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Accounting for over 40% of the total energy consumption, the global building sector is pivotal for achieving carbon peak and neutrality objectives. The intricate nature of building carbon emissions, influenced by spatial, temporal, and multifactor coupling, poses challenges on implementing carbon-neutral technologies and conservation strategies. This study focuses on nearly zero energy buildings in China and employs system dynamics to predict energy consumption and carbon emissions according to various scenarios, unveiling influencing patterns and viable emission reduction pathways. The results highlight the substantial impact of enhancing energy conservation awareness as this leads to a 36.4% reduction in energy consumption and a 44.2% reduction in carbon emissions. To attain energy efficiency and carbon reduction goals, a comprehensive approach is essential, encompassing improved building performance, heightened resident energy awareness, increased renewable energy use, and energy landscape adjustments. These findings inform future building energy and carbon emission regulations and offer valuable policy insights.

Summary: Gestational diabetes mellitus (GDM), the most prevalent metabolic disorder during pregnancy, has long-term risks of metabolic diseases in offspring. However, the underlying mechanisms remain unclear. Here, we analyzed single-cell transcriptional data of cord blood mononuclear cells (CBMCs) from fetuses of healthy and GDM mothers, peripheral blood mononuclear cells from children and adolescents, and coronary plaques myeloid cells from atherosclerosis. Our results demonstrated that monocytes in cord blood were characterized with down-regulated proinflammatory-related pathways and up-regulated proliferation-related pathways. And monocytes in cord blood from GDM mothers were featured with expanded CXCL8+IL1B+ subclusters, enhanced crosstalk with neutrophil granulocytes and augmented adhesive and phagocytic abilities. Interestingly, CXCL8+IL1B+ monocytes influenced by GDM had transcriptome similarity with those of coronary plaques myeloid cells from individuals with atherosclerotic cardiovascular disease. Collectively, our data reveal adverse impact of maternal GDM environment on fetal monocytes and propose potential mechanisms between maternal GDM and offspring atherosclerosis.

Neuropathic pain is a chronic disease that severely afflicts the life and emotional status of patients, but currently available treatments are often ineffective. Novel therapeutic targets for the alleviation of neuropathic pain are urgently needed. Rhodojaponin VI, a grayanotoxin from Rhododendron molle, showed remarkable antinociceptive efficacy in models of neuropathic pain, but its biotargets and mechanisms are unknown. Given the reversible action of rhodojaponin VI and the narrow range over which its structure can be modified, we perforwmed thermal proteome profiling of the rat dorsal root ganglion to determine the protein target of rhodojaponin VI. N-Ethylmaleimide-sensitive fusion (NSF) was confirmed as the key target of rhodojaponin VI through biological and biophysical experiments. Functional validation showed for the first time that NSF facilitated trafficking of the Cav2.2 channel to induce an increase in Ca2+ current intensity, whereas rhodojaponin VI reversed the effects of NSF. In conclusion, rhodojaponin VI represents a unique class of analgesic natural products targeting Cav2.2 channels via NSF.

ABSTRACT: Specific pathogen-free ducks are important high-grade laboratory animals, with a key role in research related to poultry biosecurity, production, and breeding. However, the genetic characteristics of experimental duck varieties remain poorly explored. Herein we performed whole-genome resequencing to construct a single nucleotide polymorphism genetic map of the genomes of 3 experimental duck varieties [Jinding ducks (JD), Shaoxing ducks (SX), and Fujian Shanma ducks (SM)] to determine their genetic characteristics and identify selection signatures. Subsequent analyses of population structure and genetic diversity revealed that each duck variety formed a monophyletic group, with SM showing richer genetic diversity than JD and SX. Further, on exploring shared selection signatures, we found 2 overlapping genomic regions on chromosome Z of all experimental ducks, which comprised immune response-related genes (IL7R and IL6ST). Moreover, growth and skeletal development (IGF1R and GDF5), meat quality (FoxO1), and stress resistance (HSP90B1 and Gpx8-b) candidate gene loci were identified in strongly selected signatures specific to JD, SM, and SX, respectively. Our results identified the population genetic basis of experimental ducks at the whole-genome level, providing a framework for future molecular investigations of genetic variations and phenotypic changes. We believe that such studies will eventually contribute to the management of experimental animal resources.

Differentiation of preadipocytes into functional adipocytes could be a major target for repressing obesity-induced insulin resistance (IR). However, the molecular mechanisms involved in adipogenesis and the development of IR are unclear. We report, for the first time, that miR-574-5p, a novel miRNA, promotes adipogenesis to suppress IR. An increase in the level of miR-574-5p significantly induced the differentiation of preadipocytes into mature adipocytes. Conversely, reduction of miR-574-5p levels blocked the differentiation of preadipocytes in vitro. In a dual-luciferase reporter assay, it was shown that homeobox A5 (HOXA5) promoted the transcription of miR-574-5p to induce the differentiation of preadipocytes. Hdac9, a direct downstream target of miR-574-5p, was involved in the regulation of adipocyte differentiation. The overexpression of miR-574-5p also promoted adipogenesis in subcutaneous fat to alleviate IR in high-fat-diet-fed mice. Additionally, miR-574-5p expression was significantly higher in the subcutaneous adipose tissue of obese patients without type 2 diabetes than in those with type 2 diabetes. There was an increase in HOXA5 expression and a decrease in histone deacetylase 9 (HDAC9) expression in the subcutaneous fat of obese patients without type 2 diabetes. These results suggest that miR-574-5p may be a potential therapeutic target for combating obesity-related IR.

Single-cell RNA-sequencing (scRNA-seq) presents better insights into cell behavior in the context of a complex tumor microenvironment by profiling single-cell populations. However, the mechanisms underlying treatment failure in hepatocellular carcinoma (HCC) are poorly understood. In this study, we performed deep scRNA-seq on immune cells under the isolation in peripheral blood, cancer tissues, and nearby common tissues of four HCC cases and two non-cancer controls, and 212,494 cells were included in the analysis. We identified distinct immune cell subtypes, enriched pathways for differential genes, and delineated associated developmentally relevant trajectories. APOC1 was found over-expressed in tumor-associated macrophages (TAMs) of HCC tissues than in normal tissues. Inhibition of APOC1 reversed the M2 phenotype to the M1 phenotype via the ferroptosis pathway in TAMs from HCC. Tumors in APOC1 −/− C57BL/6 mice demonstrated consistent attenuation compared to wild-type (WT) mice. Mass spectrometry results revealed that the relative proportion of M2 macrophages, B cells, and CD4+ T cells in the APOC1 −/− group exhibited a downward expression compared with the WT group, whereas CD8+ T cells, M1 macrophages, and NK cells exhibited an upward trend. Finally, APOC1 was found to be negatively correlated with the expression of PD1/PD-L1 in human HCC samples. In conclusion, the present study demonstrated that inhibiting APOC1 can promote the transformation of M2 macrophages into M1 macrophages via the ferroptosis pathway, thereby reshaping the tumor immune microenvironment and improving the anti-PD1 immunotherapy for HCC, providing a new strategy for improving the therapeutic effect of anti-PD1, and bringing new hope to HCC patients.

Seven indole alkaloid glycosides containing a 1′-(4″-hydroxy-3″,5″-dimethoxyphenyl)ethyl unit (1–7) were isolated from an aqueous extract of Isatis indigotica leaves (da qing ye). Their structures were determined by spectroscopic data analysis combined with enzymatic hydrolysis as well as comparison of their experimental CD (circular dichroism) and calculated ECD (electrostatic circular dichroism) spectra. Based on analysis of [α]D20 and/or Cotton effect (CE) data of 1–7, two simple roles to assign location and/or configuration of β-glycopyranosyloxy and 1′-(phenyl)ethyl units in the indole alkaloid glycosides are proposed. Stereoselectivity in plausible biosynthetic pathways of 1–7 is discussed. Compounds 3 and 4 and their mixture in a 3:2 ratio showed activity against KCNQ2 in CHO cells. The mixture of 5 and 6 (3:2) exhibited antiviral activity against influenza virus H1N1 PR8 with IC50 64.7 μmol/L (ribavirin, IC50 54.3 μmol/L), however, the individual 5 or 6 was inactive. Preliminary structure–activity relationships were observed.

Introduction and objective: The purpose of this study was to investigate the expression levels and prognostic roles of α-fetoprotein (AFP), carcinoembryonic antigen (CEA), and Ki67 in tumor tissues of intrahepatic cholangiocarcinoma (ICC) patients. Patients or materials and methods: The study involved ninety-two ICC patients with complete clinicopathological data and follow-up information, who had previously undergone radical surgery. AFP, CEA, CD10, CD34, and Ki67 were detected in tumor tissues using immunohistochemistry. Statistical tests were used to identify independent risk factors and their associations with overall survival (OS) and disease-free survival (DFS). Results: AFP, CEA and Ki67 were strongly correlated with prognosis. Univariate analysis indicated that higher AFP (P = 0.002), CEA (P

Since cancer incidence and mortality are rapidly growing worldwide, it is imperative to develop the effective tumor models in vitro for anti-cancer drug screening. Cellular spheroid as an excellent simple 3D model can bridge the gap between cell culture and live tissue. Although numerous approaches for generating cellular spheroids emerges, the long cultivation time and the heterospheroids formation with multiple cell types are still challenging. In the present study, a mask-free method of multicellular heterospheroids arrays formation using digital micromirror device (DMD)-based hydrogel fabricating system and microfluidic system is proposed. Microwell arrays were designed and manufactured online based on shadowed light which shows high flexible. Besides, heterospheroids with multiple cells controlled in different ratios can be generated and cultured for a long time in microfluidic system. Furthermore, the drug screening shows that heterospheroids have high rate of drug resistance compared with homospheroids and combinatorial drugs works better than the single drugs. These studies provide a 3D heterospheroids generating process for high-throughput combinatorial anti-cancer drug screening with potential cancer therapeutic application. Keywords: 3D heterospheroids generation, Microwells fabrication, Drug screening

The controlled patterning of microdroplets or microwires at precise positions plays an essential role in micro/nano device applications. In this context, we propose a novel and efficient method called tip-assisted electrohydrodynamic (EHD) printing that combines the tip-assisted electric field intensity enhancement effect and the high-resolution capability of EHD printing. The tip-assisted electric field enhancement effect is first systematically investigated by simulation analysis. Under optimized experimental conditions, we obtain microdroplet arrays and microwires down to sizes of 2.3 μm and controlled micropatterns composed of droplet arrays or microwires with sizes smaller than the inner diameter of nozzle by means of the tip-assisted technique. We find that with our designed tip-assisted nozzle, solutions with a high viscosity of >2000 cps can be extracted from the nozzle, and the printing resolution can increase by nearly five times the current resolution. Our results demonstrate that tip-assisted EHD printing provides a potential and flexible method for precision and controlled manufacturing of micropatterns. Keywords: Electrohydrodynamic (EHD) printing, Tip-assisted EHD, Micropatterning, High-resolution printing

Geographical regions profoundly influence the flavor characteristics of Congou black tea (CBT). In this study, 35 CBT samples from 7 geographical regions were comprehensively characterized by integrated multiple intelligent sensory technologies and untargeted metabolomics analysis. A satisfactory discrimination was achieved through the fusion of multiple intelligent sensory technologies (R2Y = 0.918, Q2 = 0.859). A total of 104 non-volatile and 169 volatile metabolites were identified by UHPLC-HRMS and GC–MS, respectively. Of these, 45 critical differential non-volatile metabolites and 76 pivotal differential volatile metabolites were pinpointed based on variable importance in projection >1 and p

In the present study, the comprehensive quality of Congou black tea (CBT) including aroma, taste, and liquid color was investigated by a combination of gas chromatography electronic nose (GC-E-Nose), electronic tongue (E-tongue), and electronic eye (E-eye). An excellent discrimination of different quality grades of CBT was accomplished through the fusion of GC-E-Nose, E-tongue, and E-eye combined with orthogonal partial least squares discriminant analysis, with parameters of R2Y = 0.803 and Q2 = 0.740. Moreover, the quantitative evaluation of CBT quality was successfully achieved by partial least squares regression analysis, with the absolute error within 1.39 point, and the relative error within 1.62%. Additionally, 12 key variables were screened out by stepwise multiple linear regression analysis, which significantly contributed to the comprehensive quality score of CBT. Our results suggest that the fusion of multiple intelligent sensory technologies offers great potential and practicability in the quality evaluation of black tea.

Aroma plays a pivotal role in the quality of black tea. However, the acceptability of black tea is greatly limited by the green off-flavor (GOF) resulting from the inappropriate processing control. In this study, the key odorants causing GOF were investigated by volatolomics, and their dynamic changes and formation pathways were in-depth understood. Significant alterations in volatile metabolites were observed in the withering stage. A total of 14 key odorants were identified as contributors to GOF, including 2-methylpropanal, 3-methylbutanal, 1-hexanol, nonanal, (E, E)-2,4-heptadienal, benzaldehyde, linalool, (E, E)-3,5-octadiene-2-one, β-cyclocitral, phenylacetaldehyde, (E, E)-2,4-nonadienal, methyl salicylate, geraniol, and β-ionone. Among them, (E, E)-2,4-heptadienal (OAV = 3913), characterized by fatty, green, and oily aromas, was considered to be the most important contributor causing GOF. Moreover, it was found that lipid degradation served as the primary metabolic pathway for GOF. This study provides a theoretical foundation for off-flavor control and quality improvement of black tea.

Lipids are important tea aroma precursors. Due to the complexity of black tea processing involving both enzymatic and thermal reactions, the role of lipids in black tea aroma formation remained unclear. Herein, the dynamic changes of lipids and volatiles during black tea processing were simultaneously analyzed by lipidomics and volatolomics using ultra-high-performance liquid chromatography coupled to Q-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive) and gas chromatography-tandem mass spectrometry (GC-MS/MS). The lipidomics method was validated in linearity, reproducibility, and recovery, which showed a high reliability. A total of 374 lipids and 88 volatiles were detected. Among them, 362 lipids and 29 fatty acid-derived volatiles (FADVs) were significantly altered depending on different processing stages. During the enzyme-driven stages of black tea processing (withering, rolling and fermentation), monogalactosyldiacylglycerol (MGDG), phosphatidylcholine (PC), and phosphatidylethanolamine (PE) were largely downregulated (

Rolling represents an essential stage in congou black tea processing. However, the influence of rolling pressure on tea flavor and non-volatile compounds remains unclear. Herein, a combination of untargeted metabolomics, tea pigments quantification, E-tongue, colorimeter and sensory evaluation was used to evaluate the effect of rolling pressure on black tea quality. As the rolling pressure increased, theaflavins (TFs), thearubigins (TRs), and theabrownins (TBs) significantly elevated. The tea metabolic profiles fluctuated and 47 metabolites were identified as key differential metabolites including flavan-3-ols, flavonol/flavone glycosides, phenolic acids, amino acids. These substances altered possibly due to the variations in enzymatic oxidation of tea phenolics and amino acids. Overall, black tea with moderate rolling pressure presented higher sweetness, lower bitterness, and higher quality index (10 TFs + TRs)/TBs. The results were verified by a validation batch. This study provided new insights into the regulation of rolling pressure and a guidance for black tea processing.

Shaking is an innovative technology employed in black tea processing to enhance flavor. However, the effects of shaking on the evolutionary mechanisms of volatile metabolites (VMs) remain unclear. In this study, we compared the effects of a shaking–withering method with those of traditional withering on the flavor and VMs transformation of black tea. The results showed that black tea treated with shaking exhibited excellent quality with floral and fruity aroma. Based on gas chromatography-tandem mass spectrometry, 128 VMs (eight categories) were detected. Combining variable importance projection with odor activity value analysis, eight key differential VMs were identified. Shaking could promote the oxidative degradation of fatty acids and carotenoids and modulate the biosynthesis of terpenoids to facilitate the formation of floral/fruity VMs (such as (Z)-hexanoic acid-3-hexenyl ester, ethyl hexanoate, trans-β-ionone, and decanal). Our findings provide theoretical guidance for the production of high-quality black tea with floral and fruity aromas.

Despite the importance of fixation in determining green tea quality, its role in reducing the bitter and astringent taste of this beverage remains largely unknown. Herein, an electromagnetic roller-hot-air–steam triple-coupled fixation (ERHSF) device was developed, and its operating parameters were optimized (steam volume: 20 kg/h; hot-air temperature: 90 °C; hot-air blower speed: 1200 r/min). Compared with conventional fixation treated samples, the ratio of tea polyphenols to free amino acids and ester-catechins to simple-catechins in ERHSF-treated samples was reduced by 11.0% and 3.2%, reducing bitterness and astringency of green tea; amino acids, soluble sugars, and chlorophyll contents were significantly increased, enhancing the freshness, sweetness, and greenness; the color indexes, such as L/L* value of brightness and -a/-a* value of greenness, were also improved, and ERHSF-treated samples had the highest sensory scores. These results provided theoretical support and technical guidance for precise quality improvement of summer-autumn green tea.

For the short circuit current test requirement of copper platoon at the entrance of a hybrid current-limiting fuse, the magnetic field distribution simulation model of copper platoon in both steady and transient current state were built. The influence of external magnetic field of copper platoon on the sensor measurement accuracy were analyzed in steady and transient state current. COMSOL simulation software was used to find the intersection point of magnetic induction intensity corresponding to steady-state and transient-state current with amplitude of 10 kA to determine the installation position of Hall element. In order to ensure the measurement accuracy, the installation position of Hall element was optimized by adding ferromagnetic materials, and the method of the final installation position of Hall element was obtained and verified by experiments. It was indicated that the simulation results was well consistent with the experiment results, which verified the correctness of the finite element model and the feasibility of the design. This design reduces the error of hall current sensor from 37% to 3.5%, which can be used as a reference for the research and development of small DC hybrid fuse.

In this study, four kinds of Longjing tea, the famous flat green tea and the protected geographical indication product in China, were used to explore the quality difference of the same green tea due to the cultivar, geographic origin, and storage time under the premise of consistent picking conditions and processing technology using the widely targeted metabolomics. Results showed that 483 flavonoid metabolites with 10 subgroups of flavonoids were screened and 118 differential flavonoid metabolites were identified. The number and subgroups of differential flavonoid metabolites produced by different cultivars of Longjing tea were the largest, followed by storage time, and third by the geographic origin. Glycosidification and methylation or methoxylation were the main structural modifications of differential flavonoid metabolites. This study has enriched the understanding of the effects of the cultivar, the geographic origin, and the storage time on the flavonoid metabolic profiles of Longjing tea, and provided worthy information for the traceability of green tea.

Storage time is one of the important factors affecting the aroma quality of Pu-erh tea. In this study, the dynamic changes of volatile profiles of Pu-erh teas stored for different years were investigated by combining gas chromatography electronic nose (GC-E-Nose), gas chromatography-mass spectrometry (GC–MS), and gas chromatography-ion mobility spectrometry (GC-IMS). GC-E-Nose combined with partial least squares-discriminant analysis (PLS-DA) realized the rapid discrimination of Pu-erh tea with different storage time (R2Y = 0.992, Q2 = 0.968). There were 43 and 91 volatile compounds identified by GC–MS and GC-IMS, respectively. A satisfactory discrimination (R2Y = 0.991, and Q2 = 0.966) was achieved by using PLS-DA based on the volatile fingerprints of GC-IMS. Moreover, according to the multivariate analysis of VIP > 1.2 and univariate analysis of p

Second-drying is a key process of green tea manufacturing, however, hitherto the effect of second-drying methods on green tea quality has not been assessed. In this study, we compared the effect of three heat transfer drying methods (heat radiation, heat convection, and heat conduction) on green tea quality. Gas chromatography-tandem dual mass spectrometry was used to detect volatile compounds, while absolute quantitative methods were used to detect the non-volatile ones. We identified 45 non-volatile metabolites, 101 volatile metabolites, and 15 objective flavor indicators. Seventeen differential non-volatiles and 8 differential volatiles were screened. Microwave second-drying in heat radiation was the optimal method for green tea flavor, as it can promote the retention of chlorophyll, the degradation of flavonoid glycosides, and the enrichment of amino acids, soluble sugars, nonanal, trans-β-ionone, linalool, and jasmone. The results provide a theoretical basis and technical guidance for the precise and directional processing of high-quality green tea.