Differential mRNA and lncRNA Expression Profiles Associated with Early Pregnancy Loss in ART Patients.

Early pregnancy loss (EPL) is the most common complication in assisted reproductive technology (ART). However, the precise causes for nearly 50% patients remain unexplained. In the current study, we aimed to discover the differentially expressed profiling of mRNAs and lncRNAs by RNA sequencing (RNA-seq). Human chorionic villi tissues were collected from patients with EPL and natural control (NC) group. RNA sequencing (RNA-seq) of these specimens was performed for transcriptome analysis. As a result, we identified a total of 141 mRNAs and 137 lncRNAs that were significantly differentially expressed between villi tissues from EPL and NC. Functional enrichment analyses indicated enrichment of differentially expressed genes involved in pathways were associated with growth hormone receptor binding, PI3K-Akt signaling pathway, Jak-STAT signaling pathway, transcriptional misregulation in cancer, metabolic pathways and Rap1 signaling pathway. Additionally, the co-expression networks (lncRNA-miRNA-mRNA) was constructed based on the correlation analysis between the differentially expressed RNAs.7 mRNAs and 6 lncRNAs were successfully technically validated with RT-PCR. In conclusion, our results suggest a direction for the further study of EPL-related mRNAs and lncRNAs and may ultimately assist in understanding the pathogenesis of EPL.

Targeting STING in dendritic cells alleviates psoriatic inflammation by suppressing IL-17A production.

Psoriasis is a common chronic inflammatory skin disease driven by the aberrant activation of dendritic cells (DCs) and T cells, ultimately leading to increased production of cytokines such as interleukin (IL)-23 and IL-17A. It is established that the cGAS-STING pathway is essential for psoriatic inflammation, however, the specific role of cGAS-STING signaling in DCs within this context remains unclear. In this study, we demonstrated the upregulation of cGAS-STING signaling in psoriatic lesions by analyzing samples from both clinical patients and imiquimod (IMQ)-treated mice. Using a conditional Sting-knockout transgenic mouse model, we elucidated the impact of cGAS-STING signaling in DCs on the activation of IL-17- and IFN-γ-producing T cells in psoriatic inflammation. Ablation of the Sting hampers DC activation leads to decreased numbers of IL-17-producing T cells and Th1 cells, and thus subsequently attenuates psoriatic inflammation in the IMQ-induced mouse model. Furthermore, we explored the therapeutic potential of the STING inhibitor C-176, which reduces psoriatic inflammation and enhances the anti-IL-17A therapeutic response. Our results underscore the critical role of cGAS-STING signaling in DCs in driving psoriatic inflammation and highlight a promising psoriasis treatment.

UBE2C promotes myoblast differentiation and skeletal muscle regeneration through the Akt signaling pathway.

Ubiquitin-conjugation enzyme E2C (UBE2C) is a crucial component of the ubiquitin-proteasome system that is involved in numerous cancers. In this study, we find that UBE2C expression is significantly increased in mouse embryos, a critical stage during skeletal muscle development. We further investigate the function of UBE2C in myogenesis. Knockdown of UBE2C inhibits C2C12 cell differentiation and decreases the expressions of MyoG and MyHC, while overexpression of UBE2C promotes C2C12 cell differentiation. Additionally, knockdown of UBE2C, specifically in the tibialis anterior muscle (TA), severely impedes muscle regeneration in vivo. Mechanistically, we show that UBE2C knockdown reduces the level of phosphorylated protein kinase B (p-Akt) and promotes the degradation of Akt. These findings suggest that UBE2C plays a critical role in myoblast differentiation and muscle regeneration and that UBE2C regulates myogenesis through the Akt signaling pathway.

Effects of ultrasonic power on drying kinetics and product quality of licorice extract during ultrasound-assisted vacuum drying.

BACKGROUND: Licorice extract is an important raw material for food additives and medicine. The quality of licorice extract is dictated by the drying process. The commonly used drying methods of licorice extract are not efficient in obtaining high-quality products so alternative techniques need to be developed and researched. In this study, ultrasound-assisted vacuum drying (UAVD) was first utilized to improve drying efficiency and produce a higher-quality product. The changes in water mobility of licorice extract during drying were characterized using low-field nuclear magnetic resonance. In addition, the effects of ultrasonic power on the drying dynamics, the contents of liquiritin and glycyrrhizic acid, the antioxidant capacity and the microstructure formation of licorice extract during the whole drying process were investigated. RESULTS: The drying times for licorice extract to reach equilibrium moisture content were reduced by 9.09-69.70% with UAVD at 40-200 W compared with that without ultrasonic treatment (0 W). Moreover, the proportions of bound water and semi-bound water in fresh concentrate were 3.75% and 96.25%. It was also found that high ultrasonic power promoted the flow of water and the formation of porous structure in licorice extract, which led to the improvement of drying efficiency. The contents of liquiritin (2.444%) and glycyrrhizic acid (6.514%) were retained to a large degree in the dried product at an ultrasonic power of 80 W. The DPPH inhibition rate of UAVD samples with different ultrasonic powers ranged from 84.07 ± 0.46% to 90.65 ± 0.22%. CONCLUSION: UAVD has the advantages of high efficiency and low energy consumption, which may be an alternative technology for vacuum drying widely used in industry. © 2024 Society of Chemical Industry.

Residue analysis and dietary risk assessment of abamectin in fresh corn, bitter melon, and Fritillaria.

To clarify the residue behavior and possible dietary risk of abamectin in fresh corn, bitter melon, and Fritillaria, a method was developed for the simultaneous determination of abamectin residues in fresh corn, bitter melon, and Fritillaria by QuEChERS (quick, easy, cheap, effective, rugged, safe) ultra-performance liquid chromatography-tandem mass spectrometry. The mean recovery of abamectin in fresh corn, bitter melon, and Fritillaria was 86.48%-107.80%, and the relative standard deviation was 2.07%-10.12%. The detection rates of abamectin residues in fresh corn, bitter melon, and Fritillaria were 62.50%, 87.50%, and 80.00%, respectively. The residues of abamectin in fresh corn, bitter melon, and Fritillaria were not more than 0.020, 0.019, and 0.087 mg/kg, respectively. Based on these results, dietary risk assessment showed that the risk content of abamectin residues in long- and short-term dietary exposure for Chinese consumers was 61.57% and 0.41%-1.11%, respectively, indicating that abamectin in fresh corn, bitter melon, and Fritillaria in the market would not pose a significant risk to consumers.

Butanol accelerated entropy-driven DNA walking machine for rapid and ultrasensitive determination of alkaline phosphatase activity.

Alkaline phosphatase (ALP) as an important biomarker as well as an index for the pasteurization degree of dairy food. However, there is a dilemma between the sensitivity and time-cost of ALP determination based on nucleic acid amplification approach. Herein, an ultrasensitive and rapid detection method for the ALP assay was developed based on entropy-driven DNA machine. In our design, the ALP catalyzed dephosphorylation of detection probe, which inhibited the digestion effect of lambda exonuclease. The remaining probe as a linker to tether the walking strand proximity to the surface of track strand modified gold nanoparticle, activating entropy-driven DNA machine. Accompany with walking strand moving, a large amount of assembled dye-labelled strand dissociated from gold nanoparticle with fluorescence recovery. More importantly, to further improve the walking efficiency, butanol was introduced to accelerated the signal amplification at interface, which short the incubation time from several hours to 5 min. Under the optimum condition, the change of fluorescence intensity was proportion to the concentration of ALP in the range from 0.05 U L-1 to 5 U L-1 with an ultralow limit of detection of 2.07 × 10-3 U L-1 was achieved, which is superior to other reported methods. Furthermore, the proposed method also successfully applied for the spiked milk sample assay with satisfactory recovery in the range of 98.83%-103.00%. This work proposed a new strategy for the application of entropy-driven DNA machine in the field of rapid and ultrasensitive detection.

Monocyte count is associated with the severity of human adenovirus pneumonia in hospitalized children aged less than 6 years.

BACKGROUND: Human Adenovirus (HAdV) pneumonia is common in young children and infants. Overall, 7-8% of all viral respiratory illnesses among children for less than 5 years are induced by HAdVs. Unfortunately little is known about the role of monocyte count in the disease severity. METHODS: Data were gathered from 595 children (age < 6 years) who were diagnosed with HAdV infection at the 1st People's Hospital (Changde City, China) between January 2019 and December 2019. There were 181 cases of severe adenovirus pneumonia. RESULTS: The correlation between the patients' monocyte count and the severity of HAdV pneumonia was estimated by performing a multiple linear regression analysis. The results showed a negative association (OR: 0.53, 95% CI 0.31 to 0.89, P < 0.05). We further built Generalized Additive Models (GAMs) and demonstrated that the monocyte count had a non-linear association with severe HAdV pneumonia. The inflection point of monocyte count detected in the two-stage linear regression model was 1.5. On the left side of this point, the monocyte count was negatively interrelated (OR: 0.26, 95% CI 0.13 to 0.52, P < 0.001), while on the opposite side, there was a positive association (OR: 7.48, 95% CI 1.30 to 43.08, P < 0.05). CONCLUSIONS: Based on the results of this investigation, we established a link between monocyte count and the severity of HAdV pneumonia. Monocyte count is negatively associated with severe HAdV pneumonia. The inflection point of monocyte count detected in the two-stage linear regression model was 1.5 × 109/L.

Quantitative ion character-activity relationship methods for assessing the ecotoxicity of soil metal(loid)s to lettuce.

New pollution elements introduced by the rapid development of modern industry and agriculture may pose a serious threat to the soil ecosystem. To explore the ecotoxicity and risk of these elements, we systematically studied the acute toxicity of 18 metal(loid)s toward lettuce using hydroponic experiments and quantitative relationships between element toxicity and ionic characteristics using ion-grouping and ligand-binding theory methods, thereby establishing a quantitative ion character-activity relationship (QICAR) model for predicting the phytotoxicity threshold of data-poor elements. The toxicity of 18 ions to lettuce differed by more than four orders of magnitude (0.05-804.44 µM). Correlation and linear regression analysis showed that the ionic characteristics significantly associated with this toxicity explained only 23.8-50.3% of the toxicity variation (R2Adj = 0.238-0.503, p < 0.05). Relationships between toxicity and ionic properties significantly improved after separating metal(loid) ions into soft and hard, with R2Adj of 0.793 and 0.784 (p < 0.05), respectively. Three ligand-binding parameters showed different predictive effects on lettuce metal(loid) toxicity. Compared with the binding constant of the biotic ligand model (log K) and the hard ligand scale (HLScale) (p > 0.05), the softness consensus scale (σCon) was significantly correlated with toxicity and provided the best prediction (R2Adj = 0.844, p < 0.001). We selected QICAR equations based on soft-hard ion classification and σCon methods to predict phytotoxicity of metal(loid)s, which can be used to derive ecotoxicity for data-poor metal(loid)s, providing preliminary assessment of their ecological risks.

Exploring the Mechanism of Ionic Liquids to Improve the Extraction Efficiency of Essential Oils Based on Density Functional Theory and Molecular Dynamics Simulation.

In this paper, Amomi fructus (Latin) was used to explore the mechanism of ionic liquids (ILs) in improving the extraction efficiency of essential oils. Microwave assisted ionic liquid treatment followed by a hydro-distillation (MILT-HD) process for isolating Amomi fructus essential oil was optimized by multi-objective optimization. Under optimum operating conditions, the IL-assisted extraction method not only enhances extraction efficiency but also reduces energy demands and CO2 emissions. Since the hydrogen bond structure network of cellulose in the cell wall is an important reason for hindering diffusion of essential oils, the mechanism of ILs was explored by density functional theoretical (DFT) and molecular dynamics (MD) simulations. According to DFT calculations, ILs can facilitate the cleavage of cellulose chains and have strong non-covalent interactions with cellulose. Based on the MD simulations, the degree of destruction of the cellulose hydrogen bond structure was explored. According to the DFT and MD simulations, the ILs can significantly destroy cellulose structure, thereby promoting essential oil release from the plant. These results were confirmed by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). This work is conducive to better understand the MILT-HD process for isolating essential oil and comprehensively understand the mechanism of ILs in the extraction process.

Vertical GaN Power MOSFET with Integrated Fin-Shaped Diode for Reverse Conduction.

A vertical GaN power MOSFET featuring an integrated fin-shaped non-junction diode (FDMOS) is proposed to improve reverse conduction and switching characteristics. Its static and dynamic characteristics are studied and analyzed by Sentaurus TCAD simulation. Compared with the conventional MOSFET (Con. MOS) with a body diode as a freewheeling diode (FWD), the FDMOS uses the integrated fin-shaped diode to reverse conduction, and thus, a low reverse turn-on voltage VON of 0.66 V is achieved, with a decreasing of 77.9%. Moreover, the Qrr of the FDMOS is reduced to 1.36 µC from 1.64 µC of the Con. MOS, without the minority carrier injection. The gate charge (QGD) of the FDMOS is significantly reduced because the fin structure reduces the gate area and transforms some part of CGD to CGS, and thus, a low switching loss is realized. The QGD, the turn-on loss (Eon) and the turn-off loss (Eoff) of the FDMOS are decreased by 56.8%, 33.8% and 53.8%, respectively, compared with those of the Con. MOS. In addition, the FDMOS is beneficial to reduce the parasitic inductance and the total chip area compared with the conventional method of using an externally connected Schottky diode as an FWD.

High Performance Flip-Structure Enhancement-Mode HEMT with Face-to-Face Double Gates.

A novel double gates flip-structure enhancement-mode (E-mode) high electron mobility transistor with step field plate (DFF HEMT) is proposed. It features face-to-face double gates, including a top trench MIS gate with a step field plate and a bottom planar MIS gate, which is shorted together. In the on-state, the double gates not only can restore the 2DEG by the higher electric potential, but also can form the electron accumulation layers, and thus increase the saturation output current and reduce the on-resistance. The face-to-face double gates together deplete the 2DEG by using the work function difference to realize E-mode, instead of by etching the AlGaN layer under the gate for the conventional MIS gate E-mode HEMT. The double-gate structure not only avoids etch damage, but also maintains both high threshold voltage and low on-resistance. Meanwhile, the step gate field plate modulates E-field distribution to increase the BV. In order to easily fabricate, the trench gate with step field plate must be located on the top of device, forming the flip-structure. The flip-structure is also beneficial to decrease the leakage current in the substrate. The simulated Vth, BV and Id of the DFF HEMT are 0.8 V, 465 V and 494 mA/mm, respectively. The FOM of the DFF HEMT is 79.8% and 444.2% higher than those of the conventional MIS-FP HEMT and MIS HEMT.

Notch signaling leads to a slower progression of embryonic myogenic differentiation in Landrace than in Langtang pigs.

Delving into porcine embryonic myogenesis is the key to elucidate the complex regulation of breed-specific differences in growth performance and meat production. Increasing evidence proves that pigs with less meat production show earlier embryonic myogenesis, but little is known about the underlying mechanisms. In this study, we examine the longissimus dorsi muscle (LDM) by immunohistochemistry and confirm that the differentiation of myogenic progenitors is increased ( P<0.05) in Lantang (LT, fatty) pigs compared with that in Landrace (LR, lean) pigs, which results in more ( P<0.001) differentiated myoblasts (Pax7 -/MyoD +) and less ( P<0.001) myogenic progenitors (Pax7 +/MyoD -) in LT pigs at 35 days post-conception (35dpc). Additionally, embryonic myogenic progenitors isolated from LT pigs show greater ( P<0.001) differentiation capacity with earlier expression of MyoD compared with those from LR pigs. Moreover, Notch signaling is more active ( P<0.05) in LR pig myogenic progenitors than in LT pig myogenic progenitors. Inhibition of Notch signaling in LR myogenic progenitors suppresses Pax7 expression and increases MyoD expression, thus promoting myogenic differentiation. Consistently, the process of myogenic progenitors differentiating into myoblasts in ex vivo embryo limbs is accelerated when Notch signaling is inhibited. These results indicate that Notch signaling facilitates the maintenance of myogenic progenitors and antagonizes myogenic differentiation by promoting Pax7 expression and preventing MyoD expression in LR pigs.

Evaluation of coating uniformity for the digestion-aid tablets by portable near-infrared spectroscopy.

Process analysis can effectively stabilize pharmaceutical quality and optimize the control of production process. For the sustained-release digestion-aid tablets, the coating film thickness is an important indicator to measure the quality of products. Traditional method mainly spot-checks tablets and measures with visual microscopy, which is time-consuming and laborious. This study attempted to use a portable near-infrared spectroscopy for rapid detection of a Chinese medicine tablets from production line. First, PLS regression models were established for coating film at twelve different locations of the tablet section, and the results showed that the correlation coefficients of training and validation sets were all over 0.80. Subsequently, the twelve locations were divided into six groups to further establish regressions. After chemometrics optimization, the optimal of six group models were generally better than single location models, with Rc2 and Rv2 all above 0.85, and RMSEV values all below 2.0. The mean relative error of prediction of the optimal model was 9.49%. The pharmaceutical process detection based on the portable NIR spectroscopy met the demand of managing digestion-aid tablet coating data conveniently. The proposed approach can successfully realize on-site and online pharmaceutical monitoring and has a promising practical value.

Snapback-Free Reverse-Conducting SOI LIGBT with an Integrated Self-Biased MOSFET.

A novel snapback-free RC-LIGBT with integrated self-biased N-MOSFET is proposed and investigated by simulation. The device features an integrated self-biased N-MOSFET(ISM) on the anode active region. One side of the ISM is shorted to the P + anode electrode of RC-LIGBT and the other side is connected to the N + anode via a floating ohmic contact. The adaptively turn-on/off of the ISM contributes to improve the static and dynamic performance of the ISM RC-LIGBT. In the forward-state, due to the off-state of the ISM, the snapback could be effectively suppressed without requiring extra device area compared to the SSA (separated shorted anode) and STA (segmented trenches in the anode) LIGBTs. In the reverse conduction, the ISM is turned on and the parasitic NPN in the ISM is punched through, which provides a current path for the reverse current. Meanwhile, during the turn-off and reverse recovery states, the ISM turns on, providing a rapid electron extraction path. Thus, a superior tradeoff between the on-state voltage drop (Von) and turnoff loss (Eoff) as well as an improved reverse recovery characteristic can be obtained. Compared to the STA device, the proposed ISM RC-LIGBT reduces Eoff by 21.5% without snapback. Its reverse recovery charge is reduced by 53.7%/58.6% compared to that of the SSA LIGBT with Lb = 40/60 µm at the same Von. Due to the prominent static and dynamic characteristic, the power loss of ISM RC-LIGBT in a completed switching cycle is reduced.

[Quality control mode based on engineering quality view of Chinese medicine pharmacy].

Due to the characteristics of confusing varieties of Chinese medicinal materials, different sources, complex chemical composition, non-standard preparation process, and non-standard pharmaceutical equipment, the quality of Chinese medicinal preparations is difficult to be controlled and evaluated effectively under the current quality control mode and method of Chinese medicinal preparation. The present study proposed an engineering quality view of Chinese medicine pharmacy and a strategy to control the quality of Chinese medicinal preparations based on the current situation. The "overall, dialectical, and dynamic" multi-factor engineering quality view, covering original medicinal materials, preparation technologies, pharmaceutical equipment, and Chinese medicinal preparations, ensures the traceable process, measurable procedures, and feedback quality. The quality control mode of Chinese medicinal preparation with controllable sources, standardized preparation technologies, green pharmaceutical equipment, and intelligent manufacturing is built up.

Severity and factors of menopausal symptoms in middle-aged women in Gansu Province of China: a cross-sectional study.

OBJECTIVE: To investigate the severity and risk factors of menopausal symptoms in the middle-aged women in Gansu Province of China. METHODS: In this cross-sectional study, a total of 7319 women (aged 40-55 years) attended the health survey in Gansu Province in China were enrolled. Information on demographics, menopausal status, reproductive history, and history of chronic diseases was collected via a structured questionnaire. Severity of menopausal symptom was evaluated by the Modified Kupperman Menopausal Index. Ordinal logistic regression model was applied to explore its risk factors. RESULTS: A total of 7319 participants were included in present study, among them, 3606 (49.27%) had moderate or severe menopausal symptom. Compared with premenopausal women, perimenopausal and postmenopausal women have a higher mKMI score. We observed that older age, higher BMI, non-married status, longer duration of menstruation (≥ 7 days), number of pregnancy (> 3 times), longer duration of breastfeeding (> 12 months), peri- or post-menopausal status, and menopause hormone therapy was positively associated with menopausal symptom score, while higher level of family income, educational and physical activity, and history of gynecological, breast or chronic disease were negatively associated with the score. CONCLUSIONS: Numerous factors were associated with the severity of menopausal symptom among the Chinese women. Because it was gradually increased with aging, more attention is warranted to manage the menopausal symptom.

Using quantitative ion character-activity relationship (QICAR) method in evaluation of metal toxicity toward wheat.

It is important to assess the toxic effects posed by soil pollutants toward plants. However, plant toxicology experiments normally involve a considerable amount of manpower, consumables and time. Therefore, the use of metal toxicity prediction models, independent of toxicity tests, is critical. In this study, we investigated the toxicity of different metal ions to wheat using hydroponic experiments. We employed the methods of soft-hard ion grouping, soft-hard ligand theory and K (conditional binding constant based on the biotic ligand model principle) in combination with hydroponic experiments to explore the application of quantitative ion character-activity relationships in predicting phytotoxicity. The results showed that the toxicity of the 19 metal ions tested varied significantly, with EC50 ranging from 0.27 µM to 4463.36 µM. The linear regression relationships between the toxicity of these metal ions and their physicochemical properties were poor (R2 = 0.237-0.331, p < 0.05). These relationships were improved after grouping the metals according to the soft-hard theory (R2 = 0.527-0.744 and p < 0.05 for soft ions; R2 = 0.445-0.743 and p < 0.05 for hard ions). The application of soft-hard ligand theory, based on the binding affinity of the metals to the ligands, showed poor prediction of the phytotoxicity of metals, with R2 = 0.413 (p = 0.024) for the softness consensus scale (σCon) and R2 = 0.348 (p = 0.218) for the normalized hard ligands scale (HLScale). However, the method of K provided the closest fit in predicting toxicity (R2 = 0.803, p < 0.001). Our results showed that the application of soft-hard ion grouping and log K can improve prediction of the phytotoxicity of metals relatively well, which can potentially be used for deriving the toxicity of elements with limited toxicity data.

KDM4A regulates myogenesis by demethylating H3K9me3 of myogenic regulatory factors.

Histone lysine demethylase 4A (KDM4A) plays a crucial role in regulating cell proliferation, cell differentiation, development and tumorigenesis. However, little is known about the function of KDM4A in muscle development and regeneration. Here, we found that the conditional ablation of KDM4A in skeletal muscle caused impairment of embryonic and postnatal muscle formation. The loss of KDM4A in satellite cells led to defective muscle regeneration and blocked the proliferation and differentiation of satellite cells. Myogenic differentiation and myotube formation in KDM4A-deficient myoblasts were inhibited. Chromatin immunoprecipitation assay revealed that KDM4A promoted myogenesis by removing the histone methylation mark H3K9me3 at MyoD, MyoG and Myf5 locus. Furthermore, inactivation of KDM4A in myoblasts suppressed myoblast differentiation and accelerated H3K9me3 level. Knockdown of KDM4A in vitro reduced myoblast proliferation through enhancing the expression of the cyclin-dependent kinase inhibitor P21 and decreasing the expression of cell cycle regulator Cyclin D1. Together, our findings identify KDM4A as an important regulator for skeletal muscle development and regeneration, orchestrating myogenic cell proliferation and differentiation.

Association Between Parity and the Age at Menopause and Menopausal Syndrome in Northwest China.

This study evaluated the relationships between parity and the age at menopause and menopausal syndrome among Chinese women in Gansu. A total of 7236 women aged 40 to 55 years met study eligibility criteria. The modified Kupperman Menopausal Index scale was used to assess the severity of menopausal syndrome. Cox regression was applied to estimate hazard ratio and 95% confidence interval, and logistic regression was performed to calculate odds ratio and confidence interval. The mean age at menopause was 47.91 ± 3.31 years. There is no relationship between parity and age at menopause. Women with nulliparity or multiparity seemed to have higher risks of moderate and severe menopausal syndrome. The potential beneficial effects of one or two births on menopausal syndrome were also observed by applying the multivariable logistic regression analysis, particularly in urogenital symptoms. Women with nulliparity and multiparity appeared to be at the higher risks of menopause syndrome.

Predicting the combined toxicity of binary metal mixtures (Cu-Ni and Zn-Ni) to wheat.

In order to investigate and model toxicity and interactions between metals in mixtures, inhibition of wheat root elongation in response to additions of single-metals of copper (Cu), zinc (Zn), and nickel (Ni) and of binary mixed-metal combinations of Cu-Ni and Zn-Ni was tested, using water culture experiments under different Mg concentrations and pH values. A biotic ligand model (BLM) of single-metal Cu, Zn, and Ni was established. The results showed that the toxicity of Cu, Zn or Ni in isolation decreased with increasing Mg concentration whereas the effects of pH on Cu, Zn, or Ni toxicity were related not only to free Cu2+, Zn2+, and Ni2+ concentrations, but also to inorganic metal complexes. In binary mixtures, the two metals in the Cu-Ni mixture showed a weakly antagonistic effect, whereas the two metals in the Zn-Ni mixture showed greater antagonism. Using data from single-metal Cu, Zn, and Ni BLMs, combined with the toxicity index and the overall amounts of metal ions bound to the biotic ligands, one simple model was developed. This model consisted of the toxic unit (TUM, no competition included) and two extended BLMs, BLM-TUf (f as a function of TU, including competition between Mg2+ and metal ions) and BLM-fmix (including the competition between Mg2+ and metal ions, as well as between free metal ions). They were then used to predict the joint toxicity of Cu-Ni and Zn-Ni binary mixtures to wheat. Both of the extended BLMs could provide more accurate predictions of toxic effects of Cu-Ni and Zn-Ni than TUM. BLM-fmix performed best for the Zn-Ni binary mixture (r2 = 0.93; root-mean-square error, RMSE = 9.87). On the other hand, for the Cu-Ni mixture, the predictive effect based on BLM-TUf (r2 = 0.93; RMSE = 9.60) was similar to that of BLM-fmix (r2 = 0.93; RMSE = 9.56). The results provide a theoretical basis for the evaluation and remediation of soils contaminated with mixtures of heavy metals.