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Anaphylactoid reactions are common clinical acute adverse drug reactions that can exacerbate a patient’s condition and produce effects that may become life-threatening. Therefore, it is important to establish a novel method to evaluate drugs for anaphylactoid reactions. In this study, we developed a sensitive and rapid method to detect histamine release from LAD2 cells using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and constructed a relative release index based on various release curve parameters, including allergen release time and sudden change rate, to evaluate the potential and strength of allergen-induced anaphylactoid reactions. This LAD2 release model was used to evaluate anaphylactoid reactions induced by ciprofloxacin, norfloxacin, lomefloxacin, moxifloxacin, and baicalin. The results positively correlated with those obtained with an Evans blue ear test and negatively correlated with the Ca 2+ influx EC 50 . In summary, the current study established a novel in vitro method to analyze the properties of histamine release from LAD2 cells and characterize the sensitization and strength of sensitization of drugs or components that may induce anaphylactoid reactions.

Background Fingerprint analysis and simultaneous multi-components determination are crucial for the holistic quality control of traditional Chinese medicines (TCMs). Yet, reference standards (RS) are often commercially unavailable and with other shortages, which severely impede the application of these technologies. Methods A digital reference standard (DRS) strategy and the corresponding software called DRS analyzer, which supports chromatographic algorithms, spectrum algorithms, and the combination of these algorithms, was developed. The extensive function also enabled the DRS analyzer to recommend the chromatographic column based on big data. Results Various quality control methods of fingerprints of 11 compounds in polyphenolic acid extract of Salvia miltiorrhiza ( S. miltiorrhiza ) were developed based on DRS analyzer, involving relative retention time (RRT) method, linear calibration using two reference substances (LCTRS) technique, RRT combined with Photon Diode Array (PDA) method, LCTRS combined with PDA method. Additionally, the column database of samples was established. Finally, our data demonstrated that the DRS analyzer could accurately identify 11 compounds of the samples, using only one or two physical RSs. Conclusions The DRS strategy is an automated, intelligent, objective, accurate, eco-friendly, universal, sharing, and promising method for overall quality control of TCMs that requires the usage of fewer RSs.

Mitochondria are fundamental organelles that play a crucial role in cellular energy metabolism, substance metabolism, and various essential cellular signaling pathways. The dysfunction of mitochondria is significantly implicated in the onset and progression of aging, neurodegenerative diseases, metabolic disorders, and tumors, thereby rendering mitochondria-targeted regulation, a vital strategy for disease prevention and treatment. The recently developed mitochondrial membrane chromatography (MMC) technique, which immobilizes mitochondrial proteins as a chromatographic separation medium, has shown great potential for efficiently screening mitochondria-targeted modulators from complex compound library. In contrast to traditional screening methods, MMC has no need to purify mitochondrial proteins and can preserve its in situ and physiological conformation. Consequently, it presents broader application prospects for screening mitochondrial modulators as well as investigating receptor-ligand interactions involving any target protein associated with mitochondria. This review aims to elucidate the critical role of mitochondria in the development and progression of major chronic diseases, discuss recent advancements and applications of MMC, and propose future directions for MMC in the identification of novel mitochondrial modulators. [Display omitted] •Proposed strategies for preventing and treating major chronic diseases through mitochondrial-targeted regulation.•Defined the concept of mitochondrial membrane chromography and detailed the protocol.•Summarized the applications of mitochondrial membrane chromatography.

Hepatocellular carcinoma (HCC) is one of the most common tumor types and remains a major clinical challenge. Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC. However, few mitophagy inhibitors have been approved for clinical use in humans. Pyrimethamine (Pyr) is used to treat infections caused by protozoan parasites. Recent studies have reported that Pyr may be beneficial in the treatment of various tumors. However, its mechanism of action is still not clearly defined. Here, we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis. Mechanistically, Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells. In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29 (SNAP29)-vesicle-associated membrane protein 8 (VAMP8) interaction. Moreover, Pyr acted synergistically with sorafenib (Sora) to induce apoptosis and inhibit HCC proliferation in vitro and in vivo. Pyr enhances the sensitivity of HCC cells to Sora, a common chemotherapeutic, by inhibiting mitophagy. Thus, these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor. Notably, Pyr and Sora combination therapy could be a promising treatment for malignant HCC. [Display omitted] •Pyr regulates mitophagy by interfering with autophagosome-lysosome formation.•Pyr blocks autolysosomes formation by inhibiting SNAP29-VAMP8 interactions.•Pyr upregulates BNIP3 and induces the interaction of SNAP29 with BNIP3.•Restoration of the interaction between SNAP29 and VAMP8 by BNIP3 depletion.•Pyr enhances the sensitivity of HCC to Sora in vitro and in vivo.

【目的】探究黑龙江省松嫩平原土地盐碱化时空动态变化及其影响因素。【方法】利用遥感数据解译、土壤反射率反演、相关分析和相对贡献率分析研究松嫩平原土地盐碱化面积的时空演化特征并识别土地盐碱化面积变化的主要影响因素。【结果】松嫩平原2000—2020年土地盐碱化面积总体呈下降趋势，下降速率为-13.67 km2/5 a。随着农作物播种面积与GDP的增加，齐齐哈尔市土地盐碱化程度加剧；GDP、农作物播种面积和人口数量增多加剧了绥化市盐碱化程度；哈尔滨市土地盐碱化正逐步改善，主要影响因素为GDP、农作物播种面积和牲畜数量。【结论】松嫩平原土地盐碱化面积变化主要促进因素为社会经济发展、农牧业发展，直接影响因素为气候变化，在盐碱地改良与治理过程中，应针对以上因素提出有针对性的治理措施，减少盐碱化土地面积，提高土地利用效率；同时地下水埋深呈缓慢上升趋势，因此应建立完备的灌溉和排水设施，以避免土壤次生盐碱化。

【Objective】 Soil salinization is a dynamic process, affected by numerous factors. Understanding its spatiotemporal variation in a region and catchment is important for management. In this paper, we present the soil salinity dynamics and its determinants in Songnen Plain of Heilongjiang province. 【Method】 The calculation was based on remote sensing imagery of the region acquired from 2000—2020. We used correlation analysis and relative contribution rate analysis to map the spatiotemporal distribution of soil salinity in this region. 【Result】 On average, areas affected by salt in the region had decreased from 2000 to 2020, at a rate of 2.73 km2/a. But this is mainly due to the reduced soil salinization in some regions, as other regions actually had seen an increase in soil salinization. In particular, soil salinization in Qiqihar had increased because of the increase in cropped lands and GDP. Suihua also saw soil salinity rising due to increased plant areas and population. In contrast, soil salinity in Daqing and Harbin had decreased, due to the increase in surface water resources and decrease in evaporation for Daqing, and the change in cropped land and livestock industry for Harbin. 【Conclusion】 Change in soil salinization from 2000 to 2020 in Songnen Plain varied, with some areas seeing an increase and others witnessing a decline. In addition to climate change, other reasons underlying such variations in soil salinization include economic development, change in cropping systems and livestock industry. To ameliorate soil salinization and improve land quality, this region should consider improving irrigation and drainage facilities and controlling the groundwater depth not exceeding a critical level.

Background: Fingerprint analysis and simultaneous multi-components determination are crucial for the holistic quality control of traditional Chinese medicines (TCMs). Yet, reference standards (RS) are often commercially unavailable and with other shortages, which severely impede the application of these technologies. Methods: A digital reference standard (DRS) strategy and the corresponding software called DRS analyzer, which supports chromatographic algorithms, spectrum algorithms, and the combination of these algorithms, was developed. The extensive function also enabled the DRS analyzer to recommend the chromatographic column based on big data. Results: Various quality control methods of fingerprints of 11 compounds in polyphenolic acid extract of Salvia miltiorrhiza (S. miltiorrhiza) were developed based on DRS analyzer, involving relative retention time (RRT) method, linear calibration using two reference substances (LCTRS) technique, RRT combined with Photon Diode Array (PDA) method, LCTRS combined with PDA method. Additionally, the column database of samples was established. Finally, our data demonstrated that the DRS analyzer could accurately identify 11 compounds of the samples, using only one or two physical RSs. Conclusions: The DRS strategy is an automated, intelligent, objective, accurate, eco-friendly, universal, sharing, and promising method for overall quality control of TCMs that requires the usage of fewer RSs.

Fusion with host cell membrane is the main mechanism of infection of SARS-CoV-2. Here, we propose a new strategy to double block SARS-CoV-2 membrane fusion by using Harringtonine (HT), a small-molecule antagonist. By using cell membrane chromatography (CMC), we found that HT specifically targeted the SARS-CoV-2 S protein and host cell TMPRSS2, and then confirmed that HT can inhibit pseudotyped virus membrane fusion. Furthermore, HT successfully blocked SARS-CoV-2 infection, especially in the delta and Omicron mutant. Since HT is a small-molecule antagonist, it is minimally affected by the continuous variation of SARS-CoV-2. Our findings show that HT is a potential small-molecule antagonist with a new mechanism of action against SARS-CoV-2 infection, and thus HT mainly targets the S protein, and thus, greatly reduces the damage of the S protein's autotoxicity to the organ system, has promising advantages in the clinical treatment of COVID-19. Competing Interest Statement The authors have declared no competing interest.

Background: The novel coronavirus disease (2019-nCoV) has been affecting global health since the end of 2019 and there is no sign that the epidemic is abating. The major issue for controlling the infectious is lacking efficient prevention and therapeutic approaches. Chloroquine (CQ) and Hydroxychloroquine (HCQ) have been reported to treat the disease, but the underlying mechanism remains controversial. Purpose: The objective of this study is to investigate whether CQ and HCQ could be ACE2 blockers and used to inhibit 2019-nCoV virus infection. Methods: In our study, we used CCK-8 staining, flow cytometry and immunofluorescent staining to evaluate the toxicity and autophagy of CQ and HCQ, respectively, on ACE2 high-expressing HEK293T cells (ACE2h cells). We further analyzed the binding character of CQ and HCQ to ACE2 by molecular docking and surface plasmon resonance (SPR) assays, 2019-nCoV spike pseudotyped virus was also used to observe the viropexis effect of CQ and HCQ in ACE2h cells. Results: Results showed that HCQ is slightly more toxic to ACE2h cells than CQ. Both CQ and HCQ could bind to ACE2 with KD =(7.31±0.62)e-7 M and (4.82±0.87)e-7 M, respectively. They exhibit equivalent suppression effect for the entrance of 2019-nCoV spike pseudotyped virus into ACE2h cells. Conclusions: CQ and HCQ both inhibit the entrance 2019-nCoV into cells by blocking the binding of the virus with ACE2. Our findings provide novel insights into the molecular mechanism of CQ and HCQ treatment effect on virus infection. Competing Interest Statement The authors have declared no competing interest.

Attenuation exists in seismic wave propagation in subsurface layers, and relatively high attenuation occurs in oil-bearing reservoirs. Inversion of frequency components of observed seismic data generates values of attenuation factor 1/Q, which produces potential results for determining oil-bearing reservoirs. Beginning with expressions of seismic wave velocity in attenuating media, we involve P-wave maximum attenuation factor to rewrite P-wave velocity driven by an attenuating rock physics model, and we also employ an empirical relationship between P-wave attenuation factor and S-wave attenuation factor to express S-wave velocity in terms of P-wave maximum attenuation factor. Using the derived P- and S-wave velocities, we extend Zoeppritz equations to compute reflection coefficient for an interface separating two attenuating media. Under the assumption that contrasts in elastic properties of two media across the interface are small and the background attenuation is weak, we propose a linearized reflection coefficient of PP-wave as a function of contrasts in elastic parameters (i.e., P-wave velocity, S-wave velocity and density) and attenuation factor, and expression of elastic impedance (EI) is also presented. Based on the EI, we demonstrate an approach of estimating elastic parameters and attenuation factor from frequency components of partially incidence-stacked seismic data, which is implemented as a two-step inversion involving the prediction of EI datasets using a model-based damping least-squares algorithm and nonlinear inversion for elastic parameters and attenuation factor. Noisy synthetic seismic data generated using the extended Zoeppritz equations are employed to verify the robustness and stability of the proposed inversion approach. Applying the proposed approach to a real dataset acquired over an oil-bearing reservoir, we obtain convincing results of P-wave velocity, S-wave velocity, density and attenuation factor, which can reasonably match corresponding well log data.