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Abstract Wireless capsule endoscopy (WCE) offers a non-invasive evaluation of the digestive system, eliminating the need for sedation and the risks associated with conventional endoscopic procedures. Its significance lies in diagnosing gastrointestinal tissue irregularities, especially in the small intestine. However, existing commercial WCE devices face limitations, such as the absence of autonomous lesion detection and treatment capabilities. Recent advancements in micro-electromechanical fabrication and computational methods have led to extensive research in sophisticated technology integration into commercial capsule endoscopes, intending to supersede wired endoscopes. This Review discusses the future requirements for intelligent capsule robots, providing a comparative evaluation of various methods’ merits and disadvantages, and highlighting recent developments in six technologies relevant to WCE. These include near-field wireless power transmission, magnetic field active drive, ultra-wideband/intrabody communication, hybrid localization, AI-based autonomous lesion detection, and magnetic-controlled diagnosis and treatment. Moreover, we explore the feasibility for future “capsule surgeons”.

Abstract Activation of the Hippo pathway by angiomotins to limit colorectal cancer progression is prevalent, whereas the regulation of angiomotins remains elusive. In this study, we uncover the involvement of an upregulated E3 ubiquitin ligase called RNF166, which destabilizes angiomotins, activates YAP, and is associated with a poor prognosis in colorectal cancer patients. Mechanistically, RNF166 specifically recognizes PARsylated angiomotin, a modification mediated by tankyrase at specific amino acid residues (D506, E513, E516, and E528). The tankyrase inhibitor XAV939, effectively prevents RNF166-dependent destabilization of angiomotins and subsequent activation of YAP. Additionally, YAP-5SA, a constitutively active form of YAP, rescues colorectal cancer progression following knockdown of RNF166. Importantly, the C-terminus of RNF66, particularly the Di19-ZF domain, is the crucial region responsible for recognizing ADP-ribosylated angiomotins. Together, this work not only sheds light on the regulation of the Hippo pathway in colorectal cancer but also uncovers a novel poly(ADP-ribose)-binding domain, which may serve as a potential therapeutic target for intervention.

Abstract Cholesterol 25‐hydroxylase (CH25H), an enzyme involved in cholesterol metabolism, regulates inflammatory responses and lipid metabolism. However, its role in kidney disease is not known. The author found that CH25H transcript is expressed mostly in glomerular and peritubular endothelial cells and that its expression increased in human and mouse diabetic kidneys. Global deletion of Ch25h in Leprdb/db mice aggravated diabetic kidney disease (DKD), which is associated with increased endothelial cell apoptosis. Treatment of 25‐hydroxycholesterol (25‐HC), the product of CH25H, alleviated kidney injury in Leprdb/db mice. Mechanistically, 25‐HC binds to GTP‐binding protein ADP‐ribosylation factor 4 (ARF4), an essential protein required for maintaining protein transport in the Golgi apparatus. Interestingly, ARF4's GTPase‐activating protein ASAP1 is also predominantly expressed in endothelial cells and its expression increased in DKD. Suppression of ARF4 activity by deleting ARF4 or overexpressing ASAP1 results in endothelial cell death. These results indicate that 25‐HC binds ARF4 to inhibit its interaction with ASAP1, and thereby resulting in enhanced ARF4 activity to confer renoprotection. Therefore, treatment of 25‐HC improves kidney injury in DKD in part by restoring ARF4 activity to maintain endothelial cell survival. This study provides a novel mechanism and a potential new therapy for DKD.

Introduction:Exercise, health, and the gut microbiota (GM) are strongly correlated. Research indicates that professional athletes, especially ultra-marathon runners, have unique GM characteristics. However, more research has focused on elite athletes, with little attention given to amateur sports enthusiasts, especially those in the middle-aged population. Therefore, this study focuses on the impact of long-term running on the composition and potential functions of the GM in middle-aged individuals.Methods:We compared the GM of 25 middle-aged serious runnerswith 22 sedentary healthy controls who had minimal exercise habitsusing 16S rRNA gene sequencing. Additionally, we assessed dietary habits using a food frequency questionnaire.Results and Discussion:Statistical analysis indicates that there is no significant difference in dietary patterns between the control group and serious runners. Diversity analysis results indicate that there is no significant difference in α diversity between the two groups of GM, but there is a significant difference in β diversity. Analysis of the composition of GM reveals that Ruminococcus and Coprococcus are significantly enriched in serious runners, whereas Bacteroides, Lachnoclostridium, and Lachnospira are enriched in the control group. Differential analysis of functional pathway prediction results reveals significant differences in the functional metabolism levels of GM between serious runners and the control group. Further correlation analysis results indicate that this difference may be closely related to variations in GM. In conclusion, our results suggest that long-term exercise can lead to changes in the composition of the GM. These changes have the potential to impact the overall health of the individual by influencing metabolic regulation.

Genetic diseases are currently diagnosed by functional mutations. However, only some mutations are associated with disease. It is necessary to establish a quick prediction model for clinical screening. Pathogenic mutations in NGLY1 cause a rare autosomal recessive disease known as congenital disorder of deglycosylation (NGLY1-CDDG). Although NGLY1-CDDG can be diagnosed through gene sequencing, clinical relevance of a detected mutation in NGLY1 needs to be further confirmed. In this study, taken NGLY1-CDDG as an example, a comprehensive and practical predictive model for pathogenic mutations on NGLY1 through an NGLY1/Glycopeptide complex model was constructed, the binding sites of NGLY1 and glycopeptides were simulated, and an in vitro enzymatic assay system was established to facilitate quick clinical decisions for NGLY1-CDDG patients. The docking model covers 42 % of reported NGLY1-CDDG missense mutations (5/12). All reported mutations were subjected to in vitro enzymatic assay in which 18 mutations were dysfunctional (18/30). In addition, a full spectrum of functional R328 mutations was assayed and 11 mutations were dysfunctional (11/19). In this study, a model of NGLY1 and glycopeptides was built for potential functional mutations in NGLY1. In addition, the effect of potential regulatory compounds, including N-acetyl-l-cysteine and dithiothreitol, on NGLY1 was examined. The established in vitro assay may serve as a standard protocol to facilitate rapid diagnosis of all mutations in NGLY1-CDDG. This method could also be applied as a comprehensive and practical predictive model for the other rare genetic diseases.

ObjectiveIn order to solve the problem that noise detection inside a cabin is difficult due to the complexity and narrow space, a local space planning method of a manipulator based on the goal-oriented rapidly-exploring random tree (RRT) algorithm is proposed. MethodA six-degrees-of-freedom (6-DOF) manipulator is used as the carrier, and a fixture is installed at the end of the manipulator. The four fixed points inside the cabin are used as the reference points to study the mechanical arm in the local space. The trajectory planning is traversed and the reference point-1 is taken as an example to measure the noise of its 6 measurement surfaces and 147 measurement points. The noise signal and the position and attitude information of the space to be measured are matched and analyzed, and the environmental noise of the current measurement point is fed back to form a sound pressure cloud map. ResultsThe experimental results show that the robotic arm can realize trajectory planning and noise measurement for all measurement points corresponding to the four reference points without collision. ConclusionThe proposed method has practical value in being able to realize intelligent planning and internal noise detection in narrow cabin areas.

Abstract Background Staphylococcus haemolyticus (S. haemolyticus) is the main etiological factor in skin and soft tissue infections (SSTI). S. haemolyticus infections are an important concern worldwide, especially with the associated biofilms and drug resistance. Herein, we investigated the inhibitory effect of Flavaspidic acid BB obtained from plant extractions on clinical S. haemolyticus strains and their biofilms. Moreover, we predicted its ability to bind to the protein-binding site by molecular simulation. Since the combination of Hsp70 and RNase P synthase after molecular simulation with flavaspidic acid BB is relatively stable, enzyme-linked immunosorbent assay (ELISA) was used to investigate Hsp70 and RNase P synthase to verify the potential antimicrobial targets of flavaspidic acid BB. Results The minimum inhibitory concentrations (MIC) of flavaspidic acid BB on 16 clinical strains of S. haemolyticus was 5 ~ 480 µg/mL, and BB had a slightly higher inhibitory effect on the biofilm than MUP. The inhibitory effect of flavaspidic acid BB on biofilm formation was better with an increase in the concentration of BB. Molecular simulation verified its ability to bind to the protein-binding site. The combination of ELISA kits showed that flavaspidic acid BB promoted the activity of Hsp70 and inhibited the activity of RNase P, revealing that flavaspidic acid BB could effectively inhibit the utilization and re-synthesis of protein and tRNA synthesis, thus inhibiting bacterial growth and biofilm formation to a certain extent. Conclusions This study could potentially provide a new prospect for the development of flavaspidic acid BB as an antibacterial agent for resistant strains.

4,4-Dimethylsterols constitute a unique class of phytosterols responsible for regulating endogenous cannabinoid system (ECS) functions. However, precise mechanism through which 4,4-dimethylsterols affect fat metabolism and the linkage to the ECS remain unresolved. In this study, we identified that 4,4-dimethylsterols, distinct from 4-demethseterols, act as inhibitors of fatty acid amide hydrolases (FAAHs) both in vivo and in vitro. Genetic ablation of FAAHs (faah-1) abolishes the effects of 4,4-dimethylsterols on fat accumulation and locomotion behavior in a Caenorhabditis elegans model. We confirmed that dietary intervention with 4,4-dimethylsterols in a high-fat diet (HFD) mouse model leads to a significant reduction in body weight (>11.28%) with improved lipid profiles in the liver and adipose tissues and increased fecal triacylglycerol excretion. Untargeted and targeted metabolomics further verified that 4,4-dimethylsterols influence unsaturated fatty acid biosynthesis and elevate oleoyl ethanolamine levels in the intestine. We propose a potential molecular mechanism in which 4,4-dimethylsterols engage in binding interactions with the catalytic pocket (Ser241) of FAAH-1 protein due to the shielded polarity, arising from the presence of 2 additional methyl groups (CH3). Consequently, 4,4-dimethylsterols represent an unexplored class of beneficial phytosterols that coordinate with FAAH-1 activity to reduce fat accumulation, which offers new insight into intervention strategies for treating diet-induced obesity.

Seed vigor (SV) is a crucial trait determining the quality of crop seeds. Currently, over 80% of China’s cotton-planting area is in Xinjiang Province, where a fully mechanized planting model is adopted, accounting for more than 90% of the total fiber production. Therefore, identifying SV-related loci and genes is crucial for improving cotton yield in Xinjiang. In this study, three seed vigor-related traits, including germination potential, germination rate, and germination index, were investigated across three environments in a panel of 355 diverse accessions based on 2,261,854 high-quality single-nucleotide polymorphisms (SNPs). A total of 26 significant SNPs were detected and divided into six quantitative trait locus regions, including 121 predicted candidate genes. By combining gene expression, gene annotation, and haplotype analysis, two novel candidate genes (Ghir_A09G002730 and Ghir_D03G009280) within qGR-A09-1 and qGI/GP/GR-D03-3 were associated with vigor-related traits, and Ghir_A09G002730 was found to be involved in artificial selection during cotton breeding by population genetic analysis. Thus, understanding the genetic mechanisms underlying seed vigor-related traits in cotton could help increase the efficiency of direct seeding by molecular marker-assisted selection breeding.

Abstract Tumor-associated macrophages (TAMs) are highly heterogeneous and play vital roles in tumor progression. Here we adopted a C57BL/6 mouse model imitating the late-stage colorectal liver metastasis (CRLM) by Mc38 colorectal cancer cell injection via the portal vein. With serial sections of CRLM biopsies, we defined 7–9 days post-injection as the critical period for tumor neovascularization, which was initiated from the innate liver vessels via vessel cooption and extended by vascular mimicry and thereof growth of CD34+cells. In samples with increasing-sized liver metastases, the infiltrated Ly6C+ CD11b+ F4/80− monocytes steadily gained the expression of F4/80, a Kupffer cell marker, before transformed into Ly6C− CD11bint F4/80+ cells, which, the same phenotype was also adapted by Ly6C− CD11b− F4/80+ Kupffer cells. F4/80+ TAMs showed proximity to neovascularization and tumor vessels, functionally angiogenic in vivo; and greatly promoted the activation of a few key angiogenic markers such as VEGFA, Ki67, etc. in endothelial cells in vitro. Depletion of macrophages or diversion of macrophage polarization during neovascularization impeded tumor growth and vascularization and resulted in greatly reduced F4/80+ TAMs, yet increased CD11b+ cells due to inhibition of TAM differentiation. In summary, our results showed dynamic and spatial–temporal F4/80+ TAM transformation within the tumor microenvironment and strengthened its role as perivascular and angiogenic TAMs in CRLM.

ObjectiveThis paper aims to evaluate the impact of flow-induced vibration on the receiver performance of low-frequency magnetic antenna in an underwater environment, investigating the electromagnetic-induced noise of antenna under different vibration conditions. MethodsFirst, a fluid excitation antenna vibration model is established using COMSOL software, then an antenna vibration-induced noise model is constructed to simulate electromagnetic-induced noise. Finally, outdoor experiments to measure the antenna vibration-induced noise are carried out. Results The results show that the stronger the antenna vibration is, the greater the electromagnetic-induced noise is. When the antenna vibration acceleration reaches 0.029 4 m/s², the electromagnetic-induced noise above the pT level will be caused, and the normal communication signal will be submerged. ConclusionThe results show that the proposed model in this paper can be used to evaluate the vibration-induced noise of low frequency magnetic antenna.

Fenofibrate is known as a lipid-lowering drug. Although previous studies have reported that fenofibrate exhibits potential antitumor activities, IC50 values of fenofibrate could be as high as 200 μM. Therefore, we investigated the antitumor activities of six synthesized fenofibrate derivatives. We discovered that one compound, SIOC-XJC-SF02, showed significant antiproliferative activity on human hepatocellular carcinoma (HCC) HCCLM3 cells and HepG2 cells (the IC50 values were 4.011 μM and 10.908 μM, respectively). We also found this compound could inhibit the migration of human HCC cells. Transmission electron microscope and flow cytometry assays demonstrated that this compound could induce apoptosis of human HCC cells. The potential binding sites of this compound acting on human HCC cells were identified by mass spectrometry-cellular thermal shift assay (MS-CETSA). Molecular docking, Western blot, and enzyme activity assay-validated binding sites in human HCC cells. The results showed that fumarate hydratase may be a potential binding site of this compound, exerting antitumor effects. A xenograft model in nude mice demonstrated the anti-liver cancer activity and the mechanism of action of this compound. These findings indicated that the antitumor effect of this compound may act via activating fumarate hydratase, and this compound may be a promising antitumor candidate for further investigation.

Abstract Background Cardiac damage is the leading cause of death in uremic patients. This study aimed to evaluate the application of non-invasive myocardial work index (NIMWI) by echocardiography in assessing the left ventricular (LV) systolic function in uremic patients. Methods Twenty-six uremic patients and 27 age- and sex-matched healthy volunteers were enrolled in the study. Except for the conventional echocardiographic parameters, the LV myocardial work (MW) parameters including GWI (myocardial global work index), GCW (global constructive work), GWW (global wasted work), and GWE (global work efficiency) were calculated in study participants. Differences in MW parameters between the uremic and normal groups were compared by independent-sample t-test. Receiver operating characteristic (ROC) curves were constructed for MW parameters to detect abnormal LV systolic function in uremic patients. Results Compared with the normal group, GWW was significantly increased and GWE decreased in the uremic group (P

Background: Spatial transcriptome (ST) provides molecular profiles of tumor cells at the spatial level, which brings new progress to the research of tumors and the tumor microenvironment. This study summarizes the experiences and lessons learned in the spatial section preparation of two different pathological types of nose and skull base tumors at our institution, with the aim of offering guidelines to researchers to avoid wasting precious samples and provide a basis for the application of ST in clinical practice. Methods: Frozen tissue blocks from patients with squamous cell carcinoma and adenocarcinoma of the nose and skull base diagnosed at our institution were prepared. The effects of different procedures and pathological tissue types on slide quality were explored and evaluated using RNA integrity number (RIN) and HE scores as criteria. The effects of different RIN values on ST sequencing data were explored. Results: A total of 43 samples were obtained from 26 patients, including 22 with squamous carcinomas and 21 with adenocarcinomas. Thirteen samples with satisfactory RNA quality control and good histological morphology were sequenced for ST. Sample isolation time 7 in ST sequencing results was found, indicating that RIN ≥6 can be used as a criterion for qualified RNA quality control. Therefore, fresh tissues washed as soon as possible with cold PBS and then dried using OCT for snap freezing are currently the best method for preparing spatial sections of nose and skull base tumor tissues of different pathological types. Conclusion: This study is the first to investigate the feasibility of applying ST to different pathological types of nose and skull base tumors and to demonstrate the widespread application of ST in tumors. Rational optimization of spatial slide preparation procedures and exploration of individualized pre-sequencing protocols are used as the first stage to ensure the quality of spatial sequencing and lay the foundation for subsequent spatial analysis.

Abstract Immunosuppressive tumor microenvironment is a crucial factor that impedes the success of tumor immunotherapy, and tumor-associated macrophages (TAMs) are essential for the formation of tumor immunosuppressive microenvironment. Hyaluronic acid (HA) is highly important brick for glioblastoma microenvironment, but whether it contributes to TAM polarization and glioblastoma immunosuppressive microenvironment is less well known. In our study, we observed that disrupting glioblastoma HA synthesis or blocking HA binding to its receptor CD44 on macrophages increased the proportion of M1 macrophages by upregulating SIRPα in macrophages, the underlying mechanism was elevated SIRPα enhanced STAT1 phosphorylation and suppressed STAT3 phosphorylation in macrophages. Subsequently, the induced macrophages could inhibit glioblastoma growth via a feedback effect. In addition, 4-methylumbelliferone (4MU), a cholecystitis drug, can disrupt the CD47/SIRPα axis by disturbing glioblastoma HA synthesis. Collectively, these findings indicated that HA plays a crucial role in macrophages polarization and CD47/SIRPα signaling between glioblastoma cells and macrophages, and suppressing the HA pathway may be a new immunotherapeutic approach for glioblastoma.

Mine fires are one of the common major disasters in underground mining. In addition to the external fire sources generated by mining equipment and mechanical and electrical equipment during operations, coal is exposed to air during mining, and spontaneous combustion is also the main cause of mine fires. In order to reduce the hidden danger of coal mines caused by spontaneous coal combustion during lignite mining, the microbial inhibition of coal spontaneous combustion is proposed in this paper. Via SEM, pore size analysis, and NMR and FT-IR experiments, the mechanism of coal spontaneous combustion is discussed and revealed. The modification of lignite before and after the addition of retardants is analyzed from the perspective of microstructure, and the change in flame retardancy of the lignite treated with two retardants compared with raw coal is explored. The results show that, compared with raw coal, a large number of calcium carbonate particles are attached to the surface of the coal sample after bioinhibition treatment, and the total pore volume and specific surface area of the coal sample after bioinhibition treatment are decreased by 68.49% and 74.01%, respectively, indicating that bioinhibition can effectively plug the primary pores. The results of NMR and Fourier infrared spectroscopy show that the chemical structure of the coal sample is mainly composed of aromatic carbon, followed by fatty carbon and carbonyl carbon. In addition, the contents of active groups (hydroxyl, carboxyl, and methyl/methylene) in lignite after bioretardation are lower than those in raw coal, and methyl/methylene content is decreased by 96.5%. The comparison shows that the flame-retardant performance of biological retardants is better than that of chemical retardants, which provides an effective solution for the efficient prevention and control of spontaneous combustion disasters in coal mines.

N-glycanase 1 (NGLY1) is an essential enzyme involved in the deglycosylation of misfolded glycoproteins through the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, which could hydrolyze N-glycan from N-glycoprotein or N-glycopeptide in the cytosol. Recent studies indicated that NGLY1 inhibition is a potential novel drug target for antiviral therapy. In this study, structure-based virtual analysis was applied to screen candidate NGLY1 inhibitors from 2960 natural compounds. Three natural compounds, Poliumoside, Soyasaponin Bb, and Saikosaponin B2 showed significantly inhibitory activity of NGLY1, isolated from traditional heat-clearing and detoxifying Chinese herbs. Furthermore, the core structural motif of the three NGLY1 inhibitors was a disaccharide structure with glucose and rhamnose, which might exert its action by binding to important active sites of NGLY1, such as Lys238 and Trp244. In traditional Chinese medicine, many compounds containing this disaccharide structure probably targeted NGLY1. This study unveiled the leading compound of NGLY1 inhibitors with its core structure, which could guide future drug development.

BackgroundPrimary neuroendocrine neoplasm of the breast (BNEN) is an uncommon breast neoplasm, and in most cases, it presents as hormone receptors positive and HER-2 negative. Moreover, in neuroendocrine neoplasms (NENs), the signet ring feature is a rare morphological subtype, and only a few cases have been reported. Here, we report the case of a primary breast neuroendocrine neoplasm with an unusual signet ring cell appearance in this paper. The documentation of this case, combined with a review of the literature, may add to existing knowledge about the outcome and management of this rare tumor.MethodsIn the present review, we describe a unique case of HER-2-positive primary BNEN with a signet ring feature that has not been reported in English. Additionally, we performed a literature search of the PubMed and Web of Science databases and calculated statistics for clinical data and follow-up.ResultsOur literature search, excluding non-English literature, identified 15 articles with data from 24 cases, including ours. The mean age was 51.25 years (range, 30–79 years), and there were 13 male patients (54%) and 11 female patients (46%). Of the 24 cases, some cases (11/24) were associated with lymph node metastases, a few cases (6/24) had distant metastasis, and the vast majority of cases (23/24) occurred in the digestive system. Primary hepatic signet ring cell neuroendocrine tumor showed slow progression and good prognosis. Lymph node involvement was identified in one of eight (12.5%) documented cases, and one of eight (12.5%) reported cases presented with distant metastatic disease. However, the prognosis of neuroendocrine tumors with signet ring cells in the pancreas and stomach was poor. Lymph node involvement was identified in 9 of 15 (60%) documented cases, and 5 of 15 (33.3%) reported cases presented with distant metastatic disease.ConclusionNENs with a signet ring feature is uncommon, and this is the first case report of its occurrence in the breast. Current knowledge is limited to anecdotal experience based on case reports and small case series. We provide a literature review to summarize knowledge about this rare entity.

Abstract Background There are two genetically distinct subspecies of cattle, Bos taurus taurus and Bos taurus indicus, which arose from independent domestication events. The two types of cattle show substantial phenotypic differences, some of which emerge during fetal development and are reflected in birth outcomes, including birth weight. We explored gene expression profiles in the placenta and four fetal tissues at mid-gestation from one taurine (Bos taurus taurus; Angus) and one indicine (Bos taurus indicus; Brahman) breed and their reciprocal crosses. Results In total 120 samples were analysed from a pure taurine breed, an indicine breed and their reciprocal cross fetuses, which identified 6456 differentially expressed genes (DEGs) between the two pure breeds in at least one fetal tissue of which 110 genes were differentially expressed in all five tissues examined. DEGs shared across tissues were enriched for pathways related to immune and stress response functions. Only the liver had a substantial number of DEGs when reciprocal crossed were compared among which 310 DEGs were found to be in common with DEGs identified between purebred livers; these DEGs were significantly enriched for metabolic process GO terms. Analysis of DEGs across purebred and crossbred tissues suggested an additive expression pattern for most genes, where both paternal and maternal alleles contributed to variation in gene expression levels. However, expression of 5% of DEGs in each tissue was consistent with parent of origin effects, with both paternal and maternal dominance effects identified. Conclusions These data identify candidate genes potentially driving the tissue-specific differences between these taurine and indicine breeds and provide a biological insight into parental genome effects underlying phenotypic differences in bovine fetal development.

BackgroundThe capacity to distinguish hypertrophic cardiomyopathy (HCM) from hypertensive left ventricular hypertrophy (H-LVH) based on morphological features obtained by conventional echocardiography is limited. We investigated the global myocardial work of the left ventricle in two types of hypertrophies using the non-invasive myocardial work index (NMWI).MethodsConventional echocardiography was performed on 107 subjects with preserved left ventricular ejection fraction (LVEF ≥ 50%), who comprised patients with HCM (n = 40), H-LVH (n = 35), and healthy people with normal blood pressure and left ventricular structure (n = 32). Except for the conventional echocardiographic parameters, the left ventricular myocardial work parameters based on pressure-strain loops, including global myocardial work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE), were evaluated in three groups. Multivariate discriminant analysis and receiver operating characteristic (ROC) curve were used to evaluate the incremental value of NMWI for distinguishing HCM from H-LVH.ResultsCompared to the control group, GWI and GCW were significantly lower in HCM patients (P < 0.05), whereas GWI was significantly higher in H-LVH patients. GWW was higher and GWE was significantly decreased in both HCM and H-LVH patients than in the control group (P < 0.05). Multivariate discriminant analysis and ROC curve revealed that the inter-ventricular septum thickness (IVST)/left ventricular posterior wall thickness (LVPWT) and GCW were each able to distinguish HCM from H-LVH. The combination of IVST/LVPWT and GCW discriminated HCM and H-LVH with a higher predictive accuracy of 94.7%.ConclusionNMWI may provide additional information in evaluating the myocardial function in patients with HCM and H-LVH. Myocardial work combined with conventional echocardiography could improve the clinical diagnostic accuracy of distinguishing HCM and H-LVH.

Previously, we showed that mouse immunity-related guanosine triphosphatase (GTPase) family M protein 1 (Irgm1) promotes malignant melanoma progression by inducing cellular autophagy flux and metastasis. Human IRGM, a truncated protein functionally distinct from its mouse counterpart, has several splice isoforms. In this study, we analyzed the association of IRGM and human melanoma clinical prognosis and investigated the function of IRGM in human melanoma cells. Data from the training cohort (n = 144) showed that overexpression of IRGM is proportional to melanoma genesis and clinical stages in human tissue chips. A validation cohort (n = 78) further confirmed that IRGM is an independent risk factor promoting melanoma progression and is associated with poor survival of patients. Among IRGM isoforms, we found that IRGMb is responsible for such correlation. In addition, IRGM promoted melanoma cell survival through autophagy, both in vitro and in vivo. We further showed that the blockade of translocation of high-mobility group box 1 (HMGB1) from the nucleus to cytoplasm inhibits IRGM1-mediated cellular autophagy and reduces cell survival. IRGM functions as a positive regulator of melanoma progression through autophagy and may serve as a promising prognostic marker and therapeutic target.

This paper establishes a shareholder-stock bipartite network based on the data of large shareholders’ shareholding in the Shanghai A-share market of China in 2021. Based on the shareholder-stock bipartite network, the statistically validated network model is applied to establish a shareholder projected network and a stock projected network, whose structural characteristics can intuitively reveal the overlapping portfolios among different shareholders, as well as shareholder allocation structures among different stocks. The degree of nodes in the shareholder projected network obeys the power law distribution, the network aggregation coefficient is large, while the degree of most nodes in the stock projected network is small and the network aggregation coefficient is low. Furthermore, the two projected networks’ community structures are analyzed, respectively. Most of the communities in the shareholder projected network and stock projected network are small-scaled, indicating that the majority of large shareholders hold different shares from each other, and the investment portfolios of large shareholders in different stocks are also significantly different. Finally, by comparing the stock projected sub-network obtained from the shareholder-stock bipartite sub-network in which the degree of shareholder nodes is 2 and the original stock projected network, the effectiveness of the statistically validated network model, and the community division method on the research of the shareholder-stock bipartite network are further verified. These results have important implications for understanding the investment behavior of large shareholders in the stock market and contribute to developing investment strategies and risk management practices.

Abstract Background Circular RNAs (circRNAs) are a class of endogenous single-strand RNA transcripts with crucial regulation in human cancers. The objective of this study is to investigate the role of circ_0082182 in CRC and its specific functional mechanism. Methods The quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure the levels of circ_0082182, microRNA-411 (miR-411) and microRNA-1205 (miR-1205). Cell proliferation was detected by Cell counting Kit-8 (CCK-8) and colony formation assays. Flow cytometry was used for determining cell cycle and cell apoptosis. Cell apoptosis was also assessed by caspase3 and caspase9 activities. Cell migration and invasion were examined using scratch assay and transwell assay. The interaction between circ_0082182 and miRNA was validated by the dual-luciferase reporter and biotinylated RNA pull-down assays. Wnt/β-catenin pathway and epithelial-mesenchymal transition (EMT)-associated proteins were quantified by Western blot. Xenograft model was established for the research of circ_0082182 in vivo. Results Circ_0082182 was upregulated in CRC and could predict the poor prognosis of CRC patients. Functionally, circ_0082182 promoted CRC cell proliferation, cell cycle progression, and metastasis while inhibited apoptosis. Subsequently, circ_0082182 was shown to act as the sponges of miR-411 and miR-1205. MiR-411 and miR-1205 were identified as tumor inhibitors in CRC. Furthermore, circ_0082182 promoted the CRC progression via sponging miR-411 and miR-1205. Moreover, circ_0082182 facilitated the Wnt/β-catenin pathway and EMT process by targeting miR-411 and miR-1205. In vivo, circ_0082182 accelerated the CRC tumorigenesis and EMT process by activating the Wnt/β-catenin pathway by downregulating the expression of miR-411 or miR-1205. Conclusion This study showed that circ_0082182 functioned as an oncogene in the developing process of CRC by sponging miR-411 or miR-1205 to activate the Wnt/β-catenin pathway. Circ_0082182 might be a molecular target in the diagnosis and treatment of CRC.

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in southern China and southeast Asia. Emerging evidence revealed that long noncoding RNAs (lncRNAs) might play important roles in the development and progression of many cancers, including NPC. The functions and mechanisms of the vast majority of lncRNAs involved in NPC remain unknown. In this study, a novel lncRNA RP11-624L4.1 was identified in NPC tissues using next-generation sequencing. In situ hybridization (ISH) was used to analyze the correlation between RP11-624L4.1 expression and the clinicopathological features or prognosis in NPC patients. RNA-Protein Interaction Prediction (RPISeq) predictions and RNA-binding protein immunoprecipitation (RIP) assays were used to identify RP11-624L4.1’s interactions with cyclin-dependent kinase 4 (CDK4). As a result, we found that RP11-624L4.1 is hyper-expressed in NPC tissues, which was associated with unfavorable prognosis and clinicopathological features in NPC. By knocking down and overexpressing RP11-624L4.1, we also found that it promotes the proliferation ability of NPC in vitro and in vivo through the CDK4/6-Cyclin D1-Rb-E2F1 pathway. Overexpression of CDK4 in knocking down RP11-624L4.1 cells can partially rescue NPC promotion, indicating its role in the RP11-624L4.1-CDK4/6-Cyclin D1-Rb-E2F1 pathway. Taken together, RP11-624L4.1 is required for NPC unfavorable prognosis and proliferation through the CDK4/6-Cyclin D1-Rb-E2F1 pathway, which may be a novel therapeutic target and prognostic in patients with NPC.

Nosocomial infection by multi-drug resistance Elizabethkingia spp. is an emerging concern with severe clinical consequences, particularly in immunocompromised individuals and infants. Efficient control of this infection requires quick and reliable methods to determine the appropriate drugs for treatment. In this study, a total of 31 Elizabethkingia spp., including two standard strains (ATCC 13253 and FMS-007) and 29 clinical isolates obtained from hospitals in China were subjected to single cell Raman spectroscopy analysis coupled with deuterium probing (single cell Raman-DIP). The results demonstrated that single cell Raman-DIP could determine antimicrobial susceptibility of Elizabethkingia spp. in 4 h, only one third of the time required by standard broth microdilution method. The method could be integrated into current clinical protocol for sepsis and halve the report time. The study also confirmed that minocycline and levofloxacin are the first-line antimicrobials for Elizabethkingia spp. infection.

The blood-brain barrier (BBB) comprises a single layer of endothelial cells and maintains a safe and homeostatic environment for proper neuronal function and synaptic transmission. BBB is not a discrete physical barrier, but a complex, dynamic, and adaptable interface. BBB continues to mature under the influence of the neural environment within a short period of time after birth. However, the basic mechanism of BBB formation and maintenance remains a mystery. Early studies have identified two structural characteristics of microvascular endothelium: special tight junctions (TJs) and a very low transcellular vesicle transport rate. Previous studies believed that BBB damage was mainly due to the destruction of tight junctions, and the role of vesicle transcytosis was neglected, so there was a lack of research on its impact on blood-brain barrier. It is urgent to get a better clarification of the unique structural and functional characteristics of the BBB endothelium to explain the role of BBB injury in neurological diseases. RNA sequencing was used to study the molecular characterization of cerebral cortex vascular endothelium by isolating them from neonatal, adolescent and adult rats. For investigation the maintenance mechanism of the BBB, we focused on the cellular and molecular regulation of barrier formation and the two characteristics of microvascular endothelial cells. Interestingly, we found that during the development of the blood-brain barrier, although the tight junctions gradually mature, endothelial cell transcytosis is gradually enhanced, resulting in an increase in the permeability of the blood-brain barrier. This study suggested that under physiological conditions, low vesicle transport is playing an important role in maintaining the integrity of the blood-brain barrier. This study not only summarized the unique characteristics of microvascular endothelial cells, but also illustrated a clarified mechanism of the development and maintenance of BBB which can provide new therapeutic opportunities for central nervous system drug delivery. Raw data of RNA sequencing were deposited in NCBI Sequence Read Archive database (PRJNA790676).

Liver cirrhosis (LC) is a fibrotic lesion of liver tissue caused by the repeated progression of chronic hepatitis. The traditional Chinese medicine Gexia-Zhuyu formula (GXZY) has a therapeutic effect on LC. However, its pharmacological mechanisms on LC remain elucidated. Here, we used the network pharmacology approach to explore the action mechanisms of GXZY on LC. The compounds of GXZY were from the traditional Chinese medicine systems pharmacology (TCMSP) database, and their potential targets were from SwissTargetPrediction and STITCH databases. The disease targets of LC came from GeneCards, DisGeNET, NCBI gene, and OMIM databases. Then we constructed the protein-protein interaction (PPI) network to obtain the key target genes. And the gene ontology (GO), pathway enrichment, and expression analysis of the key genes were also performed. Subsequently, the potential action mechanisms of GXZY on LC predicted by the network pharmacology analyses were experimentally validated in LC rats and LX2 cells. A total of 150 components in GXZY were obtained, among which 111 were chosen as key compounds. The PPI network included 525 targets, and the key targets were obtained by network topological parameters analysis, whereas the predicted key genes of GXZY on LC were AR, JUN, MYC, CASP3, MMP9, GAPDH, and RELA. Furthermore, these key genes were related to pathways in cancer, hepatitis B, TNF signaling pathway, and MAPK signaling pathway. The in vitro and in vivo experiments validated that GXZY inhibited the process of LC mainly via the regulation of cells proliferation and migration through reducing the expression of MMP9. In conclusion, through the combination of network pharmacology and experimental verification, this study offered more insight molecular mechanisms of GXZY on LC.

Abstract Orienteering has gradually changed from a professional sport to a civilian sport. Especially in recent years, orienteering has been widely popularized. Many colleges and universities in China have also set up this course. With the improvement of people’s living conditions, orienteering has really become a leisure sport in modern people’s life. The reduced difficulty of sports enables more people to participate, but it also exposes a series of problems. As the existing positioning technology is relatively backward, the progress in personnel tracking, emergency services, and other aspects is slow. To solve these problems, a new intelligent orienteering application system is developed based on the Internet of things. ZigBee network architecture is adopted in the system. ZigBee is the mainstream scheme in the current wireless sensor network technology, which has many advantages such as convenient carrying, low power consumption, and signal stability. Due to the complex communication environment in mobile signal, the collected information is processed by signal amplification and signal anti-interference technology. By adding anti-interference devices, video isolators and other devices, the signal is guaranteed to the maximum extent. In order to verify the actual effect of this system, through a number of experimental studies including the relationship between error and traffic radius and the relationship between coverage and the number of anchor nodes, the data shows that the scheme studied in this paper has a greater improvement in comprehensive performance than the traditional scheme, significantly improving the accuracy and coverage. Especially the coverage is close to 100% in the simulation experiment. This research has achieved good results and can be widely used in orienteering training and competition.

Taurine and indicine cattle have different desirable traits making them better adapted to different climates across the world. Here, Low et al. describe a pipeline to produce haplotype-resolved, chromosome-level genomes of Angus and Brahman cattle breeds from a crossbred individual and report on comparisons of the two genomes.

Metamaterials have been receiving an increasing amount of interest in recent years. As a type of metamaterial, pentamode materials (PMs) approximate the elastic properties of liquids. In this study, a finite-element analysis was conducted to predict the mechanical properties of PM structures by altering the thin wall thicknesses and layer numbers to obtain an outstanding load-bearing capacity. It was found that as the thin wall thickness increased from 0.15 to 0.45 mm, the compressive modulus of the PM structures increased and the Poisson’s ratio decreased. As the layer number increased, the Poisson’s ratio of the PM structures increased rapidly and reaches a stable value ranging from 0.50 to 0.55. Simulation results of the stress distribution in the PM structures confirmed that stress concentrations exist at the junctions of the thin walls and weights. For validation, Ti–6Al–4V specimens were fabricated by selective laser melting (SLM), and the mechanical properties of these specimens (i.e., Poisson’s ratio and elastic modulus) were experimentally studied. Good consistency was achieved between the numerical and experimental results. This work is beneficial for the design and development of PM structures with simultaneous load-bearing capacity and pentamodal properties. Keywords: Metamaterials, Pentamode materials, Finite-element analysis, Selective laser melting

In this research, a novel approach called SMOTE-FRS is proposed for movement prediction and trading simulation of the Chinese Stock Index 300 (CSI300) futures, which is the most crucial financial futures in the Chinese A-share market. First, the SMOTE- (Synthetic Minority Oversampling Technique-) based method is employed to address the sample unbalance problem by oversampling the minority class and undersampling the majority class of the futures price change. Then, the FRS- (fuzzy rough set-) based method, as an efficient tool for analyzing complex and nonlinear information with high noise and uncertainty of financial time series, is adopted for the price change multiclassification of the CSI300 futures. Next, based on the multiclassification results of the futures price movement, a trading strategy is developed to execute a one-year simulated trading for an out-of-sample test of the trained model. From the experimental results, it is found that the proposed method averagely yielded an accumulated return of 6.36%, a F1-measure of 65.94%, and a hit ratio of 62.39% in the four testing periods, indicating that the proposed method is more accurate and more profitable than the benchmarks. Therefore, the proposed method could be applied by the market participants as an alternative prediction and trading system to forecast and trade in the Chinese financial futures market.

Objective. To explore the correlation between traditional Chinese medicine (TCM) constitutions and insomnia by studying the distribution characteristics of different TCM constitutions in an outpatient insomnia population. Methods. From November 2020 to March 2021, 258 patients in the outpatient department of the Traditional Medicine Department of Tongren Hospital were interviewed using some questionnaires (Athens Insomnia Scale and constitution of traditional Chinese medicine), and correlation analysis was conducted. Results. The participants consisted of 152 (58.91%) insomniacs and 106 (41.09%) noninsomniacs. The top four biased constitutions of the insomniac population (the same patient may have two or more constitutions simultaneously), as determined from the proportions of constitutions in ascending order, are as follows: Qi deficiency constitution, 95 cases (62.50%); Yang deficiency constitution, 85 cases (45.95%); blood stasis, 70 cases (37.84%); and qi stagnation, 65 cases (35.14%). The results of the Spearman correlation analysis showed that the standard scores of qi deficiency, Yang deficiency, blood stasis, and Qi stagnation were positively correlated with the total score of AIS (P

Polycyclic aromatic hydrocarbons (PAHs) in oil are affected by many factors, including temperature, time, and PAHs precursors. Phenolic compounds, as beneficial endogenous components of oil, are often associated with the inhibition of PAHs. However, studies have found that the presence of phenols may lead to increased levels of PAHs. Therefore, this study took Camellia oleifera (C. oleifera) oil as the research object, in order to study the effect of catechin in the formation of PAHs under different heating conditions. The results showed that PAH4 were generated rapidly during the lipid oxidation induction period. When the addition of catechin was >0.02%, more free radicals were quenched than generated, thus inhibiting the generation of PAH4. ESR, FT-IR, and other technologies were employed to prove that when the catechin addition was

Abstract Background Mammalian X chromosomes are mainly euchromatic with a similar size and structure among species whereas Y chromosomes are smaller, have undergone substantial evolutionary changes and accumulated male specific genes and genes involved in sex determination. The pseudoautosomal region (PAR) is conserved on the X and Y and pair during meiosis. The structure, evolution and function of mammalian sex chromosomes, particularly the Y chromsome, is still poorly understood because few species have high quality sex chromosome assemblies. Results Here we report the first bovine sex chromosome assemblies that include the complete PAR spanning 6.84 Mb and three Y chromosome X-degenerate (X-d) regions. The PAR comprises 31 genes, including genes that are missing from the X chromosome in current cattle, sheep and goat reference genomes. Twenty-nine PAR genes are single-copy genes and two are multi-copy gene families, OBP, which has 3 copies and BDA20, which has 4 copies. The Y chromosome X-d1, 2a and 2b regions contain 11, 2 and 2 gametologs, respectively. Conclusions The ruminant PAR comprises 31 genes and is similar to the PAR of pig and dog but extends further than those of human and horse. Differences in the pseudoautosomal boundaries are consistent with evolutionary divergence times. A bovidae-specific expansion of members of the lipocalin gene family in the PAR reported here, may affect immune-modulation and anti-inflammatory responses in ruminants. Comparison of the X-d regions of Y chromosomes across species revealed that five of the X-Y gametologs, which are known to be global regulators of gene activity and candidate sexual dimorphism genes, are conserved.

Background: Type 2 diabetes mellitus (T2DM) is a common risk factor for cardiovascular diseases. The aims of this study were to evaluate the changes in the left ventricular myocardial work in T2DM patients using the left ventricular pressure-strain loop (PSL) technique, and to explore the risk factors for the left ventricular myocardial work impairment.Methods: Fifty patients with T2DM and 50 normal controls (NCs) were included in the study. In addition to conventional echocardiography and two-dimensional speckle tracking echocardiography, the left ventricular myocardial work parameters were measured using PSL technology.Results: The absolute value for global longitudinal strain (GLS), global work index (GWI) and, global constructive work (GCW) were significantly decreased in the T2DM group (P < 0.05), while the left ventricular ejection fraction (LVEF) was not significantly different between the T2DM and NC groups. Multivariable linear regression analysis showed that hemoglobin A1c (HbA1c) was independently related to GWI (β = −0.452, P < 0.05), while HbA1c and the diabetes duration were independently related to GCW (β = −0.393, P < 0.05 and β = −0.298, P < 0.05, respectively).Conclusions: Changes in the left ventricular myocardial systolic function in T2DM patients were identified using PSL technology. HbA1c was shown to be an independent risk factor affecting GWI, while HbA1c and diabetes duration were demonstrated to be independent risk factors affecting GCW.

Cancer treatment is a significant challenge for the global health system, although various pharmacological and therapeutic discoveries have been made. It has been widely established that cancer is associated with epigenetic modification, which is reversible and becomes an attractive target for drug development. Adding chemical groups to the DNA backbone and modifying histone proteins impart distinct characteristics on chromatin architecture. This process is mediated by various enzymes modifying chromatin structures to achieve the diversity of epigenetic space and the intricacy in gene expression files. After decades of effort, epigenetic modification has represented the hallmarks of different cancer types, and the enzymes involved in this process have provided novel targets for antitumor therapy development. Epigenetic drugs show significant effects on both preclinical and clinical studies in which the target development and research offer a promising direction for cancer therapy. Here, we summarize the different types of epigenetic enzymes which target corresponding protein domains, emphasize DNA methylation, histone modifications, and microRNA-mediated cooperation with epigenetic modification, and highlight recent achievements in developing targets for epigenetic inhibitor therapy. This article reviews current anticancer small-molecule inhibitors targeting epigenetic modified enzymes and displays their performances in different stages of clinical trials. Future studies are further needed to address their off-target effects and cytotoxicity to improve their clinical translation.

Arctigenin (ATG) is the major active component of a Chinese herbal remedy known to reduce proteinuria in patients with diabetic kidney disease (DKD). Here, Zhong et al. identify PP2A as a pharmacological target of ATG in podocytes, and find that PP2A is responsible for some of the beneficial effects of ATG in mouse models of DKD.

Although the conventional locally resonant acoustic metamaterials (LRAMs) have shown better sound absorption performance in the low frequency band, the effective frequency range of the sound absorption performance is quite narrow relatively. To overcome this drawback, a novel type of multilayered locally resonant acoustic metamaterials (M-LRAMs) is proposed in this paper. The sound absorption performance of the proposed LRAMs can be broadened and enhanced by coupled resonance with embedding multilayered locally resonant scatterers into the matrix structure. The finite element method (FEM) is employed to investigate the band gap characteristics and the sound absorption performance of the proposed M-LRAMs. The coupled resonance effects of the scatterers on the band gap characteristics and the sound absorption performance of acoustic metamaterials are studied as well. Moreover, the effects of the physical parameters of matrix, the thickness of each layer, the number of locally resonant scatterers and the materials of the scatterers on sound absorption performance are investigated. Results indicate that coupled resonance can broaden band gaps and engender multiple band gaps, and the M-LRAMs have many advantages in underwater sound absorption over the conventional LRAMs due to the enhanced coupled resonance effects. Keywords: Underwater sound absorption, M-LRAMs, Multilayered locally resonant scatterers, Band gaps

To effectively deliver lutein, hydrothermally prepared tea seed cake protein nanoparticles (TSCPN) were used to fabricate Pickering emulsion, and the bioaccessibility of lutein encapsulated by Pickering emulsion and the conventional emulsion was evaluated in vitro. The results indicated that the average size and absolute value of zeta potential of TSCPN increased along with the increase in the protein concentration, and 2% protein concentration was adopted to prepare TSCPN. With the increase in the concentration of TSCPN, the size of Pickering emulsion decreased from 337.02 μm to 89.36 μm, and when the TSCPN concentration was greater than 0.6%, all emulsions exhibited good stability during the 14 days storage. Combined with the microstructure result, 1.2% TSCPN was used to stabilize Pickering emulsion. With the increase in ionic concentration (0–400 mM), the particle size of the emulsions increased while the absolute value of zeta potential decreased. TSCPN-based Pickering emulsion was superior to the conventional emulsion for both lutein encapsulation (96.6 ± 1.0% vs. 82.1 ± 1.4%) and bioaccessibility (56.0 ± 1.1% vs. 35.2 ± 1.2%). Thus, TSCPN-based Pickering emulsion in this study have the potential as an effective carrier for lutein.

Lung adenocarcinoma (LUAD) is one of the most malignant tumors with high morbidity and mortality worldwide due to the lack of reliable methods for early diagnosis and effective treatment. It’s imperative to study the mechanism of its development and explore new biomarkers for early detection of LUAD. In this study, the Gene Expression Omnibus (GEO) dataset GSE43458 and The Cancer Genome Atlas (TCGA) were used to explore the differential co-expressed genes between LUAD and normal samples. Three hundred sixity-six co-expressed genes were identified by differential gene expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA) method. Those genes were mainly enriched in ameboidal-type cell migration (biological process), collagen-containing extracellular matrix (cell component), and extracellular matrix structure constituent (molecular function). The protein-protein network (PPI) was constructed and 10 hub genes were identified, including IL6, VWF, CDH5, PECAM1, EDN1, BDNF, CAV1, SPP1, TEK, and SELE. The expression level of hub genes was validated in the GEPIA database, compared with normal tissues, VWF is lowly expressed and SPP1 is upregulated in LUAD tissues. The survival analysis showed increased expression of SPP1 indicated unfavorable prognosis whereas high expression of VWF suggested favorable prognosis in LUAD (p < 0.05). Based on the immune infiltration analysis, the relationship between SPP1 and VWF expression and macrophage, neutrophil, and dendritic cell infiltration was weak in LUAD. Quantitative real-time PCR (qRT-PCR) and western blotting were used to validate the expression of VWF and SPP1 in normal human bronchial epithelial (HBE) cell and three LUAD cell lines, H1299, H1975, and A549. Immunohistochemistry (IHC) was further performed to detect the expression of VWF in 10 cases LUAD samples and matched normal tissues. In summary, the data suggest that VWF is a potential novel biomarker for prognosis of LUAD.

To achieve zero-energy building target, both China and the US have planned pathway by formulating guidelines and standards. China has published National China technical standard for nearly zero energy building (CTS-NZEB), which defines detailed principles of zero-energy building. The US LEED zero energy evaluation system has been released based on LEED rating system. Defined target and scope have been introduced in this evaluation system; however, there are no technical and detailed approaches in the rating system. To support future projects achieving the LEED Zero Energy certification in China, accessible applications have been analyzed in perspectives of technology and economy in this article. The comparison and analysis results show that the strategies and technical index of CTS-NZEB can be adopted comprehensively in LEED Zero Energy rating system for Chinese buildings except for renewable energy resources because air source or ground source heat pump system, which are extensively used in China but not acceptable in LEED Zero Energy rating system. High-performance strategies, including low U-value envelope, exterior shading devices, high air tightness envelope, high-efficiency heating, ventilation, and air-conditioning system, and low thermal bridge impact, can be applied to pursue LEED Zero Energy rating system. The incremental costs of NZEBs in China are also supported by government through market and financial policies. This would make significant impacts on Chinese buildings to achieve the LEED Zero Energy target.

We previously used global Hipk2-null mice in various models of kidney disease to demonstrate the central role of homeodomain-interacting protein kinase 2 (HIPK2) in renal fibrosis development. However, renal tubular epithelial cell–specific (RTEC-specific) HIPK2 function in renal fibrogenesis has yet to be determined. Here, we show that modulation of tubular HIPK2 expression and activity affects renal fibrosis development in vivo. The loss of HIPK2 expression in RTECs resulted in a marked diminution of renal fibrosis in unilateral ureteral obstruction (UUO) mouse models and HIV-associated nephropathy (HIVAN) mouse models, which was associated with the reduction of Smad3 activation and downstream expression of profibrotic markers. Conversely, WT HIPK2 overexpression in RTECs accentuated the extent of renal fibrosis in the setting of UUO, HIVAN, and folic acid–induced nephropathy in mice. Notably, kinase-dead HIPK2 mutant overexpression or administration of BT173, an allosteric inhibitor of HIPK2-Smad3 interaction, markedly attenuated the renal fibrosis in these mouse models of kidney disease, indicating that HIPK2 requires both the kinase activity and its interaction with Smad3 to promote TGF-β–mediated renal fibrosis. Together, these results establish an important RTEC-specific role of HIPK2 in kidney fibrosis and further substantiate the inhibition of HIPK2 as a therapeutic approach against renal fibrosis.

The effects and safety of electron beam irradiation (EBI) treatment on the detoxification of aflatoxin B1 (AFB1) in the peanut meal were evaluated in this article. The AFB1 degradation was predominantly affected by both initial AFB1 and water concentrations. The degradation of AFB1 in the selected concentrations (0.5–5 ppm) was proven to follow pseudo first-order reaction kinetics (R2 > 0.95). The AFB1 degradation was faster when the initial concentration was 5 ppm and the moisture content was 21.47%, in comparison with the initial concentration of 1 ppm and 0.5 ppm and the moisture content of 14.32% and 8.74%, respectively. The Ames and cytotoxicity tests were employed to evaluate the residual toxicity of EBI-treated peanut meal. The mutagenic activity of EB-treated samples was completely lost compared with that of untreated samples and the degradation products in peanut meal has almost no cell toxicity.

As renewable energy increasingly penetrates into electricity-heat integrated energy system (IES), the severe challenges arise for system reliability under uncertain generations. A two-stage approach consisting of pre-scheduling and re-dispatching coordination is introduced for IES under wind power uncertainty. In pre-scheduling coordination framework, with the forecasted wind power, the robust and economic generations and reserves are optimized. In re-dispatching, the coordination of electric generators and combined heat and power (CHP) unit, constrained by the pre-scheduled results, are implemented to absorb the uncertain wind power prediction error. The dynamics of building and heat network is modeled to characterize their inherent thermal storage capability, being utilized in enhancing the flexibility and improving the economics of IES operation; accordingly, the multi-timescale of heating and electric networks is considered in pre-scheduling and re-dispatching coordination. In simulations, it is shown that the approach could improve the economics and robustness of IES under wind power uncertainty by taking advantage of thermal storage properties of building and heat network, and the reserves of electricity and heat are discussed when generators have different inertia constants and ramping rates.

Summary: Lymph nodes (LNs) are constructed of intricate networks of endothelial and mesenchymal stromal cells. How these lymphoid stromal cells (LSCs) regulate lymphoid tissue remodeling and contribute to immune responses remains poorly understood. We performed a comprehensive functional and transcriptional analysis of LSC responses to skin viral infection and found that LSC subsets responded robustly, with different kinetics for distinct pathogens. Recruitment of cells to inflamed LNs induced LSC expansion, while B cells sustained stromal responses in an antigen-independent manner. Infection induced rapid transcriptional responses in LSCs. This transcriptional program was transient, returning to homeostasis within 1 month of infection, yet expanded fibroblastic reticular cell networks persisted for more than 3 months after infection, and this altered LN composition reduced the magnitude of LSC responses to subsequent heterologous infection. Our results reveal the complexity of LSC responses during infection and suggest that amplified networks of LN stromal cells support successive immune responses. : Lymph nodes are constructed of intricate networks of stromal cells. Gregory et al. reveal a robust yet transient transcriptional program in lymph node stromal cells induced by virus infection. Previously primed lymph nodes sustained amplified networks of stromal cells that supported subsequent immune responses. Keywords: lymphoid stromal cells, fibroblastic reticular cells, endothelial cells, lymph nodes, immune response, virus infection, lymphocytes

Smchd1 is an epigenetic repressor with important functions in healthy cellular processes and disease. To elucidate its role in transcriptional regulation, we performed two independent genome-wide RNA-sequencing studies comparing wild-type and Smchd1 null samples in neural stem cells and lymphoma cell lines. Using an R-based analysis pipeline that accommodates observational and sample-specific weights in the linear modeling, we identify key genes dysregulated by Smchd1 deletion such as clustered protocadherins in the neural stem cells and imprinted genes in both experiments. Here we provide a detailed description of this analysis, from quality control to read mapping and differential expression analysis. These data sets are publicly available from the Gene Expression Omnibus database (accession numbers GSE64099 and GSE65747). Keywords: RNA-sequencing, voom, Sample variability, Epigenetics

Nemo-like kinase (NLK) is an evolutionary conserved serine/threonine protein kinase implicated in development, proliferation and apoptosis regulation. Here we identified NLK as a gene product induced in the hearts of mice subjected to pressure overload or myocardial infarction injury, suggesting a potential regulatory role with pathological stimulation to this organ. To examine the potential functional consequences of increased NLK levels, cardiac-specific transgenic mice with inducible expression of this gene product were generated, as well as cardiac-specific Nlk gene-deleted mice. NLK transgenic mice demonstrated baseline cardiac hypertrophy, dilation, interstitial fibrosis, apoptosis and progression towards heart failure in response to two surgery-induced cardiac disease models. In contrast, cardiac-specific deletion of Nlk from the heart, achieved by crossing a Nlk-loxP allele containing mouse with either a mouse containing a β-myosin heavy chain promoter driven Cre transgene or a tamoxifen inducible α-myosin heavy chain promoter containing transgene driving a MerCreMer cDNA, protected the mice from cardiac dysfunction following pathological stimuli. Mechanistically, NLK interacted with multiple proteins including the transcription factor Stat1, which was significantly increased in the hearts of NLK transgenic mice. These results indicate that NLK is a pathological effector in the heart.