Revealing the impact of autophagy-related genes in rheumatoid arthritis: Insights from bioinformatics.

Background: Rheumatoid arthritis is a systemic inflammatory autoimmune disease that severely impacts physical and mental health. Autophagy is a cellular process involving the degradation of cellular components in lysosomes. However, from a bioinformatics perspective, autophagy-related genes have not been comprehensively elucidated in rheumatoid arthritis. Methods: In this study, we performed differential analysis of autophagy-related genes in rheumatoid arthritis patients using the GSE93272 dataset from the Gene Expression Omnibus database. Marker genes were screened by least absolute shrinkage and selection operator. Based on marker genes, we used unsupervised cluster analysis to elaborate different autophagy clusters, and further identified modules strongly associated with rheumatoid arthritis by weighted gene co-expression network analysis. In addition, we constructed four machine learning models, random forest model, support vector machine model, generalized linear model and extreme gradient boosting based on marker genes, and based on the optimal machine learning model, a nomogram model was constructed for distinguishing between normal individuals and rheumatoid arthritis patients. Finally, five external independent rheumatoid arthritis datasets were used for the validation of our results. Results: The results showed that autophagy-related genes had significant expression differences between normal individuals and osteoarthritis patients. Through least absolute shrinkage and selection operator screening, we identified 31 marker genes and found that they exhibited significant synergistic or antagonistic effects in rheumatoid arthritis, and immune cell infiltration analysis revealed significant changes in immune cell abundance. Subsequently, we elaborated different autophagy clusters (cluster 1 and cluster 2) using unsupervised cluster analysis. Next, further by weighted gene co-expression network analysis, we identified a brown module strongly associated with rheumatoid arthritis. In addition, we constructed a nomogram model for five marker genes (CDKN2A, TP53, ATG16L2, FKBP1A, and GABARAPL1) based on a generalized linear model (area under the curve = 1.000), and the predictive efficiency and accuracy of this nomogram model were demonstrated in the calibration curves, the decision curves and the five external independent datasets were validated. Conclusion: This study identified marker autophagy-related genes in rheumatoid arthritis and analyzed their impact on the disease, providing new perspectives for understanding the role of autophagy-related genes in rheumatoid arthritis and providing new directions for its individualized treatment.

Antiviral defense in plant stem cells.

Undifferentiated plant and animal stem cells are essential for cell, tissue, and organ differentiation, development, and growth. They possess unusual antiviral immunity which differs from that in specialized cells. By comparison to animal stem cells, we discuss how plant stem cells defend against viral invasion and beyond.

Material basis and molecular mechanisms of Chaihuang Qingyi Huoxue Granule in the treatment of acute pancreatitis based on network pharmacology and molecular docking-based strategy.

Objectives: This study aimed to analyze active compounds and signaling pathways of CH applying network pharmacology methods, and to additionally verify the molecular mechanism of CH in treating AP. Materials and methods: Network pharmacology and molecular docking were firstly used to identify the active components of CH and its potential targets in the treatment of AP. The pancreaticobiliary duct was retrogradely injected with sodium taurocholate (3.5%) to create an acute pancreatitis (AP) model in rats. Histological examination, enzyme-linked immunosorbent assay, Western blot and TUNEL staining were used to determine the pathway and mechanism of action of CH in AP. Results: Network pharmacological analysis identified 168 active compounds and 276 target proteins. In addition, there were 2060 targets associated with AP, and CH had 177 targets in common with AP. These shared targets, including STAT3, IL6, MYC, CDKN1A, AKT1, MAPK1, MAPK3, MAPK14, HSP90AA1, HIF1A, ESR1, TP53, FOS, and RELA, were recognized as core targets. Furthermore, we filtered out 5252 entries from the Gene Ontology(GO) and 186 signaling pathways from the Kyoto Encyclopedia of Genes and Genomes(KEGG). Enrichment and network analyses of protein-protein interactions predicted that CH significantly affected the PI3K/AKT signaling pathway, which played a critical role in programmed cell death. The core components and key targets showed strong binding activity based on molecular docking results. Subsequently, experimental validation demonstrated that CH inhibited the phosphorylation of PI3K and AKT in pancreatic tissues, promoted the apoptosis of pancreatic acinar cells, and further alleviated inflammation and histopathological damage to the pancreas in AP rats. Conclusion: Apoptosis of pancreatic acinar cells can be enhanced and the inflammatory response can be reduced through the modulation of the PI3K/AKT signaling pathway, resulting in the amelioration of pancreatic disease.

Resistance mechanism of Phomopsis longicolla to fludioxonil is associated with modifications in PlOS1, PlOS4 and PlOS5.

Phomopsis longicolla, a causal agent of soybean root rot, stem blight, seed decay, pod and stem canker, which seriously affects the yield and quality of soybean production worldwide. The phenylpyrrole fungicide fludioxonil exhibits a broad spectrum and high activity against phytopathogenic fungi. In this study, the baseline sensitivity of 100 P. longicolla isolates collected from the main soybean production areas of China to fludioxonil were determined. The result showed that the EC50 values of all the P. longicolla isolates ranged from 0.013 to 0.035 µg/ml. Furthermore, 12 fludioxonil-resistance (FluR) mutants of P. longicolla were generated from 6 fludioxonil-sensitive (FluS) isolates. and the resistance factors (RF) of 12 FluR mutants were >3500. Sequence alignment showed that multiple mutation types were found in PlOS1, PlOS4 or/and PlOS5 of FluR mutants. All the FluR mutants exhibited fitness penalty in mycelial growth, conidiation, virulence and osmo-adaptation. Under fludioxonil or NaCl treatment condition, the glycerol accumulation was significantly increased in FluS isolates, but was slightly increased in FluR mutants, and the phosphorylation level of most FluR mutants was significantly decreased when compared to the FluS isolates. Additionally, positive cross-resistance was observed between fludioxonil and procymidone but not fludioxonil and pydiflumetofen, pyraclostrobin or fluazinam. This is first reported that the baseline sensitivity of P. longicolla to fludioxonil, as well as the biological and molecular characterizations of P. longicolla FluR mutants to fludioxonil. These results can provide scientific directions for controlling soybean diseases caused by P. longicolla using fludioxonil.

A novel method of tunneling retroperitoneoscopic adrenalectomy: a prospective study.

BACKGROUND: To introduce the surgical technique and our team's extensive experience with tunnel method in laparoscopic adrenalectomy. METHODS: From July 2019 to June 2022, we independently designed and conducted 83 cases of " Tunnel Method Laparoscopic Adrenalectomy," a prospective study. There were 45 male and 38 female patients, ages ranged from 25 to 73 years(mean: 44.6 years).The cases included 59 adrenal cortical adenomas, 9 pheochromocytomas, 6 cysts, 4 myelolipomas, 1 ganglioneuroma, and 4 cases of adrenal cortical hyperplasia. In terms of anatomical location, there were 39 cases on the left side, 42 on the right side, and 2 bilateral cases. Tumor diameters ranged from 0.6 to 5.9 cm(mean: 2.9 cm). Utilizing ultrasound monitoring, percutaneous puncture was made either directly to the target organ or its vicinity, and the puncture path was manually marked. Then, under the direct view of a single-port single-channel laparoscope, the path to the target organ in the retroperitoneum or its vicinity was further delineated and separated. This approach allowed for the insertion of the laparoscope and surgical instruments through the affected adrenal gland, thereby separating the surface of the target organ to create sufficient operational space for the adrenalectomy. RESULTS: All 83 surgeries were successfully completed. A breakdown of the surgical approach reveals that 51 surgeries were done using one puncture hole, 25 with two puncture holes, and 7 with three puncture holes. The operation time ranged from 31 to 105 min (mean: 47 min), with a blood loss of 10 to 220mL (mean: 40 mL). Notably, there were no conversions to open surgery and no intraoperative complications. Postoperative follow-up ranged from 6 to 28 months, during which after re-examination using ultrasound, CT, and other imaging methods, there were no recurrences or other complications detected. CONCLUSIONS: The completion of the tunnel method laparoscopic adrenalectomy represents a breakthrough, transitioning from the traditional step-by-step separation of retroperitoneal tissues to reach the target organ in conventional retroperitoneoscopic surgery. This method directly accesses the target organ, substantially reducing the damage and complications associated with tissue separation in retroperitoneoscopic surgery, As a result, it provides a new option for minimally invasive surgery of retroperitoneal organs and introduces innovative concepts to retroperitoneoscopic surgery.

Zeb1-controlled metabolic plasticity enables remodeling of chromatin accessibility in the development of neuroendocrine prostate cancer.

Cell plasticity has been found to play a critical role in tumor progression and therapy resistance. However, our understanding of the characteristics and markers of plastic cellular states during cancer cell lineage transition remains limited. In this study, multi-omics analyses show that prostate cancer cells undergo an intermediate state marked by Zeb1 expression with epithelial-mesenchymal transition (EMT), stemness, and neuroendocrine features during the development of neuroendocrine prostate cancer (NEPC). Organoid-formation assays and in vivo lineage tracing experiments demonstrate that Zeb1+ epithelioid cells are putative cells of origin for NEPC. Mechanistically, Zeb1 transcriptionally regulates the expression of several key glycolytic enzymes, thereby predisposing tumor cells to utilize glycolysis for energy metabolism. During this process, lactate accumulation-mediated histone lactylation enhances chromatin accessibility and cellular plasticity including induction of neuro-gene expression, which promotes NEPC development. Collectively, Zeb1-driven metabolic rewiring enables the epigenetic reprogramming of prostate cancer cells to license the adeno-to-neuroendocrine lineage transition.

Injectable Modified Sodium Alginate Microspheres for Enhanced Operative Efficiency and Safety in Endoscopic Submucosal Dissection.

Endoscopic submucosal dissection (ESD) is an effective method for resecting early-stage tumors in the digestive system. To achieve a low injection pressure of the injected fluid and continuous elevation of the mucosa following injection during the ESD technique, we introduced an innovative injectable sodium-alginate-based drug-loaded microsphere (Cipro-ThSA) for ESD surgery, which was generated through an emulsion reaction involving cysteine-modified sodium alginate (ThSA) and ciprofloxacin. Cipro-ThSA microspheres exhibited notable adhesiveness, antioxidant activity, and antimicrobial properties, providing a certain level of postoperative wound protection. In vitro cell assays confirmed the decent biocompatibility of the material. Lastly, according to animal experiments involving submucosal elevation of porcine colons, Cipro-ThSA microspheres ensure surgically removable lift height while maintaining the mucosa for approximately 246% longer than saline, which could effectively reduce surgical risks while providing sufficient time for operation. Consequently, the Cipro-ThSA microsphere holds great promise as a novel submucosal injection material, in terms of enhancing the operational safety and effectiveness of ESD surgery.

Inhibitory Properties of Cinnamon Bark Oil against Postharvest Pathogen Penicillium digitatum In Vitro.

Penicillium digitatum is a major postharvest pathogen that threatens the global citrus fruit industry and causes great economic losses annually. In the present study, inhibitory properties of cinnamon bark oil (CBO) against P. digitatum in vitro were investigated. Results indicated that 0.03% CBO could efficiently inhibit the spore germination, germ tube elongation, mycelial growth, colonial expansion and conidial accumulation of P. digitatum. The results of fluorescein diacetate (FDA) and MitoTraker Orange (MTO) staining also proved the suppression effects of CBO against P. digitatum. Meanwhile, CBO could inhibit green mold rots induced by P. digitatum in citrus fruit when the working concentration of CBO exceeded 0.06%. In addition, the expressions of 12 genes critical for the growth and virulence of P. digitatum were also significantly regulated under CBO stress. Through a transcriptomic analysis, a total of 1802 common differentially expressed genes (DEGs) were detected in P. digitatum after 4 h and 8 h of CBO treatment. Most of the DEG products were associated with carbohydrate, amino acid and lipid metabolism. They directly or indirectly led to the disturbance of the membrane and the generation of reactive oxygen species (ROS). Our results may deepen the understanding of antifungal properties of CBO against P. digitatum and provide the theoretical foundation to uncover the antifungal mechanism of CBO at the molecular level.

X-ray image enhancement with multi-scale local edge preserving filter based on fuzzy entropy.

BACKGROUND: Recently, X-rays have been widely used to detect complex structural workpieces. Due to the uneven thickness of the workpiece and the high dynamic range of the X-ray image itself, the detailed internal structure of the workpiece cannot be clearly displayed. OBJECTIVE: To solve this problem, we propose an image enhancement algorithm based on a multi-scale local edge-preserving filter. METHODS: Firstly, the global brightness of the image is enhanced through logarithmic transformation. Then, to enhance the local contrast, we propose utilizing the gradient decay function based on fuzzy entropy to process the gradient and then incorporate the gradient into the energy function of the local edge-preserving filter (LEP) as a constraint term. Finally, multiple base layers and detail layers are obtained through filtering multi-scale decomposition. All detail layers are enhanced and fused using S-curve mapping to improve contrast further. RESULTS: This method is competitive in both quantitative indices and visual perception quality. CONCLUSIONS: The experimental results demonstrate that the proposed method significantly enhances various complex workpieces and is highly efficient.

Recent Progress in Peptide-Based Molecular Probes for Disease Bioimaging.

Recent strides in molecular pathology have unveiled distinctive alterations at the molecular level throughout the onset and progression of diseases. Enhancing the in vivo visualization of these biomarkers is crucial for advancing disease classification, staging, and treatment strategies. Peptide-based molecular probes (PMPs) have emerged as versatile tools due to their exceptional ability to discern these molecular changes with unparalleled specificity and precision. In this Perspective, we first summarize the methodologies for crafting innovative functional peptides, emphasizing recent advancements in both peptide library technologies and computer-assisted peptide design approaches. Furthermore, we offer an overview of the latest advances in PMPs within the realm of biological imaging, showcasing their varied applications in diagnostic and therapeutic modalities. We also briefly address current challenges and potential future directions in this dynamic field.

History and future of water footprint in the Yangtze River Delta of China.

Quantifying the drivers of water footprint evolution in the Yangtze River Delta is vital for the optimization of China's total water consumption. The article aims to decompose and predict the water footprint of the Yangtze River Delta and provide policy recommendations for optimizing water use in the Yangtze River Delta. The paper applies the LMDI method to decompose the water footprint of the Yangtze River Delta and its provinces into five major drivers: water footprint structure, water use intensity, R&D scale, R&D efficiency, and population size. Furthermore, this paper combines scenario analysis and Monte Carlo simulation methods to predict the potential evolution trends of water footprint under the basic, general, and enhanced water conservation scenario, respectively. The results show that (1) the expansion of R&D scale is the main factor promoting the growth of water footprint, the improvement of R&D efficiency, and the reduction of water intensity are the main factors inhibiting the increase of water footprint, and the water footprint structure and population size have less influence on water footprint. (2) The evolution trend of water footprint of each province under three scenarios is different. Compared to the basic scenario, the water footprint decreases more in Shanghai, Zhejiang, and Anhui under the general and enhanced water conservation scenario. The increase in water footprint in Jiangsu under the enhanced scenario is smaller than that of the general water conservation scenario.

FSformer: A combined frequency separation network and transformer for LDCT denoising.

Low-dose computed tomography (LDCT) has been widely concerned in the field of medical imaging because of its low radiation hazard to humans. However, under low-dose radiation scenarios, a large amount of noise/artifacts are present in the reconstructed image, which reduces the clarity of the image and is not conducive to diagnosis. To improve the LDCT image quality, we proposed a combined frequency separation network and Transformer (FSformer) for LDCT denoising. Firstly, FSformer decomposes the LDCT images into low-frequency images and multi-layer high-frequency images by frequency separation blocks. Then, the low-frequency components are fused with the high-frequency components of different layers to remove the noise in the high-frequency components with the help of the potential texture of low-frequency parts. Next, the estimated noise images can be obtained by using Transformer stage in the frequency aggregation denoising block. Finally, they are fed into the reconstruction prediction block to obtain improved quality images. In addition, a compound loss function with frequency loss and Charbonnier loss is used to guide the training of the network. The performance of FSformer has been validated and evaluated on AAPM Mayo dataset, real Piglet dataset and clinical dataset. Compared with previous representative models in different architectures, FSformer achieves the optimal metrics with PSNR of 33.7714 dB and SSIM of 0.9254 on Mayo dataset, the testing time is 1.825 s. The experimental results show that FSformer is a state-of-the-art (SOTA) model with noise/artifact suppression and texture/organization preservation. Moreover, the model has certain robustness and can effectively improve LDCT image quality.

Molten salt synthesis of MXene-derived hierarchical titanate for effective strontium removal.

The removal and recovery of radioactive Sr(II) from wastewater and seawater has been of great concern due to the negative environmental impacts of nuclear energy development and the potential risk of nuclear accidents. Herein, a facile molten salt synthesis strategy was developed to systematically investigated the reaction of different types of MXenes with nitrates. Among the products, K+ intercalated hierarchical titanate nanostructures (K-HTNs) obtained from the direct chemical transformation of multilayered Ti3C2Tx exhibited unique layered structures, good physicochemical properties, and outstanding adsorption performance for Sr(II). The maximum adsorption capacity of Sr(II) by K-HTNs reached 204 mg·g-1 at ambient temperature, and the good regeneration and reusability of the titanate was also demonstrated. K-HTNs showed preferential selectivity for Sr(II) in different environmental media containing competing ions, and the removal efficiency of Sr(II) in real seawater was as high as 93.3 %. The removal mechanism was elaborated to be the exchange of Sr2+ with K+/H+ in the interlayers of K-HTNs, and the adsorbed Sr(II) had a strong interaction with Ti-O- termination on the titanate surface. Benefiting from the merits of rapid and scalable synthesis and excellent adsorption performance, MXene-derived K-HTNs have broad application prospects for the purification of 90Sr-contaminated wastewater and seawater.

New Method for 5'-Nucleotidase Preparation and Evaluation of Its Catalytic Activity.

In this study, we established a new methodology for preparing 5'-nucleotidase (5'-NT) with the aim of enhancing our understanding of its enzyme activity and laying a basis for regulating the content of umami-enhancing nucleotides in pork. 5'-NT was prepared with Sephadex gel filtration and reverse-phase high-performance liquid chromatography, and its enzymatic properties and catalytic activity were evaluated. The results show that the molecular weight of the prepared 5'-NT was 57 kDa, the optimal catalytic temperature was 40 °C, and the optimal pH was 8. Zn2+, and sucrose showed inhibitory effects on the activity of 5'-NT, while K+, Na+, Ca2+, Mg2+, glucose, fructose, and trehalose promoted the activity of the studied compound. The prepared 5'-NT exhibited higher catalytic activity and selectivity against IMP compared with its commercial counterpart, while its catalytic activity against XMP was not significant (p > 0.05). In brief, we established a new methodology for preparing 5'-NT, enhancing our understanding of its enzyme activity and providing a solid basis for regulating the content of umami-enhancing nucleotides in pork through the control of endogenous 5'-NT activity.

The discovery of three-dimensional Van Hove singularity.

Arising from the extreme/saddle point in electronic bands, Van Hove singularity (VHS) manifests divergent density of states (DOS) and induces various new states of matter such as unconventional superconductivity. VHS is believed to exist in one and two dimensions, but rarely found in three dimension (3D). Here, we report the discovery of 3D VHS in a topological magnet EuCd2As2 by magneto-infrared spectroscopy. External magnetic fields effectively control the exchange interaction in EuCd2As2, and shift 3D Weyl bands continuously, leading to the modification of Fermi velocity and energy dispersion. Above the critical field, the 3D VHS forms and is evidenced by the abrupt emergence of inter-band transitions, which can be quantitatively described by the minimal model of Weyl semimetals. Three additional optical transitions are further predicted theoretically and verified in magneto-near-infrared spectra. Our results pave the way to exploring VHS in 3D systems and uncovering the coordination between electronic correlation and the topological phase.

Influencing factors comparing different vault groups after phakic implantable collamer lens implantation: review and meta-analysis.

BACKGROUND: Studies on the factors affecting vault after posterior chamber phakic Implantable Collamer Lens (ICL) have been carried out, but most of them are single-centered and subjective selections of parameters. The present study aimed to systematically analyze the factors for vault. METHODS: A systematic review of case series, case-control, and cohort studies derived from the articles published in PubMed, the Cochrane Library, Embase, Web of Science, CNKI, CBM, Wanfang and VIP, as well as ClinicalTrials, which were conducted to search for studies on factors of vault using four core terms: phakic intraocular lenses, vault, risk factor and observational study, from January 01, 1997, to February 20, 2023. The included studies were meta-analyzed quantitatively and described qualitatively. Subsequently, meta-regression and subgroup analysis were used. RESULTS: We identified 13 studies (1,607 subjects), and 14 factors were considered. Meta-analysis showed that anterior chamber depth (ACD), horizontal corneal white-to-white (hWTW), ICL-size, and age are dual effects of the abnormal vaults; anterior chamber volume (ACV) and lens thickness (LT) are a one-way effect; while axial length (AL), ICL- spherical equivalent (ICL-SE) and Km are insignificant. In addition, descriptive analysis of anterior chamber angle (ACA), horizontal sulcus to sulcus (hSTS), ciliary processes height (T value), crystalline lens rise (CLR), and gender showed that all factors except gender tend to have significant effects on vault. Sensitivity analysis showed stable combined results. Country and design respectively affect the heterogeneity in ACD and ICL-size at low vault, while design affects the heterogeneity in ACD at high vault. No publication bias exists. CONCLUSIONS: Vault after ICL is related to multiple factors, especially anterior segmental biologic parameters, and they are weighted differently. We hope to provide a reference for the selection and adjustment of ICL.

Toward exclusive stereocomplex crystallization of high-molecular-weight poly(L-lactic acid)/poly(D-lactic acid) blends with outstanding heat resistance via incorporating selective nucleating agents.

In high molecular weight poly(L-lactic acid)/poly(D-lactic acid) (HMW PLLA/PDLA) blends, the construction of exclusive stereocomplex crystals (SC) with high crystallinity and strong melt memory remains a great challenge. In the present study, various norbornene dicarboxylate complexes (TMXNa, Mg, Al, or Ca) were employed as the stereo-selective nucleating agents (NAs), and their effect on the crystallization characteristics, rheological behavior, and heat resistance of PLLA/PDLA blends were thoroughly studied. Strikingly, TMX-Al facilitated the construction of exclusive SC with over 50 % crystallinity and excellent melt memory. The dense SC crystals network structure boosted the heat resistance of L/D-xAl blends with a VST as high as 145 °C. The strengthened intermolecular interaction fostered the generation of pre-ordered structure in the melt and enhanced chain interdiffusion, which contributed to intermolecular nucleation and SC crystallization in L/D-xAl blend. This study opens up a new avenue for melt processing and application development of SC-PLA materials.

Investigation of New Accelerometer Based on Capacitive Micromachined Ultrasonic Transducer (CMUT) with Ring-Perforation Membrane.

Capacitive micromachined ultrasonic transducer (CMUT) has been widely studied due to its excellent resonance characteristics and array integration. This paper presents the first study of the CMUT electrostatic stiffness resonant accelerometer. To improve the sensitivity of the CMUT accelerometer, this paper innovatively proposes the CMUT ring-perforation membrane structure, which effectively improves the acceleration sensitivity by reducing the mechanical stiffness of the elastic membrane. The acceleration sensitivity is 10.9 (Hz/g) in the acceleration range of 0-20 g, which is 100% higher than that of the conventional CMUT structure. This research contributes to the acceleration measurement field of CMUT and can effectively contribute to the breakthrough of vibration acceleration monitoring technology in aerospace, medical equipment, and automotive electronics.