Exploiting tertiary lymphoid structures gene signature to evaluate tumor microenvironment infiltration and immunotherapy response in colorectal cancer.

Background: Tertiary lymphoid structures (TLS) is a particular component of tumor microenvironment (TME). However, its biological mechanisms in colorectal cancer (CRC) have not yet been understood. We desired to reveal the TLS gene signature in CRC and evaluate its role in prognosis and immunotherapy response. Methods: The data was sourced from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Based on TLS-related genes (TRGs), the TLS related subclusters were identified through unsupervised clustering. The TME between subclusters were evaluated by CIBERSORT and xCell. Subsequently, developing a risk model and conducting external validation. Integrating risk score and clinical characteristics to create a comprehensive nomogram. Further analyses were conducted to screen TLS-related hub genes and explore the relationship between hub genes, TME, and biological processes, using random forest analysis, enrichment and variation analysis, and competing endogenous RNA (ceRNA) network analysis. Multiple immunofluorescence (mIF) and immunohistochemistry (IHC) were employed to characterize the existence of TLS and the expression of hub gene. Results: Two subclusters that enriched or depleted in TLS were identified. The two subclusters had distinct prognoses, clinical characteristics, and tumor immune infiltration. We established a TLS-related prognostic risk model including 14 genes and validated its predictive power in two external datasets. The model's AUC values for 1-, 3-, and 5-year overall survival (OS) were 0.704, 0.737, and 0.746. The low-risk group had a superior survival rate, more abundant infiltration of immune cells, lower tumor immune dysfunction and exclusion (TIDE) score, and exhibited better immunotherapy efficacy. In addition, we selected the top important features within the model: VSIG4, SELL and PRRX1. Enrichment analysis showed that the hub genes significantly affected signaling pathways related to TLS and tumor progression. The ceRNA network: PRRX1-miRNA (hsa-miR-20a-5p, hsa-miR-485-5p) -lncRNA has been discovered. Finally, IHC and mIF results confirmed that the expression level of PRRX1 was markedly elevated in the TLS- CRC group. Conclusion: We conducted a study to thoroughly describe TLS gene signature in CRC. The TLS-related risk model was applicable for prognostic prediction and assessment of immunotherapy efficacy. The TLS-hub gene PRRX1, which had the potential to function as an immunomodulatory factor of TLS, could be a therapeutic target for CRC.

Higher diversity of sulfur-oxidizing bacteria based on soxB gene sequencing in surface water than in spring in Wudalianchi volcanic group, NE China.

INTRODUCTION: Sulfur-oxidizing bacteria (SOB) play a key role in the biogeochemical cycling of sulfur. OBJECTIVES: To explore SOB diversity, distribution, and physicochemical drivers in five volcanic lakes and two springs in the Wudalianchi volcanic field, China. METHODS: This study analyzed microbial communities in samples via high-throughput sequencing of the soxB gene. Physical-chemical parameters were measured, and QIIME 2 (v2019.4), R, Vsearch, MEGA7, and Mothur processed the data. Alpha diversity indices and UPGMA clustering assessed community differences, while heat maps visualized intra-sample variations. Canoco 5.0 analyzed community-environment correlations, and NMDS, Adonis, and PcoA explored sample dissimilarities and environmental factor correlations. SPSS v.18.0 tested for statistical significance. RESULTS: The diversity of SOB in surface water was higher than in springs (more than 7.27 times). We detected SOB affiliated to ß-proteobacteria (72.3 %), α-proteobacteria (22.8 %), and γ-proteobacteria (4.2 %) distributed widely in these lakes and springs. Rhodoferax and Cupriavidus were most frequent in all water samples, while Rhodoferax and Bradyrhizobium are dominant in surface waters but rare in springs. SOB genera in both habitats were positively correlated. Co-occurrence analysis identified Bradyrhizobium, Blastochloris, Methylibium, and Metyhlobacterium as potential keystone taxa. Redundancy analysis (RDA) revealed positive correlations between SOB diversity and total carbon (TC), Fe2+, and total nitrogen (TN) in all water samples. CONCLUSION: The diversity and community structure of SOB in volcanic lakes and springs in the Wudalianchi volcanic group were clarified. Moreover, the diversity and abundance of SOB decreased with the variation of water openness, from open lakes to semi-enclosed lakes and enclosed lakes.

Exploring the pharmacological mechanism of Glycyrrhiza uralensis against KOA through integrating network pharmacology and experimental assessment.

Knee osteoarthritis (KOA), a major health and economic problem facing older adults worldwide, is a degenerative joint disease. Glycyrrhiza uralensis Fisch. (GC) plays an integral role in many classic Chinese medicine prescriptions for treating knee osteoarthritis. Still, the role of GC in treating KOA is unclear. To explore the pharmacological mechanism of GC against KOA, UPLC-Q-TOF/MS was conducted to detect the main compounds in GC. The therapeutic effect of GC on DMM-induced osteoarthritic mice was assessed by histomorphology, µCT, behavioural tests, and immunohistochemical staining. Network pharmacology and molecular docking were used to predict the potential targets of GC against KOA. The predicted results were verified by immunohistochemical staining Animal experiments showed that GC had a protective effect on DMM-induced KOA, mainly in the improvement of movement disorders, subchondral bone sclerosis and cartilage damage. A variety of flavonoids and triterpenoids were detected in GC via UPLC-Q-TOF/MS, such as Naringenin. Seven core targets (JUN, MAPK3, MAPK1, AKT1, TP53, RELA and STAT3) and three main pathways (IL-17, NF-κB and TNF signalling pathways) were discovered through network pharmacology analysis that closely related to inflammatory response. Interestingly, molecular docking results showed that the active ingredient Naringenin had a good binding effect on anti-inflammatory-related proteins. In the verification experiment, after the intervention of GC, the expression levels of pp65 and F4/80 inflammatory indicators in the knee joint of KOA model mice were significantly downregulated. GC could improve the inflammatory environment in DMM-induced osteoarthritic mice thus alleviating the physiological structure and dysfunction of the knee joint. GC might play an important role in the treatment of knee osteoarthritis.

Aberrant methylation and expression of TNXB promote chondrocyte apoptosis and extracullar matrix degradation in hemophilic arthropathy via AKT signaling.

Recurrent joint bleeding in hemophilia patients frequently causes hemophilic arthropathy (HA). Drastic degradation of cartilage is a major characteristic of HA, but its pathological mechanisms has not yet been clarified. In HA cartilages, we found server matrix degradation and increased expression of DNA methyltransferase proteins. We thus performed genome-wide DNA methylation analysis on human HA (N=5) and osteoarthritis (OA) (N=5) articular cartilages, and identified 1228 differentially methylated regions (DMRs) associated with HA. Functional enrichment analyses revealed the association between DMR genes (DMGs) and extracellular matrix (ECM) organization. Among these DMGs, Tenascin XB (TNXB) expression was down-regulated in human and mouse HA cartilages. The loss of Tnxb in F8-/- mouse cartilage provided a disease-promoting role in HA by augmenting cartilage degeneration and subchondral bone loss. Tnxb knockdown also promoted chondrocyte apoptosis and inhibited phosphorylation of AKT. Importantly, AKT agonist showed chondroprotective effects following Tnxb knockdown. Together, our findings indicate that exposure of cartilage to blood leads to alterations in DNA methylation, which is functionally related to ECM homeostasis, and further demonstrate a critical role of TNXB in HA cartilage degeneration by activating AKT signaling. These mechanistic insights allow development of potentially new strategies for HA cartilage protection.

Case report: A left forearm mass with eccentric intramedullary ulnar destruction diagnosed as alveolar rhabdomyosarcoma and treated by wide resection and free vascularized fibular graft.

Background: Alveolar Rhabdomyosarcoma is a profoundly malignant soft-tissue sarcoma that predominantly affects children and adolescents. However, the medical field lacks consensus regarding the optimal surgical approach to be undertaken in cases where this tumor causes local bone destruction in the upper limb. Case description: A 17-year-old male presented a mass in his left forearm and CT and MRI indicated that the mass had penetrated the ulnar cortex and infiltrating the medulla, resulting in the formation of an eccentric trans-ventricular tumor focus. The sizable tumor affected the volar muscles of the forearm as well as the ulnar bone marrow, exerting pressure on the ulnar artery and vein. It was confirmed by needle biopsy that the mass is alveolar rhabdomyosarcoma. Following two courses of neoadjuvant chemotherapy, the tumor was widely excised en bloc. Autologous fibula with a vascular pedicle was utilized for reconstruction during the procedure. In the postoperative follow-up, no local recurrence of the tumor was observed. Furthermore, the patient retained satisfactory wrist flexion and pronation function in the left forearm. Conclusions: Alveolar rhabdomyosarcoma is an uncommon and highly aggressive form of soft tissue sarcoma. Scientific management necessitates a multidisciplinary approach, combining chemotherapy with surgery. In cases where the tumor invaded into compartment of the bone, careful consideration should be given to the boundaries of tumor resection, the extent of osteotomy, and the approach to musculoskeletal reconstruction when designing the surgical plan. Through reporting our own case and thoroughly reviewing previous clinical experiences, we aim to provide valuable insights for the treatment of this particular disease.

A novel selenium nanocomposite modified by AANL inhibits tumor growth by upregulating CLK2 in lung cancer.

Lung cancer is a malignant tumor with high mortality and drug resistance. Therefore, it is urgent to explore natural and nontoxic drugs to treat lung cancer. In this study, the natural active ingredient AANL extracted from Agrocybe aegirita was used to modify nanoselenium by an oxidation-reduction method. Transmission electron microscope detection and infrared spectroscopy showed that a novel selenium nanocomposite named AANL-SeNPs was successfully prepared. The results of nanoscale characterization showed that AANL-SeNPs had good stability and uniform dispersion in aqueous solution by zeta potential and spectrum analysis. At the cellular level, we found that AANL-SeNPs significantly inhibited the cell viability of lung cancer cells, and the cell inhibition rate of 60 nM AANL-SeNPs was 39 % in H157 cells, 67 % in H147 cells, and 62 % in A549 cells. The IC50 value of AANL-SeNPs was 51.85 nM in A549 cells and 81.57 nM in H157 cells. Moreover, AANL-SeNPs could inhibit the cell proliferation and migration, and enhance the sensitivity of lung cancer cells to osimertinib and has no toxic to normal cells. In vivo, AANL-SeNPs significantly slowed tumor growth in tumor-bearing mice by establishing a subcutaneous transplantation tumor model for lung cancer, and the tumor size was smaller and was reduced about 79 % in 2 mg/kg AANL-SeNPs group compared with PBS group. Mechanistically, a total of 38 differentially expressed proteins were identified by data-independent acquisition mass spectrometry. A significantly upregulated protein, CDC-like kinase 2 (CLK2), was screened and validated for further analysis, which showed that the expression levels of CLK2 were increased in H157 and H1437 cells after AANL-SeNPs treatment. The results obtained in this study suggest that a novel selenium nanocomposite AANL-SeNPs, which inhibits lung cancer by upregulating the expression of CLK2.

Modeling and Reliability Analysis of MEMS Gyroscope Rotor Parameters under Vibrational Stress.

Vibrational environments can cause drift or changes in Micro-Electro-Mechanical System (MEMS) gyroscope rotor parameters, potentially impacting their performance. To improve the effective use of MEMS gyroscopes, this study introduced a method for evaluating the reliability of parameter degradation under vibration. We analyzed the working principle of MEMS gyroscope rotors and investigated how vibration affects their parameters. Focusing on zero bias and scale factor as key performance indicators, we developed an accelerated degradation model using the distributional assumption method. We then collected degradation data for these parameters under various vibration conditions. Using the Copula function, we established a reliability assessment approach to evaluate the degradation of the MEMS gyroscope rotor's zero bias and scale factor under vibration, enabling the determination of reliability for these parameters. Experimental findings confirmed that increasing stress levels lead to reduced failure times and increased failure rates for MEMS gyroscope rotors, with significant changes observed in the zero bias parameter. Our evaluation method effectively characterizes changes in the reliability of the MEMS gyroscope rotor's scale factor and zero bias over time, providing valuable information for practical applications of MEMS gyroscopes.

The CsmiR397a-CsLAC17 module regulates lignin biosynthesis to balance the tenderness and gray blight resistance in young tea shoots.

Lignin accumulation can enhance the disease resistance of young tea shoots (Camellia sinensis). It also greatly reduces their tenderness, which indirectly affects the quality and yield of tea. Therefore, the regulation of lignin biosynthesis appears to be an effective way to balance tenderness and disease resistance in young tea shoots. In this study, we identified a laccase gene, CsLAC17, that is induced during tenderness reduction and gray blight infection in young tea shoots. Overexpression of CsLAC17 significantly increased the lignin content in transgenic Arabidopsis, enhancing their resistance to gray blight and decreasing stem tenderness. In addition, we found that CsLAC17 was negatively regulated by the upstream CsmiR397a by 5'-RLM-RACE, dual-luciferase assay, and transient expression in young tea shoots. Interestingly, the expression of CsmiR397a was inhibited during tenderness reduction and gray blight infection of young tea shoots. Overexpression of CsmiR397a reduced lignin accumulation, resulting in decreased resistance to gray blight and increased stem tenderness in transgenic Arabidopsis. Furthermore, the transient overexpression of CsmiR397a and CsLAC17 in tea leaves directly confirms the function of the CsmiR397a-CsLAC17 module in lignin biosynthesis and its effect on disease resistance. These results suggest that the CsmiR397a-CsLAC17 module is involved in balancing tenderness and gray blight resistance in young tea shoots by regulating lignin biosynthesis.

Synergistic analysis of lignin degrading bacterial consortium and its application in rice straw fiber film.

Fiber film have received widespread attention due to its green friendliness. We can use microorganisms to degrade lignin in straw to obtain cellulose and make fiber films. Herein, a group of high-temperature (50 °C) lignin degrading bacterial consortium (LDH) was enriched and culture conditions for lignin degradation were optimized. Combined with high-throughput sequencing technology, the synergistic effect of LDH-composited bacteria was analyzed. Then LDH was used to treat rice straw for the bio-pulping experiment. The results showed that the lignin of rice straw was degraded 32.4 % by LDH at 50 °C for 10 d, and after the optimization of culture conditions, lignin degradation rate increased by 9.05 % (P < 0.001). The bacteria that compose in LDH can synergistically degrade lignin. Paenibacillus can encode all lignin-degrading enzymes present in the LDH. Preliminary tests of LDH in the pulping industry have been completed. This study is the first to use high temperature lignin degrading bacteria to fabricate fiber film.

Boosting Efficiency in Piezo-Photocatalysis Process Using Poled Ba0.7Sr0.3TiO3 Nanorod Arrays for Pollutant Degradation and Hydrogen Production.

Recently, the combination of the piezoelectric effect in the photocatalytic process, referred to as piezo-photocatalysis, has gained considerable attention as a promising approach for enhancing the degradation of organic pollutants. In this investigation, we studied the piezo-photocatalysis by fabricating arrays of barium strontium titanate (Ba0.7Sr0.3TiO3) nanorods (BST NRs) on a glass substrate as recoverable catalysts. We found that the degradation rate constant k of the rhodamine B solution achieved 0.0447 min-1 using poled BST NRs in the piezo-photocatalytic process, indicating a 2-fold increase in efficiency compared to the photocatalytic process (0.00183 min-1) utilizing the same material. This is mainly ascribed to the generation of the piezopotential in the poled BST NRs under ultrasonic vibration. Moreover, the BST NR array demonstrated a hydrogen (H2) production rate of 411.5 µmol g-1 h-1. In the photoelectrochemical process, the photocurrent density of poled BST NRs achieved 1.97 mA cm-2 at an applied potential of 1.23 V (ERHE (reversible hydrogen electrode)) under ultrasonic vibrations, representing a 1.7-fold increase compared with the poled BST NRs without ultrasonic vibrations. The measurement results from the liquid chromatograph mass spectrometer (LC-MS) demonstrated the formulation of a degradation pathway for rhodamine B molecules. Moreover, ab initio molecular dynamics (AIMD) simulation results demonstrate the dominance of hydroxyl radicals (•OH) rather than superoxide radicals (•O2-) in the degradation process. This study not only benefits the understanding of the principle of the piezo-photocatalytic process but also provides a new perspective for improving the catalytic efficiency for organic pollutants degradation.

YTHDC1 promotes the malignant progression of gastric cancer by promoting ROD1 translocation to the nucleus.

RNA-binding proteins (RBPs) make vital impacts on tumor progression and are important potential targets for tumor treatment. Previous studies have shown that RBP regulator of differentiation 1 (ROD1), enriched in the nucleus, is abnormally expressed and functions as a splicing factor in tumors; however, the mechanism underlying its involvement in gastric cancer (GC) is unknown. In this study, ROD1 is found to stimulate GC cell proliferation and metastasis and is related to poor patient prognosis. In vitro experiments showed that ROD1 influences GC proliferation and metastasis through modulating the imbalance of the level of the oncogenic gene OIP5 and the tumor suppressor gene GPD1L. Further studies showed that the N6-methyladenosine (m6A) "reader" protein YTHDC1 can interact with ROD1 and regulate the balance of the expression of the downstream molecules OIP5/GPD1L by promoting the nuclear enrichment of ROD1. Therefore, YTHDC1 stimulates GC development and progression through modulating nuclear enrichment of the splicing factor ROD1.

Isolation, purification, and biological activities of polysaccharides from Amorpha fruticosa flowers.

The extraction, isolation, structural characterisation and biological activities of polysaccharides from Amorpha fruticosa flowers were investigated. First, the crude polysaccharide AFP was extracted, and two major purified polysaccharide fractions AFP-2 and AFP-3 were isolated. The molecular weight and monosaccharide compositions of AFP-2 and AFP-3 were determined. Then the antioxidant activities of AFP, AFP-2 and AFP-3 were assessed by DPPH radical, ß-Carotene bleaching and hydroxyl radical assays. All three tested polysaccharides showed good antioxidant activity while AFP was the strongest one. The study also showed that AFP, AFP-2 and AFP-3 have good tyrosinase inhibition, moisture absorption and retention activities. The results will provide a helpful reference for the application of polysaccharide from Amorpha fruticosa flowers as a natural cosmetic ingredient.

Recent advances in IgG4-related autoimmune pancreatitis.

The incidence of IgG4-related autoimmune pancreatitis (IgG4-AIP) is high in Asia and other countries, and unnecessary treatment is often undertaken due to both missed diagnosis and misdiagnosis in clinical practice. Although IgG4-AIP has attracted increasing attention, the details of IgG4-AIP pathogenesis and systemic immune response, including its relationship to tumor pathogenesis, are still unclear. In recent years, research on serum immunological detection, pathological features, clinical manifestations, diagnosis and treatment measures for IgG4-AIP has gradually increased. It is of great importance to summarize and discuss the latest progress regarding IgG4-AIP disease.

[Snoring noise removal method for bowel sound signal during sleep].

Monitoring of bowel sounds is an important method to assess bowel motility during sleep, but it is seriously affected by snoring noise. In this paper, the complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) method was applied to remove snoring noise from bowel sounds during sleep. Specifically, the noisy bowel sounds were first band-pass filtered, then decomposed by the CEEMDAN method, and finally the appropriate components were selected to reconstruct the pure bowel sounds. The results of semi-simulated and real data showed that the CEEMDAN method was better than empirical mode decomposition and wavelet denoising method. The CEEMDAN method is used to remove snoring noise from bowel sounds during sleep, which lays an important foundation for using bowel sounds to assess the intestinal motility during sleep.

Clinical Efficacy of Neuroendoscopy Combined with Intracranial Pressure Monitoring for the Treatment of Hypertensive Intracerebral Hemorrhage.

OBJECTIVE: To compare the differences in postoperative complications and prognosis between patients treated with neuroendoscopy versus conventional craniotomy surgery for hypertensive intracerebral hemorrhage (HICH). METHODS: In this retrospective study, a total of 107 patients with HICH were included. Among them, 58 underwent neuroendoscopy (Group A), while 49 underwent conventional craniotomy under microscopic guidance (Group B). Intracranial pressure monitoring was applied in both groups. The clinical data, incidence of postoperative complications, preoperative and postoperative intracranial pressure values, and rate of favorable prognosis were compared between the 2 groups. RESULTS: No significant difference in baseline clinical data upon admission was observed between the 2 groups (P > 0.05). The preoperative intracranial pressure did not differ between the 2 groups (P > 0.05), but the postoperative intracranial pressure in Group A was significantly lower than that in Group B (P < 0.05). After intervention with the different surgical approaches, Group A showed a significantly lower incidence of postoperative cerebral infarction and a significantly higher rate of favorable prognosis compared with Group B (P < 0.05). CONCLUSIONS: Neuroendoscopy combined with Intracranial pressure monitoring is a safe and reliable approach for the treatment of HICH that reduces the incidence of postoperative cerebral infarction and improves the recovery of neurological function after surgery.

Mechanosensing by Piezo1 and its implications in the kidney.

Piezo1 is an essential mechanosensitive transduction ion channel in mammals. Its unique structure makes it capable of converting mechanical cues into electrical and biological signals, modulating biological and (patho)physiological processes in a wide variety of cells. There is increasing evidence demonstrating that the piezo1 channel plays a vital role in renal physiology and disease conditions. This review summarizes the current evidence on the structure and properties of Piezo1, gating modulation, and pharmacological characteristics, with special focus on the distribution and (patho)physiological significance of Piezo1 in the kidney, which may provide insights into potential treatment targets for renal diseases involving this ion channel.

Synergistic effect of two bacterial strains promoting anaerobic digestion of rice straw to produce methane.

A large amount of agricultural waste causes global environmental pollution. Biogas production by microbial pretreatment is an important way to utilize agricultural waste resources. In this study, Sporocytophaga CG-1 (A, cellulolytic strain) was co-cultured with Bacillus clausii HP-1 (B, non-cellulolytic strain) to analyze the effect of pretreatment of rice straw on methanogenic capacity of anaerobic digestion (AD). The results showed that weight loss rate of filter paper of co-culture combination is 53.38%, which is 29.37% higher than that of A. The synergistic effect of B on A can promote its degradation of cellulose. The cumulative methane production rate of the co-culture combination was the highest (93.04 mL/g VS substrate), which was significantly higher than that of A, B and the control group (82.38, 67.28 and 67.70 mL/g VS substrate). Auxiliary bacteria can improve cellulose degradation rate by promoting secondary product metabolism. These results provide data support for the application of co-culture strategies in the field of anaerobic digestion practices.

Long noncoding RNAs underlie multiple domestication traits and leafhopper resistance in soybean.

The origin and functionality of long noncoding RNA (lncRNA) remain poorly understood. Here, we show that multiple quantitative trait loci modulating distinct domestication traits in soybeans are pleiotropic effects of a locus composed of two tandem lncRNA genes. These lncRNA genes, each containing two inverted repeats, originating from coding sequences of the MYB genes, function in wild soybeans by generating clusters of small RNA (sRNA) species that inhibit the expression of their MYB gene relatives through post-transcriptional regulation. By contrast, the expression of lncRNA genes in cultivated soybeans is severely repressed, and, consequently, the corresponding MYB genes are highly expressed, shaping multiple distinct domestication traits as well as leafhopper resistance. The inverted repeats were formed before the divergence of the Glycine genus from the Phaseolus-Vigna lineage and exhibit strong structure-function constraints. This study exemplifies a type of target for selection during plant domestication and identifies mechanisms of lncRNA formation and action.

Ensemble Extreme Learning Machine Method for Hemoglobin Estimation Based on PhotoPlethysmoGraphic Signals.

Non-invasive detection of hemoglobin (Hb) concentration is of great clinical value for health screening and intraoperative blood transfusion. However, the accuracy and stability of non-invasive detection still need to be improved to meet clinical requirement. This paper proposes a non-invasive Hb detection method using ensemble extreme learning machine (EELM) regression based on eight-wavelength PhotoPlethysmoGraphic (PPG) signals. Firstly, a mathematical model for non-invasive Hb detection based on the Beer-Lambert law is established. Secondly, the captured eight-channel PPG signals are denoised and fifty-six feature values are extracted according to the derived mathematical model. Thirdly, a recursive feature elimination (RFE) algorithm is used to select the features that contribute most to the Hb prediction. Finally, a regression model is built by integrating several independent ELM models to improve prediction stability and accuracy. Experiments conducted on 249 clinical data points (199 cases as the training dataset and 50 cases as the test dataset) evaluate the proposed method, achieving a root mean square error (RMSE) of 1.72 g/dL and a Pearson correlation coefficient (PCC) of 0.76 (p < 0.01) between predicted and reference values. The results demonstrate that the proposed non-invasive Hb detection method exhibits a strong correlation with traditional invasive methods, suggesting its potential for non-invasive detection of Hb concentration.