were measured. We used cluster analysis to assess the overall health status. The modeling results showed that the tennis players performed better in terms of VEF than the nonplayers (10.55 ± 0.58 vs. 8.69 ± 0.52, p < 0.01, R2ad = 0.367), while the wall shear stress positively correlated with VEF (r = 0.505, p < 0.05), after controlling for age and physical activity levels. Regular tennis exercise may be a protective factor for VEF, and further study should be performed to research the role of hemodynamics in tennis exercise.

KEADA: Identifying Key Classes in Software Systems Using Dynamic Analysis and Entropy-Based Metrics.

Software maintenance is indispensable in the software development process. Developers need to spend a lot of time and energy to understand the software when maintaining the software, which increases the difficulty of software maintenance. It is a feasible method to understand the software through the key classes of the software. Identifying the key classes of the software can help developers understand the software more quickly. Existing techniques on key class identification mainly use static analysis techniques to extract software structure information. Such structure information may contain redundant relationships that may not exist when the software runs and ignores the actual interaction times between classes. In this paper, we propose an approach based on dynamic analysis and entropy-based metrics to identify key classes in the Java GUI software system, called KEADA (identifying KEy clAsses based on Dynamic Analysis and entropy-based metrics). First, KEADA extracts software structure information by recording the calling relationship between classes during the software running process; such structure information takes into account the actual interaction of classes. Second, KEADA represents the structure information as a weighted directed network and further calculates the importance of each node using an entropy-based metric OSE (One-order Structural Entropy). Third, KEADA ranks classes in descending order according to their OSE values and selects a small number of classes as the key class candidates. In order to verify the effectiveness of our approach, we conducted experiments on three Java GUI software systems and compared them with seven state-of-the-art approaches. We used the Friedman test to evaluate all approaches, and the results demonstrate that our approach performs best in all software systems.

KIN17 promotes tumor metastasis by activating EMT signaling in luminal-A breast cancer.

BACKGROUND: Breast cancer (BC), the most common cause of cancer death in women, overtook lung cancer as the leading cause of cancer worldwide in 2020. Although many studies have proposed KIN17 as a biomarker of tumorigenesis in different cancer types, its role in tumor metastasis, particularly in BC metastasis, has been underexplored. This study aimed to explore the role of KIN17 in BC metastasis. METHODS: Survival analyses was performed to identify the association between KIN17 expression and BC patient survival in silico. Using lentivirus constructs, we developed bidirectional KIN17 expression (KD, knockdown; OE, overexpression) cellular models of luminal-A (Lum-A) breast cancer MCF-7 cells. We performed in vitro wound healing, transwell with and without Matrigel assays, and in vivo tail-vein metastasis assay to evaluate the migration and invasion abilities of MCF-7 with stable KIN17 knockdown or overexpression. Western blotting was performed to compare the changes in protein expression. RESULTS: We found that KIN17 expression was associated with poor overall survival (OS), relapse-free survival (RFS), distant metastasis-free survival (DMFS) and post-progression survival (PPS), particularly in Lum-A breast cancer patients. Later, we found that KIN17 knockdown inhibited migration and invasion of MCF-7 cells via regulating EMT-associated signaling pathways in vitro and decreases metastatic spread of the disease in vivo. In contrast, KIN17 overexpression promoted migration and invasion of MCF-7 cells in vitro and increased the metastatic spread of the disease in vivo. CONCLUSIONS: Overall, our findings provide preliminary data which suggests KIN17 of importance to target in metastatic Lum-A patients.

Correction: Xiang, Y.M.; Pan, W.F.; Jiang, H.B.; Zhu, Y.F.; Li, H. Measuring Software Modularity Based on Software Networks. Entropy 2019, 21, 344.

The authors wish to make the following corrections to the paper [...].

Sliding Trend Fuzzy Approximate Entropy as a Novel Descriptor of Heart Rate Variability in Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is a common sleep disorder that is often associated with reduced heart rate variability (HRV), thus reflecting modulation of the autonomic system. Sliding trend fuzzy approximate entropy (SlTr-fApEn), which is based on the empirical mode decomposition (EMD) method, has been proposed as a novel index for analyzing HRV with OSA. This study included 60 electrocardiogram recordings from the PhysioNet database (40 OSA recordings and 20 healthy recordings) with apnea or no apnea in 5-minute segments. HRV indices obtained by sliding trend analysis were compared to those obtained by time-frequency domain analysis. Among all indices, the ratio of low-frequency power and high-frequency power (LF/HF) and sliding trend indices could significantly differentiate OSA recordings from normal recordings (p < 0.05). The OSA screening accuracy of SlTr-fApEn (85%) was higher than that of LF/HF (80%). Disease state analysis showed significant differences in SlTr-fApEn among the control group, normal OSA group, and apnea OSA group (p < 0.05). Therefore, SlTr-fApEn can reflect the complexity of autonomic changes during a short time period.

Measuring Software Modularity Based on Software Networks.

Modularity has been regarded as one of the most important properties of a successful software design. It has significant impact on many external quality attributes such as reusability, maintainability, and understandability. Thus, proposing metrics to measure the software modularity can be very useful. Although several metrics have been proposed to characterize some modularity-related attributes, they fail to characterize software modularity as a whole. A complex network uses network models to abstract the internal structure of complex systems, providing a general way to analyze complex systems as a whole. In this paper, we introduce the complex network theory into software engineering and employ modularity, a metric widely used in the field of community detection in complex network research, to measure software modularity as a whole. First, a specific piece of software is represented by a software network, feature coupling network (FCN), where methods and attributes are nodes, couplings between methods and attributes are edges, and the weight on the edges denotes the coupling strength. Then, modularity is applied to the FCN to measure software modularity. We apply the Weyuker's criteria which is widely used in the field of software metrics, to validate the modularity as a software metric theoretically, and also perform an empirical evaluation using open-source Java software systems to show its effectiveness as a software metric to measure software modularity.

The Interaction Analysis between the Sympathetic and Parasympathetic Systems in CHF by Using Transfer Entropy Method.

Congestive heart failure (CHF) is a cardiovascular disease associated with autonomic dysfunction, where sympathovagal imbalance was reported in many studies using heart rate variability (HRV). To learn more about the dynamic interaction in the autonomic nervous system (ANS), we explored the directed interaction between the sympathetic nervous system (SNS) and the parasympathetic nervous system (PNS) with the help of transfer entropy (TE). This article included 24-h RR interval signals of 54 healthy subjects (31 males and 23 females, 61.38 ± 11.63 years old) and 44 CHF subjects (8 males and 2 females, 19 subjects' gender were unknown, 55.51 ± 11.44 years old, 4 in class I, 8 in class II and 32 in class III~IV, according to the New York Heart Association Function Classification), obtained from the PhysioNet database and then segmented into 5-min non-overlapping epochs using cubic spline interpolation. For each segment in the normal group and CHF group, frequency-domain features included low-frequency (LF) power, high-frequency (HF) power and LF/HF ratio were extracted as classical estimators of autonomic activity. In the nonlinear domain, TE between LF and HF were calculated to quantify the information exchanging between SNS and PNS. Compared with the normal group, an extreme decrease in LF/HF ratio (p = 0.000) and extreme increases in both TE(LF→HF) (p = 0.000) and TE(HF→LF) (p = 0.000) in the CHF group were observed. Moreover, both in normal and CHF groups, TE(LF→HF) was a lot greater than TE(HF→LF) (p = 0.000), revealing that TE was able to distinguish the difference in the amount of directed information transfer among ANS. Extracted features were further applied in discriminating CHF using IBM SPSS Statistics discriminant analysis. The combination of the LF/HF ratio, TE(LF→HF) and TE(HF→LF) reached the highest screening accuracy (83.7%). Our results suggested that TE could serve as a complement to traditional index LF/HF in CHF screening.

[Quantitative partitioning of soil selenium in the selenium-rich area of Northern Zhejiang Plain].

To clarify the contribution of different component of selenium is the basis for evaluation of the sustainable development and utilization of selenium-rich soil. Xiuzhou district, where the soil is rich in selenium, was chosen as the study area, and its soil selenium content was qualitatively separated as the natural background component and the exogenous component through cross-validation of integrated geo-analysis and multivariate statistics. Subsequently, the contribution rate of the different component of the selenium content was separated quantitatively using frequency distribution functions. The results showed that the natural background component accounted for 90% in the soil selenium content and the exogenous component accounted for 10%, which indicated that the land sources rich in selenium in Xiuzhou district has the potential for sustainable development and utilization.