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Abstract In a multicenter case–control investigation, we assessed the efficacy of the Electrooculogram Signal Analysis (EOG-SA) method, which integrates attention-related visual evocation, electrooculography, and nonlinear analysis, for distinguishing between intellectual and developmental disabilities (IDD) and typical development (TD) in children. Analyzing 127 participants (63 IDD, 64 TD), we applied nonlinear dynamics for feature extraction. Results indicated EOG-SA’s capability to distinguish IDD, with higher template thresholds and Correlation Dimension values correlating with clinical severity. The template threshold proved a robust indicator, with higher values denoting severe IDD. Discriminative metrics showed areas under the curve of 0.91 (template threshold) and 0.85/0.91 (D2), with sensitivities and specificities of 77.6%/95.9% and 93.5%/71.0%, respectively. EOG-SA emerges as a promising tool, offering interpretable neural biomarkers for early and nuanced diagnosis of IDD.

Abstract A long-standing hypothesis proposes that certain RNA(s) must exhibit structural roles in microtubule assembly. Here, we identify a long noncoding RNA (TubAR) that is highly expressed in cerebellum and forms RNA–protein complex with TUBB4A and TUBA1A, two tubulins clinically linked to cerebellar and myelination defects. TubAR knockdown in mouse cerebellum causes loss of oligodendrocytes and Purkinje cells, demyelination, and decreased locomotor activity. Biochemically, we establish the roles of TubAR in promoting TUBB4A–TUBA1A heterodimer formation and microtubule assembly. Intriguingly, different from the hypomyelination-causing mutations, the non-hypomyelination-causing mutation TUBB4A-R2G confers gain-of-function for an RNA-independent interaction with TUBA1A. Experimental use of R2G/A mutations restores TUBB4A–TUBA1A heterodimer formation, and rescues the neuronal cell death phenotype caused by TubAR knockdown. Together, we uncover TubAR as the long-elusive structural RNA for microtubule assembly and demonstrate how TubAR mediates microtubule assembly specifically from αβ-tubulin heterodimers, which is crucial for maintenance of cerebellar myelination and activity.

Self-tapping screws (STS) are an effective fastener to enhance wooden moment-resisting joints. However, the effects of the arrangement and insertion angle of STS on the mechanical properties of wooden joints are less studied. Therefore, this study investigated the influence of these two factors on the mechanical properties of wooden joints by conducting cyclic loading tests using glulam moment-resisting joints reinforced by STS with different arrangements (round and square) and insertion angles (45° and 90°). The failure modes, bearing performances, and energy dissipation capacities were considered. The results showed that the insertion angle affected the bearing and energy dissipation capacity of the joints significantly, while the effect of arrangement was slight. The anti-rotation bending moments of the joints reinforced by inclined STS were higher by 31.7% and 13.5% when the arrangement of STS was circular and rectangular respectively compared with the joints reinforced by vertical STS under compression state, and were lower by 17.5 % and 22.9 % under tensile state. The restoring force characteristics of the joints were similar when the insertion angle of STS was the same. Furthermore, the joints had optimal ductility and stiffness when the arrangement was rectangular, and the insertion angle was 45°.

Abstract Nasopharyngeal (NP) swab is one of the most effective sampling devices for clinical specimens. However, commercial NP swabs often release samples through diluents, lowering analyte concentration and causing inaccurate detections. Here, we developed 3D-printed open-cell microlattice NP swabs with user-friendly high-efficiency controlled sample release (CR) mode. Compared with traditional NP swabs, our microlattice NP swabs show higher (~7–11 times) flexibility, larger (~2.3 times) and customizable release volume, higher (dozens to thousands of times) release concentration, high recovery efficiency (~100%), and the ability to quantify analyte levels. Our microlattice NP swabs have been thus demonstrated to improve the sensitivity and accuracy of antibody detection experiments using rapid detection kits. This study offers a promising approach to enhance sensitivity and accuracy in clinical specimen detections, and is beneficial to inspire the design of a wider range of biomedical devices based on 3D-printed microlattice metamaterials.

This paper presents an experimental and theoretical study on the in-plane mechanical behavior of orthogonal ribbed beam floors made of poplar Laminated Veneer Lumber(LVL) and Oriented strand Board(OSB) panels. Eight full-scale specimens with plane dimensions of 4800 mm×3600 mm were designed and fabricated. Four-point bending tests were carried out to investigate the bearing capacity, in-plane stiffness, ductility of the floor by considering the rib-beam height, loading direction and floor type. The New Zealand standard NZSEE-2006 was employed to develop the formula for calculating the mid-span deformation of a floor specimen. It was found that the main failure modes of the floor specimens were slip, tilt and pull-out of the nails between the poplar LVL rib-beam and OSB panels. The internal rib beams and connectors of the specimens were largely intact. When the height of the rib-beams was the same, the stiffness, bearing capacity and ductility of the box floor specimens were better than those of the traditional floor ones. Increasing the height-span ratio of rib-beam could effectively improve the in-plane structural performance of a floor specimen. The bearing capacity of the same traditional floor specimens or box floor ones loading along the short side was higher than that loading along the long side. The formula for calculating the horizontal lateral displacement of the floor span was established by using the modified equivalent beam theory. The theoretically calculated values were in good agreement with the experimentally testing results.

The current trends in climate change have captured the attention of stakeholders across multiple industries, including the building sector. With the introduction of innovative building materials such as mass timber products (MTPs), it has become essential to evaluate their environmental performance. In response, a variety of life cycle assessment (LCA) software programs are available to meet this need. However, it is crucial to understand how different LCA software and databases might influence the results. This study was aimed at exploring the impact of two widely used LCA software programs, SimaPro and Athena Impact Estimator, on LCA results. Two buildings were employed to conduct this study, a traditional institutional building and a mass timber building currently under construction. By comparing the numerical outputs from both software programs, it was discovered that while both could reach similar conclusions regarding the environmental impacts of a building, their use is limited to comparative purposes only. The software programs produced distinct numerical values in their outputs and attributed the sources of impacts differently, indicating they cannot be used interchangeably. However, either SimaPro or Athena Impact Estimator was suitable for estimating the global warming potential of a building during stages A1 to A3.

Compared with natural wood, laminated veneer lumber has the characteristics of high strength, flexible specifications, excellent stability, and good economy. In order to study the bearing capacity of LVL trusses, the mechanical properties of LVL materials were tested. The static load test was carried out by using 3 pieces of LVL truss, and the load-deflection relationship, load-strain relationship, bearing capacity and failure mode of LVL trusses were studied. Based on the simplified joint analysis method, the metal plate connection and bolted truss were analyzed, and the bearing capacity calculation formula was developed. The results show that the upper chord instability is the main failure mode for large-span light LVL truss. A simplified formula for bearing capacity of LVL truss was proposed, and the predicted results were in good agreement with the experimental results. Finally, an application example of LVL truss engineering design and construction is briefly introduced. The research can provide technical support for the promotion and application of LVL truss of lightweight poplar wood.

Abstract Background Recurrent lateral patellar dislocation (RLPD) poses a significant threat to patients’ quality of life due to knee pain, patellofemoral cartilage damage, and potential traumatic arthritis. Predictive scoring systems have been developed to assess the risk of RLPD; however, their relative accuracy remains uncertain. Purpose To investigate the accuracy of the multiple regression models to predict the individual risk of recurrent LPD. Methods The Patellar Instability probability calculator (PIP), Recurrent Instability of the Patella Score (RIP), and Patellar Instability Severity Score (PIS) scoring rules were measured in 171 patients with a history of patellar dislocation and 171 healthy individuals. Three prediction models were calculated based on the data to predict the risk of recurrent lateral patellar dislocation. The inter-observer and intra-observer reliability of each measurement parameter was evaluated. The predictive capacity of the three-prediction model was investigated using the receiver operating characteristic curve. Results In the case group of 171 patients, PIS accurately predicted recurrent lateral Patella dislocation in 143 patients. RIP was 96, and PIP was 83. The positive predictive values were 92.9%, 64%, and 68% respectively. In the control group of 171 patients, the PIS was validated in 160 patients who would not experience dislocations. RIP was 117, and PIP was 50. The negative predictive values were 85.1%, 60.9%, and 36.2%, respectively. The area under the curve score for the PIS was 0.866, and the RIP was 0.673. the PIP was 0.678. Conclusion RIP and PIP did not work to predict LPD. PIS can accurately predict recurrent lateral patellar dislocation. It can aid doctors in making treatment decisions. Level of evidence Level III, retrospective comparative study.

Abstract High-resolution seismic image is critically important for mining minerals. In this study, we collected seismic data from a local dense seismic array consisting of 154 stations around the Anyuan mining area and its adjacent region of Pingxiang City, Jiangxi Province in South China, and applied the ambient noise tomography (ANT) method to image the shear wave velocity structure in the study area. Shallow crustal velocities at depths less than 3.3 km were determined by direct inversion of Rayleigh wave group velocity dispersion curves at the period range of 0.5–5.0 s. Overall, the S-wave velocity structure has a tight correlation with surface geological and tectonic features in the study area. The shear wave velocity structure in the shallow crust of the Anyuan Mine and its adjacent areas displayed distinct low-velocity anomalies, which can be attributed to the depression of sedimentary structures and coal mining activities in the Pingxiang-Leping region. The zones surrounding the Anyuan fault (AYF) and Wangkeng fault (WKF) zones exhibited low-velocity anomalies from the ground surface to ~ 3.3 km underground. And the low-velocity anomalies at depths less than 1.2 km could be related to the sedimentary environment of coal mine and the coal mining activities, while the low-velocity anomalies at depths below 1.2 km are caused by the presence of fracture medium, oil and gas in the fault zone. The shear wave velocity changes sharply across the AYF, and the characteristics of the velocity change interface indicate that the AYF is inclined toward the northwest, with its extension reaching depths of approximately 3 km underground. Graphical Abstract

Wood sandwich panels are widely utilized in residential, commercial, and industrial settings due to their excellent thermal insulation characteristics, ease of installation, and high strength-to-weight ratio. This review provides an overview on experimental outcomes demonstrating the structural integrity and versatility of wood sandwich panels. It highlights recent advancements in meeting payload requirements and their effectiveness in reducing costs and weights for prefabricated houses. The review focuses on structural applications and material efficiency, showcasing their roles in lightweight, durable constructions for retrofitting and new projects. The potential of novel, sustainable materials in construction is explored, addressing current challenges and emphasizing the diverse applications and environmental benefits of wood-based sandwich panels, underscoring their importance in advancing energy-efficient and sustainable construction.

Trembling aspen (Populus tremuloides) is one of the major species within Populus, a predominant genus of hardwoods in North America. However, its utilization has been limited to pulp and paper or wood-based composite boards. This study aimed at evaluating the major physical and mechanical properties of trembling aspen lumber, with an ultimate objective of using this species to produce engineered wood products (EWPs). The testing materials consisted of 2 × 4 (38 mm × 89 mm) trembling aspen lumber pieces in lengths of 8, 10, and 12 feet (2.44, 3.05, and 3.66 m) with two visual grades, select structural (SS) and No. 2. Machine Stress-Rated (MSR), and longitudinal stress wave (LSW), edgewise third-point bending (EWB), and axial tension tests were conducted on the lumber. It was found that, (1) by increasing the maximum knot size by a half-inch from one-quarter inch, the minimum modulus of elasticity (MOE) measured using the MSR, the mean, and the fifth-percentile ultimate tensile strength (UTS) decreased by about 8.8%, 20.1%, and 29.8%, respectively. (2) Approximately 44% of the trembling aspen lumber met the 1450f-1.3E grade for MSR lumber, and 62% qualified for the 1200f-1.2E grade. (3) There was a great potential for manufacturing cross-laminated timber (CLT) of grade E3, with a rejection rate of about 29%. (4) The mean UTS and MOE values of the SS-grade trembling aspen lumber were 22.88 MPa and 9519 MPa, respectively, being 25.5% and 11.3% lower than that of Spruce–Pine–Fir (S-P-F) lumber. The fifth-percentile UTS and MOE values were 11.57 MPa and 7404 MPa, respectively, marking a decrease of 13.3% and 1.5% compared to the S-P-F lumber. (5) The oven-dried specific gravity (SG) of the trembling aspen wood was 0.40, which was about 3.5% larger than the value provided in the Wood Handbook.

We collected high-quality teleseismic events recorded by 12 broadband seismographs deployed in the Anyuan Coal Mine and its adjacent areas in Pingxiang City, Jiangxi Province for nearly two years. The H-κ-c stacking method was employed to obtain the crustal thickness and Poisson's ratio distribution, then the characteristics of crustal structure below the stations were obtained by using the time-domain linear inversion method. The crustal thickness in the Anyuan Coal Mine and its adjacent areas ranges from approximately 32 ∼ 35 ​km, with an average thickness of 33 ​km, which is consistent with the crustal thickness results in South China from previous studies using the receiver function method. The average Poisson's ratio of the crustal bulk composition in the study area varies between 0.22 and 0.25, which is lower than the global value with a 0.27 average, indicating a predominantly intermediate-acidic or felsic crustal composition. There is a weak negative correlation between Poisson's ratio and crustal thickness estimates in the Anyuan Coal Mine and its adjacent areas, suggesting that the absence of mafic-ultramafic materials in the lower crust is associated with the process of crustal delamination. The velocity inversion results indicate that the crustal structure including three velocity discontinuity interfaces, with the first at a depth of approximately 1.5 ​km, the second at about 10 ∼ 15 ​km, and the third being the Moho. The study also indicates that the results obtained by the H-κ-c stacking method are significantly better than those obtained by the H-κ method, effectively reducing the standard deviation and dispersion of crustal thickness and vP/vS ratio.

Tuft cells are a type of rare epithelial cells that have been recently found to utilize taste signal transduction pathways to detect and respond to various noxious stimuli and pathogens, including allergens, bacteria, protists and parasitic helminths. It is, however, not fully understood how many different types of pathogens they can sense or what exact molecular mechanisms they employ to initiate targeted responses. In this study, we found that an anaerobic pathobiont microbe, Ruminococcus gnavus (R. gnavus), can induce tuft cell proliferation in the proximal colon whereas the microbe’s lysate can stimulate these proximal colonic tuft cells to release interleukin-25 (IL-25). Nullification of the Gng13 and Trpm5 genes that encode the G protein subunit Gγ13 and transient receptor potential ion channel Trpm5, respectively, or application of the Tas2r inhibitor allyl isothiocyanate (AITC), G protein Gβγ subunit inhibitor Gallein or the phospholipase Cβ2 (PLCβ2) inhibitor U73122 reduces R. gnavus-elicited tuft cell proliferation or IL-25 release or both. Furthermore, Gng13 conditional knockout or Trpm5 knockout diminishes the expression of gasdermins C2, C3 and C4, and concomitantly increases the activated forms of caspases 3, 8 and 9 as well as the number of TUNEL-positive apoptotic cells in the proximal colon. Together, our data suggest that taste signal transduction pathways are not only involved in the detection of R. gnavus infection, but also contribute to helping maintain gasdermin expression and prevent apoptotic cell death in the proximal colon, and these findings provide another strategy to combat R. gnavus infection and sheds light on new roles of taste signaling proteins along with gasdermins in protecting the integrity of the proximal colonic epithelium.

Hydrocolloids as Additives have been used for improving the quality of frozen dough for a long time. In this work, the effects of sodium carboxymethyl cellulose (CMC) on quality changes of frozen dough in storage were studied. The water loss rate of the dough and water holding capacity were measured. Rheological and texture properties of the frozen dough were measured by a rheometer and a texture analyzer, respectively. Scanning electron microscopy (SEM) was used to characterize surface network structure and protein structure changes of the frozen dough. Our results reveal that the addition of CMC can inhibit the formation of ice crystals and recrystallization, thus effectively stabilizing the molecular structure of starch, and resulting in more uniform moisture distribution in the frozen dough. When 3% addition of CMC, the water holding capacity of the two kinds of dough reached the best, and the water loss rate of corn dough reached the lowest. The cohesion of the two kinds of dough reaches the maximum with 3 wt% addition of CMC, while the hardness and chewiness of wheat and corn multigrain dough reaches the maximum with 3 wt% and 4 wt% addition of CMC, respectively. The results show proper CMC addition (3 wt% and 4 wt%) finally improves the stability and qualities of the frozen dough. The research concerning the effects of CMC on quality of frozen dough provides better understanding for the frozen food industry.

Cross-laminated timber (CLT), a wood product with excellent shear resistance, is often used in modern timber constructions. Using the standards ASTM D1761-12 (2020) and NDS-2012 (2012), this study investigated the connection properties of shear bolts and screws in CLT panels. The specimens were made from spruce-pine-fir lumber and installed on a test platform using one high-strength bolt or eight screws, and then an upward load was applied to the top of the specimen. The results showed that the bolt connection provided a higher ultimate bearing capacity and elastic stiffness. The bolt exhibited virtually no deformation, and the CLT panel did not noticeably deteriorate when the connection was damaged. The distance between the bolt hole and the bottom of the CLT specimen and the angle between the outer-layer grain direction of the CLT panel and the load direction were both measured. Changes in the ductility coefficient value had an obvious effect on the connection performance of the shear bolts when the outer-layer grain direction of the CLT panel was consistent with the load direction. Contrastingly, when the outer-layer grain direction of the CLT panel was perpendicular to the load direction, the effect was negligible, and the yield load was nearly unchanged.

Considering the unidirectional layout of ribbed beams and simple structure in traditional wooden floors, it is not suitable for large-span wooden buildings. Six groups of floor ribbed beams with plane size of 4.8 m×3.6 m were designed and manufactured by using poplar laminated veneer lumber (LVL), among which five floor specimens were orthogonal ribbed beams and the other one was traditional. A bending performance test was carried out to analyze the influence of different ribbed beam spacing and high span ratio on the mechanical performance of poplar LVL orthogonal ribbed beams, and its results were compared with that of the traditional floor with ribbed beams. The results showed that the box floors with orthogonal ribbed beams had good integrity during the bending process. Moreover, the change of the high span ratio had an important influence on the bending performance of the box floors with orthogonal ribbed beams, and the change of the spacing of the ribbed beams had a relatively small influence on the flexural performance of the box floors with orthogonal ribbed beams. Under the same conditions, the bending performance of the box floors with orthogonal ribbed beams was better than that of traditional floor.

Small-diameter round timber is a kind of by-product mainly from the thinning operation of the plantations. It is plentiful and inexpensive, and is generally destined for non-structural applications. The small-diameter round timber is rarely used as structural members. This study was aimed to provide an innovative but simple way to use the small-diameter round timber as structural members. Three kinds of composite members were developed to be used in light frame wood construction, i.e. the built-up studs, the wood-steel joists and the wood-steel roof trusses. The shearwalls and diaphragms made of the developed composite members were also examined. To facilitate the fabrication, the configurations of these members were described in details. Efforts were also made to investigate the structural performances of these members via full-scale tests. It was found that the developed composite members could be used as substitutes of dimension lumber in the framework of light frame construction. The developed members could be also pre-fabricated as standard components in a mill and assembled on site. As a result, application of small-diameter round timber as structural members developed would be an efficient way to increase use of forest resource from plantation and lower the construction cost of light frame buildings.

The segmentation of pepper leaves from pepper images is of great significance for the accurate control of pepper leaf diseases. To address the issue, we propose a bidirectional attention fusion network combing the convolution neural network (CNN) and Swin Transformer, called BAF-Net, to segment the pepper leaf image. Specially, BAF-Net first uses a multi-scale fusion feature (MSFF) branch to extract the long-range dependencies by constructing the cascaded Swin Transformer-based and CNN-based block, which is based on the U-shape architecture. Then, it uses a full-scale feature fusion (FSFF) branch to enhance the boundary information and attain the detailed information. Finally, an adaptive bidirectional attention module is designed to bridge the relation of the MSFF and FSFF features. The results on four pepper leaf datasets demonstrated that our model obtains F1 scores of 96.75%, 91.10%, 97.34% and 94.42%, and IoU of 95.68%, 86.76%, 96.12% and 91.44%, respectively. Compared to the state-of-the-art models, the proposed model achieves better segmentation performance. The code will be available at the website: https://github.com/fangchj2002/BAF-Net.

There has been remarkable progress in the conservation and reproduction of giant pandas. However, the physiology of the gestation period in pandas remains poorly understood. The metabolic processes from estrus to pregnancy are dynamic and precisely regulated, playing a crucial role in pregnancy and related dysfunctions. In this study, we conducted a metabolomic analysis of 37 blood samples collected from pandas in estrus, acyclic, and potential pregnant states, employing rigorous screening to minimize the influence of diet. Our findings suggest that a reduced appetite can serve as an indicator for evaluating implantation time, representing a characteristic response to pregnancy and aiding in the prediction of delivery time in pregnant pandas. Metabolomic results indicate great metabolism variation from estrus to pregnancy, highlighting the association between amino acid metabolism and pregnancy outcomes. Compared to other pandas, individuals who successfully bred exhibit significantly elevated levels of arginine and histidine, even 2 months before experiencing a reduced appetite. Furthermore, the lipid profile undergoes distinct dynamic changes only in estrus samples. In summary, our study comprehensively characterizes the metabolism of giant pandas during gestation and proposes arginine and histidine as potential novel biomarkers for detecting the pregnancy state of giant pandas. [ABSTRACT FROM AUTHOR]

Mixed pedigree kinase 4 (MLK4) is a member of the serine/threonine kinases mixed pedigree kinase (MLKs) family. Few reports on immune-related targets in Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), and the role of MLK4 in cervical cancer remains to be studied. The expression of MLK4 in CESC was analyzed by TCGA database containing 306 CESC tissues and 3 peritumoral tissue samples, and the effect of MLK4 on immune invasion was evaluated using the Deseq2 package(Benjamini-Hochberg corrected p-value < 0.05 and log2 fold change ≥|2|). Tissue microarray was used to verify the expression of MLK4 in CESC patients, and it was found that MLK4 was significantly overexpressed in CESC, and significantly correlated with WHO grade. Multiple analysis algorithms revealed that the high expression of MLK4 was negatively correlated with immune cell infiltration in CESC. Analysis showed that MLK4 expression was negatively correlated with the infiltration of various immune cells including CD8+T cells, and MLK4 mRNA expression was positively correlated with immune checkpoints PD-L1,CTLA4, LAG3, and negatively correlated with immune promotion genes CD86 and CD80. Furthermore, vitro assays were performed to investigate the biological characteristics of MLK4 in C33A cells. The EDU and transwell assays demonstrated that the decrease in MLK4 expression in C33A cells resulted in a decrease in cell proliferation and invasion. The silencing of MLK4 resulted in a significant increase in the expression of inflammatory cytokines IL-1β(p

The 9-(R)-HODE is an active compound isolated from cortex lycii that showed significant hypoglycemic effects in our previous in vitro study. In this study, 9-(R)-HODE’s in vivo hypoglycemic activity and effect on alleviating diabetic complications, together with its molecular mechanism, was investigated using a metabolomics approach. The monitored regulation on dynamic fasting blood glucose, postprandial glucose, body weight, biochemical parameters and histopathological analysis confirmed the hypoglycemic activity and attenuation effect, i.e., renal lesions, of 9-(R)-HODE. Subsequent metabolomic studies indicated that 9-(R)-HODE induced metabolomic alterations primarily by affecting the levels of amino acids, organic acids, alcohols and amines related to amino acid metabolism, glucose metabolism and energy metabolism. By mediating the related metabolism or single molecules related to insulin resistance, e.g., kynurenine, myo-inositol and the branched chain amino acids leucine, isoleucine and valine, 9-(R)-HODE achieved its therapeutic effect. Moreover, the mediation of kynurenine displayed a systematic effect on the liver, kidney, muscle, plasma and faeces. Lipidomic studies revealed that 9-(R)-HODE could reverse the lipid metabolism disorder in diabetic mice mainly by regulating phosphatidylinositols, lysophosphatidylcholines, lysophosphatidylcholines, phosphatidylserine, phosphatidylglycerols, lysophosphatidylglycerols and triglycerides in both tissues and plasma. Treatment with 9-(R)-HODE significantly modified the structure and composition of the gut microbiota. The SCFA-producing bacteria, including Rikenellaceae and Lactobacillaceae at the family level and Ruminiclostridium 6, Ruminococcaceae UCG 014, Mucispirillum, Lactobacillus, Alistipes and Roseburia at the genus level, were increased by 9-(R)-HODE treatment. These results were consistent with the increased SCFA levels in both the colon content and plasma of diabetic mice treated with 9-(R)-HODE. The tissue DESI‒MSI analysis strongly confirmed the validity of the metabolomics approach in illustrating the hypoglycemic and diabetic complications-alleviation effect of 9-(R)-HODE. The significant upregulation of liver glycogen in diabetic mice by 9-(R)-HODE treatment validated the interpretation of the metabolic pathways related to glycogen synthesis in the integrated pathway network. Altogether, 9-(R)-HODE has the potential to be further developed as a promising candidate for the treatment of diabetes.

Obesity is a recognized epidemic worldwide, and the accumulation of excess free saturated fatty acids (SFAs) in cells induces cellular lipotoxic damage and increases the risk of a wide spectrum of metabolic diseases including type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). Monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) have been reported to combat SFA-induced cellular damage. However, the comparative studies of the two types of unsaturated fatty acids (UFAs) are still limited. We investigated the effects of different MUFAs and PUFAs in the human hepatocyte line L-02 cells in vitro, and in high-fat-diet (HFD)-induced obese C57BL/6 mice in vivo. The results of the in vitro study showed that SFAs induced significant cellular lipotoxic damage, but the combination of MUFAs/PUFAs with SFAs significantly improved the impaired cell viability. Particularly, oleic acid (OA) was superior to eicosapentaenoic acid (EPA), Docosahexaenoic acid (DHA), and arachidonic acid (AA) in terms of its anti-apoptotic effect and inhibition of endoplasmic reticulum (ER) stress. In vivo, both olive-oil-enriched (HFD + OO) and fish-oil-enriched high-fat diets (HFD + FO) reduced hepatic steatosis and improved insulin sensitivity in obese mice. However, FO induced an abnormal increase in serum aspartate aminotransferase (AST) and an increase in the oxidative stress indicator Malondialdehyde (MDA). Liver-targeted lipidomic analysis showed that liver lipid metabolites under the two types of UFA dietary interventions differed from the HFD group, modulating the abundance of some lipid metabolites such as triglycerides (TGs) and glycerophospholipids. Furthermore, the FO diet significantly increased the abundance of the associated FA 20:5 long-chain lipid metabolites, whereas the OO diet regulated the unsaturation of all fatty acids in general and increased the abundance of FA 18:1 in the overall lipid metabolites, especially TGs, which may primarily contribute to the FO, and OO drove protection in NAFLD.

The history, status quo, and prospect of tiny houses in North America were reviewed. The market demand for tiny houses in North America was analyzed according to the needs in various market segments, such as shelters for low-income and homeless people, recreational housing for vacationers, and the restoration and reconstruction after disasters. This study also discussed tiny housing communities for retirees, tourism companies offering tiny housing accommodation, and government-sponsored tiny housing projects for post-disaster reconstruction. Throughout years of promotion by tiny house enthusiasts, medium advocators, and construction practitioners, more and more people have come to realize the advantages of the tiny houses made of wood, such as energy conservation, low carbon footprint, and sustainable development. In summary, the market for tiny house in North America is in a stage of rapid development.

Summary: Glycyrrhetinic acid (GA) is a natural product of licorice with mitochondria targeting properties and shows broad anticancer activities, but its targets and underlying mechanisms remain elusive. Here, we identified the mitochondrial enzyme serine hydroxymethyltransferase 2 (SHMT2) as a target of GA by using chemical proteomics. Binding to and inhibiting the activity of SHMT2 by GA were validated in vitro and in vivo. Knockout of SHMT2 or inhibiting SHMT2 with GA restricts mitochondrial energy supplies by downregulating mitochondrial oxidative phosphorylation (OXPHOS) and fatty acid β-oxidation, and consequently suppresses cancer cell proliferation and tumor growth. Crystal structures of GA derivatives indicate that GA occupies SHMT2 folate-binding pocket and regulates SHMT2 activity. Modifications at GA carboxylic group with diamines significantly improved its anticancer potency, demonstrating GA as a decent structural template for SHMT2 inhibitor development.

Abstract Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) expressing microRNAs have been highlighted in human diseases. However, the detailed molecular mechanism of hucMSCs-derived exosomal miR-18b-3p on preeclampsia (PE) remains further investigation. We aimed to investigate the effect of exosomes and miR-18b-3p/leptin (LEP) on occurrence of PE. The morphology of the hucMSC and hucMSC-exosomes (Exos) was identified. The exosomes were infected with different lentivirus expressing miR-18b-3p to explore the role of miR-18b-3p in PE. The PE rat model was established by intraperitoneal injection of N-nitro-l-arginine methyl ester. The expression of LEP and miR-18b-3p was tested in PE rat placenta tissues. Also, the effect of exosomes on LEP and miR-18b-3p expression was detected. The systolic blood pressure (SBP), proteinuria, inflammatory factors, the weight of fetal rat and placenta and cell apoptosis in PE rats were detected. Finally, the relationship between miR-18b-3p and LEP was verified using dual-luciferase reporter gene assay and RNA pull-down assay. Exosomes, restoring miR-18b-3p or inhibiting LEP reduced SBP and proteinuria of PE rats as well as increased the weight of fetal rat and placenta, decreased serum levels of inflammatory factors as well as suppressed apoptotic cells of PE rats, exerting a suppressive effect on PE progression. miR-18b-3p was decreased and LEP was increased in placenta tissues of PE rats. LEP was the direct target gene of miR-18b-3p. Upregulation of miR-18b-3p or treatment of the exosomes suppressed LEP expression and reduced PE occurrence, while downregulation of miR-18b-3p had contrary effects. Downregulated LEP reversed the effect of miR-18b-3p reduction on PE rats. HucMSCs-derived exosomal miR-18b-3p targets LEP to participate in the occurrence and development of PE. This study may provide a novel theoretical basis for the mechanism and investigation of PE.

Background: To investigate the gene regulation of tumor cells in the process of different organ metastasis on a xenograft mouse model and screen the genes involved in the organ-target metastasis of tumor cells. Methods: A multi-organ metastasis model was constructed with a human ovarian clear cell carcinoma cell line (ES-2) based on a severe immunodeficiency mouse strain (NCG). Differentially expressed tumor proteins among multi-organ metastases were successfully characterized by microliter liquid chromatography-high-resolution mass spectrometry, sequence-specific data analysis and multivariate statistical data analysis. Liver metastases were selected as typical for subsequent bioinformatic analysis. Selected liver metastasis-specific genes in ES-2 cells were validated by sequence-specific quantitation including high resolution-multiple reaction monitoring quantification at protein level and quantitative real-time polymerase chain reaction at mRNA level. Results: From the mass spectrometry data, a total of 4503 human proteins were identified using the sequence-specific data analysis strategy. Of them, 158 proteins were selected as specifically regulated genes in liver metastases for subsequent bioinformatics studies. Based on Ingenuity Pathway Analysis (IPA) pathway analysis and sequence-specific quantitation, Ferritin light chain (FTL), lactate dehydrogenase A (LDHA) and long-chain-fatty-acid–CoA ligase 1 (ACSL1) were finally validated as specifically upregulated proteins in liver metastases. Conclusions: Our work provides a new approach to analyze gene regulation in tumor metastasis in xenograft mouse model. In presence of a large number of mouse protein interference, we validated the up-regulation of human ACSL1, FTL and LDHA in ES-2 liver metastases, which reflects the adaptive regulation of tumor cells to the liver microenvironment through metabolic reprogramming.

This study investigated the influence of pressing temperature and moisture content on the mechanical properties of wood compressed in radial direction. Jack pine (Pinus banksiana) and balsam poplar (Populus balsamifera) specimens were tested under a combination of pressing temperature (20 °C, 55 °C, 90 °C, and 125 °C) and wood moisture content (2%, 7%, 12%, and 17%). The yield stress (σy) and modulus of elasticity (MOE) of the specimens were determined from the stress- strain response. It was found that an increase in either pressing temperature or moisture content of wood generally caused a decrease in the mechanical properties for both species. The t-test results revealed that jack pine specimens are more sensitive to changes in pressing temperature and wood moisture content than balsam poplar. For jack pine specimens, at any of the pressing temperatures, the moisture content of 12% was found to be a crucial level to start a significant decrease in σy and MOE, while at any of the moisture content, a change in temperature from 55 °C to 90 °C exhibited a significant change in σy and MOE. The regression models developed can be used to predict σy and MOE as a function of temperature and moisture content.

A test equipment was developed, which allows for real time observation of the deformation behavior of wood cellular structure under a compression load applied in radial direction. Compression tests were performed on jack pine (Pinus banksiana) and balsam poplar (Populus balsamifera) specimens to explore the relationship between the yield stress and the first failure occurring in wood cell layers during radial compression. The microstructural changes for P. banksiana and P. balsamifera wood below and above the yield point were analyzed. The study results showed that for P. banksiana the first failure of wood cells occurred at the first earlywood layer, while for P. balsamifera it occurred at the layer with the largest vessels. The first failure of wood cell layer for each species tested was found to correspond to the yield point on the stress-strain curve. A new method of determining the yield stress for wood specimens under radial compression was developed.

In order to address concerns related to global warming and increased atmospheric carbon content, the life cycle assessment (LCA) tool has demonstrated usefulness in the building and construction sector. The LCA is used to evaluate environmental impacts concerning all stages of the building process from “cradle” to “grave”. The LCA helps promote sustainable development by considering environmental indicators such as stratospheric ozone depletion, eutrophication, global warming potential, and many more. It is of an interest to know the degree of impact on a given environmental indicator if an input is changed in terms of the type or amount of the materials used. The LCA software Athena IE4B was employed to analyze data of a selected timber building. This study was aimed at evaluating the sensitivity of LCA analysis on a hybrid timber building, which was done via two case studies. Case 1 focused on changes in the volume of wood materials, meanwhile Case 2 focused on simultaneous changes in the volume of materials for wood, steel, and concrete. In Case 1, it was observed increasing wood materials increased environmental indicators, with stratospheric ozone depletion being the most sensitive and global warming potential as the least sensitive. Case 2 discovered that proportionally increasing wood materials in relation to steel and concrete materials decreased environmental indicators, with eutrophication being the most sensitive and stratospheric ozone depletion as the least sensitive. This study helped support the feasibility of using Athena IE4B for LCA analysis in the initial assessment of a building.

Chemoresistance is the major restriction on the clinical use of cisplatin. Aberrant changes in protein glycosylation are closely associated with drug resistance. Comprehensive study on the role of protein glycosylation in the development of cisplatin resistance would contribute to precise elucidation of the complicated mechanism of resistance. However, comprehensive characterization of glycosylated proteins remains a big challenge. In this work, we integrated proteomic and N-glycoproteomic workflow to comprehensively characterize the cisplatin resistance-related membrane proteins. Using this method, we found that proteins implicated in cell adhesion, migration, response to drug, and signal transduction were significantly altered in both protein abundance and glycosylation level during the development of cisplatin resistance in the non-small cell lung cancer cell line. Accordingly, the ability of cell migration and invasion was markedly increased in cisplatin-resistant cells, hence intensifying their malignancy. In contrast, the intracellular cisplatin accumulation was significantly reduced in the resistant cells concomitant with the down-regulation of drug uptake channel protein, LRRC8A, and over-expression of drug efflux pump proteins, MRP1 and MRP4. Moreover, the global glycosylation was elevated in the cisplatin-resistant cells. Consequently, inhibition of N-glycosylation reduced cell resistance to cisplatin, whereas promoting the high-mannose or sialylated type of glycosylation enhanced the resistance, suggesting that critical glycosylation type contributes to cisplatin resistance. These results demonstrate the high efficiency of the integrated proteomic and N-glycoproteomic workflow in discovering drug resistance-related targets, and provide new insights into the mechanism of cisplatin resistance.

Background: Lipid metabolism disorders play a key role in the pathogenesis of squamous cell carcinoma (SqCC). Herein we used lipidomics to study the tissue lipid profiles of 40 patients with SqCC. Methods: Lipidomics, based on ultrahigh-performance liquid chromatography-Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry, was applied to identify altered lipid metabolites between tumor and adjacent noninvolved tissues (ANIT), and partial least squares-discriminant analysis model facilitated the identification of differentially abundant lipids. The area under the receiver operator characteristic curve and variable importance in projection scores of the aforementioned model were calculated to select lipid profiles. Metabolic pathway analyses were completed using Kyoto Encyclopedia of Genes and Genomes and MetaboAnalyst. Results: Differences in lipid profiles were found between tumor and ANIT, early- and advanced-stage SqCC, and positive and negative lymph node metastases. The lipid profile panel was composed of five lipids—PC(44:4), diacylglycerol(36:5), sphingomyelin(d18:1/20:0), phosphatidylinositol(46:7), and HexCer-AP(t8:0/32:2 + O)—and could effectively differentiate between tumor and ANIT. Further, pathway analyses revealed alterations in several lipid metabolism pathways, including glycerophospholipid metabolism, glycosylphosphatidylinositol anchor biosynthesis, linoleic acid metabolism, glycerolipid metabolism, and sphingolipid metabolism. Conclusion: Our data revealed several changes in the tissue lipid profiles of patients with SqCC; moreover, we identified a lipid profile panel that could effectually distinguish tumor tissues from ANIT. We believe that our results provide new insights into the biological behavior of lung SqCC.

Human spermatozoa proteomics exposed to some physical, biological or chemical stressors is being explored. However, there is a lack of optimized sample preparation methods to achieve in-depth protein coverage for sperm cells. Meanwhile, it is not clear whether antibiotics can regulate proteins to affect sperm quality. Here, we systematically compared a total of six different protein extraction methods based the combination of three commonly used lysis buffers and physical lysis strategies. The urea buffer combined with ultrasonication (UA-ultrasonication) produced the highest protein extraction rate, leading to the deepest coverage of human sperm proteome (5685 protein groups) from healthy human sperm samples. Since the antibiotics, amoxicillin and clarithromycin, have been widely used against H. pylori infection, we conduct a longitudinal study of sperm proteome via data-independent acquisition tandem mass spectrometry (DIA-MS/MS) on an infected patient during on and off therapy with these two drugs. The semen examination and morphological analysis were performed combined with proteomics analysis. Our results indicated that antibiotics may cause an increase in the sperm concentration and the rate of malformed sperm and disrupt proteome expression in sperm. This work provides an optimized extraction method to characterize the in-depth human sperm proteome and to extend its clinical applications.

Deciphering the glycosylation of the viral envelope (Env) glycoprotein is critical for evaluating viral escape from the host’s immune response and developing vaccines and antiviral drugs. However, it is still challenging to precisely decode the site-specific glycosylation characteristics of the highly glycosylated Env proteins, although glycoproteomics have made significant advances in mass spectrometry techniques and data analysis tools. Here, we present a hybrid dissociation technique, EThcD-sceHCD, by combining electron transfer/higher-energy collisional dissociation (EThcD) and stepped collision energy/higher-energy collisional dissociation (sceHCD) into a sequential glycoproteomic workflow. Following this scheme, we characterized site-specific N/O-glycosylation of the human immunodeficiency virus type 1 (HIV-1) Env protein gp120. The EThcD-sceHCD method increased the number of identified glycopeptides when compared with EThcD, while producing more comprehensive fragment ions than sceHCD for site-specific glycosylation analysis, especially for accurate O-glycosite assignment. Finally, eighteen N-glycosites and five O-glycosites with attached glycans were assigned unambiguously from heavily glycosylated gp120. These results indicate that our workflow can achieve improved performance for analysis of the N/O-glycosylation of a highly glycosylated protein containing numerous potential glycosites in one process. Knowledge of the glycosylation landscape of the Env glycoprotein will be useful for understanding of HIV-1 infection and development of vaccines and drugs.

The densely glycosylated spike (S) proteins that are highly exposed on the surface of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) facilitate viral attachment, entry, and membrane fusion. We have previously reported all the 22 N-glycosites and site-specific N-glycans in the S protein protomer. Herein, we report the O-glycosylation landscapes of SARS-CoV-2 S proteins, which were characterized through high-resolution mass spectrometry. Following digestion with trypsin and trypsin/Glu-C, and de-N-glycosylation using PNGase F, we determined the GalNAc-type O-glycosylation pattern of S proteins, including O-glycosites and the six most common O-glycans occupying them, via Byonic identification and manual validation. Finally, 255 intact O-glycopeptides composed of 50 peptides sequences and 43 O-glycosites were discovered by higher energy collision-induced dissociation (HCD), and three O-glycosites were confidently identified by electron transfer/higher energy collision-induced dissociation (EThcD) in the insect cell-expressed S protein. Most glycosites were modified by non-sialylated O-glycans such as HexNAc(1) and HexNAc(1)Hex (1). In contrast, in the human cell-expressed S protein S1 subunit, 407 intact O-glycopeptides composed of 34 peptides sequences and 30 O-glycosites were discovered by HCD, and 11 O-glycosites were unambiguously assigned by EThcD. However, the measurement of O-glycosylation occupancy hasn’t been made. Most glycosites were modified by sialylated O-glycans such as HexNAc(1)Hex (1)NeuAc (1) and HexNAc(1)Hex (1)NeuAc (2). Our results reveal that the SARS-CoV-2 S protein is an O-glycoprotein; the O-glycosites and O-glycan compositions vary with the host cell type. These comprehensive O-glycosylation landscapes of the S protein are expected to provide novel insights into the viral binding mechanism and present a strategy for the development of vaccines and targeted drugs.

The differences of physical and mechanical properties of different laminations, such as softwood, hardwood or other structural composite lumber, in hybrid cross-laminated timber (HCLT), lead to their dimensional stability and bonding performance more complex than generic cross-laminated timber (CLT). In this paper, the spruce-pine-fir (SPF) dimension lumber and construction oriented strand board (COSB) were employed to fabricate HCLT. The effects of four configurations and three adhesives on the dimensional stability and bonding performance of CLT and HCLT were evaluated in term of the water absorption (WA), thickness swelling (TS), block shear strength (BSS), wood failure percentage (WFP) and rate of delamination (RD). The results showed that with the increase of the COSB laminations, the WA of HCLT specimens decreased, and the values of TS, BBS and WFP increased. The configuration had a significant influence on the dimensional stability, BBS and WFP of the specimen. The adhesive had a significant influence on the dimensional stability and some bonding performances of the specimen. The phenol resorcinol formaldehyde (PRF) specimens had the lowest average RD value compared with the one-component polyurethane (PUR) and emulsion polymer isocyanate (EPI) specimens. Failures were prone to occur in the middle of the thickness of COSB lamination during block shear and delamination tests. The outcome of this paper could help the engineering application of HLCT.

Increased reclamation activity has adversely affected the conservation of coastal environments. The interactions between reclamation activities and their interference with the natural and functional properties of coastal zones increase the difficulty of marine spatial planning and eco-environmental management. In this study, an evaluation method for describing the intensity of the reclamation activity (RAI) based on regional planning theory and human–marine coordination theory was proposed, and a quantitative evaluation index system was constructed. The method was applied to Shandong Province in China via geographic information system (GIS) spatial analysis. The results reveal that there was an obvious increase in the RAI from 1974 to 2021, with the total reclamation scale index and coordination of reclamation activities index being the most prominent. In addition, it was found that 2007–2017 was the peak period of infilling reclamation in Shandong Province. The natural coastlines are mainly occupied by enclosed mariculture and saltern, which should be strictly managed. The proposed index system can effectively identify the spatiotemporal characteristics of the reclamation intensity and can be used to efficiently determine management priorities. It provides a theoretical basis for regional reclamation management and can be conveniently adopted by management departments for coastal environmental protection.

Increased maritime vessel activity has adversely affected the conservation of marine environments. The mobility and diverse operations of vessels increase the difficulty of marine spatial planning and protected-area management. This study proposed a “source-pathway-carrier-impact-response” (SPCIR) model to describe marine ecological stress caused by vessels (VES) and constructed a comprehensive assessment index system. The method was applied to the Bohai Sea in China using automatic identification system (AIS) data and geographic information system (GIS) spatial analysis. The results showed an obvious increase in VES from 2014 to 2018, with noise pollution, light pollution, and hydrodynamic interaction being the most prominent. Cargo vessels and oil tankers were the main stressors. Vessel activity seriously affected agriculture and fishery functions as well as marine-reserved zones in the Bohai Sea. The proposed SPCIR model can effectively identify the level and spatiotemporal characteristics of various vessel-related impacts and efficiently determine management priorities. It can provide a theoretical basis for marine area management and be conveniently adopted by management departments in various regions.

Recent studies have shown that long noncoding RNAs (lncRNAs) are critical regulators in the central nervous system (CNS). However, their roles in the cerebellum are currently unclear. In this work, we identified the isoform 204 of lncRNA Gm2694 (designated as lncRNA-Promoting Methylation (lncRNA-PM)) is highly expressed in the cerebellum and derived from the antisense strand of the upstream region of Cerebellin-1 (Cbln1), a well-known critical cerebellar synaptic organizer. LncRNA-PM exhibits similar spatiotemporal expression pattern as Cbln1 in the postnatal mouse cerebellum and activates the transcription of Cbln1 through Pax6/Mll1-mediated H3K4me3. In mouse cerebellum, lncRNA-PM, Pax6/Mll1, and H3K4me3 are all associated with the regulatory regions of Cbln1. Knockdown of lncRNA-PM in cerebellum causes deficiencies in Cbln1 expression, cerebellar synaptic integrity, and motor function. Together, our work reveals an lncRNA-mediated transcriptional activation of Cbln1 through Pax6-Mll1-H3K4me3 and provides novel insights of the essential roles of lncRNA in the cerebellum.