The C5AR1/TNFSF13B axis alleviates osteoarthritis by activating the PI3K/Akt/GSK3ß/Nrf2/HO-1 pathway to inhibit ferroptosis.

Chondrocyte ferroptosis induces the occurrence of osteoarthritis (OA). As a key gene of OA, C5a receptor 1 (C5AR1) is related to ferroptosis. Here, we investigated whether C5AR1 interferes with chondrocyte ferroptosis during OA occurrence. C5AR1 was downregulated in PA-treated chondrocytes. Overexpression of C5AR1 increased the cell viability and decreased ferroptosis in chondrocytes. Moreover, Tumor necrosis factor superfamily member 13B (TNFSF13B) was downregulated in PA-treated chondrocytes, and knockdown of TNFSF13B eliminated the inhibitory effect of C5AR1 on ferroptosis in chondrocytes. More importantly, the PI3K/Akt/GSK3ß/Nrf2/HO-1 pathway inhibitor LY294002 reversed the inhibition of C5AR1 or TNFSF13B on ferroptosis in chondrocytes. Finally, we found that C5AR1 alleviated joint tissue lesions and ferroptosis in rats and inhibited the progression of OA in the rat OA model constructed by anterior cruciate ligament transection (ACLT), which was reversed by interfering with TNFSF13B. This study shows that C5AR1 reduces the progression of OA by upregulating TNFSF13B to activate the PI3K/Akt/GSK3ß/Nrf2/HO-1 pathway and thereby inhibiting chondrocyte sensitivity to ferroptosis, indicating that C5AR1 may be a potential therapeutic target for ferroptosis-related diseases.

High sensitivity humidity sensor based on the U-shaped tapered no-core fiber coated with MXene.

Ti3C2Tx MXene is an emerging two-dimensional material that has good potential in relative humidity (RH) measurement because of its unique layer structure, strong hydrophilic nature, and large specific surface area. Here, a high-performance RH sensor integrating Ti3C2TX MXene nanosheets and U-shaped tapered no-core fiber (UTNCF) is proposed. The sensing principle is based on mode interference. The change of ambient RH leads to the change of the refractive index (RI) of Ti3C2Tx MXene, which eventually leads to the shift of the transmission spectrum of the sensing probe. The average sensitivity is 1.11 nm/%RH in the RH range of 45% to 80%, and the response time is 25 ms. The proposed micro-nano fiber RH sensor has the advantages of high sensitivity, fast response, good repeatability, and stability. In addition, the proposed sensor has a broad application prospect in human respiratory monitoring, industrial and agricultural production, and environmental monitoring.

Acid tolerance response of Salmonella during the squid storage and its amine production capacity analysis.

Salmonella exhibits a strong inducible acid tolerance response (ATR) under weak acid conditions, and can also induce high-risk strains that are highly toxic, acid resistant, and osmotic pressure resistant to aquatic products. However, the induction mechanism is not yet clear. Therefore, this study aims to simulate the slightly acidic, low-temperature, and high-protein environment during squid processing and storage. Through λRed gene knockout, exploring the effects of low-acid induction, long-term low-temperature storage, and two-component regulation on Salmonella ATR. In this study, we found the two-component system, PhoP/PhoQ and PmrA/PmrB in Salmonella regulates the amino acid metabolism system and improves bacterial acid tolerance by controlling arginine and lysine. Compared with the two indicators of total biogenic amine and diamine content, biogenic amine index and quality index were more suitable for evaluating the quality of aquatic products. The result showed that low-temperature treatment could inhibit Salmonella-induced ATR, which further explained the ATR mechanism from the amino acid metabolism.

Development of new matrix reference materials for quantitative urine analysis in drug tests.

Accurate quantitative analyses require standardized methods to control and improve the analytical process in the laboratory. The availability of urine reference materials (RMs) may offer a feasible option to improve the accuracy of urine analysis and to control matrix effects. This paper presents the complete process of the development of matrix RMs in urine, including sample preparation, homogeneity, and stability studies, as well as uncertainty assessment. A freeze-drying process was developed, and freeze-dried human and pig urine samples were prepared and verified to have comparable homogeneity to liquid samples and higher stability than liquid human, pig, and artificial urine samples at 4℃ or room temperature and under extreme conditions. A total of 21 authentic urine samples from August 2022 were measured with freeze-dried RMs and spiked urine samples, and the reliability of the quantification of the RMs was compared. The freeze-dried human urine matrix RM appeared to be an excellent tool for daily quality control, as it showed high stability and gave the most consistent results with spiked samples.

Development and validation of models for predicting preterm birth and gestational latency following emergency cervical cerclage: A multicenter cohort study.

INTRODUCTION: Emergency cervical cerclage is a recognized method for preventing mid-trimester pregnancy loss and premature birth; however, its benefits remain controversial. This study aimed to establish preoperative models predicting preterm birth and gestational latency following emergency cervical cerclage in singleton pregnant patients with a high risk of preterm birth. MATERIAL AND METHODS: We retrospectively reviewed data from patients who received emergency cerclage between 2015 and 2023 in three institutions. Patients were grouped into a derivation cohort (n = 141) and an independent validation cohort (n = 61). Univariate and multivariate logistic and Cox regression analyses were used to identify independent predictive variables and establish the models. Harrell's C-index, time-dependent receiver operating characteristic curves and areas under the curves, calibration curve, and decision curve analyses were performed to assess the models. RESULTS: The models incorporated gestational weeks at cerclage placement, history of prior second-trimester loss and/or preterm birth, cervical dilation, and preoperative C-reactive protein level. The C-index of the model for predicting preterm birth before 28 weeks was 0.87 (95% CI: 0.82-0.93) in the derivation cohort and 0.82 (95% CI: 0.71-0.92) in the independent validation cohort; The C-index of the model for predicting gestational latency was 0.70 (95% CI: 0.66-0.75) and 0.78 (95% CI: 0.71-0.84), respectively. In the derivation set, the areas under the curves were 0.84, 0.81, and 0.84 for predicting 1-, 3- and 5-week pregnancy prolongation, respectively. The corresponding values for the external validation were 0.78, 0.78, and 0.79, respectively. Calibration curves showed a good homogeneity between the observed and predicted ongoing pregnant probabilities. Decision curve analyses revealed satisfactory clinical usefulness. CONCLUSIONS: These novel models provide reliable and valuable prognostic predictions for patients undergoing emergency cerclage. The models can assist clinicians and patients in making personalized clinical decisions before opting for the cervical cerclage.

Development and validation of a nomogram for individualized prediction of spontaneous extremely preterm birth at < 28 weeks in twin pregnancy: a retrospective cohort study.

PURPOSE: To develop a nomogram to predict spontaneous preterm birth at < 28 weeks in pregnant women with twin pregnancies. METHODS: We retrospectively studied the medical records of twin-pregnancy women with asymptomatic cervical dilation or cervical shortening between December 2015 to February 2022 in two hospitals. Data from one center was used to develop the model and data from the other was used to evaluate the model. RESULTS: A total of 270 twin pregnancies were enrolled in the study. We incorporated 4 items (cervical length, cervical dilation, C-reactive protein and the use of cerclage) to build the 28-week nomogram with satisfactory discrimination and calibration when applied to the validation sets. The C index for the 28-week nomogram in the development and external cohort was 0.88 (95% CI, 0.84-0.93) and 0.89 (95% CI, 0.80-0.98), respectively. The nomogram reached a sensitivity of 70.70%, specificity of 97.10%, positive predicted value of 95.61% and negative predicted value of 78.77%. Moreover, the decision curve analysis indicated that the nomogram showed positive clinical benefit. CONCLUSION: We developed and validated a nomogram with good performance in predicting individual risk of spontaneous preterm birth at < 28 in twin pregnancy.

Ethanol Oxidation via 12-Electron Pathway on Spiky Au@AuPd Nanoparticles Assisted by Near-Infrared Light.

In this work, ethanol oxidation reaction (EOR) via 12-electron (C1-12e) pathway on spiky Au@AuPd nanoparticles (NPs) with ultrathin AuPd alloy shells is achieved in alkaline media with the assistance of the near-infrared (NIR) light. It is found that OH radicals can be produced from the OHads species adsorbed on the surfaces of Pd atoms led by surface plasmon resonance (SPR) effect of spiky Au@AuPd NPs under the irradiation of NIR light. Moreover, OH radicals play the key role for the achievement of EOR proceeded by the desirable C1-12e pathway because OH radicals can directly break the C-C bonds of ethanol. Accordingly, the electrocatalytic performance of spiky Au@AuPd NPs toward EOR under NIR light is greatly improved. For instance, their mass activity can be up to 33.2 A mgpd -1 in the 0.5 m KOH solution containing 0.5 m ethanol, which is about 158 times higher than that of commercial Pd/C catalysts (0.21 A mgpd -1 ) and is better than those of the state-of-the-art Pd-based catalysts reported in literature thus far, to the best of our knowledge. Moreover, their highest mass activity can be further improved to 118.3 A mgpd -1 in the 1.5 m KOH solution containing 1.25 m ethanol.

Nontargeted screening based on EI-MS spectra using statistical methods: An investigative study of synthetic indole/indazole cannabinoids.

RATIONALE: Mass spectrometry has evolved into a highly powerful tool for qualitative and quantitative chemical analyses. However, the identification of trace amounts of previously unknown structures in complex chemical matrix environments remains challenging. The rapid emergence of new synthetic cannabinoid substances is a typical example of this. Existing laboratory techniques are mostly based on methods used for lists of known illegal compounds. This situation poses a challenge to traditional data analysis and the risk of missing the compounds. Therefore, we propose to develop and validate a statistical model to classify newly emerging synthetic cannabinoid substances into a structural class or subclass. METHODS: We obtained 70 electrospray ionization spectra of indole/indazole synthetic cannabinoids from both the actual standard analysis and the SWGDRUG mass spectral library (version 3.10). Each sample consisted of 330 m/z variables and corresponding relative intensities. We first cleared the variables with a variance below 0.1. Principal component analysis (PCA) was performed on the variance-filtered data, and the two principal components were retained to generate new data for hierarchical clustering. After hierarchical clustering, we used the receiver operating characteristic method in this cluster. RESULTS: Seventy synthetic indole/indazole cannabinoids were classified into four clusters. The side chain of cluster 1 is mainly fluorobenzyl, cluster 2 is pentyl, cluster 3 includes compounds from several structures, and cluster 4 is mainly fluoropentyl. The most relevant characteristic ions are m/z 109, m/z 252, and m/z 253 for cluster 1; m/z 144 and m/z 214 for cluster 2; and m/z 232 and m/z 233 for cluster 4. CONCLUSIONS: This study provides a more objective and less time-consuming solution for characterizing synthetic cannabinoids. And this work validates the ability of PCA to extract characteristic fragment ions.

Linc-ROR drive adriamycin resistance by targeting AP-2α/Wnt/ß-catenin axis in hepatocellular carcinoma.

Adriamycin is widely used as a chemotherapeutic strategy for advanced hepatocellular carcinoma (HCC). However, the clinical response was disappointing because of the acquired drug resistance with long-term usage. Revealing the underlying mechanism could provide promising therapeutics for the drug-resistant patients. The recently identified linc-ROR (long intergenic non-protein-coding RNA, regulator of reprogramming) has been found to be an oncogene in various cancers, and it also demonstrated to mediate drug resistance and metastasis. We thereby wonder whether this lincRNA could mediate adriamycin chemoresistance in HCC. In this study, linc-ROR was found to be upregulated in adriamycin-resistant HCC cells. And its overexpression accelerated epithelial-mesenchymal transition (EMT) program and adriamycin resistance. Conversely, its silence suppressed EMT and made HCC cells sensitize to adriamycin in vitro and in vivo. Further investigation revealed that linc-ROR physically interacted with AP-2α, mediated its stability by a post-translational modification manner, and sequentially activated Wnt/ß-catenin pathway. Furthermore, linc-ROR expression was positively associated with ß-catenin expression in human clinical specimens. Taken together, linc-ROR promoted tumorigenesis and adriamycin resistance in HCC via a linc-ROR/AP-2α/Wnt/ß-catenin axis, which could be developed as a potential therapeutic target for the adriamycin-resistant patients.

Occurrence, Distribution, and Trophic Transfer of Pharmaceuticals and Personal Care Products in the Bohai Sea.

The ubiquitous presence of pharmaceuticals and personal care products (PPCPs) in environments has aroused global concerns; however, minimal information is available regarding their multimedia distribution, bioaccumulation, and trophic transfer in marine environments. Herein, we analyzed 77 representative PPCPs in samples of surface and bottom seawater, surface sediments, and benthic biota from the Bohai Sea. PPCPs were pervasively detected in seawater, sediments, and benthic biota, with antioxidants being the most abundant PPCPs. PPCP concentrations positively correlated between the surface and bottom water with a decreasing trend from the coast to the central oceans. Higher PPCP concentrations in sediment were found in the Yellow River estuary, and the variations in the physicochemical properties of PPCPs and sediment produced a different distribution pattern of PPCPs in sediment from seawater. The log Dow, but not log Kow, showed a linear and positive relationship with bioaccumulation and trophic magnification factors and a parabolic relationship with biota-sediment accumulation factors. The trophodynamics of miconazole and acetophenone are reported for the first time. This study provides novel insights into the multimedia distribution and biomagnification potential of PPCPs and suggests that log Dow is a better indicator of their bioaccumulation and trophic magnification.

Brand-Specific Toxicity of Tire Tread Particles Helps Identify the Determinants of Toxicity.

The widespread occurrence of tire tread particles (TPs) has aroused increasing concerns over their impacts. However, how they affect the soil fauna remains poorly understood. Here, based on systematically assessing the toxicity of TPs on soil model speciesEnchytraeus crypticusat environmentally relevant concentrations through both soil and food exposure routes, we reported that TPs affected gut microbiota, intestinal histopathology, and metabolites of the worms both through particulate- and leachate-induced effects, while TP leachates exerted stronger effects. The dominant role of TP leachates in TP toxicity was further explained by the findings that worms did not ingest TPs with a particle size of over 150 µm and actively avoided consuming TP particles. Moreover, by comparing the effects of different brands of TPs as well as new and aged TPs, we demonstrated that it was mainly TP leachates that resulted in the ubiquity of the disturbance in the worm's gut microbiota among different brands of TPs. Notably, the large variations in leachate compositions among different brands of TPs provided us a unique opportunity to identify the determinants of TP toxicity. These results provide novel insights into the toxicity of TPs to soil fauna and a reference for toxicity reduction of tires.

Perioperative and oncologic outcomes of laparoscopic versus open liver resection for combined hepatocellular-cholangiocarcinoma: a propensity score matching analysis.

BACKGROUND: Laparoscopic liver resection (LLR) has now been established as a safe and minimally invasive technique that is deemed feasible for treating hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). However, the role of LLR in treating combined hepatocellular-cholangiocarcinoma (cHCC-CC) patients has been rarely reported. This study aimed to assess the efficacy of LLR when compared with open liver resection (OLR) procedure for patients with cHCC-CC. METHODS: A total of 229 cHCC-CC patients who underwent hepatic resection (34 LLR and 195 OLR patients) from January 2014 to December 2018 in Zhongshan Hospital, Fudan University were enrolled and underwent a 1:2 propensity score matching (PSM) analysis between the LLR and OLR groups to compare perioperative and oncologic outcomes. Overall survival (OS) and recurrence-free survival (RFS) parameters were assessed by the log-rank test and the sensitivity analysis. RESULTS: A total of 34 LLR and 68 OLR patients were included after PSM analysis. The LLR group displayed a shorter postoperative hospital stay (6.61 vs. 8.26 days; p value < 0.001) when compared with the OLR group. No significant differences were observed in the postoperative complications' incidence or a negative surgical margin rate between the two groups (p value = 0.409 and p value = 1.000, respectively). The aspartate aminotransferase (AST), alanine aminotransferase (ALT), and inflammatory indicators in the LLR group were significantly lower than those in the OLR group on the first and third postoperative days. Additionally, OS and RFS were comparable in both the LLR and OLR groups (p value = 0.700 and p value = 0.780, respectively), and similar results were obtained by conducting a sensitivity analysis. CONCLUSION: LLR can impart less liver function damage, better inflammatory response attenuation contributing to a faster recovery, and parallel oncologic outcomes when compared with OLR. Therefore, LLR can be recommended as a safe and effective therapeutic modality for treating selected cHCC-CC patients, especially for those with small tumors in favorable location.

Data envelopment analysis on the efficiency of vaccination services and its influencing factors in Beijing, China.

OBJECTIVES: Vaccination is an important part of public health services. We aim to assess the efficiency of vaccination services in Beijing, the capital of China, and to further study the influencing factors of efficiency. METHODS: Using the immunization service data of Beijing, China in 2020, we firstly developed a data envelopment analysis (DEA) model to calculate the score of vaccination efficiency. Secondly, we used DEA model scenario simulations with different combinations of input-output factors to derive the magnitude of the effect of each input factor on the efficiency. Finally, combined with the data from the Beijing Regional Statistical Yearbook 2021, we developed the Tobit model to examine the effect of external social environmental factors on efficiency. RESULTS: The average scores of efficiency of POVs (Point of Vaccination) in different areas of Beijing vary greatly. Different input factors had different degrees of positive effects on the efficiency score. In addition, the number of populations served by POV was positively associated with efficiency, the GDP and financial allocation of the POVs' district was also positively associated with efficiency score, while the total dependency ratio of the POVs' district was negatively associated with efficiency score. CONCLUSION: The efficiency of vaccination services varied considerably across POVs. Constrained by limited resources, efficiency scores can be increased by increasing input factors that have a larger impact on efficiency score and reducing those that have a smaller impact on efficiency. In addition, the social environment should be considered in allocating vaccination resources, and more resources should be invested in areas with low levels of economic development, low financial allocation, and high population.

Influences of Trypsin Pretreatment on the Structures, Composition, and Functional Characteristics of Skin Gelatin of Tilapia, Grass Carp, and Sea Perch.

Fish skin gelatin is an important functional product in the food, cosmetics, and biomedicine industries, and establishing a green and effective fish skin gelatin extraction method is an effective way to obtain high-quality gelatin and improve its production efficiency. In this study, a trypsin method was used to extract the skin gelatin of sea perch, tilapia, and grass carp, and the microstructures of skin gelatin of these three fish species were analyzed, with such functional characteristics as thermal stability, gel strength, and emulsifying properties measured. The study results show that the skin gelatin of sea perch and tilapia obtained through the trypsin method has a relatively big molecular mass, a dense network structure, and a stable trihelix conformation. In addition, the skin gelatin of these three fish species has a relatively high ß-turn content in the secondary structure, good gel strength, and water absorption properties. The compositions of the collagen-associated proteins in the skin gelatins of these three fish species extracted with the trypsin method are significantly different from each other, with positive effects of decorin and biglycan on the stability of the network structure of gelatin and a certain damaging effect of metalloendopeptidase on the network structure of gelatin. The skin gelatin of tilapia has high thermal stability and good emulsifying performance. Therefore, this gelatin type has bright application prospects in such fields as food processing, cosmetics, and drug development. In contrast, the skin gelatin of grass carp has poor functional properties. Therefore, there are significant differences among the structures and functions of skin gelatin extracted from different kinds of fish through the trypsin method. This finding has provided a useful reference for the production of customized fish gelatin according to demand.

Orthotopic Versus Allotopic Implantation: Comparison of Radiological and Pathological Characteristics.

BACKGROUND: In experimental animal models, implantation location might influence the heterogeneity and overall development of the tumor, leading to an interpretation bias. PURPOSE: To investigate the effects of implantation location in experimental tumor model using magnetic resonance imaging (MRI) and pathological findings. STUDY TYPE: Prospective. SUBJECTS: Forty-five breast cancer-bearing mice underwent orthotopic (N = 15) and heterotopic (intrahepatic [N = 15] and subcutaneous [N = 15]) implantation. FIELD STRENGTH/SEQUENCE: Sequences including: T1-weighted turbo spin echo sequence, T2-weighted blade sequence, diffusion-weighted imaging, pre- and post-contrast T1 mapping, multi-echo T2 mapping at 3.0 T. ASSESSMENT: MRI was performed at 7, 14, and 21 days after implantation. Native T1, post-contrast T1, T2, and apparent diffusion coefficient (ADC) of tumors, the tumor volume and necrosis volume within tumor were obtained. Lymphocyte cells from H&E staining, Ki67-positive, and CD31-positive cells from immunohistochemistry were determined. STATISTICAL TESTS: One-way analysis of variance and Spearman's rank correlation were performed. P value <0.05 was considered statistically significant. RESULTS: The tumor volume (intrahepatic vs. orthotopic vs. subcutaneous: 587.50 ± 77.62 mm3 vs. 814.00 ± 43.85 mm3 vs. 956.13 ± 119.22 mm3 ), necrosis volume within tumor (89.10 ± 26.60 mm3 vs. 292.41 ± 57.92 mm3 vs. 179.91 ± 31.73 mm3 , respectively), ADC at day 21 (543.41 ± 42.28 vs. 542.92 ± 99.67 vs. 369.83 ± 42.90, respectively), and post-contrast T1 at all timepoints (day 7: 442.00 ± 11.52 vs. 435.00 ± 22.90 vs. 394.33 ± 29.95; day 14: 459.00 ± 26.11 vs. 436.83 ± 26.01 vs. 377.00 ± 27.83; day 21: 463.50 ± 23.49 vs. 458.00 ± 34.28 vs. 375.00 ± 30.55) were significantly different between three groups. Necrosis volumes of subcutaneous and intrahepatic tumors were significantly lower than those of orthotopic tumors. The CD31-positive rate in the intrahepatic implantation was significantly higher than in orthotopic and subcutaneous groups. Necrosis volume (r = -0.71), ADC (r = -0.85), and post-contrast T1 (r = -0.75) were strongly correlated with vascular invasion index. DATA CONCLUSION: Orthotopic and heterotopic tumors have their unique growth kinetics, necrosis volume, and vascular invasion. Non-invasive MR quantitative parameters, including ADC and post-contrast T1, may reflect vascular invasion in mice. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 3.

Characterizing Fibrosis and Inflammation in a Partial Bile Duct Ligation Mouse Model by Multiparametric Magnetic Resonance Imaging.

BACKGROUND: Partial bile duct ligation (PBDL) model is a reliable cholestatic fibrosis experimental model that showed complex histopathological changes. Magnetic resonance imaging (MRI) features of PBDL have not been well characterized. PURPOSE: To investigate the potential of MRI parameters in assessing fibrosis in PBDL and explore the relationships between MRI and pathological features. ANIMAL MODEL: Established PBDL models. POPULATION: Fifty-four mice were randomly divided into four timepoints PBDL groups and one sham group. FIELD STRENGTH/SEQUENCE: 3.0 T; MRI sequences included T1-weighted fast spin-echo (FSE), T2-weighted single shot FSE, variable flip angle T1 mapping, multi-echo SE T2 mapping, multi-echo gradient-echo T2* mapping, and multi-b-value diffusion-weighted imaging. ASSESSMENT: MRI examination was performed at the corresponding timepoints after surgery. Native T1, ΔT1 (T1native-T1post), T2, T2*, apparent diffusion coefficient (ADC) values, histogram parameters (skewness and kurtosis), intravoxel incoherent motion parameters (f, D, and D* ) within the entire ligated (PBDL), non-ligated liver (PBDL), and whole liver (sham) were obtained. Fibrosis and inflammation were assessed in Masson and H&E staining slices using the Metavir and activity scoring system. STATISTICAL TESTS: One-way ANOVA, Spearman's rank correlation, and receiver operating characteristic curves were performed. P < 0.05 was considered statistically significant. RESULTS: Fibrosis and inflammation were finally staged as F3 and A3 in ligated livers but were not observed in non-ligated or sham livers. Ligated livers displayed significantly elevated native T1, ΔT1, T2, and reduced ADC and T2* than other livers. Spearman's correlation showed better correlation with inflammation (r = 0.809) than fibrosis (r = 0.635) in T2 and both ΔT1 and ADC showed stronger correlation with fibrosis (r = 0.704 and r = -0.718) than inflammation (r = 0.564 and r = -0.550). Area under the curve (AUC) for ΔT1 performed the highest (0.896). When combined with all relative parameters, AUC increased to 0.956. DATA CONCLUSION: Multiparametric MRI can evaluate and differentiate pathological changes in PBDL. ΔT1 and ADC better correlated with fibrosis while T2 stronger with inflammation. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Magnetic Resonance Imaging-Based Nomogram to Antenatal Predict Cesarean Delivery for Cephalopelvic Disproportion in Primiparous Women.

BACKGROUND: Cephalopelvic disproportion (CPD)-related obstructed labor is associated with maternal and neonatal morbidity and mortality. Accurate prediction of whether a primiparous woman is at high risk of an unplanned cesarean delivery would be a major advance in obstetrics. PURPOSE: To develop and validate a predictive model assessing the risk of cesarean delivery in primiparous women based on MRI findings. STUDY TYPE: Prospective. POPULATION: A total of 150 primiparous women with clinical findings suggestive of CPD. FIELD STRENGTH/SEQUENCE: T1-weighted fast spin-echo sequences, single-shot fast spin-echo (SSFSE) T2-weighted sequences at 1.5 T. ASSESSMENT: Pelvimetry and fetal biometry were assessed independently by two radiologists. A nomogram model combined that the clinical and MRI characteristics was constructed. STATISTICAL TESTS: Univariable and multivariable logistic regression analyses were applied to select independent variables. Receiver operating characteristic (ROC) analysis was performed, and the discrimination of the model was assessed by the area under the curve (AUC). Calibration was assessed by calibration plots. Decision curve analysis was applied to evaluate the net clinical benefit. A P value below 0.05 was considered to be statistically significant. RESULTS: In multivariable modeling, the maternal body mass index (BMI) before delivery, bilateral femoral head distance, obstetric conjugate, fetal head circumference, and fetal abdominal circumference was significantly associated with the likelihood of cesarean delivery. The discrimination calculated as the AUC was 0.838 (95% confidence interval [CI]: 0.774-0.902). The sensitivity and specificity of the nomogram model were 0.787 and 0.764, and the positive predictive and negative predictive values were 0.696 and 0.840, respectively. The model demonstrated satisfactory calibration (calibration slope = 0.945). Moreover, the decision curve analysis proved the superior net benefit of the model compared with each factor included. DATA CONCLUSION: Our study might provide a nomogram model that could identify primiparous women at risk of cesarean delivery caused by CPD based on MRI measurements. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

The RNA-binding protein SND1 promotes the degradation of GPX4 by destabilizing the HSPA5 mRNA and suppressing HSPA5 expression, promoting ferroptosis in osteoarthritis chondrocytes.

BACKGROUND: Heat shock protein family A member 5 (HSPA5), a recently identified suppressor of ferroptosis, was reported to potentially regulating osteoarthritis. However, the exact role of HSPA5 and how its expression was regulated in osteoarthritis are largely unclear. METHODS: Rat primary chondrocytes were treated with 10 ng/mL IL-1ß for 24 h and incubated with ferrostatin-1 (a ferroptosis inhibitor). Cell viability, production of TNF-α, ROS and MDA, expression levels of collagen II, MMP13, GPX4, and SND1, and Fe2+ concentration were detected. Gain- and loss-of-function manipulations were performed to investigate the effect of HSPA5 on chondrocyte functions, and SND1 shRNA (sh-SND1) was transfected into IL-1ß-treated primary chondrocytes alone or together with sh-HSPA5. Furthermore, the interaction between HSPA5 and GPX4 and the regulation of HSPA5 on GPX4 were explored. Finally, SND1 was knocked down in the rats with osteoarthritis, and the histopathology, expression of HSPA5-GPX4 axis, and levels of oxidative stress markers were evaluated. RESULTS: IL-1ß treatment could enhance extracellular matrix (ECM) degradation (collagen II reduced and MMP13 increased), promote ferroptosis, manifested by decreased cell viability, increased levels of TNF-α, ROS, MDA, and Fe2+ concentrations, and decreased level of GPX4 protein, and increase SND1 expression in chondrocytes, which could be reversed by ferrostatin-1. Knockdown of SND1 enhanced ECM degradation and suppressed ferroptosis IL-1ß-treated chondrocytes, which could be eliminated by knockdown of HSPA5. SND1 bound with HSPA5 at the 3'UTR and destabilized the HSPA5 mRNA. HSPA5 protein directly bound with GPX4 protein and positively regulate its expression. HSPA5 overexpression suppressed IL-1ß-induced chondrocyte ferroptosis, while this effect was counteracted by GPX4 silencing. Knockdown of SND1 upregulated HSPA5 and GPX4 in rat cartilage, inhibited inflammatory damage and ferroptosis, and alleviated OA progression. CONCLUSION: The RNA-binding protein SND1 promotes the degradation of GPX4 by destabilizing the HSPA5 mRNA and suppressing HSPA5 expression, promoting ferroptosis in osteoarthritis chondrocytes.

Construction of new oxime esters of cholesterol containing piperic acid-like fragments as insecticidal agents against Aphis citricola Van der Goot (Homoptera: Aphididae) and Plutella xylostella Linnaeus (Lepidoptera: Plutellidae).

In order to application of cholesterol as pesticidal agents, a series of oxime esters of cholesterol containing piperic acid-like fragments were semi-synthesized by modification of cholesterol at the C-3 and C-6 positions. Their structures were characterized by 1H NMR, HRMS and mp, and their purity was determined by HPLC. Against Aphis citricola Van der Goot, derivatives Ib (R = 4-FPh) and In (R = 3,4-ethylenedioxystyryl) exhibited 5.0 and 4.8 folds more pronounced aphicidal activity of their precursor cholesterol. Against Plutella xylostella Linnaeus, compounds Ia (R = Ph) and If (R = 3,4-methylenedioxyphenyl) showed 2.2 and 2.0 folds more potent insecticidal activity of cholesterol. Their SARs were also observed.

Expression of p38MAPK and its regulation of apoptosis under high temperature stress in the razor clam Sinonovacula constricta.

p38MAPK is a key branch of the MAPK (mitogen-activated protein kinase) pathway that plays an important role in physiological processes such as apoptosis, cell proliferation and growth. In this experiment, we screened and identified one p38MAPK gene in the razor clam Sinonovacula constricta, which encoded 359 amino acids and was widely expressed in various adult tissues. After 24 h of high temperature stress at 34 °C, the transcript expression of p38MAPK showed significant changes in all tested tissues. In particular in the gill and hepatopancreas tissues, where the expression increased 1.81 and 7.83 times compared with the control group, respectively (P < 0.01). Furthermore, we examined the expression of the apoptosis suppressor gene Bcl-2 and pro-apoptosis gene Bax by knock-down of p38MAPK with dsRNA interference in the gill and hepatopancreas tissues. The obvious up-regulation expression of Bcl-2 and significant suppression of Bax were observed, respectively (P < 0.01). Moreover, the TUNEL staining technique was used to detect apoptosis before and after interference. The degree of apoptosis in the gill and hepatopancreas tissues was reduced after interference with p38MAPK, and the ROS content was significantly reduced (P < 0.01). The results suggested that p38MAPK had a regulatory role in the heat tolerance of razor clams.