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Objective To detect the serum level of microRNA (miR)-155-5p in IgA nephropathy patients and examine its clinical significance. Methods The patients with IgA nephropathy followed up for 3 years were selected. Serum level of miR-155-5p was detected by real-time fluorescent quantitative polymerase chain reaction (PCR). Based upon declining rate of renal function (RF), they were assigned into two groups of RF progression (A, n=42) and relatively stable RF (B, n=63). Inter-group differences in clinical and laboratory parameters were compared. Logistic regression analysis was performed for identifying the risk factors for RF progression. Pearson’s or Spearman’s correlation analysis was performed for assessing the correlation between serum level of miR-155-5p and baseline estimated glomerular filtration rate (eGFR), urinary protein quantification, declining rate of RF and renal pathological data. Receiver operating characteristic (ROC) curve was plotted for evaluating the capability of miR-155-5p level for judging the progress of RF. Results As compared with group B, group A had a higher prevalence of hypertension (88.09% vs 19.05%), greater baseline urinary protein quantification [(3.11±2.16)g/24 h vs (1.07±0.87)g/24 h], higher baseline blood creatinine [(106.74±51.27)μmol/L vs (86.90±36.90)μmol/L] and higher total kidney pathology T score (61 vs 13, P

Plastic bronchitis (PB) constitutes a life-threatening pulmonary disorder, predominantly attributed to Mycoplasma pneumoniae (MP) infection. The pathogenic mechanisms involved remain largely unexplored, leading to the absence of reliable approaches for early diagnosis and clear treatment. Thus, the present investigation aimed to develop an MP-induced mouse model of PB, thereby enhancing our understanding of this complex condition. In the first stage, healthy BALB/c mice were utilized to investigate the optimal methods for establishing PB. This involved the application of nebulization (15–20 min) and intratracheal administration (6–50 μL) with 2-chloroethyl ethyl sulfide (CEES) concentrations ranging from 4.5% to 7.5%. Subsequently, the MP model was induced by administering an MP solution (2 mL/kg/day, 108 CFU/50 μL) via the intranasal route for a duration of five consecutive days. Ultimately, suitable techniques were employed to induce plastic bronchitis in the MP model. Pathological changes in lung tissue were analyzed, and immunohistochemistry was employed to ascertain the expression levels of vascular endothelial growth factor receptor 3 (VEGFR-3) and the PI3K/AKT/mTOR signaling pathway. The administration of 4.5% CEES via a 6 µL trachea was the optimal approach to establishing a PB model. This method primarily induced neutrophilic inflammation and fibrinous exudate. The MP-infected group manifested symptoms indicative of respiratory infection, including erect hair, oral and nasal secretions, and a decrease in body weight. Furthermore, the pathological score of the MP+CEES group surpassed that of the groups treated with MP or CEES independently. Notably, the MP+CEES group demonstrated significant activation of the VEGFR-3 and PI3K/AKT/mTOR signaling pathways, implying a substantial involvement of lymphatic vessel impairment in this pathology. This study successfully established a mouse model of PB induced by MP using a two-step method. Lymphatic vessel impairment is a pivotal element in the pathogenetic mechanisms underlying this disease entity. This accomplishment will aid in further research into treatment methods for patients with PB caused by MP.

Objective To develop and validate an individualized prediction model for risk of restenosis in patients with arteriosclerosis obliterans (ASO) after percutaneous transluminal angioplasty (PTA). Methods A case-control trial was conducted on 137 patients who received PTA treatment for ASO in the Department of Vascular Surgery of the First Affiliated Hospital of Chongqing Medical University from February 2020 to May 2022. Their clinical data were collected and analyzed. The patients were assigned into training set (n=97) and validation set (n=40) at a ratio of 7 ∶3. The primary endpoint was the occurrence of restenosis within 12 months after interventional procedure. Based on the training set, single and multiple factor Cox regression models were used to screen the independent influencing factors of restenosis within 12 months. Then the obtained regression coefficients were then employed to establish a prediction model and draw a nomogram. The data from the training and validation sets were adopted to validate the model internally and externally, and the area under the receiver operating characteristic curve (AUC) and calibration chart were used to evaluate the model's recognition. The decision curve chart was established to evaluate the benefit of using the model to treat patients. Results Intravascular ultrasound guidance, lesion type, preoperative residual outflow tract, lesion length, and intraoperative treatment were independent predictors of restenosis after PTA in ASO patients (P < 0.05) and included in the model. The AUC of the nomograph for model's internal validation was 0.84 (95%CI: 0.75~0.92), with a specificity and sensitivity of 0.797 and 0.737, respectively. The AUC of the external validation using the validation set was 0.86 (95%CI: 0.74~0.98), with a specificity and sensitivity of 0.963 and 0.615, respectively. The calibration curve in the 2 cohort groups showed that the predictive value of the nomogram matched the actual observation. The decision curve indicated that this model could significantly increase the net benefit to patients. Conclusion Our nomogram prediction model can predict vessel patency of ASO patient within 12 months after PTA, and it has been developed and validated as an individualized risk prediction model for this specific group.

Food material is the key factor of food 3D printing. This review summarized the characteristics of food materials (protein, starch, hydrogel and fat) commonly used in food 3D printing at present, analyzed the influence of different material combinations on the forming performance. Moreover, suggestions on how to improve the printing effect of difficult printing materials were also provided, and the technical bottleneck of food materials development faced in food 3D printing nowadays were noticed. Finally, the direction of food 3D printing technology in the future was prospected.

Dynamin-Related-Protein 1 (DRP1) critically regulates mitochondrial and peroxisomal fission in multicellular organisms. However, the impact of DRP1 on other organelles, especially its direct influence on ER functions remains largely unclear. Here, we report that DRP1 translocates to endoplasmic reticulum (ER) in response to β-adrenergic stimulation. To further investigate the function of DRP1 on ER-lipid droplet (LD) dynamics and the metabolic subsequences, we generated an adipose tissue-specific DRP1 knockout model (Adipo-Drp1flx/flx ). We found that the LDs in adipose tissues of Adipo-Drp1flx/flx mice exhibited more unilocular morphology with larger sizes, and formed less multilocular structures upon cold exposure. Mechanistically, we discovered that abnormal LD morphology occurs because newly generated micro-LDs fail to dissociate from the ER due to DRP1 ablation. Conversely, the ER retention of LDs can be rescued by the overexpressed DRP1 in the adipocytes. The alteration of LD dynamics, combined with abnormal mitochondrial and autophagy functions in adipose tissue, ultimately lead to abnormalities in lipid metabolism in Adipo-Drp1flx/flx mice.

为实现脱臭馏出物绿色、清洁、高效甲酯化，达到环保生产的目的，通过单因素实验和响应面实验对生物酶法催化脱臭馏出物甲酯化反应的工艺条件进行了优化，测定了反应前后维生素 E含量的变化，并将新工艺应用于实际生产线。结果表明：生物酶法催化脱臭馏出物甲酯化的最佳反应条件为加水量1%(以脱臭馏出物质量计)、甲醇用量11.5%(以脱臭馏出物质量计)、固定化脂肪酶用量0.3%(以脱臭馏出物质量计)、反应温度35.6 ℃，在最佳条件下反应8 h脱臭馏出物中游离脂肪酸酯化率达到92.59%，甘油酯酯化率达到94.95%；生物酶法催化脱臭馏出物甲酯化反应过程中维生素 E损失少，收率达到93%；与浓硫酸催化甲酯化工艺相比，产品维生素E(50%维生素E)总收率提高了3.47百分点，植物甾醇总收率提高了3.26百分点。综上，生物酶法催化脱臭馏出物甲酯化，可以得到较高的酯化率，提高了产品维生素 E和植物甾醇收率。 In order to realize the green, clean and efficient methyl esterification of deodorized distillates and achieve the goal of environmental protection, the reaction conditions of the bioenzyme-catalyzed methyl esterification of deodorized distillates were optimized by single-factor experiment and response surface methodology, and the changes of vitamin E content before and after the reaction were measured. In addition, the new process was applied to the actual production line. The results showed that the optimal reaction conditions for the methyl esterification of deodorized distillates catalyzed by bioenzyme were as follows: water dosage 1%(based on the mass of deodorized distillates), methanol dosage 11.5% (based on the mass of deodorized distillates), immobilized lipase dosage 0.3% (based on the mass of deodorized distillates), reaction temperature 35.6 ℃. Reaction under the optimal conditions for 8 h, the esterification rate of free fatty acid and glycerol ester in the deodorized distillates reached 92.59% and 94.95%, respectively. In the methyl esterification of the bioenzyme-catalyzed deodorized distillates, the loss of vitamin E was low, and its yield reachedg 93%. The total yield of vitamin E (50% vitamin E) increased by 3.47 percentage points and the total yield of phytosterols increased by 3.26 percentage points compared with the concentrated sulfuric acid catalyzed methyl esterification process. In conclusion, the bioenzyme-catalyzed methyl esterification of deodorized distillates posses higher esterification rates and yields of vitamin E and phytosterols.

Abstract This study aims to evaluate the risk of lead pollution in 9 kinds of vegetables consumed by residents in 20 provinces/cities of China. Sampling data and vegetable consumption data from 20 provinces/cities in 2019 were used. Combined with dietary exposure assessment, the vegetable categories and provinces were paired, and a risk classification model based on spectral clustering algorithms was proposed. The results of the spectral clustering algorithm showed that the risk level of lead pollution in vegetables can be divided into five levels. The combination of vegetable‐province/cities at the risk level of 1 and 2 accounted for 92.78%, and that at the risk level of 4 and 5 accounted for 2.22%. The high‐risk combinations were fresh edible fungus–Shaanxi, fresh edible fungus–Sichuan, and fresh edible fungus–Shanghai and bean sprouts–Guangdong. In the proposed model, objective data were used as the classification index, and the spectral clustering algorithm was employed to select the optimal risk classification in a data‐driven way. As a result, the influence of subjective factors was effectively reduced, the risk of lead pollution in vegetables was classified, and the results were scientific and accurate. This study provides a scientific basis of supervision priorities for regulatory departments.

Background: Nirmatrelvir/Ritonavir is an orally administered anti-SARS-Cov-2 drug used in mild-to-moderate COVID-19 patients. Our retrospective cohort study aims to evaluate the efficacy and safety of Nirmatrelvir/Ritonavir in severe hospitalized patients with Omicron infection, as well as in patients at high risk for progression to critical illness in real-world settings. Methods: A total of 350 patients received Nirmatrelvir/Ritonavir while 350 matched controls did not. Patients with confirmed COVID-19 were administered Nirmatrelvir 300 mg and Ritonavir 100 mg orally twice a day for 5 days, with the medication initiated on the first day after admission. The primary endpoint of the study was a composite outcome of hospitalization or death from any cause within 28 days. Secondary endpoints included the occurrence of adverse events and the evaluation of serum levels of IL-6 and viral load. Results: We documented the mortality risk from any cause within 28 days, viral load, serum IL-6 levels, and adverse events. Nirmatrelvir/Ritonavir reduced the 28-day risk of all-cause mortality by 86% (P =.011, hazard ratio (HR) = 0.14, 95% confidence interval (CI) = 0.03, 0.64). At baseline, the serum level of IL-6 was significantly higher in the antiviral treatment group compared to the control group (P <.001), but no significant difference (P =.990) was found between the two groups at discharge. In CKD patients undergoing hemodialysis, no significant worsening of renal function was observed in the Nirmatrelvir/Ritonavir treatment group compared to the control group. Conclusion: Nirmatrelvir/Ritonavir may reduce the 28-day risk of all-cause mortality in critically ill patients with COVID-19 and in patients at high risk for critical disease progression. [ABSTRACT FROM AUTHOR]

Single‐atom nanozymes (SAzymes) with atomically dispersed active sites are potential substitutes for natural enzymes. A systematic study of its multiple functions can in‐depth understand SAzymes's nature, which remains elusive. Here, we develop a novel ultrafast synthesis of sputtered SAzymes by in situ bombarding‐embedding technique. Using this method, sputtered copper (Cu) SAzymes (CuSA) is developed with unreported unique planar Cu‐C3 coordinated configuration. To enhance the tumor‐specific targeting, we employ a bioorthogonal approach to engineer CuSA, denoted as CuSACO. CuSACO not only exhibits minimal off‐target toxicity but also possesses exceptional ultrahigh catalase‐, oxidase‐, peroxidase‐like multienzyme activities, resulting in reactive oxygen species (ROS) storm generation for effective tumor destruction. Surprisingly, CuSACO can release Cu ions in the presence of glutathione (GSH) to induce cuproptosis, enhancing the tumor treatment efficacy. Notably, CuSACO′s remarkable photothermal properties enables precise photothermal therapy (PTT) on tumors. This, combined with nanozyme catalytic activities, cuproptosis and immunotherapy, efficiently inhibiting the growth of orthotopic breast tumors and gliomas, and lung metastasis. Our research highlights the potential of CuSACO as an innovative strategy to utilize multiple mechanism to enhance tumor therapeutic efficacy, broadening the exploration and development of enzyme‐like behavior and physiological mechanism of action of SAzymes. [ABSTRACT FROM AUTHOR]

Plastic bronchitis (PB) constitutes a life-threatening pulmonary disorder, predominantly attributed to Mycoplasma pneumoniae (MP) infection. The pathogenic mechanisms involved remain largely unexplored, leading to the absence of reliable approaches for early diagnosis and clear treatment. Thus, the present investigation aimed to develop an MP-induced mouse model of PB, thereby enhancing our understanding of this complex condition. In the first stage, healthy BALB/c mice were utilized to investigate the optimal methods for establishing PB. This involved the application of nebulization (15–20 min) and intratracheal administration (6–50 μL) with 2-chloroethyl ethyl sulfide (CEES) concentrations ranging from 4.5% to 7.5%. Subsequently, the MP model was induced by administering an MP solution (2 mL/kg/day, 108 CFU/50 μL) via the intranasal route for a duration of five consecutive days. Ultimately, suitable techniques were employed to induce plastic bronchitis in the MP model. Pathological changes in lung tissue were analyzed, and immunohistochemistry was employed to ascertain the expression levels of vascular endothelial growth factor receptor 3 (VEGFR-3) and the PI3K/AKT/mTOR signaling pathway. The administration of 4.5% CEES via a 6 µL trachea was the optimal approach to establishing a PB model. This method primarily induced neutrophilic inflammation and fibrinous exudate. The MP-infected group manifested symptoms indicative of respiratory infection, including erect hair, oral and nasal secretions, and a decrease in body weight. Furthermore, the pathological score of the MP+CEES group surpassed that of the groups treated with MP or CEES independently. Notably, the MP+CEES group demonstrated significant activation of the VEGFR-3 and PI3K/AKT/mTOR signaling pathways, implying a substantial involvement of lymphatic vessel impairment in this pathology. This study successfully established a mouse model of PB induced by MP using a two-step method. Lymphatic vessel impairment is a pivotal element in the pathogenetic mechanisms underlying this disease entity. This accomplishment will aid in further research into treatment methods for patients with PB caused by MP. [ABSTRACT FROM AUTHOR]

Altered progesterone responsiveness leads to female infertility and cancer, but underlying mechanisms remain unclear. Mice with uterine-specific ablation of GATA binding protein 2 (Gata2) are infertile, showing failures in embryo implantation, endometrial decidualization, and uninhibited estrogen signaling. Gata2 deficiency results in reduced progesterone receptor (PGR) expression and attenuated progesterone signaling, as evidenced by genome-wide expression profiling and chromatin immunoprecipitation. GATA2 not only occupies at and promotes expression of the Pgr gene but also regulates downstream progesterone responsive genes in conjunction with the PGR. Additionally, Gata2 knockout uteri exhibit abnormal luminal epithelia with ectopic TRP63 expressing squamous cells and a cancer-related molecular profile in a progesterone-independent manner. Lastly, we found a conserved GATA2-PGR regulatory network in both human and mice based on gene signature and path analyses using gene expression profiles of human endometrial tissues. In conclusion, uterine Gata2 regulates a key regulatory network of gene expression for progesterone signaling at the early pregnancy stage.

Hickory (Carya cathayensis) kernel is rich in powerful bioactive flavonoids, which can remove excess free radicals in the human body and play an important role in regulating the physiological metabolism of the plant. This study investigated the changes of flavonoids in hickory exocarp and embryo during development. In this study, 72 DEGs involved in the regulation of flavonoid biosynthesis in fruits were identified, and TT4, CCoAOMT1, UGT71D1, C4H, F3H, TT8, FLS1, and LDOX were identified as the core genes of flavonoid biosynthesis. A total of 144 flavonoid-related metabolites were detected by metabolite analysis. Transcriptome and metabolome analysis combined to construct the flavonoid biosynthesis regulatory pathway in the development stage of hickory fruit. Our results provide a theoretical basis for the exploration and regulation of functional genes related to flavonoid biosynthesis and metabolism in hickory and other plants and the breeding of new walnut varieties.