Brain region-specific roles of brain-derived neurotrophic factor in social stress-induced depressive-like behavior.

Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response. Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region-specific, particularly involving the corticolimbic system, including the ventral tegmental area, nucleus accumbens, prefrontal cortex, amygdala, and hippocampus. Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology. In this review, we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression. We focused on associated molecular pathways and neural circuits, with special attention to the brain-derived neurotrophic factor-tropomyosin receptor kinase B signaling pathway and the ventral tegmental area-nucleus accumbens dopamine circuit. We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature, severity, and duration of stress, especially in the above-mentioned brain regions of the corticolimbic system. Therefore, BDNF might be a biological indicator regulating stress-related processes in various brain regions.

Patient-specific 3D-printed Brace for Adolescent Idiopathic Scoliosis: A Prospective Cohort Study.

OBJECTIVE: To evaluate the efficacy, safety of patient-tailored 3D printed brace in the treatment of adolescent idiopathic scoliosis (AIS), and to compare the health-related quality of life (HRQoL) of patients treated with two different types of brace. MATERIALS AND METHODS: From September 2017 to August 2020, 103 AIS patients requiring non-operative management were prospectively recruited in this study. All patients were followed up every 6 months, clinical and radiological examination were assessed at each follow-up time. Full-length anteroposterior X-ray of the spine in the standing position was performed obtained. At the last follow-up, each patient completed a standardized HRQoL questionnaire. Compliance is defined as that the patient insists on wearing the brace for ≥ 23h every day (full-time wearing) and follow-up every 6 months until bone maturity.The rate of major curve Cobb progression was defined that maximum Cobb Angle of major curve greater than 6° compared with that at the initial diagnosis, or aggravated to more than 45° so that orthopedic surgery was recommended during treatment, which was defined as the rate of conversion to surgery. The effects of these two types of braces on the rate of major curve Cobb progression and HRQoL were analyzed by independent sample t-test ad Chi-square test. RESULTS: The thickness was 4 mm for thoracolumbosacral orthosis (TLSO) and 3 mm for 3D-printed brace (3DPB). In addition, compared with the material used in TLSO, the weight (600-800 grams) of the 3DPB materials with the same area is reduced by about 25-30%. 55 patients (49.1%) and 48 patients (33.1%) were respectively included in the 3DPB cohort and the TLSO cohort.The maximum Cobb angle of major curve in the 3DPB cohort was significantly lower than those in the TLSO cohort at 6 months, 12 months and the last follow-up (p < 0.01). The thoracic kyphosis (TK) and lumbar lordosis (LL) of the two cohorts at the last follow-up were lower than those before brace treatment, in addition, there was a significant difference in TK (p = 0.001) and LL (p = 0.004) between the two cohorts at the follow-up. The scores of physical function, pain, self-image, mental health and treatment satisfaction in the Chinese version of SRS-22 in the 3DPB cohort were higher than those in the TLSO cohort (p < 0.01 and p < 0.05, respectively). The scores of the 3DPB cohort were significantly higher than those of the TLSO group in the four dimensions (p = 0.008, 0.013, 0.015, and 0.002, respectively) of the EuroQol-5D health description system except for mobility, and the overall health status of EuroQol-5D was higher for the 3DPB cohort (p < 0.001). At the last follow-up, One patient in the 3DPB cohort and ten patients in the TLSO cohort had major curve Cobb progression of greater than 6°, and the rate of major curve Cobb progression in 3DPB cohort was significantly lower than that in the TLSO cohort (OR 14.2, 95% CI 1.7∼115.8, p < 0.01). One patient in the 3DPB and seven patients in the TLSO cohorts received subsequent surgery or was recommended for surgery, and the rate of conversion to surgery was significantly lower than in the 3DPB cohort (OR 9.2, 95% CI 1.1∼77.9, p < 0.05). CONCLUSIONS: Patient-tailored 3D-printed brace is lighter, thinner, and more comfortable than conventional braces in the treatment of AIS. It can substantially improve the HRQoL of patients and can significantly reduce the progression of major curve Cobb progression and rate of conversion of surgery.

FBXO7 ubiquitinates PRMT1 to suppress serine synthesis and tumor growth in hepatocellular carcinoma.

Cancer cells are often addicted to serine synthesis to support growth. How serine synthesis is regulated in cancer is not well understood. We recently demonstrated protein arginine methyltransferase 1 (PRMT1) is upregulated in hepatocellular carcinoma (HCC) to methylate and activate phosphoglycerate dehydrogenase (PHGDH), thereby promoting serine synthesis. However, the mechanisms underlying PRMT1 upregulation and regulation of PRMT1-PHGDH axis remain unclear. Here, we show the E3 ubiquitin ligase F-box-only protein 7 (FBXO7) inhibits serine synthesis in HCC by binding PRMT1, inducing lysine 37 ubiquitination, and promoting proteosomal degradation of PRMT1. FBXO7-mediated PRMT1 downregulation cripples PHGDH arginine methylation and activation, resulting in impaired serine synthesis, accumulation of reactive oxygen species (ROS), and inhibition of HCC cell growth. Notably, FBXO7 is significantly downregulated in human HCC tissues, and inversely associated with PRMT1 protein and PHGDH methylation level. Overall, our study provides mechanistic insights into the regulation of cancer serine synthesis by FBXO7-PRMT1-PHGDH axis, and will facilitate the development of serine-targeting strategies for cancer therapy.

Heatstroke Comorbid with SARS-CoV-2 Infection: A Case Report and Literature Review.

Background: Hyperthermia and multiple organ dysfunction syndrome (MODS) are the main characteristics of heatstroke and COVID-19. Differentiating between these illnesses is crucial during a summer COVID-19 pandemic, but cases of heatstroke comorbid with COVID-19 are rarely reported. Case description: We report the first case of heatstroke comorbid with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in a 52-year-old male. After receiving intravenous antibiotics, organ protection measures, and treatment for coagulation disorders, his fever and coma resolved. However, he developed dyspnea and cerebral hemorrhage after several days. This patient experienced a multi-pathogen pulmonary infection and an intractable coagulopathy that ultimately resulted in MODS and death. Conclusion: The combination of heatstroke and SARS-CoV-2 infection exacerbated inflammation, immune abnormalities, and coagulation disorders. The interaction between inflammation and coagulation disturbances contributed to the underlying mechanism in this case, highlighting the importance of early anti-infection, treatment for coagulopathy, immune regulation, and organ protection as crucial interventions.

Clinical characteristics and risk factors in patients with SARS-CoV-2 Omicron variant infection complicated with cardiovascular diseases.

Objective: To investigate the clinical characteristics and risk factors of patients with SARS-CoV-2 Omicron variant infection complicated with cardiovascular diseases. Methods: A retrospective analysis of general clinical data was conducted on patients with SARS-CoV-2 omicron infection complicated with hypertension, coronary heart disease, and heart failure admitted to one hospital in Guangdong Province from December 1, 2022, to February 28, 2023. Clinical symptoms, laboratory tests, imaging examinations, treatment, and clinical outcomes were collected. Multivariate logistic regression analysis was used to analyze the risk factors for mortality in patients with SARS-CoV-2 Omicron variant infection complicated with cardiovascular diseases. ROC curves were drawn to evaluate the predictive value of CRP, D-dimer, and CK-MB in predicting the risk of death. Results: A total of 364 confirmed cases were included, divided into the asymptomatic group, mild to moderate group, and severe to critically ill group based on the symptoms of COVID-19. There were 216 males (59.34%) and 148 females (40.66%), with a median age of 75 years. The differences between the three groups in terms of sex and age were statistically significant (p < 0.05). The top three underlying diseases were hypertension (288 cases, 79.12%), coronary heart disease (100 cases, 27.47%), and diabetes (84 cases, 23.08%). The differences in unvaccinated and triple-vaccinated patients among the three groups were statistically significant (p < 0.05). The common respiratory symptoms were cough in 237 cases (65.11%) and sputum production in 199 cases (54.67%). In terms of laboratory tests, there were statistically significant differences in neutrophils, lymphocytes, red blood cells, C-reactive protein, D-dimer, aspartate aminotransferase, and creatinine among the three groups (p < 0.05). In imaging examinations, there were statistically significant differences among the three groups in terms of unilateral pulmonary inflammation, bilateral pulmonary inflammation, and bilateral pleural effusion (p < 0.05). There were statistically significant differences among the three groups in terms of antibiotic treatment, steroid treatment, oxygen therapy, nasal cannula oxygen inhalation therapy, non-invasive ventilation, and tracheal intubation ventilation (p < 0.05). Regarding clinical outcomes, there were statistically significant differences among the three groups in terms of mortality (p < 0.05). Multivariate logistic regression analysis showed that CRP (OR = 1.012, 95% CI = 1.004-1.019) and D-dimer (OR = 1.117, 95% CI = 1.021-1.224) were independent risk factors for patient mortality. The predictive value of CRP, D-dimer, and CK-MB for the risk of death was assessed. D-dimer had the highest sensitivity (95.8%) in predicting patient mortality risk, while CRP had the highest specificity (84.4%). Conclusion: For patients with COVID-19 and concomitant cardiovascular diseases without contraindications, early administration of COVID-19 vaccines and booster shots can effectively reduce the mortality rate of severe cases. Monitoring biomarkers such as CRP, D-dimer, and CK-MB and promptly providing appropriate care can help mitigate the risk of mortality in patients.

A new mountain pitviper of the genus Ovophis Burger in Hoge & Romano-Hoge, 1981 (Serpentes, Viperidae) from Yunnan, China.

Based on a molecular phylogenetic analysis and morphological comparison, a new species of mountain pitviper, Ovophisjenkinsi sp. nov., is described. The new species was collected in Yingjiang County, Yunnan Province, China. It can be distinguished from congeneric species by the following characters: (1) internasals in contact or separated by one small scale; (2) second supralabial entire and bordering the loreal pit; (3) dorsal scales in 23 (25)-21 (23, 25)-19 (17, 21) rows; (4) 134-142 ventrals; (5) 40-52 pairs of subcaudals; (6) third supralabial larger than fourth in all examined specimens of Ovophisjenkinsi sp. nov.; (7) deep orange-brown or dark brownish-grey markings on dorsal head surface; (8) background color of dorsal surface deep orange-brown or dark brownish-grey; (9) both sides of dorsum display dark brown trapezoidal patches; (10) scattered small white spots on dorsal surface of tail.

Inhibition of ß2-adrenergic receptor regulates necroptosis in prostate cancer cell.

As the malignant tumor with the highest incidence in male, prostate cancer poses a significant threat to the reproductive health of elderly men. Our previous studies have shown that promoting necroptosis of cancer cells can effectively inhibit cancer cell proliferation. This study includes lentivirus-mediated knockdown of ß2AR which resulted in stable transfectants that exhibited an increased ability to form clones compared to that of the negative control group. In the protein and mRNA levels, necroptosis associated RIP and mixed lineage kinase domain-like (MLKL) were significantly higher in the treatment group than they were in the control group. Furthermore, cells treated with propranolol exhibited necrotic morphology as observed by transmission electron microscopy. The combination of ß2AR suppression and necroptosis inhibitors resulted in a more potent suppression of cell proliferation compared to that observed in the control and negative control groups. Additionally, it elevated in the necrosis rate as determined by flow cytometry. Immunofluorescence staining revealed enhanced RIP and MLKL expression in the sh-ß2AR group compared to levels in the negative control group. Co-immunoprecipitation experiments detected an interaction between ß2AR and RIP. MLKL and RIPK3 levels were significantly higher in xenograft tumor sections from the sh-ß2AR group compared to levels in the sh-NC group. To conclude, our research indicates the proliferation of PC-3 and DU-145 cprostate cancer cells can be suppressed by inhibiting ß2AR, and this occurs through the RIP/MLKL-mediated pathway of necroptosis.

Tissue-Specific Distribution and Maternal Transfer of Persistent Organic Halogenated Pollutants in Frogs.

Persistent organic pollutants pose a great threat to amphibian populations, but information on the bioaccumulation of contaminants in amphibians remains scarce. To examine the tissue distribution and maternal transfer of organic halogenated pollutants (OHPs) in frogs, seven types of tissues from black-spotted frog (muscle, liver, kidney, stomach, intestine, heart, and egg) were collected from an e-waste-polluted area in South China. Among the seven frog tissues, median total OHP concentrations of 2.3 to 9.7 µg/g lipid weight were found (in 31 polychlorinated biphenyl [PCB] individuals and 15 polybrominated diphenyl ether [PBDE], dechlorane plus [syn-DP and anti-DP], bexabromobenzene [HBB], polybrominated biphenyl] PBB153 and -209], and decabromodiphenyl ethane [DBDPE] individuals). Sex-specific differences in contaminant concentration and compound compositions were observed among the frog tissues, and eggs had a significantly higher contaminant burden on the whole body of female frogs. In addition, a significant sex difference in the concentration ratios of other tissues to the liver was observed in most tissues except for muscle. These results suggest that egg production may involve the mobilization of other maternal tissues besides muscle, which resulted in the sex-specific distribution. Different parental tissues had similar maternal transfer mechanisms; factors other than lipophilicity (e.g., molecular size and proteinophilic characteristics) could influence the maternal transfer of OHPs in frogs. Environ Toxicol Chem 2024;00:1-12. © 2024 SETAC.

Establishment and validation of multiclassification prediction models for pulmonary nodules based on machine learning.

BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide. This study aimed to establish novel multiclassification prediction models based on machine learning (ML) to predict the probability of malignancy in pulmonary nodules (PNs) and to compare with three published models. METHODS: Nine hundred fourteen patients with PNs were collected from four medical institutions (A, B, C and D), which were organized into tables containing clinical features, radiologic features and laboratory test features. Patients were divided into benign lesion (BL), precursor lesion (PL) and malignant lesion (ML) groups according to pathological diagnosis. Approximately 80% of patients in A (total/male: 632/269, age: 57.73 ± 11.06) were randomly selected as a training set; the remaining 20% were used as an internal test set; and the patients in B (total/male: 94/53, age: 60.04 ± 11.22), C (total/male: 94/47, age: 59.30 ± 9.86) and D (total/male: 94/61, age: 62.0 ± 11.09) were used as an external validation set. Logical regression (LR), decision tree (DT), random forest (RF) and support vector machine (SVM) were used to establish prediction models. Finally, the Mayo model, Peking University People's Hospital (PKUPH) model and Brock model were externally validated in our patients. RESULTS: The AUC values of RF model for MLs, PLs and BLs were 0.80 (95% CI: 0.73-0.88), 0.90 (95% CI: 0.82-0.99) and 0.75 (95% CI: 0.67-0.88), respectively. The weighted average AUC value of the RF model for the external validation set was 0.71 (95% CI: 0.67-0.73), and its AUC values for MLs, PLs and BLs were 0.71 (95% CI: 0.68-0.79), 0.98 (95% CI: 0.88-1.07) and 0.68 (95% CI: 0.61-0.74), respectively. The AUC values of the Mayo model, PKUPH model and Brock model were 0.68 (95% CI: 0.62-0.74), 0.64 (95% CI: 0.58-0.70) and 0.57 (95% CI: 0.49-0.65), respectively. CONCLUSIONS: The RF model performed best, and its predictive performance was better than that of the three published models, which may provide a new noninvasive method for the risk assessment of PNs.

ABCB1-mediated docetaxel resistance reversed by erastin in prostate cancer.

Docetaxel (Doc) currently serves as the primary first-line treatment for patients with castrate-resistant prostate cancer (CRPC). Erastin, a small molecule compound, can trigger inhibition of the cystine-glutamate reverse transport system and other pathways, leading to iron-dependent cell death (ferroptosis). Beyond its role in inducing cancer cell death, erastin demonstrates potential when combined with chemotherapy drugs to heighten cancer cell drug susceptibility. However, the augmentation by erastin of the effects of Doc treatment on prostate cancer, and the underlying mechanisms involved, remain unclear. In the present study, we determined the role and the underlying molecular mechanism of erastin against CRPC. The results showed that CRPC cell lines were resistant to Doc, and the expression of ferroptosis-related factors in drug-resistant cell lines was downregulated. Erastin, in synergy with Doc, exerts a pro-apoptotic effect. Erastin significantly inhibited the activity of ATP-binding cassette subfamily B member 1 (ABCB1) but did not change its protein expression and localization. Finally, in mice, erastin treatment dramatically reduced tumor growth in vivo. Taken together, our findings demonstrate that erastin enhances Doc-induced apoptosis to a certain extent and reverses Doc resistance in prostate cancer by inhibiting the activity of multidrug-resistant protein ABCB1.

Organic Ligand Engineering for Tailoring Electron-Phonon Coupling in 2D Hybrid Perovskites.

In the emerging two-dimensional organic-inorganic hybrid perovskites, the electronic structures and carrier behaviors are strongly impacted by intrinsic electron-phonon interactions, which have received inadequate attention. In this study, we report an intriguing phenomenon of negative carrier diffusion induced by electron-phonon coupling in (2T)2PbI4. Theoretical calculations reveal that the electron-phonon coupling drives the band alignment in (2T)2PbI4 to alternate between type I and type II heterostructures. As a consequence, photoexcited holes undergo transitions between the organic ligands and inorganic layers, resulting in abnormal carrier transport behavior compared to other two-dimensional hybrid perovskites. These findings provide valuable insights into the role of electron-phonon coupling in shaping the band alignments and carrier behaviors in two-dimensional hybrid perovskites. They also open up exciting avenues for designing and fabricating functional semiconductor heterostructures with tailored properties.

Pituitary MRI Radiomics Improves Diagnostic Performance of Growth Hormone Deficiency in Children Short Stature: A Multicenter Radiomics Study.

RATIONALE AND OBJECTIVES: To develop an efficient machine-learning model using pituitary MRI radiomics and clinical data to differentiate growth hormone deficiency (GHD) from idiopathic short stature (ISS), making the diagnostic process more acceptable to patients and their families. MATERIALS AND METHODS: A retrospective cohort of 297 GHD and 300 ISS children (4-12 years) were enrolled as training and validation cohorts (8:2 ratio). An external cohort from another institution (49 GHD and 51 ISS) was employed as the testing cohort. Radiomics features extracted from the anterior pituitary gland on sagittal T1-weighted image (1.5 T or 3.0 T) were used to develop a radiomics model after feature selection. Hematological biomarkers were selected to create a clinical model and combine with the optimal radiomics features to create a clinical-radiomics model. The area under the receive operating characteristic curve (AUC) and Delong test compared the diagnostic performance of the previously mentioned three models across different validation and testing cohorts. RESULTS: 17 radiomics features were selected for the radiomics model, and total protein, total cholesterol, free triiodothyronine, and triglyceride were utilized for the clinical model. In the training and validation cohorts, the diagnostic performance of the clinical-radiomics model (AUC=0.820 and 0.801) was comparable to the radiomics model (AUC=0.812 and 0.779, both P >0.05), both outperforming the clinical model (AUC=0.575 and 0.593, P <0.001). In the testing cohort, the clinical-radiomics model exhibited the highest AUC of 0.762 than the clinical and radiomics model (AUC=0.604 and 0.741, respectively, P <0.05). In addition, the clinical and radiomics models demonstrated similar diagnostic performance in the testing cohort (P >0.05). CONCLUSION: Integrating radiomics features from conventional pituitary MRI with clinical indicators offers a minimally invasive approach for identifying GHD and shows robustness in a multicenter setting.

In Vitro and In Vivo Evaluating Bioaccessibility, Bioavailability, and Antioxidant Activities of Butterfly Pea Flower Containing Bioactive Constitutes.

The antioxidant properties of butterfly pea flower (BF), which is rich in natural anthocyanins, have garnered significant attention. The impact of digestion and metabolism on BF extracts and evaluate their subsequent antioxidant activities in vivo were explored in the present study. After in vitro digestion, 42.03 ± 2.74% of total anthocyanins from BF extracts remained, indicating a negative influence of the digestion process on the bioaccessibility of phenolic compounds derived from BF. Furthermore, UPLC-LTQ-Orbitrap-MS2 analysis identified a total of four prototypes and twenty-seven metabolites in rat plasma or urine samples following the intake of BF extracts. The kinetics of key metabolites including delphinidin 3-glucoside (D3G), cyanidin-3-glucoside (C3G), and 4-hydroxybenzoic acid were subsequently determined in blood, and the Cmax values were 69.034 ± 8.05 nM and 51.65 ± 3.205 nM. These key metabolites derived from BF anthocyanins, including C3G and D3G, and flavonoid quercetin exhibited main antioxidant attributes that improved the plasmic and hepatic activities of various antioxidant enzymes and the total antioxidant capacity (T-AOC) and malondialdehyde (MDA) in a D-galactose-induced rat model. These findings provide insights into the bioaccessibility and bioavailability of bioactive constitutes derived from BF extracts, which are crucial for determining the actual efficacy of BF as well as developing functional foods based on BF.

Rational engineering of Halomonas salifodinae to enhance hydroxyectoine production under lower-salt conditions.

Hydroxyectoine is an important compatible solute that holds potential for development into a high-value chemical with broad applications. However, the traditional high-salt fermentation for hydroxyectoine production presents challenges in treating the high-salt wastewater. Here, we report the rational engineering of Halomonas salifodinae to improve the bioproduction of hydroxyectoine under lower-salt conditions. The comparative transcriptomic analysis suggested that the increased expression of ectD gene encoding ectoine hydroxylase (EctD) and the decreased expressions of genes responsible for tricarboxylic acid (TCA) cycle contributed to the increased hydroxyectoine production in H. salifodinae IM328 grown under high-salt conditions. By blocking the degradation pathway of ectoine and hydroxyectoine, enhancing the expression of ectD, and increasing the supply of 2-oxoglutarate, the engineered H. salifodinae strain HS328-YNP15 (ΔdoeA::PUP119-ectD p-gdh) produced 8.3-fold higher hydroxyectoine production than the wild-type strain and finally achieved a hydroxyectoine titer of 4.9 g/L in fed-batch fermentation without any detailed process optimization. This study shows the potential to integrate hydroxyectoine production into open unsterile fermentation process that operates under low-salinity and high-alkalinity conditions, paving the way for next-generation industrial biotechnology. KEY POINTS: • Hydroxyectoine production in H. salifodinae correlates with the salinity of medium • Transcriptomic analysis reveals the limiting factors for hydroxyectoine production • The engineered strain produced 8.3-fold more hydroxyectoine than the wild type.

The delayed senescence in harvested blueberry by hydrogen-based irrigation is functionally linked to metabolic reprogramming and antioxidant machinery.

Molecular hydrogen is beneficial for fruits quality improvement. However, the mechanism involved, especially cellular metabolic responses, has not been well established. Here, the integrated widely targeted metabolomics analysis (UPLC-MS/MS) and biochemical evidence revealed that hydrogen-based irrigation could orchestrate, either directly or indirectly, an array of physiological responses in blueberry (Vaccinium spp.) during harvesting stage, especially for the delayed senescence in harvested stage (4 °C for 12 d). The hubs to these changes are wide-ranging metabolic reprogramming and antioxidant machinery. A total of 1208 distinct annotated metabolites were identified, and the characterization of differential accumulated metabolites (DAMs) revealed that the reprogramming, particularly, involves phenolic acids and flavonoids accumulation. These changes were positively matched with the transcriptional profiles of representative genes for their synthesis during the growth stage. Together, our findings open a new window for development of hydrogen-based agriculture that increases the shelf-life of fruits in a smart and sustainable manner.

Targeted degradation of NDUFS1 by agrimol B promotes mitochondrial ROS accumulation and cytotoxic autophagy arrest in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a global public health problem with increased morbidity and mortality. Agrimol B, a natural polyphenol, has been proved to be a potential anticancer drug. Our recent report showed a favorable anticancer effect of agrimol B in HCC, however, the mechanism of action remains unclear. Here, we found agrimol B inhibits the growth and proliferation of HCC cells in vitro as well as in an HCC patient-derived xenograft (PDX) model. Notably, agrimol B drives autophagy initiation and blocks autophagosome-lysosome fusion, resulting in autophagosome accumulation and autophagy arrest in HCC cells. Mechanistically, agrimol B downregulates the protein level of NADH:ubiquinone oxidoreductase core subunit S1 (NDUFS1) through caspase 3-mediated degradation, leading to mitochondrial reactive oxygen species (mROS) accumulation and autophagy arrest. NDUFS1 overexpression partially restores mROS overproduction, autophagosome accumulation, and growth inhibition induced by agrimol B, suggesting a cytotoxic role of agrimol B-induced autophagy arrest in HCC cells. Notably, agrimol B significantly enhances the sensitivity of HCC cells to sorafenib in vitro and in vivo. In conclusion, our study uncovers the anticancer mechanism of agrimol B in HCC involving the regulation of oxidative stress and autophagy, and suggests agrimol B as a potential therapeutic drug for HCC treatment.

A comparison of the determination of multiple pesticide residues in fruits, vegetables, and edible fungi using gas chromatography combined with filtration purification and solid-phase extraction.

The multiplug filtration clean-up (m-PFC) and solid-phase extraction (SPE) pretreatment methods were employed to process 8 representative matrices in fruits, vegetables, and edible fungi, respectively. 37 pesticide residues were determined using gas chromatography equipped with ECD and FPD detectors. The measurement data were compared and analyzed following m-PFC purification and gas chromatography analysis, and both accuracy and precision met the (EU) 2021/808 requirements, achieving recovery rates for the 8 matrices ranging from 67.0% to 112.8% (averaging over 83.8% recovery), and RSDs between 0.2% and 15.2%. The 37 pesticides exhibited good linearity between 0.05 and 1.6 µg mL-1, and the matrix effect was found to be weaker compared to that of the Florisil solid-phase extraction method. The detection limits ranged from 0.0001 to 0.03 µg kg-1, with 31 pesticides showing lower detection limits compared to the SPE method. The application of this method to 150 real samples resulted in the detection of 17 pesticides across all samples. Fewer pigments were detected in m-PFC purified solutions compared to Florisil PR SPE when analyzed by liquid chromatography. m-PFC achieved more thorough adsorption of endogenous substances like pigments, reducing instrument contamination, utilizing less organic solvent, and simplifying the operation. This purification step offers clear advantages, allowing for the processing of larger sample batches in a short time. It can serve as a replacement for SPE methods like Florisi PR in batch detection of fruit and vegetable samples.

Investigation of key miRNAs and Target-mRNA in Kaposi's sarcoma using bioinformatic methods.

Kaposi's sarcoma (KS) is the second most common tumor in human immunodeficiency virus (HIV) infected patients worldwide. While many miRNAs have been confirmed to be involved in KS biological processes, no relevant studies have combined miRNA and mRNA expression profiles using KS patient tissue biopsies. In this study, we performed transcriptome sequencing on tumor and normal tissues from four KS patients and identified differentially expressed mRNA and miRNA, further performed target gene prediction and enrichment analysis. 19,551 target-mRNAs were identified by predicting 106 miRNAs, with 553 overlapping with 571 significantly differentially expressed mRNAs. Enrichment analysis showed significant involvement of the Ubiquitin-mediated proteolysis pathway. Additionally, the miRNA-mRNA interaction network was established, and the topological score of Cytohubba's algorithm was calculated for comparison with three other datasets. The Mutual Clustering Coefficient (MCC) scoring ranking placed ZBTB34, NFIB, and RORA as the top three mRNAs, while hsa-miR-16-5p, hsa-miR-27a-3p, hsa-miR-340-5p, hsa-miR-182-5p, and hsa-miR-186-5p ranked as the top five miRNAs. Hsa-miR-101-3p is the only miRNA that appears both in the top 10 MCC scores and at the intersection of the other two datasets. Finally, qRT-PCR was used to validate the findings at the cellular level. In summary, the miRNA analysis results indicated that hsa-miR-101-3p could be used as a potential diagnostic or therapeutic marker in future studies. Moreover, the mRNA analysis results suggested that the histone binding pathways involved in mRNAs and ubiquitin-related biological processes were closely associated with KS and could serve as promising biomarkers for the diagnosis and treatment of this disease.

Time trends in the burden of low back pain and its associated risk factors in China from 1990 to 2019.

Background: From 1990 to 2019, low back pain (LBP) was the leading cause of years lived with disability (YLDs) in China. However, the change patterns of LBP and its risk factors in China remain unclear. Methods: Data from the Global Burden of Disease Study 2019 were used. We used the join-point regression model and age-period-cohort analysis to evaluate the time trends of attributable risk factors on the burden of LBP. Results: In 2019, the risk factors included in this analysis accounted for 4.36 million YLDs of LBP, representing 42.2% of all YLDs of LBP in China, with 2.86 million due to occupational ergonomic factors, 1.74 million due to smoking, and 0.46 million due to high body mass index (BMI). The age-standardized YLD rates of LBP showed downward trends during 1990-2019, while there was a faster decline between 1990 and 1994. The curves of local drifts, which reflected the average annual percentage change across age groups, showed an increasing trend with age for high BMI and smoking, and a downward trend for occupational ergonomic factors. The YLD rates for LBP increased dramatically with age for high BMI, while it reached a peak at 40-60 years old for occupational ergonomic factors, and 65-80 years old for smoking. The period and cohort rate ratios of LBP YLD decreased in the past 3 decades for occupational ergonomic factors and smoking, while increased for high BMI. Conclusions: Our results provided strong evidence that there were diverse changing patterns for different risk factors, highlighting the need for risk-specific strategies. The translational potential of this article: China has the largest senior population and the fastest aging population in the world. Given that LBP typically occurs in the senior population, there would be an increasing LBP burden on China's health system. This suggests that effective strategies for LBP prevention should be strictly implemented in China, particularly in the senior population, which is of crucial translational potential.

WET-UNet: Wavelet integrated efficient transformer networks for nasopharyngeal carcinoma tumor segmentation.

Nasopharyngeal carcinoma is a malignant tumor that occurs in the epithelium and mucosal glands of the nasopharynx, and its pathological type is mostly poorly differentiated squamous cell carcinoma. Since the nasopharynx is located deep in the head and neck, early diagnosis and timely treatment are critical to patient survival. However, nasopharyngeal carcinoma tumors are small in size and vary widely in shape, and it is also a challenge for experienced doctors to delineate tumor contours. In addition, due to the special location of nasopharyngeal carcinoma, complex treatments such as radiotherapy or surgical resection are often required, so accurate pathological diagnosis is also very important for the selection of treatment options. However, the current deep learning segmentation model faces the problems of inaccurate segmentation and unstable segmentation process, which are mainly limited by the accuracy of data sets, fuzzy boundaries, and complex lines. In order to solve these two challenges, this article proposes a hybrid model WET-UNet based on the UNet network as a powerful alternative for nasopharyngeal cancer image segmentation. On the one hand, wavelet transform is integrated into UNet to enhance the lesion boundary information by using low-frequency components to adjust the encoder at low frequencies and optimize the subsequent computational process of the Transformer to improve the accuracy and robustness of image segmentation. On the other hand, the attention mechanism retains the most valuable pixels in the image for us, captures the remote dependencies, and enables the network to learn more representative features to improve the recognition ability of the model. Comparative experiments show that our network structure outperforms other models for nasopharyngeal cancer image segmentation, and we demonstrate the effectiveness of adding two modules to help tumor segmentation. The total data set of this article is 5000, and the ratio of training and verification is 8:2. In the experiment, accuracy = 85.2% and precision = 84.9% can show that our proposed model has good performance in nasopharyngeal cancer image segmentation.