Enhanced targeting: Production of filamentous bacteriophage monoclonal antibodies using the major coat protein pVIII as anchor.

Filamentous bacteriophage display technology has been employed in antibody discovery, drug screening, and protein-protein interaction study across various fields, including food safety, agricultural pollution, and environmental monitoring. Antifilamentous bacteriophage antibodies for identifying filamentous bacteriophage are playing a pivotal role in this technology. However, the existing antifilamentous bacteriophage antibodies lack sensitivity and specificity, and the antibodies preparation methods are cumbersome and hyposensitive. The major coat protein pVIII of filamentous bacteriophage has an advantage in quantification, which is benefit for detecting signal amplification but its full potential remains underutilized. In this study, the partial polypeptide CT21 of the major coat protein pVIII of filamentous bacteriophage was intercepted as the targeted immunogen or coating antigen to prepare antifilamentous bacteriophage antibodies. Six filamentous bacteriophage-specific monoclonal antibodies (mAbs) M5G8, M9A2, P6B5, P6D2, P8E4, and P10D4 were obtained. The limit of detections of the prepared six mAbs for detecting filamentous bacteriophage was 1.0 × 107  pfu mL-1 . These mAbs stayed stable under different pH, temperature, and exhibited high specificity in real application. This study not only provides a new idea for simplifying the preparation of antifilamentous bacteriophage antibodies which could apply in filamentous bacteriophage display, but it also presents a novel strategy for preparing antibodies against protein-specific epitopes with high sensitivity.

Multiomics Analyses Reveal the Dual Role of Flavonoids in Pigmentation and Abiotic Stress Tolerance of Soybean Seeds.

The color of the seed coat has great diversity and is regarded as a biomarker of metabolic variations. Here we isolated a soybean variant (BLK) from a population of recombinant inbred lines with a black seed coat, while its sibling plants have yellow seed coats (YL). The BLK and YL plants showed no obvious differences in vegetative growth and seed weight. However, the BLK seeds had higher anthocyanins and flavonoids level and showed tolerance to various abiotic stresses including herbicide, oxidation, salt, and alkalinity during germination. Integrated metabolomic and transcriptomic analyses revealed that the upregulation of biosynthetic genes probably contributed to the overaccumulation of flavonoids in BLK seeds. The transient expression of those biosynthetic genes in soybean root hairs increased the levels of total flavonoids or anthocyanins. Our study revealed the molecular basis of flavonoid accumulation in soybean seeds, leveraging genetic engineering for both nutritious and stress-tolerant soybean germplasm.

Analgesic Effect of Exercise on Neuropathic Pain via Regulating the Complement Component 3 of Reactive Astrocytes.

BACKGROUND: Exercise has been proven to be an efficient intervention in attenuating neuropathic pain. However, the underlying mechanisms that drive exercise analgesia remain unknown. In this study, we aimed to examine the role of complement component 3 (C3) in neuropathic pain and whether antinociceptive effects are produced by exercise via regulating C3 in mice. METHODS: In this study, using a spared nerve injury (SNI)-induced neuropathic pain mice model, C57BL/6J mice were divided into 3 groups: Sham mice, SNI mice, and SNI + Exercise (Ex) mice with 30-minute low-intensity aerobic treadmill running (10 m/min, no inclination). Paw withdrawal threshold; thermal withdrawal latency; and glial fibrillary acidic protein, C3, tumor necrosis factor-α, and interlukin-1ß expression in the spinal cord were monitored. C3 knockout (KO) mice were further used to verify the role of C3 in neuropathic pain. RESULTS: von Frey test, acetone test, and CatWalk gait analysis revealed that treadmill exercise for 4 weeks reversed pain behaviors. In addition, exercise reduced astrocyte reactivity (SNI mean = 14.5, 95% confidence interval [CI], 12.7-16.3; SNI + Ex mean = 10.3, 95% CI, 8.77-11.9, P = .0003 SNI + Ex versus SNI) and inflammatory responses in the spinal cord after SNI. Moreover, it suppressed the SNI-induced upregulation of C3 expression in the spinal cord (SNI mean = 5.46, 95% CI, 3.39-7.53; SNI + Ex mean = 2.41, 95% CI, 1.42-3.41, P = .0054 SNI + Ex versus SNI in Western blot). C3 deficiency reduced SNI-induced pain and spinal astrocyte reactivity (wild type mean = 7.96, 95% CI, 6.80-9.13; C3 KO mean = 5.98, 95% CI, 5.14-6.82, P = .0052 C3 KO versus wild type). Intrathecal injection of recombinant C3 (rC3) was sufficient to produce mechanical (rC3-Ex mean = 0.77, 95% CI, 0.15-1.39; rC3 mean = 0.18, 95% CI, -0.04 to 0.41, P = .0168 rC3-Ex versus rC3) and cold (rC3-Ex mean = 1.08, 95% CI, 0.40-1.77; rC3 mean = 3.46, 95% CI, 1.45-5.47, P = .0025 rC3-Ex versus rC3) allodynia in mice. Importantly, exercise training relieved C3-induced mechanical and cold allodynia, and the analgesic effect of exercise was attenuated by a subeffective dose of intrathecal injection of C3. CONCLUSIONS: Overall, these results suggest that exercise suppresses neuropathic pain by regulating astroglial C3 expression and function, thereby providing a rationale for the analgesic effect of exercise as an acceptable alternative approach for treating neuropathic pain.

Enhanced Treatment Options for Dural Arteriovenous Fistulas at the Craniocervical Junction: Endovascular Embolization Versus Microsurgery? A Single-Center 23-Year Experience.

OBJECTIVE: The occurrence of dural arteriovenous fistulas (DAVFs) at the craniocervical junction (CCJ) is an uncommon vascular malformation. The diagnosis and treatment of CCJ DAVFs present a formidable challenge. This study aims to investigate the effect of endovascular embolization and microsurgery on improving patient prognosis. METHODS: This retrospective study included patients diagnosed with CCJ DAVFs who received treatment at the First Affiliated Hospital of Fujian Medical University between January 2000 and January 2023. The clinical records, imaging data, and treatment methods were obtained from the hospital's medical record system. The patients were classified into microsurgery and embolization groups based on the surgical technique employed for treatment. The primary outcome measures were surgical-associated neurological dysfunction (SAND) and long-term neurological outcomes. The Cox proportional hazard regression was utilized to determine hazard ratios and 95% confidence intervals (CI) to assess the relationship between treatment methods and prognosis. Kaplan-Meier survival analysis was employed to evaluate the incidence of SAND in both cohorts. RESULTS: This study recruited 46 patients with an average age of 53.72 ± 13.83 years. In the microsurgery group, there were 12 cases (26.1%) observed. While in the embolization group, there were 34 cases (73.9%). Of these patients, 16 (34.8%) experienced SAND after treatment. In the microsurgery group, there were 8 cases (75.0%), while in the embolization group, only 8 cases (23.5%) were reported. Specifically, the embolization group exhibited a significantly lower risk of SAND [adjusted hazard ratio = 0.259, 95% CI = 0.096-0.700; P = 0.008)] compared to the microsurgery group. Additionally, the combined Borden grade 2-3 was found to be significantly associated with SAND (adjusted hazard ratio = 3.150, 95% CI = 1.132-8.766; P = 0.028). The results of the Kaplan-Meier survival analysis indicated a statistically significant difference in the occurrence of favorable functional outcomes between the 2 groups (log-rank P = 0.0081). CONCLUSIONS: CCJ DAVFs are uncommon disorders characterized by a diverse range of clinical manifestations. The functional prognosis of endovascular treatment may be superior to microsurgery.

Amino acids and their roles in tumor immunotherapy of breast cancer.

Breast cancer is the most commonly diagnosed cancer among women. The primary treatment options include surgery, radiotherapy, chemotherapy, targeted therapy and hormone therapy. The effectiveness of breast cancer therapy varies depending on the stage and aggressiveness of the cancer, as well as individual factors. Advances in early detection and improved treatments have significantly increased survival rates for breast cancer patients. Nevertheless, specific subtypes of breast cancer, particularly triple-negative breast cancer, still lack effective treatment strategies. Thus, novel and effective therapeutic targets for breast cancer need to be explored. As substrates of protein synthesis, amino acids are important sources of energy and nutrition, only secondly to glucose. The rich supply of amino acids enables the tumor to maintain its proliferative competence through participation in energy generation, nucleoside synthesis and maintenance of cellular redox balance. Amino acids also play an important role in immune-suppressive microenvironment formation. Thus, the biological effects of amino acids may change unexpectedly in tumor-specific or oncogene-dependent manners. In recent years, there has been significant progress in the study of amino acid metabolism, particularly in their potential application as therapeutic targets in breast cancer. In this review, we provide an update on amino acid metabolism and discuss the therapeutic implications of amino acids in breast cancer.

Curcumin-loaded oil body emulsions prepared by an ultrasonic and pH-driven method: Fundamental properties, stability, and digestion characteristics.

In this study, oil bodies (OBs) loaded with curcumin (Cur) were successfully prepared via an ultrasonic and pH-driven method. Ultrasonic treatment significantly improved the encapsulation efficiency (EE) and loading capacity (LC) of Cur, producing OB particles with small size, uniform distribution, and high ζ-potential absolute values. When the ultrasonic power was 200 W, the EE, LC, and ζ-potential absolute value were the greatest (88.27 %, 0.044 %, and -25.71 mV, respectively), and the OBs possessed the highest yellowness, representing the best treatment result. The confocal laser scanning microscopy (CLSM) and cryo-scanning electron microscopy (cryo-SEM) results was also intuitionally shown that. Moreover, circular dichroism (CD) proved that ultrasonic treatment could unfold the surface protein structure, further enhancing the stability. Therefore, the cream index (CI), peroxide value (POV), and thiobarbituric acid reactive substances (TBARS) were the lowest when the ultrasonic power was 200 W. In this case, the Cur loaded in OBs was well protected against hostile conditions, evidenced by the highest Cur retention rate and the lowest degradation rate constant. Finally, the in vitro gastrointestinal digestion simulation results showed that the ultrasonic treatment effectively increased the release of FFA, bioaccessibility, and stability of Cur, especially when the ultrasonic power was 200 W. This research offers a new OB-based delivery system to stabilize, deliver, and protect Cur for food processing.

Comprehensive Analysis of Regulated Cell Death in Intracranial Aneurysms.

BACKGROUND: Abnormalities in regulated cell death (RCD) are involved in multiple diseases. However, the role of RCD in intracranial aneurysms (IA) remains unknown. The aim of this study was to explore different RCD processes in the pathogenesis of IA. METHODS: Four microarray datasets (GSE75436, GSE54083, GSE13353, GSE15629) and one RNA sequencing (RNA-seq) dataset (GSE122897) were extracted from the Gene Expression Omnibus (GEO) database. The microarray datasets were merged to form the training set, while the RNA-seq dataset was used as the validation set. Differentially expressed genes (DEGs), gene set enrichment analysis (GSEA), and gene set variation analysis (GSVA) were used to investigate the role of different types of RCD, including apoptosis, necroptosis, autophagy, ferroptosis and pyroptosis in the formation of IA. A novel cell death classification system for IA was established using an unsupervised consensus clustering algorithm based on cell death signature genes. Differences in functional enrichment, cell death-related regulators, and immune infiltration between two cell death clusters were evaluated. Finally, predictive genes were identified using the least absolute shrinkage and selection operator (LASSO) regression, random forest and logistic regression, allowing a prediction model to be constructed for IA rupture. RESULTS: Multiple RCD processes were significantly activated in IAs compared to controls. A total of 33 signature genes related to cell death were identified. The IA samples were divided into two clusters based on the cell death signature. The cell death-high subtype had a relatively higher rate of rupture, and higher enrichment levels for multiple cell death processes and several signal transduction and immune-related pathways. Immune infiltration analysis showed that cell death scores were correlated with multiple immune cell types, including macrophages, mast cells, T cells and B cells. A six-gene prediction model was constructed to predict rupture. The area under curves (AUCs) for predicting rupture in the training and validation cohorts were 0.924 and 0.855, respectively. CONCLUSIONS: Comprehensively analysis of RCD in IA and found that multiple RCD types are likely to be involved in IA formation and rupture. These cell death processes were correlated with inflammation and immunity. We present novel insights into the mechanism of IA pathogenesis that should help to guide further research.

Xanthotoxol relieves itch in mice via suppressing spinal GRP/GRPR signaling.

Although pruritus, commonly known as itch, is a common and debilitating symptom associated with various skin conditions, there is a lack of effective therapies available. Xanthotoxol (XAN), a biologically active linear furocoumarin, shows potential in the treatment of various neurological disorders. In this study, we discovered that administering XAN either through intraperitoneal or intrathecal injections effectively reduced scratching behavior induced by compound 48/80 or chloroquine. Importantly, XAN also substantially alleviates chronic itch in dry skin and allergic contact dermatitis mice. Substantial progress has highlighted the crucial role of gastrin-releasing peptide (GRP)-gastrin-releasing peptide receptor (GRPR) signaling in the dorsal spinal cord in transmitting various types of itch. Our behavior tests revealed that XAN significantly alleviated scratching behaviors induced by intrathecal administration of GRP or GRPR agonist bombesin. Furthermore, XAN reduced the activation of neurons in the spinal cord caused by intrathecal administration of GRP in mice. Moreover, XAN attenuates the activation of spinal GRPR-positive neurons in itchy mice. These findings suggest that XAN mitigates itch in mice by suppressing spinal GRP/GRPR signaling, thereby establishing XAN as a promising therapeutic option for treating pruritus.

The removal of three kinds of occlusal veneers by Er: Yag laser.

OBJECTIVES: This study aimed to remove occlusal veneers of varied thicknesses and compositions by Er:Yag laser in vitro and analyze the interfacial microstructure between veneers and tooth that irradiated by laser, by which experimental evidence could be provided to support the non-invasive removal of occlusal veneerby laser. METHODS: Fresh mandibular premolars extracted for orthodontic requirements were collected for tooth preparation. Three kinds of ceramic materials (Vita Suprinity, Vita Mark Ⅱ, and Upcera Hyramic) were selected to fabricate occlusal veneer with different thicknesses (1.0, 1.5, and 2.0 mm). One week later, Er:Yag laser (2.5 W and 3.5 W) was used to irradiate and remove the occlusal veneer and recorded the timespan. After the removal operation, the micro-morphologies of samples were examined by scanning electron microscope. RESULTS: Upcera Hyramic veneer failed to be removed (>20 min); the operation span at 2.5 W, Vita Suprinity (96.0 s±16.0 s) was longer than Vita MarkⅡ(84.5 s±19.5 s) in the 1.0 mm group (P<0.05), and Vita Suprinity (246.5 s±13.5 s) was longer than Vita MarkⅡ(170.0 s±14.0 s) in the 1.5 mm group (P<0.05). At 3.5 W, Vita Suprinity (381.0 s±24.0 s) was longer than Vita MarkⅡ(341.5 s±26.5 s) in the 2.0 mm group. CONCLUSIONS: Increasing laser power could shorten the operation span and facilitate the removal of occlusal veneers with the same thickness and composition. The occlusal veneer was sustained when insufficient laser power was applied. With the same laser power and ceramic thickness, laser penetration could interfere with the integral of the ceramic structure when the laser interacted with the bonding layer. With the same ceramic composition and laser power, the operation span and laser power increased with the thickness of the occlusal veneer. However, the laser was incapable of removing occlusal resin veneer directly.

Impact of redox fluctuations on microbe-mediated elemental sulfur disproportionation and coupled redox cycling of iron.

Elemental sulfur (S0) plays a vital role in the coupled cycling of sulfur and iron, which in turn affects the transformation of carbon and various pollutants. These processes have been well characterized under static anoxic or oxic conditions, however, how the natural redox fluctuations affect the bio-mediated sulfur cycling and coupled iron cycling remain enigmatic. The present work examined S0 disproportionation as driven by natural microbial communities under fluctuating redox conditions and the contribution of S0 disproportionation to ferrihydrite transformation. Samples were incubated at either neutral or alkaline pH values, applying sequential anaerobic, aerobic and anaerobic conditions over 60 days. Under anaerobic conditions, S0 was found to undergo disproportionation to sulfate and sulfide, which subsequently reduced ferrihydrite at both pH 7.4 and 9.5. Ferrihydrite promoted S0 disproportionation by scavenging biogenic sulfide and maintaining a suitable degree of sulfate formation. After an oxic period, during the subsequent anoxic incubation, bioreduction of sulfate occurred and the biogenic sulfide reduced iron (hydr)oxides at a rate approximately 25 % lower than that observed during the former anoxic period. A 16S rDNA-based microbial community analysis revealed changes in the microbial community in response to the redox fluctuations, implying an intimate association with the coupled cycling of sulfur and iron. Microscopic and spectroscopic analyses confirmed the S0-mediated transformation of ferrihydrite to crystalline iron (hydr)oxide minerals such as lepidocrocite and magnetite and the formation of iron sulfides precipitated under fluctuating redox conditions. Finally, a reaction mechanism based on mass balance was proposed, demonstrating that bio-mediated sulfur transformation maintained a sustainable redox reaction with iron (hydr)oxides under fluctuating anaerobic-aerobic-anaerobic conditions tested in this study. Altogether, the finding of our study is critical for obtaining a more complete understanding of the dynamics of iron redox reactions and pollutant transformation in sulfur-rich aquatic environments.

Molecular Recognition Mechanism of an Anti-Amatoxins mAb and Its Application in Centrifugal Disk-Based Immunoassay.

Amatoxins are polypeptides that cause 90% of fatalities from accidental ingestion of poisonous mushrooms. Unfortunately, there are no specific antidotes against amatoxins poisoning, hence preparation of high-affinity antibodies, understanding the receptor (amatoxins) and ligand (antibody) mechanism, and establishing a straightforward screening approach are of great significance for confirming poison agents and clinical diagnosis. Here, anti-amatoxins monoclonal antibody (mAb) 9B2 was prepared and the recognition mechanism was investigated. The approach is useful for designing desirable immunogens, developing new antibodies with improved performance, and constructing effective immunoassays. Based on the mAb, we designed a centrifugal disk-like microfluidics chip and developed a fully automated immunoassay capable of detecting amatoxins poisoning in various samples including serum, urine, and mushrooms. The whole detection process could be automatically accomplished within 30 min, with a limit of detection of 0.08 to 0.12 µg/L for real samples, ∼30-fold more sensitive than conventional enzyme-linked immunosorbent assay (ELISA). Our platform not only provided a practical approach for performing poison agent confirmation and clinical diagnosis but also had important implications for improving the survival of patients with mushroom poisoning.

Antipruritic effects of geraniol on acute and chronic itch via modulating spinal GABA/GRPR signaling.

BACKGROUND AND PURPOSE: Itch (pruritus) is a common unpleasant feeling, often accompanied by the urge of scratching the skin. It is the main symptom of many systemic and skin diseases, which can seriously affect the patient's quality of life. Geraniol (GE; trans-3,7-dimethyl-2,6-octadien-1-ol) is a natural monoterpene with diverse effects, including anti-inflammatory, antioxidant, neuroprotective, anti-nociceptive, and anticancer properties. The study aims to examine the effects of GE on acute and chronic itch, and explore the underlying mechanisms. METHODS: Acute itch was investigated by using Chloroquine and compound 48/80 induced model, followed by manifestation of diphenylcyclopropenone (DCP)-induced allergic contact dermatitis and the acetone-ether-water (AEW)-induced dry skin model in mice. The scratching behavior, skin thickness, c-Fos expression, and GRPR protein expression in the spinal cord were subsequently monitored and evaluated by behavioral tests as well as pharmacological and pharmacogenetic technologies. RESULTS: Dose-dependent intraperitoneal injection of GE alleviated the acute itch, induced by chloroquine and compound 48/80, as well as increased the spinal c-Fos expression. Intrathecal administration of GE suppressed the GABAA receptor inhibitor bicuculline-induced itch, GRP-induced itch, and the GABAergic neuron inhibition-induced itch. Furthermore, the subeffective dose of bicuculline blocked the anti-pruritic effect of GE on the chloroquine and compound 48/80 induced acute itch. GE also attenuated DCP and AEW-induced chronic itch, as well as the increase of spinal GRPR expression in DCP mice. CONCLUSION AND IMPLICATIONS: GE alleviates both acute and chronic itch via modulating the spinal GABA/GRPR signaling in mice. Findings of this study reveal that GE may provide promising therapeutic options for itch management. Also, considering the pivotal role of essential oils in aromatherapy, GE has great application potential in aromatherapy for treating skin diseases, and especially the skin with severe pruritus.

Effect of RNAi-Mediated Survivin and Hypoxia-Inducible Factor 1α Gene Silencing on Proliferation, Invasion, Migration and Apoptosis of Gastric Cancer BGC-823 Cells.

In order to investigate the effects of RNAi-mediated survivin and hypoxia-inducible factor 1α (HIF-1α) gene silencing on the proliferation and apoptosis of gastric cancer BGC-823 cells, small interfering RNAs (siRNAs) targeting survivin and HIF-1α mRNAs, respectively, as well as scrambled siRNAs (SCRs) were designed and synthesized, namely siRNA-survivin group, siRNA-HIF-1α group, and SCR group. The hypoxia-sensitive gastric cancer BGC-823 cells were identified and transfected in vitro with Hifectin II under hypoxic conditions, and the expression of survivin and HIF-1α was assessed by RT-PCR and Western blotting assays, respectively. The ability of apoptosis, proliferation, invasion, and migration was measured, and the results showed that HIF-1α expression was significantly increased in BGC-823 cells under hypoxic conditions, and survival-targeted siRNA transfection decreased the expression of survivin under hypoxic conditions, while co-transfection of survivin-targeted siRNA and HIF-1α-targeted siRNA down-regulated both survivin and HIF-1α expression. Compared with the blank control group, the co-transfected siRNA group exhibited distinct characteristics, with decreased invasion and migration ability, increased apoptosis, and significantly decreased cell proliferation under hypoxic conditions. It was confirmed that the downregulation of survivin and HIF-1α in BGC-823 cells may induce anticancer effects by enhancing apoptosis and decreasing proliferation, migration, and invasion ability. The novelty lies in the application of RNAi technology to silence the expression of both survivin and HIF-1α genes in gastric cancer BGC-823 cells by single and combined interference in an established gastric cancer cell model and observed the mechanism of its effect on the proliferation and apoptosis of gastric cancer cells. Concerning the success of this highly active antiretroviral therapy of gene disruption therapies, which is the first of its kind in the world, we wonder whether we can find other better gene targets for more kinds of tumor therapy.

Neutrophils in triple-negative breast cancer: an underestimated player with increasingly recognized importance.

Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer, with limited therapeutic options readily available. Immunotherapy such as immune checkpoint inhibition has been investigated in TNBC but still encounters low overall response. Neutrophils, the most abundant leukocytes in the body, are increasingly recognized as an active cancer-modulating entity. In the bloodstream, neutrophils escort circulating tumor cells to promote their survival and stimulate their proliferation and metastasis. In the tumor microenvironment, neutrophils modulate the immune milieu through polarization between the anti-tumor and the pro-tumor phenotypes. Through a comprehensive review of recently published literature, it is evident that neutrophils are an important player in TNBC immunobiology and can be used as an important prognostic marker of TNBC. Particularly, in their pro-tumor form, neutrophils facilitate TNBC metastasis through formation of neutrophil extracellular traps and the pre-metastatic niche. These findings will help advance the potential utilization of neutrophils as a therapeutic target in TNBC.

Effect of Anthropogenic Disturbances on the Microbial Relationship during Bioremediation of Heavy Metal-Contaminated Sediment.

Soil, sediment, and waters contaminated with heavy metals pose a serious threat to ecosystem function and human health, and microorganisms are an effective way to address this problem. In this work, sediments containing heavy metals (Cu, Pb, Zn, Mn, Cd, As) were treated differently (sterilized and unsterilized) and bio-enhanced leaching experiments were carried out with the addition of exogenous iron-oxidizing bacteria A. ferrooxidans and sulfur-oxidizing bacteria A. thiooxidans. The leaching of As, Cd, Cu, and Zn was higher in the unsterilized sediment at the beginning 10 days, while heavy metals leached more optimally in the later sterilized sediment. The leaching of Cd from sterilized sediments was favored by A. ferrooxidans compared to A. thiooxidans. Meanwhile, the microbial community structure was analyzed using 16S rRNA gene sequencing, which revealed that 53.4% of the bacteria were Proteobacteria, 26.22% were Bacteroidetes, 5.04% were Firmicutes, 4.67% were Chlamydomonas, and 4.08% were Acidobacteria. DCA analysis indicated that microorganisms abundance (diversity and Chao values) increased with time. Furthermore, network analysis showed that complex networks of interactions existed in the sediments. After adapting to the acidic environmental conditions, the growth of some locally dominant bacteria increased the microbial interactions, allowing more bacteria to participate in the network, making their connections stronger. This evidence points to a disruption in the microbial community structure and its diversity following artificial disturbance, which then develops again over time. These results could contribute to the understanding of the evolution of microbial communities in the ecosystem during the remediation of anthropogenically disturbed heavy metals.

Case Report: Upper Thoracic Esophageal Paralysis Accompanying a Type 1 Leprosy Reaction.

Type 1 leprosy reactions (T1LRs) occur mainly in patients with borderline leprosy and an unstable immune status. The main symptoms of T1LRs include aggravated skin lesions and nerve damage. Nerve damage involving the glossopharyngeal and vagus nerves causes dysfunction of the nose, pharynx, larynx, and even the esophagus, which are innervated by these nerves. Here, we report a case of upper thoracic esophageal paralysis caused by vagus nerve involvement in a patient with T1LRs. Although infrequent, this serious emergency merits attention.

Comprehensively analyzing the genetic alterations, and identifying key genes in ovarian cancer.

Though significant improvements have been made in the treatment methods for ovarian cancer (OC), the prognosis for OC patients is still poor. Exploring hub genes associated with the development of OC and utilizing them as appropriate potential biomarkers or therapeutic targets is highly valuable. In this study, the differentially expressed genes (DEGs) were identified from an independent GSE69428 Gene Expression Omnibus (GEO) dataset between OC and control samples. The DEGs were processed to construct the protein-protein interaction (PPI) network using STRING. Later, hub genes were identified through Cytohubba analysis of the Cytoscape. Expression and survival profiling of the hub genes were validated using GEPIA, OncoDB, and GENT2. For exploring promoter methylation levels and genetic alterations in hub genes, MEXPRESS and cBioPortal were utilized, respectively. Moreover, DAVID, HPA, TIMER, CancerSEA, ENCORI, DrugBank, and GSCAlite were used for gene enrichment analysis, subcellular localization analysis, immune cell infiltration analysis, exploring correlations between hub genes and different diverse states, lncRNA-miRNA-mRNA co-regulatory network analysis, predicting hub gene-associated drugs, and conducting drug sensitivity analysis, respectively. In total, 8947 DEGs were found between OC and normal samples in GSE69428. After STRING and Cytohubba analysis, 4 hub genes including TTK (TTK Protein Kinase), (BUB1 mitotic checkpoint serine/threonine kinase B) BUB1B, (Nucleolar and spindle-associated protein 1) NUSAP1, and (ZW10 interacting kinetochore protein) ZWINT were selected as the hub genes. Further, it was validated that these 4 hub genes were significantly up-regulated in OC samples compared to normal controls, but overexpression of these genes was not associated with overall survival (OS). However, genetic alterations in those genes were found to be linked with OS and disease-free (DFS) survival. Moreover, this study also revealed some novel links between TTK, BUB1B, NUSAP1, and ZWINT overexpression and promoter methylation status, immune cell infiltration, miRNAs, gene enrichment terms, and various chemotherapeutic drugs. Four hub genes, including TTK, BUB1B, NUSAP1, and ZWINT, were revealed as tumor-promotive factors in OC, having the potential to be utilized as novel biomarkers and therapeutic targets for OC management.

LincRNA-p21 Promotes Cellular Senescence by Down-regulating the Wnt/ß-catenin Pathway in MPP+-treated SH-SY5Y Cells.

AIM AND OBJECTIVE: Long intergenic non-coding RNA-p21 (lincRNA-p21) plays a critical role in various senescence-associated physiological and pathological conditions. We aimed to explore the senescence-associated effects of lincRNA-p21 in 1-methyl-4-phenylpyridinium (MPP+) treated neuroblastoma SH-SY5Y cell line as a therapeutic target. MATERIALS AND METHODS: The RNA expression levels of lincRNA-p21, p53, p16, and telomere length were examined with reverse transcription-quantitative polymerase chain reaction (RTqPCR). The Telo TAGGG™ Telomerase PCR ELISA PLUS Kit was used to determine telomerase activity. Cellular viability was evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) assay. Western blot was performed to analyze ß-catenin protein expression. Besides, oxidative stress was evaluated by Jaggregate- forming delocalized lipophilic cation, 5,5',6,6'-tetrachloro-1,1',3,3'- tetraethylbenzimidazolocarbocyanine++ + iodide (JC­1) stain, fluorescence spectrophotometry, colorimetric assay, and malondialdehyde (MDA) formation. RESULTS: This research demonstrated that MPP+ caused a distinct increase in the expression of LincRNA- p21 in SH-SY5Y cells. MPP+ induced cellular senescence with decreasing cellular proliferation and viability, increasing expression levels of senescence-associated makers such as genes p53 and p16, accompanied by significantly decreasing telomere length and telomerase activity. At the same time, these effects were abolished by silencing lincRNA-p21 with small interfering RNA (siRNA). On the contrary, ß-catenin silencing contributes to reversing anti-senescent effects caused by lincRNA-p21 silencing. Moreover, modifying lincRNA-p21 exerted an anti-senescent influence depending on decreasing oxidant stress. CONCLUSION: Our study showed that in the treatment of MPP+, lincRNA-p21 might serve a role in the SH-SY5Y cell senescence by modulating the Wnt/ß-catenin pathway, as well as increasing oxidant stress. Thus, trying to target lincRNA-p21 may have important therapeutic and practical implications for PD.

Photoaging processes of polyvinyl chloride microplastics enhance the adsorption of tetracycline and facilitate the formation of antibiotic resistance.

Microplastics (MPs), antibiotics and microorganism ubiquitously coexist in aquatic environments. MPs inevitably undergo photoaging processes in aquatic environments, affecting the interactions between MPs and antibiotics and the antibiotic resistance of microorganism. In this study, the impact of photoaging processes of MPs on their adsorption behavior of tetracycline (TC) and related formation of antibiotic resistance were investigated. It was found that the photoaging processes significantly increased the adsorption capacity of TC onto MPs, with the Qe increasing from 0.387 to 0.507 mg/g at 288 K and from 0.507 to 0.688 mg/g at 308 K. The site energy distribution (SED) analysis further confirmed that the enhanced adsorption capacity was attributed to more high-energy adsorption sites acquired from MPs photoaging processes. Moreover, the enhanced adsorption of TC further facilitated the formation of seven antibiotic resistance genes (i.e., tetA, tetB, tetC, tetD, tetE, tetG, tetK) when MPs adsorbed with TC was covered by biofilm. This study helps comprehensively understand the environmental behaviors of co-existing MPs, antibiotics and microorganisms, providing a theoretical basis for evaluating and mitigating their coexistence risks.

Natural mineral-derived Fe/Mn-BC as efficient peroxydisulfate activator for 2,4-dichlorophenol removal from wastewater: Performance and sustainable catalytic mechanism.

Iron and manganese oxides/biochar composite materials (Fe/Mn-BC) are promising catalysts in the field of advanced oxidation. High purity chemical reagents are popular precursors for preparing Fe/Mn-BC, while the potential of low-cost natural minerals as precursors has been neglected. In this study, high-efficiency Fe/Mn-BC was synthesized by one-step pyrolysis method using hematite, phosphoromanganese, and bagasse. The synthesized Fe/Mn-BC removed 83.7% 2, 4-dichlorophenol (2, 4-DCP) within 30 min, about 8.8 and 10.6 times better than biochar (BC) and Fe/Mn complex, respectively. The removal of 2, 4-DCP in the Fe/Mn-BC + peroxydisulfate (PDS) system was influenced by catalyst dosage, PDS concentration, initial pH, organic acids, and chromium. Sulfate radical (SO4•-) and hydroxyl radicals (•OH) generated by Fe/Mn-BC-activated PDS have similar contribution to the degradation of 2,4-DCP. A possible removal mechanism of 2, 4-DCP in the Fe/Mn-BC + PDS system was proposed based on Electron Spin Resonance spectroscopy, free radical quenching experiments, X-ray photoelectron spectroscopy, X-ray diffraction, and electrochemical measurement. Fe0 and Fe(II) in Fe/Mn-BC play significant role in catalytic degradation of 2, 4-DCP at the early stage of the reaction (within 0-5 min). Then, the interaction between Mn and BC or structural Mn and structural Fe gradually became dominant in the later stage. Similarly, the electron transfer promoted by biochar also played an important role in this catalysis. This discovery provided a new strategy for developing iron and manganese oxides/biochar composite materials to activate PDS for the elimination of refractory organic pollutants.