Ultrasound-Based Radiomics for Predicting the WHO/ISUP Grading of Clear-Cell Renal Cell Carcinoma.

OBJECTIVE: To explore the performance of ultrasound image-based radiomics in predicting World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grading of clear-cell renal cell carcinoma (ccRCC). METHODS: A retrospective study was conducted via histopathological examination on participants with ccRCC from January 2021 to August 2023. Participants were randomly allocated to a training set and a validation set in a 3:1 ratio. The maximum cross-sectional image of the lesion on the preoperative ultrasound image was obtained, with the region of interest (ROI) delineated manually. Radiomic features were computed from the ROIs and subsequently normalized using Z-scores. Wilcoxon test and least absolute shrinkage and selection operator (LASSO) regression were applied for feature reduction and model development. The performance of the model was estimated by indicators including area under the curve (AUC), sensitivity and specificity. RESULTS: A total of 336 participants (median age, 57 y; 106 women) with ccRCC were finally included, of whom 243 had low-grade tumors (grade 1-2) and 93 had high-grade tumors (grade 3-4). A total of 1163 radiomic features were extracted from the ROIs for model construction and 117 informative radiomics features selected by Wilcoxon test were submitted to LASSO. Our ultrasound-based radiomics model included 51 features and achieved AUCs of 0.90 and 0.79 for the training and validation sets, respectively. Within the training set, the sensitivity and specificity measured 0.75 and 0.92, respectively, whereas in the validation set, the sensitivity and specificity measured 0.65 and 0.84, respectively. In the subgroup analysis, for the training and validation sets Philips AUCs were 0.91 and 0.75, Toshiba AUCs were 0.82 and 0.90, and General Electric AUCs were 0.95 and 0.82, respectively. CONCLUSION: Ultrasound-based radiomics can effectively predict the WHO/ISUP grading of ccRCC.

Exploration of the Mechanisms of Bu-Yang-Huan-Wu Decoction in the Treatment of Diabetic Peripheral Neuropathy by Integrating of Serum Pharmacochemistry and Network Pharmacology.

Diabetic peripheral neuropathy (DPN) is a significant and frequent complication of diabetes. Bu-Yang-Huan-Wu Decoction (BHD) is a classic traditional Chinese herbal prescription that is commonly used in modern clinical practice for the effective treatment of DPN, but the underlying mechanism is not yet clearly defined. The chemical constituents of BHD were characterized by UPLC-Q-Orbitrap HR MS/MS, and a total of 101 chemical components were identified, including 30 components absorbed into blood. An interaction network of "compound-target-disease" interactions was constructed based on the compounds detected absorbed in blood and their corresponding targets of diabetic neuropathy acquired from disease gene databases, and the possible biological targets and potential signalling pathways of BHD were predicted via network pharmacology analysis. Subsequently, methylglyoxal-induced (MGO-induced) Schwann cells (SCs) were used to identify the active ingredients in blood components of BHD and verify the molecular mechanisms of BHD. Through network topological analysis, 30 shared targets strongly implicated in the anti-DPN effects of BHD were identifed. Combined network pharmacology and in vitro cellular analysis, we found that the active ingredient of BHD may treat DPN by modulating the AGEs/RAGE pathway. This study provides valuable evidence for future mechanistic studies and potential therapeutic applications for patients with DPN.

[Effects of Acid Mine Drainage Leakage on Bacterial Communities in Desert Grassland Soil Profiles].

Acid mine drainage （AMD） is of great concern owing to its safety hazards and environmental risks. However, little is known about the effects of AMD leakage on soil physicochemical properties and bacterial communities in ecologically fragile desert steppe soils, especially in the soil profile. Therefore, an AMD-contaminated profile and clean profile were used as research objects respectively to investigate the effects of AMD on soil physicochemical properties and bacterial community composition, structure, and interactions in soil layers at different depths of desert grassland and, based on this, to analyze the driving factors of bacterial community changes. The results showed that AMD significantly decreased the pH and increased electrical conductivity （EC） and heavy metal content in the upper （0-40 cm） soil layer of the profile. The AMD-contaminated profile bacteria were dominated by Proteobacteria, Firmicutes, and Actinobacterota, whereas clean profile bacteria were dominated by Firmicutes and Bacteroidota, with Thermithiobacillus and Alloprevotella being the biomarkers for the contaminated and clean profiles, respectively. AMD contamination significantly reduced bacterial diversity and significantly altered bacterial community structure in the upper soil layers of the profile. The results of redundancy analysis showed that soil physicochemical properties explained 57.21% of the variation in bacterial community changes, with EC, TP, TN, As, Zn, and Pb being the main drivers of bacterial community changes. Network analyses showed that AMD contamination increased profile complexity, modularity, and intra-community competition, thereby improving bacterial community stability and resilience. In conclusion, the study provided useful information on the effects of AMD pollution on soil physicochemical properties and bacterial communities in desert steppe soils, which may help to improve the understanding of the ecological hazards of AMD pollution on soils in extreme habitats.

[Effects of Long-term Biochar Addition on Denitrification N2O Emissions from Bacteria and Fungi in Paddy Soil].

Denitrification driven by bacteria and fungi is the main source of nitrous oxide （N2O） emissions from paddy soil. It is generally believed that biochar reduces N2O emissions by influencing the bacterial denitrification process, but the relevant mechanism of its impact on fungal denitrification is still unclear. In this study, the long-term straw carbonization returning experimental field in Changshu Agricultural Ecological Experimental Base of the Chinese Academy of Sciences was taken as the object. Through indoor anaerobic culture and molecular biology technology, the relative contributions of bacteria and fungi to denitrifying N2O production in paddy soil and the related microorganism mechanism were studied under different long-term biochar application amounts （blank, 2.25 t·hm-2, and 22.5 t·hm-2, respectively, expressed by BC0, BC1, and BC10）. The results showed that compared with that in BC0, biochar treatment significantly reduced N2O emission rate, denitrification potential, and cumulative N2O emissions, and the contribution of bacterial denitrification was greater than that of fungal denitrification in all three treatments. Among them, the relative contribution rate of bacterial denitrification in BC10 （62.9%） was significantly increased compared to BC0 （50.8%）, whereas the relative contribution rate of fungal denitrification in BC10 （37.1%） was significantly lower than that in BC0 （49.2%）. The application of biochar significantly increased the abundance of bacterial denitrification functional genes （nirK, nirS, and nosZ） but reduced the abundance of fungal nirK genes. The contribution rate of fungal denitrification was significantly positively correlated with the N2O emission rate and negatively correlated with soil pH, TN, SOM, and DOC. Biochar may have inhibited the growth of denitrifying fungi by increasing pH and carbon and nitrogen content, reducing the abundance of related functional genes, thereby weakening the reduction ability of NO to N2O during fungal denitrification process. This significantly reduces the contribution rate of N2O production during the fungal denitrification process and the denitrification N2O emissions from paddy soil. This study helps to broaden our understanding of the denitrification process in paddy soil and provides a theoretical basis for further regulating fungal denitrification N2O emissions.

Clinical features of a novel compound heterozygous genotype of the BBS2 gene: a case report.

Bardet-Biedl syndrome is a rare autosomal recessive genetic disorder with heterogenous clinical manifestations. The present study reports the clinical features of a novel compound heterozygous genotype of the BBS2 gene in a 14-year-old girl and her 6-year-old sister who had complaints of early-onset low vision. Fundus images revealed retinitis pigmentosa-like changes, and full-field electroretinograms showed no amplitude for the rod or cone response in both patients. Interestingly, nystagmus was observed in the older sister. On physical examination, the sisters had moderate obesity without polydactyly, hypogonadism, or intellectual disability. Exome sequencing revealed a novel compound heterozygous genotype of BBS2 in the sisters, namely the paternally inherited NM_031885.5:c.534 + 1G > T variant and the maternally inherited NM_031885.5:c.700C > T (p.Arg234Ter) variant. Both variants were classified as pathogenic according to the American College of Medical Genetics and Genomics guidelines. This study provides useful information on the genotype-phenotype relationships of the BBS2 gene for genetic counseling and diagnosis.

MiR-338-5p, a novel metastasis-related miRNA, inhibits triple-negative breast cancer progression by targeting the ETS1/NOTCH1 axis.

Breast cancer ranks as the most prevalent cancer globally, surpassing lung cancer, with recurrence/metastasis to be its main account for the cancer-related mortality. MicroRNAs (miRNAs) participate critically in various physiological and pathological processes through posttranscriptional regulation of downstream genes. Our preliminary findings identified miR-338-5p, potentially linked to metastasis in breast cancer, a previously unexplored area. Analysis of the GSE38867 dataset revealed the decreased miR-338-5p expression in metastatic breast cancer compared to normal tissues. Cellular function experiments and a xenograft tumor model demonstrated the inhibitory function of miR-338-5p on the progression of breast cancer in vitro and in vivo. Furthermore, it downregulated the expression of mesenchymal biomarkers and NOTCH1 significantly. With the predicting targets of miR-338-5p and transcription factors of the NOTCH1 gene, coupled with dual luciferase reporter assays, it is identified ETS1 as the interactor between miR-338-5p and NOTCH1. In breast cancer tissues, as well as in our xenograft tumor model, expression of ETS1 and NOTCH1 was positively correlated using immunohistochemical staining. This study reports, for the first time, on the miR-338-5p/ETS1/NOTCH1 axis and its pivotal role in breast cancer proliferation and metastasis. These findings propose a novel therapeutic strategy for breast cancer patients and lays a foundation for its clinical detection and treatment evaluation.

Global, regional, and national burden of HIV-negative tuberculosis, 1990-2021: findings from the Global Burden of Disease Study 2021.

BACKGROUND: Tuberculosis (TB) is a major infectious disease with significant public health implications. Its widespread transmission, prolonged treatment duration, notable side effects, and high mortality rate pose severe challenges. This study examines the epidemiological characteristics of TB globally and across major regions, providing a scientific basis for enhancing TB prevention and control measures worldwide. METHODS: The ecological study used data from the Global Burden of Disease (GBD) Study 2021. It assessed new incidence cases, deaths, disability-adjusted life years (DALYs), and trends in age-standardized incidence rates (ASIRs), mortality rates (ASMRs), and DALY rates for drug-susceptible tuberculosis (DS-TB), multidrug-resistant tuberculosis (MDR-TB), and extensively drug-resistant tuberculosis (XDR-TB) from 1990 to 2021. A Bayesian age-period-cohort model was applied to project ASIR and ASMR. RESULTS: In 2021, the global ASIR for all HIV-negative TB was 103.00 per 100,000 population [95% uncertainty interval (UI): 92.21, 114.91 per 100,000 population], declining by 0.40% (95% UI: - 0.43, - 0.38%) compared to 1990. The global ASMR was 13.96 per 100,000 population (95% UI: 12.61, 15.72 per 100,000 population), with a decline of 0.44% (95% UI: - 0.61, - 0.23%) since 1990. The global age-standardized DALY rate for HIV-negative TB was 580.26 per 100,000 population (95% UI: 522.37, 649.82 per 100,000 population), showing a decrease of 0.65% (95% UI: - 0.69, - 0.57 per 100,000 population) from 1990. The global ASIR of MDR-TB has not decreased since 2015, instead, it has shown a slow upward trend in recent years. The ASIR of XDR-TB has exhibited significant increase in the past 30 years. The projections indicate MDR-TB and XDR-TB are expected to see significant increases in both ASIR and ASMR from 2022 to 2035, highlighting the growing challenge of drug-resistant TB. CONCLUSIONS: This study found that the ASIR of MDR-TB and XDR-TB has shown an upward trend in recent years. To reduce the TB burden, it is essential to enhance health infrastructure and increase funding in low-SDI regions. Developing highly efficient, accurate, and convenient diagnostic reagents, along with more effective therapeutic drugs, and improving public health education and community engagement, are crucial for curbing TB transmission.

Second-Harmonic-Generation Switching via Pressure-Suppressed Dynamical Disorder.

Second-harmonic-generation (SHG) switching is an emerging phenomenon with potential applications in bistable storage and optical switches while also serving as a sensitive probe for inversion-symmetry. Temperature-induced disorder-order phase transition has been proven to be a rational design strategy for achieving SHG bi-state switching; however, pressure-sensitive SHG switching via a disorder-order structural transition mechanism is rarely reported and lacks sensitivity and cyclicity as practical switching materials. Herein, we demonstrate the pressure-induced "dynamical disorder-order" phase transition as an effective strategy for triggering SHG and SHG switching in NH4Cl. The "dynamical disorder-order" phase transition of NH4Cl occurring at as low as 1 GPa is confirmed by comprehensive in situ high-pressure XRD, molecular vibrational spectra, and Brillouin scattering spectra. The pressure-induced SHG is responsive to a wide excitation wavelength region (800-1500 nm), and the "off-on" switching is reversible for up to 50 cycles, setting a record for pressure-driven switching materials. It is worth noting that when pressure is further increased to 14 GPa, NH4Cl exhibits another SHG "on-off" switching, which makes it the first triplet SHG "off-on-off" switching material. Molecular dynamics simulations reveal the key role of N-H···Cl hydrogen bonding in the pressure-induced "dynamic disorder-order" mechanism. Finally, we verified that chemical pressure and physical pressure can jointly regulate the SHG switching behavior of NH4X (X = Cl, Br). The pressure-driven "dynamic disorder-order" transition mechanism sheds light on the rational design of multistable SHG switching materials for photoswitches and information storage.

Unveiling the shield: Troglitazone's impact on epilepsy-induced nerve injury through ferroptosis inhibition.

BACKGROUND: Epilepsy is a widespread central nervous system disorder with an estimated 50 million people affected globally. It is characterized by a bimodal incidence peak among infants and the elderly and is influenced by a variety of risk factors, including a significant genetic component. Despite the use of anti-epileptic drugs (AEDs), drug-refractory epilepsy develops in about one-third of patients, highlighting the need for alternative therapeutic approaches. AIMS: The primary aim of this study was to evaluate the neuroprotective effects of troglitazone (TGZ) in epilepsy and to explore the potential mechanisms underlying its action. METHODS: We employed both in vitro and in vivo models to assess TGZ's effects. The in vitro model involved glutamate-induced toxicity in HT22 mouse hippocampal neurons, while the in vivo model used kainic acid (KA) to induce epilepsy in mice. A range of methods, including Hoechst/PI staining, CCK-8 assay, flow cytometry, RT-PCR analysis, Nissl staining, scanning electron microscopy, and RNA sequencing, were utilized to assess various parameters such as cellular damage, viability, lipid-ROS levels, mitochondrial membrane potential, mRNA expression, seizure grade, and mitochondrial morphology. RESULTS: Our results indicate that TGZ, at doses of 5 or 20 mg/kg/day, significantly reduces KA-induced seizures and neuronal damage in mice by inhibiting the process of ferroptosis. Furthermore, TGZ was found to prevent changes in mitochondrial morphology. In the glutamate-induced HT22 cell damage model, 2.5 µM TGZ effectively suppressed neuronal ferroptosis, as shown by a reduction in lipid-ROS accumulation, a decrease in mitochondrial membrane potential, and an increase in PTGS2 expression. The anti-ferroptotic effect of TGZ was confirmed in an erastin-induced HT22 cell damage model as well. Additionally, TGZ reversed the upregulation of Plaur expression in HT22 cells treated with glutamate or erastin. The downregulation of Plaur expression was found to alleviate seizures and reduce neuronal damage in the mouse hippocampus. CONCLUSION: This study demonstrates that troglitazone has significant therapeutic potential in the treatment of epilepsy by reducing epileptic seizures and the associated brain damage through the inhibition of neuronal ferroptosis. The downregulation of Plaur expression plays a crucial role in TGZ's anti-ferroptotic effect, offering a promising avenue for the development of new epilepsy treatments.

Exploring the antimicrobial activity of rare ginsenosides and the progress of their related pharmacological effects.

BACKGROUND: Panax ginseng C. A. Mey is a precious medicinal resource that could be used to treat a variety of diseases. Saponins are the most important bioactive components of, and rare ginsenosides (Rg3, Rh2, Rk1 and Rg5, etc.) refer to the chemical structure changes of primary ginsenosides through dehydration and desugarization reactions, to obtain triterpenoids that are easier to be absorbed by the human body and have higher activity. PURPOSE: At present, the research of P. ginseng. is widely focused on anticancer related aspects, and there are few studies on the antibacterial and skin protection effects of rare ginsenosides. This review summarizes the rare ginsenosides related to bacterial inhibition and skin protection and provides a new direction for P. ginseng research. METHODS: PubMed and Web of Science were searched for English-language studies on P. ginseng published between January 2002 and March 2024. Selected manuscripts were evaluated manually for additional relevant references. This review includes basic scientific articles and related studies such as prospective and retrospective cohort studies. CONCLUSION: This paper summarizes the latest research progress of several rare ginsenosides, discusses the antibacterial effect of rare ginsenosides, and finds that ginsenosides can effectively protect the skin and promote wound healing during use, so as to play an efficient antibacterial effect, and further explore the other medicinal value of ginseng. It is expected that this review will provide a wider understanding and new ideas for further research and development of P. ginseng drugs.

Avicularin Attenuated Lead-Induced Ferroptosis, Neuroinflammation, and Memory Impairment in Mice.

Lead (Pb) is a common environmental neurotoxicant that results in abnormal neurobehavior and impaired memory. Avicularin (AVL), the main dietary flavonoid found in several plants and fruits, exhibits neuroprotective and hepatoprotective properties. In the present study, the effects of AVL on Pb-induced neurotoxicity were evaluated using ICR mice to investigate the molecular mechanisms behind its protective effects. Our study has demonstrated that AVL treatment significantly ameliorated memory impairment induced by lead (Pb). Furthermore, AVL mitigated Pb-triggered neuroinflammation, ferroptosis, and oxidative stress. The inhibition of Pb-induced oxidative stress in the brain by AVL was evidenced by the reduction in malondialdehyde (MDA) levels and the enhancement of glutathione (GSH) and glutathione peroxidase (GPx) activities. Additionally, in the context of lead-induced neurotoxicity, AVL mitigated ferroptosis by increasing the expression of GPX4 and reducing ferrous iron levels (Fe2+). AVL increased the activities of glycogenolysis rate-limiting enzymes HK, PK, and PYG. Additionally, AVL downregulated TNF-α and IL-1ß expression while concurrently enhancing the activations of AMPK, Nrf2, HO-1, NQO1, PSD-95, SNAP-25, CaMKII, and CREB in the brains of mice. The findings from this study suggest that AVL mitigates the memory impairment induced by Pb, which is associated with the AMPK/Nrf2 pathway and ferroptosis.

[3 + 2] Annulation of Vinyl Azides with Aldehydes for the Synthesis of 3-Oxazolines via the [CO + CCN] Strategy.

Despite the widespread utilizable value of 3-oxazolines, mild and efficient access to such a class of unique structures still remains, to date, a challenge. Herein, we present a [3 + 2] annulation strategy, guided by the retrosynthetic principle of [CO + CCN], that utilizes vinyl azides as the CCN module and aldehydes as the CO module. This approach enables the efficient construction of the 3-oxazoline framework with remarkable features, including operational simplicity, environmental friendliness, and high efficiency. Notably, it solely requires the addition of inexpensive and readily available N-hydroxyphthalimide (NHPI) and air oxygen to obtain the desired product. It also provides a new way to generate the hydroxyl radical, which is produced by the homolysis of peroxycarboxylic acid. In addition, control experiments, X-ray crystallographic analysis, high-resolution mass spectrometry (HRMS), and density functional theory (DFT) calculations afford evidence for the key intermediates (hydroxyl radical, carboxyl radical, imine radical, hydroxyl substituted amide derivatives), further confirming the path for realization of 3-oxazolines.

Preparation of kakkatin derivatives and their anti-tumor activity.

BACKGROUND: Modern pharmacological studies have confirmed that plant-derived compounds from Puerariae flos (PF) has significant biological activities against liver damage, tumors and inflammation. Kakkatin is an isoflavone polyphenolic compound isolated from PF flower. However, the effect of kakkatin and its derivatives on anti-tumor has not been well explored. AIM: To design and synthesize a kakkatin derivative [6-(hept-6-yn-1-yloxy)-3-(4-hydroxyphenyl)-7-methoxy-4H-chromen-4-one (HK)] to explore its anti-tumor biological activity. METHODS: Hept-6-yn-1-yl ethanesulfonate was introduced to replace hydrogen at the hydroxyl position of kakkatin phenol, and the derivative of kakkatin was prepared; the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide was used to detect cell viability, a clone formation assay was adopted to detect cell proliferation, apoptosis, necrosis, and cell cycles were analyzed by Annexin V/propidium iodide staining and flow cytometry. Cell migration and invasion ability were evaluated by cell scratch assay and transwell assay. The potential mechanism of HK on hepatocellular carcinoma (HCC) SMMC-7721 cells was explored through network pharmacology and molecular docking, and finally real-time PCR assays was used to verify the potential targets and evaluate the biological activity of HK. RESULTS: Compared with kakkatin, the modified HK did not significantly increase the inhibitory activity of gastric cancer MGC803 cells, but the inhibitory activity of HCC SMMC-7721 cells was increased by about 30 times, with an IC50 value of 2.5 µM, and the tumor inhibition effect was better than cisplatin, which could significantly inhibit the cloning, invasion and metastasis of HCC SMMC-7721 cells, and induce apoptosis and G2/M cycle arrest. Its mechanism of action is mainly related to the upregulation of PDE3B and NFKB1 target proteins in the cAMP pathway. CONCLUSION: HK have a significant inhibitory effect on HCC SMMC-7721 cells, and the targets of their action may be PDE3B and NFKB1 proteins in the cAMP pathway, making it a good lead drug for the treatment of HCC.

Vulnerability and driving mechanism of four typical grasslands in China under the coupled impacts of climate change and human activities.

Understanding of how different grasslands types respond to climate change and human activities across different spatial and temporal dimensions is crucial for devising effective strategies to prevent grasslands degradation. In this study, we developed a novel vulnerability assessment model for grasslands that intricately evaluates the combined impact of climate change and human activities. We then applied this model to analyze the vulnerability and driving mechanism of four representative Chinese grasslands to climate change and human activities. Our findings indicate that the vulnerability of the four grasslands would show a pattern of higher in the west and lower in the east under the influence of climate change alone. However, when human activities are factored in, the vulnerability across the four grasslands tends to homogenize, with human activities notably reducing the vulnerability of alpine grasslands in the west and, conversely, increasing the vulnerability of grasslands in the east. Furthermore, our study reveals distinct major environmental drivers of grasslands vulnerability across different regions. The two western alpine grasslands exhibit higher vulnerability to annual mean temperature and isothermality compared to the eastern temperate grasslands, while their vulnerability to precipitation of the coldest quarter is lower than that of the eastern temperate grasslands. These findings are helpful for understanding the multifaceted causes and mechanisms of grasslands degradation, providing a scientific foundation for the sustainable management and conservation of grassland resources.

Investigation of the quality of life, mental status in patients with gynecological cancer and its influencing factors.

BACKGROUND: Having a gynecological tumor or undergoing treatment can be a traumatic experience for women, as it affects their self-image and sexual relationships and can lead to psychological reactions. Psychological adjustment following cancer occurrence remains a key issue among the survivors. AIM: To examine the current status of quality of life (QoL), anxiety, and depression in patients with gynecological cancer and to analyze the factors associated with it. METHODS: Data for 160 patients with gynecological malignancies treated at Shanxi Bethune Hospital from June 2020 to June 2023 were collected and analyzed retrospectively. Patients' QoL was assessed using the European Organization for Research on Treatment of Cancer Quality of Life Questionnaire Core 30 and the Functional Assessment of Cancer Therapy-General Questionnaire. Their emotional status was evaluated using the Self-Rating Anxiety/Depression Scale. The associated factors of anxiety and depression were analyzed. RESULTS: The overall QoL score of the patients 6 months after surgery was 76.39 ± 3.63 points. This included low levels of social and emotional function and severe fatigue and pain. The scores for physiological, functional, emotional, social, and family well-being exhibited an upward trend following surgery compared with those before surgery. One month after surgery, some patients experienced anxiety and depression, with an incidence of 18.75% and 18.13%, respectively. Logistic analysis revealed that good sleep was a protective factor against anxiety and depression in patients with gynecological tumors, whereas physical pain was a risk factor. CONCLUSION: Patients with gynecological malignancies often experience anxiety and depression. By analyzing the factors that affect patients' QoL, effective nursing measures can be administered.

PBMC-mediated modulation of macrophage polarization in RAW264.7 cells through STAT1/STAT6 signaling cascades.

Peripheral blood mononuclear cells (PBMC), sourced autologously, offer numerous advantages when procured: easier acquisition process, no in vitro amplification needed, decreased intervention and overall increased acceptability make PBMC an attractive candidate for cell therapy treatment. However, the exact mechanism by which PBMC treat diseases remains poorly understood. Immune imbalance is the pathological basis of many diseases, with macrophages playing a crucial role in this process. However, research on the role and mechanisms of PBMC in regulating macrophages remains scarce. This study employed an in vitro co-culture model of PBMC and RAW264.7 macrophages to explore the role and mechanisms of PBMC in regulating macrophages. The results showed that the co-culturing led to decreased expression of inflammatory cytokines and increased expression of anti-inflammatory cytokines in RAW264.7 or in the culture supernatant. Additionally, the pro-inflammatory, tissue matrix-degrading M1 macrophages decreased, while the anti-inflammatory, matrix-synthesizing, regenerative M2 macrophages increased in both RAW264.7 and monocytes within PBMC. Moreover, co-cultured macrophages exhibited a significantly decreased p-STAT1/STAT1 ratio, while the p-STAT6/STAT6 ratio significantly increased. This suggests that PBMC may inhibit M1 macrophage polarization by blocking STAT1 signaling cascades and may promote M2 macrophage polarization through the activation of STAT6 signaling cascades. Overall, this study sheds light on the role and mechanism of PBMC in regulating macrophages. Moreover, it was found that monocytes within co-cultured PBMC differentiated into M2 macrophages in the presence of macrophages. This finding provides experimental evidence for the use of PBMC in treating inflammatory diseases, especially macrophage-depleting inflammatory diseases such as osteoarthritis.

Molecular mechanism of basolateral amygdala involved in electroacupuncture-induced amelioration of cancer pain and concomitant depression based on transcriptomics techniques. / åŸºäºŽè½¬å½•ç»„å­¦æŠ€æœ¯æŽ¢è®¨åŸºåº•å¤–ä¾§æä»æ ¸å‚ä¸Žç”µé’ˆæ²»ç–—ç™Œç—›åŠå ¶è¯±å‘çš„æŠ‘éƒæƒ ç»ªçš„åˆ†å­æœºåˆ¶.

OBJECTIVES: To observe the effect of electroacupuncture (EA) of "Zusanli" (ST36) and "Sanyinjiao" (SP6) on cancer pain and concomitant negative emotion in cancer pain model mice, and to explore its molecular mechanisms in the basolateral amygdala (BLA) by using transcriptomics techniques. METHODS: C57BL/6 mice were randomized into sham operation, model and EA groups, with 10 mice in each group. The cancer pain model was established by injecting PBS suspension containing Lewis lung cancer cells into the femur. The mice in the EA group received EA stimulation(1 mA, 2 Hz) on ST36 and SP6 from the 10th day after modeling, 20 min per day for 12 successive days. The bone damage of the distal femur was observed with X-ray and H.E. staining, respectively. The mechanical pain threshold (MPT) was detected by using von Frey. The depression-like behavior was detected by using sucrose-preference test (sucrose preference index in 12 h), and the immobility (feeling of despair) duration of forced swimming within 4 min. The BLA tissue was extracted for RNA sequencing (RNA library construction, and screening differential gene profiling by transcriptomic sequencing) and bioinformatics analysis. The real-time PCR was used to validate the mRNA expression of differentially expressed genes：tumor necrosis factor superfamily 8 (Tnfsf8), bone marrow stromal cell antigen 1 (Bst1), prodynorphin (Pdyn) and voltage-gated sodium channelß4 (Scn4b). RESULTS: H.E. staining and X-ray showed significant bone damage in the distal femur in cancer pain mice. In contrast to the sham operation group, the MPT on the 1st , 4th, 7th , 10th, 14th and 21st day after modeling and sucrose preference index were significantly decreased (P<0.001, P<0.000 1), and the immobility time of the forced swimming was considerably increased in the model group (P<0.001). In contrast to the model group, the MPT values on the 14th and 21st day and sucrose preference index were obviously increased (P<0.000 1, P<0.05), and the immobility time was strikingly decreased in the EA group (P<0.01). RNA sequencing showed that a total of 404 differentially expressed genes (205 up-regulated, 199 down-regulated) were screened in the model group compared with the sham operation group, and a total of 329 differentially expressed genes (206 up-regulated and 123 down-regulated) were screened in the EA group compared with the model group. Venn diagram analysis of the differentially expressed genes showed that 45 up-regulated and 28 down-regulated genes in the model group were completely reversed by EA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the screened differentially expressed genes revealed that the above differential genes were mainly enriched in the ligand receptor activity, cytokine receptor binding, and cytokine activity related to neuro-inflammation, as well as in neuropeptide signaling pathways related to neuronal excitability, and calcium ion mediated signal transduction. The analysis of KEGG pathway showed that the differentially expressed genes were mainly enriched in the inflammation-related pathways, such as interleukin-17 pathway. Validation analysis of the differentially expressed genes showed that the expression levels of Tnfsf8 and Bst1 were significantly up-regulated in the model group compared with the sham operation group (P<0.01, P<0.05), and down-regulated by EA (P<0.01, P<0.05), while the expression levels of Pdyn and Scn4b were down-regulated in the model group in comparison with the sham operation group (P<0.01), and up-regulated by EA (P<0.05, P<0.01), which was consistent with the changing trend of the gene sequencing results. CONCLUSIONS: Acupuncture of ST36 and SP6 can significantly relieve cancer pain and concomitant negative emotion in cancer pain mice, which may be related to its functions in alleviating neuro-inflammation and relieving the abnormal activities of specific neurons in the BLA.

Visualization analysis of research hotspots and trends on gastrointestinal tumor organoids.

BACKGROUND: Gastrointestinal tumor organoids serve as an effective model for simulating cancer in vitro and have been applied in basic biology and preclinical research. Despite over a decade of development and increasing research achievements in this field, a systematic and comprehensive analysis of the research hotspots and future trends is lacking. AIM: To address this problem by employing bibliometric tools to explore the publication years, countries/regions, institutions, journals, authors, keywords, and references in this field. METHODS: The literature was collected from Web of Science databases. CiteSpace-6.2R4, a widely used bibliometric analysis software package, was used for institutional analysis and reference burst analysis. VOSviewer 1.6.19 was used for journal co-citation analysis, author co-authorship and co-citation analysis. The 'online platform for bibliometric analysis (https://bibliometric.com/app)' was used to assess the total number of publications and the cooperation relationships between countries. Finally, we employed the bibliometric R software package (version R.4.3.1) in R-studio, for a comprehensive scientific analysis of the literature. RESULTS: Our analysis included a total of 1466 publications, revealing a significant yearly increase in articles on the study of gastrointestinal tumor organoids. The United States (n = 393) and Helmholtz Association (n = 93) have emerged as the leading countries and institutions, respectively, in this field, with Hans Clevers and Toshiro Sato being the most contributing authors. The most influential journal in this field is Gastroenterology. The most impactful reference is "Long term expansion of epithelial organs from human colon, adenoma, adenocarcinoma, and Barrett's epithelium". Keywords analysis and citation burst analysis indicate that precision medicine, disease modeling, drug development and screening, and regenerative medicine are the most cutting-edge directions. These focal points were further detailed based on the literature. CONCLUSION: This bibliometric study offers an objective and quantitative analysis of the research in this field, which can be considered as an important guide for next scientific research.

Metabolome profiling and transcriptome analysis unveiling the crucial role of magnesium transport system for magnesium homeostasis in tea plants.

Magnesium (Mg2+) is a crucial nutrient for the growth and development of Camellia sinensis and is closely related to the quality of tea. However, the underlying mechanisms responding to low-Mg 2+ stress in tea plants remain largely unknown. In this study, photosynthetic parameters, metabolomics, and transcriptomics were utilized to explore the potential effects of low Mg2+ on the growth and metabolism of C. sinensis. Low-Mg2+ treatment increased the ratio of shoot dry weight to root dry weight but decreased the photosynthesis of C. sinensis. Forty and thirty metabolites were impacted by Mg2+ shortage in C. sinensis shoots and roots, respectively. Integrated transcriptome and metabolome analyses revealed the possible reasons for the decreased contents of chlorophyll and catechins and the increased theanine content in C. sinensis roots. Weighted gene co-expression network analysis indicated that the Mg2+ transport system was essential in the regulation of Mg2+ homeostasis in C. sinensis, in which CsMGT5 was identified to be the key regulator according to CsMGT5-overexpressing and complementary assays in Arabidopsis thaliana. Moreover, silencing of CsMGT5 in vivo reduced the content of chlorophyll in C. sinensis shoots. In addition, CsMGT5 might collaborate with ammonium transporters to keep the amino acid content steady, suggesting its potential application for tea quality improvement. All these findings demonstrate the key roles of CsMGTs for Mg2+ homeostasis in C. sinensis, providing a theoretical basis for Mg2+ efficient utilization in plants.