Azotosporobacter soli gen. nov., sp. nov., a novel nitrogen-fixing bacterium isolated from paddy soil.

A nitrogen-fixing strain designated SG130T was isolated from paddy soil in Fujian Province, China. Strain SG130T was Gram-staining-negative, rod-shaped, and strictly anaerobic. Strain SG130T showed the highest 16S rRNA gene sequence similarities with the type strains Dendrosporobacter quercicolus DSM 1736T (91.7%), Anaeroarcus burkinensis DSM 6283T (91.0%) and Anaerospora hongkongensis HKU 15T (90.9%). Furthermore, the phylogenetic and phylogenomic analysis also suggested strain SG130T clustered with members of the family Sporomusaceae and was distinguished from other genera within this family. Growth of strain SG130T was observed at 25-45 °C (optimum 30 °C), pH 6.0-9.5 (optimum 7.0) and 0-1% (w/v) NaCl (optimum 0.1%). The quinones were Q-8 and Q-9. The polar lipids were phosphatidylserine (PS), phosphatidylethanolamine (PE), glycolipid (GL), phospholipid (PL) and an unidentified lipid (UL). The major fatty acids (> 10%) were iso-C13:0 3OH (26.6%), iso-C17:1 (15.6%) and iso-C15:1 F (11.4%). The genomic DNA G + C content was 50.7%. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain SG130T and the most closely related type strain D. quercicolus DSM 1736T (ANI 68.0% and dDDH 20.3%) were both below the cut-off level for species delineation. The average amino acid identity (AAI) between strain SG130T and the most closely related type strain D. quercicolus DSM 1736T was 63.2%, which was below the cut-off value for bacterial genus delineation (65%). Strain SG130T possessed core genes (nifHDK) involved in nitrogen fixation, and nitrogenase activity (106.38 µmol C2H4 g-1 protein h-1) was examined using the acetylene reduction assay. Based on the above results, strain SG130T is confirmed to represent a novel genus of the family Sporomusaceae, for which the name Azotosporobacter soli gen. nov., sp. nov. is proposed. The type strain is SG130T (= GDMCC 1.3312T = JCM 35641T).

Comparative proteomics analysis of samples from hepatic cystic echinococcosis patients using data-independent acquisition approach.

Cystic echinococcosis is a zoonotic disease resulting from infection caused by the larval stage of Echinococcus granulosus. This study aimed to assess the specific proteins that are potential candidates for the development of a vaccine against E. granulosus. The data-independent acquisition approach was employed to identify differentially expressed proteins (DEPs) in E. granulosus samples. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was employed to identify several noteworthy proteins. Results: The DEPs in E. granulosus samples were identified (245 pericystic wall vs. parasite-free yellowish granuloma (PYG, 1725 PY vs. PYG, 2274 PN vs. PYG). Further examination of these distinct proteins revealed their predominant enrichment in metabolic pathways, amyotrophic lateral sclerosis, and neurodegeneration-associated pathways. Notably, among these DEPs, SH3BGRL, MST1, TAGLN2, FABP5, UBE2V2, and RARRES2 exhibited significantly higher expression levels in the PYG group compared with the PY group (P < 0.05). The findings may contribute to the understanding of the pathological mechanisms underlying echinococcosis, providing valuable insights into the development of more effective diagnostic tools, treatment modalities, and preventive strategies. SIGNIFICANCE: CE is a major public health hazard in the western regions of China, Central Asia, South America, the Mediterranean countries, and eastern Africa. Echinococcus granulosus is responsible for zoonotic disease through infection Our analysis focuses on the proteins in various samples by data-dependent acquisition (DIA) for proteomic analysis. The importance of this research is to develop new strategies and targets to protect against E. granulosus infections in humans.

Integration of single-nucleus and exosome RNA sequencing dissected inter-cellular communication and biomarkers in pancreatic ductal adenocarcinoma.

Background: Mounting evidence underscores the importance of cell communication within the tumor microenvironment, which is pivotal in tumor proliferation, invasion, and metastasis. Exosomes play a crucial role in cell-to-cell communication. Although single-cell RNA sequencing (scRNA-seq) provides insights into individual cell transcriptional characteristics, it falls short of comprehensively capturing exosome-mediated intercellular communication. Method: We analyzed Pancreatic Ductal Adenocarcinoma (PDAC) tissues, separating supernatant and precipitate for exosome purification and single-cell nucleus suspension. We then constructed Single-nucleus RNA sequencing (snRNA-seq) and small RNA-seq libraries from these components. Our bioinformatic analysis integrated these sequences with ligand-receptor analysis and public miRNA data to map the cell communication network. Results: We established intercellular communication networks using bioinformatic analysis to track exosome miRNA effects and ligand-receptor pairs. Significantly, hsa-miR-1293 emerged as a prognostic biomarker for pancreatic cancer, linked to immune evasion, increased myeloid-derived suppressor cells, and poorer prognosis. Targeting this miRNA may enhance anti-tumor immunity and improve outcomes. Conclusion: Our study offers a novel approach to constructing intercellular communication networks using snRNA-seq and exosome-small RNA sequencing. By integrating miRNA tracing with ligand-receptor analysis, we illuminate the complex interactions in the pancreatic cancer microenvironment, highlighting the pivotal role of miRNAs and identifying potential biomarkers and therapeutic targets.

Two novel Fe(III)-reducing bacteria, Geothrix campi sp. nov. and Geothrix mesophila sp. nov., isolated from paddy soils.

In this research, two novel Fe(III)-reducing bacteria, SG10T and SG198T of genus Geothrix, were isolated from the rice field of Fujian Agriculture and Forestry University in Fuzhou, Fujian Province, China. Strains SG10T and SG198T were strictly anaerobic, rod-shaped and Gram-stain-negative. The two novel strains exhibited iron reduction ability, utilizing various single organic acid as the elector donor and Fe(III) as a terminal electron acceptor. Strains SG10T and SG198T showed the highest 16S rRNA sequences similarities to the type strains of Geothrix oryzisoli SG189T (99.0-99.5%) and Geothrix paludis SG195T (99.0-99.7%), respectively. The phylogenetic trees based on the 16S rRNA gene and genome 120 conserved core genes showed that strains SG10T and SG198T belong to the genus Geothrix. Average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between the phylogenetic neighbors and the two isolated strains were 86.1-94.3% and 30.7-59.5%, respectively. The major fatty acids were iso-C15:0, anteiso-C15:0, C16:0 and iso-C13:0 3OH, and MK-8 was the main respiratory quinone. According to above results, the two strains were assigned to the genus Geothrix with the names Geothrix campi sp. nov. and Geothrix mesophila sp. nov. Type strains are SG10T (= GDMCC 1.3406 T = JCM 39331 T) and SG198T (= GDMCC 62910 T = KCTC 25635 T), respectively.

The diagnosis of acute interstitial nephritis caused by infection versus antibiotic-induced interstitial nephritis: a narrative review.

Acute interstitial nephritis (AIN) is a significant contributor to acute kidney injury and can be attributed to a variety of factors, including but not limited to allergens or drugs, infections, autoimmune or systemic diseases, and idiopathic forms of the disease. In some cases, AIN requires a therapeutic action according to a single specific etiology by handling the offending agent and applying an immunosuppressant. Although AIN can be diagnosed through renal biopsy, it is not able to pinpoint the precise cause when multiple causes are suspected to be present simultaneously. Such situations arise when a patient suffering from infection develops AIN during antibiotic therapy, the exact causative factor of which becomes a challenge for the clinicians to determine. This is attributed to the different approaches employed in different etiologies, wherein clinicians are required to maintain the current antibiotic therapy or augment the dose in cases of infection as AIN etiology, without resorting to immunosuppressant therapy as the primary objective is infection killing. In contrast, antibiotics as an etiology for AIN require an alternative drug from the antibiotics group, along with an immunosuppressant. In the interim, delaying the identification of the precise cause may result in interstitial fibrosis and chronic kidney disease. This narrative review highlights certain findings that can be typical of infection-associated ATIN compared with antibiotic-associated ATIN based on clinical history and physical examination, clinical presentation of different antibiotic drug classes, histopathological features, classical and novel biomarkers, serum and urine cytokines and chemokines, cellular biomarkers, and genetic biomarkers. Although these findings cannot provide conclusive and clear recommendations that can be useful in the clinical practice, they can entice researchers to conduct original research on these features to discover clear recommendations.

Adjuvant Transarterial Chemoembolization With Sorafenib for Portal Vein Tumor Thrombus: A Randomized Clinical Trial.

Importance: Certain patients with hepatocellular carcinoma with portal vein tumor thrombus could benefit from surgical resection, and postoperative adjuvant therapy may lower the incidence of tumor recurrence. Objective: To compare the efficacy and safety of sorafenib plus transarterial chemoembolization vs sorafenib alone as postoperative adjuvant therapy for patients with hepatocellular carcinoma with portal vein tumor thrombus. Design, Setting, and Participants: This was a phase 3, multicenter, randomized clinical trial conducted in 5 hospitals in China. A total of 158 patients were enrolled and randomized from October 2019 to March 2022, with a median follow-up of 28.4 months. Portal vein tumor thrombus was graded by the Cheng classification. Eligible patients with hepatocellular carcinoma with Cheng grade I to III portal vein tumor thrombus (ie, involving segmental or sectoral branches, right- or left-side branch, or main trunk of portal vein) were included. Interventions: Patients were randomly assigned 1:1 to receive transarterial chemoembolization with sorafenib or sorafenib alone as postoperative adjuvant therapy. Sorafenib treatment was started within 3 days after randomization, with an initial dose of 400 mg orally twice a day. In the transarterial chemoembolization with sorafenib group, transarterial chemoembolization was performed 1 day after the first administration of sorafenib. Main Outcomes and Measures: The primary end point was recurrence-free survival. Efficacy was assessed in the intention-to-treat population and safety was assessed in patients who received at least 1 dose of study treatment. Results: Of 158 patients included, the median (IQR) age was 54 (43-61) years, and 140 (88.6%) patients were male. The median (IQR) recurrence-free survival was significantly longer in the transarterial chemoembolization with sorafenib group (16.8 [12.0-NA] vs 12.6 [7.8-18.1] months; hazard ratio [HR], 0.57; 95% CI, 0.39-0.83; P = .002). The median (IQR) overall survival was also significantly longer with transarterial chemoembolization with sorafenib than with sorafenib alone (30.4 [20.6-NA] vs 22.5 [15.4-NA] months; HR, 0.57; 95% CI, 0.36-0.91; P = .02). The most common grade 3/4 adverse event was hand-foot syndrome (23 of 79 patients in the transarterial chemoembolization with sorafenib group [29.1%] vs 24 of 79 patients in the sorafenib alone group [30.4%]). There were no treatment-related deaths in either group. The transarterial chemoembolization with sorafenib group did not show additional toxicity compared with the sorafenib monotherapy group. Conclusion and Relevance: In this study, the combination of sorafenib and transarterial chemoembolization as postoperative adjuvant therapy in patients with hepatocellular carcinoma with portal vein tumor thrombus resulted in longer recurrence-free survival and overall survival than sorafenib alone and was well tolerated. Trial Registration: ClinicalTrials.gov Identifier: NCT04143191.

Relative effectiveness of a heterologous booster dose with adenovirus type 5 vectored COVID-19 vaccine versus three doses of inactivated COVID-19 vaccine in adults during a nationwide outbreak of omicron predominance, in China: a retrospective, individually matched cohort-control study.

Effectiveness of heterologous booster regimes with ad5 vectored COVID-19 vaccine in a large, diverse population during the national-scale outbreak of SARS-CoV-2 omicron predominance in China has not been reported, yet. We conducted a large-scale cohort-control study in six provinces in China, and did a retrospective survey on the COVID-19 attack risk during this outbreak. Participant aged ≥18 years in five previous trials who were primed with 1 to 3 doses of ICV received heterologous booster with either intramuscular or orally inhaled ad5 vectored COVID-19 vaccine were included in the heterologous-trial cohort. We performed propensity score-matching at a ratio of 1:4 to match participants in the heterologous-trial cohort individually with the community individuals who received three-dose of ICV as a control (ICV-community cohort). From February 4 to April 10, 2023, 41504 (74.5%) of 55710 individuals completed the survey. The median time since the most recent vaccination to the onset of the symptoms of COVID-19 was 303.0 days (IQR 293.0-322.0). The attack rate of COVID-19 in the heterologous-trial cohort was 55.8%, while that in the ICV-community cohort was 64.6%, resulting in a relative effectiveness of 13.7% (95% CI 11.9 to 15.3). In addition, a higher relative effectiveness against COVID-19 associated outpatient visits, and admission to hospital was demonstrated, which was 25.1% (95% CI 18.9 to 30.9), and 48.9% (95% CI 27.0 to 64.2), respectively. The heterologous booster with ad5 vectored COVID-19 vaccine still offered some additional protection in preventing COVID-19 breakthrough infection versus homologous three-dose regimen with ICV, 10 months after vaccination.

Vaccination with Adenovirus Type 5 Vector-Based COVID-19 Vaccine as the Primary Series in Adults: A Randomized, Double-Blind, Placebo-Controlled Phase 1/2 Clinical Trial.

This randomized, double-blind, placebo-controlled phase 1/2 trial aimed at evaluating the safety and immunogenicity of Ad5-nCoV via aerosolized or intramuscular or intramuscular-aerosolized routes in SARS-CoV-2-negative adults aged over 18 years. In the phase 1 trial, participants were sequentially enrolled into one of five regimen cohorts: Low-Dose (two doses of aerosolized Ad5-nCoV with 0.5 × 1010 viral particles [vps] per dose), Middle-Dose (two doses of aerosolized Ad5-nCoV with 1.0 × 1010 vps per dose), High-Dose (two doses of aerosolized Ad5-nCoV with 2.0 × 1010 vps per dose), Mixed (intramuscular Ad5-nCoV with 5.0 × 1010 vps [first dose] and aerosolized Ad5-nCoV with 2.0 × 1010 vps [second dose]), and Single-Dose (one dose of aerosolized Ad5-nCoV with 1.0 × 1010 vps). Eligible participants in the phase 2 trial were stratified by 18-59 years old or ≥60 years old and then were sequentially enrolled into one of six regimen cohorts: Low-Dose, Middle-Dose, High-Dose, Mixed, Single-Dose, and Intramuscular (one dose of intramuscular Ad5-nCoV with 1.0 × 1010 vps). The intervals between the two doses were 56 days. Participants were randomly allocated in 3:1 (phase 1) and 5:1 (phase 2) ratios to receive either Ad5-nCoV or the placebo in each cohort. This study is registered on ClinicalTrials.gov, NCT04840992. Most adverse reactions that occurred during the solicited period were mild and moderate. One serious adverse event (myelodysplastic syndrome) was considered potentially related to the aerosolized Ad5-nCoV. The GMTs of neutralizing antibodies in the Mixed group were the highest with 57.03 (95% CI: 23.95, 135.80) and 97.37 (95% CI: 74.30, 127.59) in phase 1 and 2 trials, respectively, 28 days after the second dose (p < 0.0001), which showed significantly higher immune responses compared to other regimens with aerosolized or intramuscular Ad5-nCoV alone.

CXCL12-CXCR4 mediates CD57+ CD8+ T cell responses in the progression of type 1 diabetes.

CD57+ CD8+ T cells, also referred as effector memory cells, are implicated in various conditions including tumor immunity, virus immunity, and most recently with autoimmunity. However, their roles in the progression and remission of T1D are still unclear. Here, we noted an increase in peripheral CD57+ CD8+ T cells in a T1D patient harboring an activator of transcription 3 (STAT3) mutation. Our in-depth study on the role of CD57+ CD8+ T cells within a T1D patient cohort revealed that these cells undergo significant compositional shifts during the disease's progression. Longitudinal cohort data suggested that CD57+ CD8+ T cell prevalence may be a harbinger of ß-cell function decline in T1D patients. Characterized by robust cytotoxic activity, heightened production of pro-inflammatory cytokines, and increased intracellular glucose uptake, these cells may be key players in the pathophysiology of T1D. Moreover, in vitro assays showed that the CXCL12-CXCR4 axis promotes the expansion and function of CD57+ CD8+ T cells via Erk1/2 signaling. Notably, the changes of serum CXCL12 concentrations were also found in individuals during the peri-remission phase of T1D. Furthermore, treatment with the CXCR4 antagonist LY2510924 reduced the immunological infiltration of CD57+ CD8+ T cells and mitigated hyperglycemia in a STZ-induced T1D mouse model. Taken together, our work has uncovered a novel role of the CXCL12-CXCR4 axis in driving CD57+ CD8+ T cells responses in T1D, and presented a promising therapeutic strategy for delaying the onset and progression of diabetes.

Enhancement of hydrogenotrophic methanogenesis for methane production by nano zero-valent iron in soils.

Nanoscale zero-valent iron (nZVI) is attracting increasing attention as the most commonly used environmental remediation material. However, given the high surface area and strong reducing capabilities of nZVI, there is a lack of understanding regarding its effects on the complex anaerobic methane production process in flooded soils. To elucidate the mechanism of CH4 production in soil exposed to nZVI, paddy soil was collected and subjected to anaerobic culture under continuous flooding conditions, with various dosages of nZVI applied. The results showed that the introduction of nZVI into anaerobic flooded rice paddy systems promoted microbial utilization of acetate and carbon dioxide as carbon sources for methane production, ultimately leading to increased methane production. Following the introduction of nZVI into the soil, there was a rapid increase in hydrogen levels in the headspace, surpassing that of the control group. The hydrogen levels in both the experimental and control groups were depleted by the 29th day of culture. These findings suggest that nZVI exposure facilitates the enrichment of hydrogenotrophic methanogens, providing them with a favorable environment for growth. Additionally, it affected soil physicochemical properties by increasing pH and electrical conductivity. The metagenomic analysis further indicates that under exposure to nZVI, hydrogenotrophic methanogens, particularly Methanobacteriaceae and Methanocellaceae, were enriched. The relative abundance of genes such as mcrA and mcrB associated with methane production was increased. This study provides important theoretical insights into the response of key microbes, functional genes, and methane production pathways to nZVI during anaerobic methane production in rice paddy soils, offering fundamental insights into the long-term fate and risks associated with the introduction of nZVI into soils.

Immunomodulatory Function of Pien Tze Huang in T Cell-Mediated Anti-tumor Activity against B16-F10, MC38 and Hep1-6 Tumor Models.

OBJECTIVE: To investigate the anti-tumor effects of Pien Tze Huang (PZH) in mouse models of B16-F10 melanoma, MC38 colorectal cancer, Hep1-6 hepatocellular carcinoma and chemically induced hepatocellular carcinoma model. METHODS: Various tumor models, including B16-F10, MC38 and Hep1-6 tumor hypodermic inoculation models, B16-F10 and Hep1-6 pulmonary metastasis models, Hep1-6 orthotopic implantation model, and chemically induced hepatocellular carcinoma model, were utilized to evaluate the anti-tumor function of PZH. Tumor growth was assessed by measuring tumor size and weight of solid tumors isolated from C57BL/6 mice. For cell proliferation and death of tumor cells in vitro, as well as T cell activation markers, cytokine production and immune checkpoints analysis, single-cell suspensions were prepared from mouse spleen, lymph nodes, and tumors after PZH treatment. RESULTS: PZH demonstrated significant therapeutic efficacy in inhibiting tumor growth (P<0.01). Treatment with PZH resulted in a reduction in tumor size in subcutaneous MC38 colon adenocarcinoma and B16-F10 melanoma models, and decreased pulmonary metastasis of B16-F10 melanoma and Hep1-6 hepatoma (P<0.01). However, in vitro experiments showed that PZH only had slight impact on the cell proliferation and survival of tumor cells (P>0.05). Nevertheless, PZH exhibited a remarkable ability to enhance T cell activation and the production of interferon gamma, tumor necrosis factor alpha, and interleukin 2 in CD4+ T cells in vitro (P<0.01 or P<0.05). Importantly, PZH substantially inhibited T cell exhaustion and boosted cytokine production by tumor-infiltrating CD8+ T cells (P<0.01 or P<0.05). CONCLUSION: This study has confirmed a novel immunomodulatory function of PZH in T cell-mediated anti-tumor immunity, indicating that PZH holds promise as a potential therapeutic agent for cancer treatment.

NUSAP1 promotes pancreatic ductal adenocarcinoma progression by drives the epithelial-mesenchymal transition and reduces AMPK phosphorylation.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, and its molecular mechanisms are unclear. Nucleolar and spindle-associated protein 1 (NUSAP1), an indispensable mitotic regulator, has been reported to be involved in the development of several types of tumors. The biological function and molecular mechanism of NUSAP1 in PDAC remain controversial. This study explored the effects and mechanism of NUSAP1 in PDAC. METHODS: Differentially expressed genes (DEGs) were screened. A protein‒protein interaction (PPI) network was constructed to identify hub genes. Experimental studies and tissue microarray (TMA) analysis were performed to investigate the effects of NUSAP1 in PDAC and explore its mechanism. RESULTS: Network analysis revealed that NUSAP1 is an essential hub gene in the PDAC transcriptome. Genome heterogeneity analysis revealed that NUSAP1 is related to tumor mutation burden (TMB), loss of heterozygosity (LOH) and homologous recombination deficiency (HRD) in PDAC. NUSAP1 is correlated with the levels of infiltrating immune cells, such as B cells and CD8 T cells. High NUSAP1 expression was found in PDAC tissues and was associated with a poor patient prognosis. NUSAP1 promoted cancer cell proliferation, migration and invasion, drives the epithelial-mesenchymal transition and reduces AMPK phosphorylation. CONCLUSIONS: NUSAP1 is an essential hub gene that promotes PDAC progression and leads to a dismal prognosis by drives the epithelial-mesenchymal transition and reduces AMPK phosphorylation.

Osimertinib-induced Keratitis and Secondary Toxic Epidermal Necrotic Drug Eruption- A Case Report and Literature Review.

BACKGROUND: Osimertinib is a third-generation Tyrosine Kinase inhibitor, mainly used in non-small cell lung cancer with EGFR mutation. Its efficacy and safety have been confirmed by clinical practice. Toxic epidermolysis necrotizing disease (TEN) is a severe drug eruption that is rare in clinics and has a high mortality rate. Toxic epidermal necrotic drug rash caused by Osimeritinib is even rarer. OBJECTIVE: To investigate the rare side effects of Osimertinib through a case of toxic Epidermal necrosis. CASE PRESENTATION: A 63-year-old female patient was diagnosed with lung adenocarcinoma with brain metastases, and genetic testing revealed an EGFR21 exon mutation. The disease progressed 24 days after the administration of gefitinib, then the patient switched to Osimertinib (80 mg QD) and, resulting in keratitis and secondary systemic toxic epidermolysis necrotizing disease (TEN). Finally, the patient died. CONCLUSION: Although the clinical use of osimertinib is becoming widespread, the side effects may not be fully understood. Clinicians should pay more attention to the occurrence of the side reaction and deal with it in time.

Acute interstitial nephritis caused by ANCA-associated vasculitis: a case based review.

Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) typically manifests as rapidly progressive glomerulonephritis with crescent formation. In this report, we present a local case of myeloperoxidase (MPO)-AAV-associated acute interstitial nephritis (AIN), showing slight pauci-immune glomerulonephritis and positive MPO-ANCA. This case is characterized by foot process effacement of podocytes in the glomerulus, a favorable prognosis, and an absence of crescentic formation. To further understand this condition, we conducted a comprehensive literature search on Google Scholar and PubMed, employing both free text words and MeSH terms related to "AAV and AIN." This search yielded 24 cases, which we analyzed for their clinical features, laboratory findings, renal pathological characteristics, and therapeutic outcomes. AAV-associated interstitial nephritis predominantly affects elderly patients and is often associated with anemia, proteinuria, hematuria, and nonspecific manifestations, including fever, anorexia, fatigue, edema, and weight loss. Most of the cases in our review were MPO-ANCA-positive and exhibited isolated interstitial inflammation. These patients typically presented with relatively lower levels of serum creatinine, 24-h urine protein levels, and MPO-ANCA titers. All patients in our study received immunosuppressive therapy, including glucocorticoids, immunosuppressants, and rituximab, with the majority achieving clinical remission. Isolated AIN in the context of AAV is a rare occurrence, but it displays distinct clinical, laboratory, and pathological features. Patients with this presentation show a positive response to immunosuppressive treatment. Nevertheless, the establishment of definitive therapy guidelines for AAV-associated AIN remains uncertain and necessitates further investigation to develop comprehensive treatment guidelines. AIN, particularly when lacking typical glomerulus lesions, may represent a novel subgroup within MPO-AAV warranting additional research and clinical attention. Key Points • This study contributes valuable scientific insights by highlighting that MPO-AAV-associated interstitial nephritis, even without crescentic formation, can exhibit podocyte foot process effacement and respond well to treatment. • The presence of AIN, independent of crescentic glomerulonephritis, suggests the potential emergence of a new subclass within MPA-AAV. • Notably, some cases of MPO-AAV-associated AIN may present with normal levels of Scr (Table 5, cases 5, 6, and 17). • This observation highlights the importance of considering renal biopsy, diagnosis, and therapy in a timely manner to prevent the development of chronic kidney disease (CKD).

The impact of MicroRNA-155 on the effect of cryoablation in paroxysmal atrial fibrillation.

Elevated plasma MicroRNA-155 (miR-155) levels are strongly associated with cardiac fibrosis and chronic inflammation processes. However, the relationship between miR-155 and paroxysmal atrial fibrillation (PAF) recurrence following cryoablation remains poorly explored. We aimed to evaluate whether elevated miR-155 is related to long-term AF recurrence following cryoablation. Preoperative miR-155 levels were determined in PAF patients undergoing initial cryoablation. Multivariate-adjusted Cox models were constructed to determine the relationship between miR-155 levels and PAF recurrence. Multivariate logistic regression analyses were performed to determine predictors of PAF recurrence.  Of the 66 enrolled patients, 13 patients (19.7%) had recurrence at the 12-month following-up. These patients had significantly higher baseline miR-155 levels than those without PAF recurrence ((AAA ± BBB) vs. (AAA ± BBB), P < 0.05). The study results showed that miR-155 expression levels were significantly higher in the experimental group than in the control group. Additionally, logistic regression analysis revealed that miR-155 expression was positively correlated with PAF recurrence after cryoablation. Elevated preoperative miR-155 levels are related to a higher risk of AF recurrence and can independently predict AF recurrence following cryoablation.

Peroxiredoxin 1 regulates crosstalk between pyroptosis and autophagy in oral squamous cell carcinoma leading to a potential pro-survival.

Peroxiredoxin 1 (Prdx1), a vital antioxidant enzyme, has been proven to play an important role in the occurrence and development of cancers, but its effects on oral squamous cell carcinoma (OSCC) remain unclear. Here, we performed bioinformatics analysis and immunohistochemical (IHC) staining to confirm that Prdx1 was higher in OSCC tissues than in normal tissues. Consistently, RT-PCR and Western blot showed elevated Prdx1 expression in OSCC cell lines compared to human oral keratinocytes (HOK), which could be knockdown by small interfering RNA (siRNA) and Lentiviral vector delivery of short hairpin RNA (shRNA). Prdx1 silencing significantly blocked OSCC cell proliferation and metastasis, as evidenced by the CCK8, colony formation, in vivo tumorigenesis experiment, wound healing, transwell assays, and changes in migration-related factors. siPrdx1 transfection increased intracellular reactive oxygen species (ROS) levels and provoked pyroptosis, proved by the upregulation of pyroptotic factors and LDH release. Prdx1 silencing ROS-independently blocked autophagy. Mature autophagosome failed to form in the siPrdx1 group. Up-regulated autophagy limited pyroptosis triggered by Prdx1 deficiency, and down-regulated pyroptosis partly reversed siPrdx1-induced autophagy defect. Collectively, Prdx1 regulated pyroptosis in a ROS-dependent way and modulated autophagy in a ROS-independent way, involving the crosstalk between pyroptosis and autophagy.

Novel research and future prospects of artificial intelligence in cancer diagnosis and treatment.

Research into the potential benefits of artificial intelligence for comprehending the intricate biology of cancer has grown as a result of the widespread use of deep learning and machine learning in the healthcare sector and the availability of highly specialized cancer datasets. Here, we review new artificial intelligence approaches and how they are being used in oncology. We describe how artificial intelligence might be used in the detection, prognosis, and administration of cancer treatments and introduce the use of the latest large language models such as ChatGPT in oncology clinics. We highlight artificial intelligence applications for omics data types, and we offer perspectives on how the various data types might be combined to create decision-support tools. We also evaluate the present constraints and challenges to applying artificial intelligence in precision oncology. Finally, we discuss how current challenges may be surmounted to make artificial intelligence useful in clinical settings in the future.

Targeting neoadjuvant chemotherapy-induced metabolic reprogramming in pancreatic cancer promotes anti-tumor immunity and chemo-response.

The molecular dynamics of pancreatic ductal adenocarcinoma (PDAC) under chemotherapy remain incompletely understood. The widespread use of neoadjuvant chemotherapy (NAC) provides a unique opportunity to investigate PDAC samples post-chemotherapy. Leveraging a cohort from Fudan University Shanghai Cancer Center, encompassing PDAC samples with and without exposure to neoadjuvant albumin-bound paclitaxel and gemcitabine (AG), we have compiled data from single-cell and spatial transcriptomes, proteomes, bulk transcriptomes, and metabolomes, deepening our comprehension of the molecular changes in PDACs in response to chemotherapy. Metabolic flux analysis reveals that NAC induces a reprogramming of PDAC metabolic patterns and enhances immunogenicity. Notably, NAC leads to the downregulation of glycolysis and the upregulation of CD36. Tissue microarray analysis demonstrates that high CD36 expression is linked to poorer survival in patients receiving postoperative AG. Targeting CD36 synergistically improves the PDAC response to AG both in vitro and in vivo, including patient-derived preclinical models.

Identification of two immune subtypes and four hub immune-related genes in ovarian cancer through multiple analysis.

Immune classification of ovarian cancer (OV) becomes more and more influential for its immunotherapy. However, current studies had few immune subtypes of OV. It is urgent to explore the immune subtypes and deeper hub immune-related genes (IRGs) of OV for follow-up treatment. A total number of 379 OV samples were obtained from UCSC online website. Single sample gene set enrichment analysis of 29 immune gene sets was used for identifying immune subtypes of OV and gene set variation analysis were used for exploring the hallmarks and Kyoto Encyclopedia of Genes and Genomes pathways of immune types. Two immunity subtypes (Immunity_H and Immunity_L) were identified by single sample gene set enrichment analysis. The OV patients in Immunity_H group had longer overall survival compared with those in Immunity_L group. The Immunity_H had higher stromal score, immune score and estimate score and the tumor purity had the adverse tendency. Besides, the gene set variation analysis enrichment results showed positive relationship between improved immunoreaction and pathways correlated to classical signaling pathway (PI3K/AKT/MTOR, P53, TNFA/NFkB signaling pathways) and immune responses (T/B cell receptor signaling pathways and primary immunodeficiency). Furthermore, 4 hub IRGs (CCR5, IL10RA, ITGAL and PTPRC) were jointly dug by weighted gene co-expression network construction and Cytoscape. Our team also explored the mutations of 4 hub IRGs and PTPRC showed nearly 7% amplification. Besides, 8 immune-checkpoint genes had higher expression in Immuity_H group compared with Immuity_L group, except CD276. The correlation between PD-1/PD-L1 and 4 hub IRGs were explored and gene set enrichment analysis were conducted to explore the underlying mechanisms of PTPRC in OV. Finally, western-blotting showed PTPRC could regulate immune checkpoint PD-L1 expression via JAK-STAT signaling pathway. In a word, 2 immune subtypes and 4 hub IRGs of OV were identified by multiple analysis.

Single-cell transcriptomics uncover hub genes and cell-cell crosstalk in patients with hypertensive nephropathy.

Hypertensive nephropathy (HTN) is one of the leading causes of end-stage renal disease, yet the molecular mechanisms are still unknown. To explore novel mechanisms and gene targets for HTN, the gene expression profiles of renal biopsy samples obtained from 2 healthy living donor controls and 5 HTN patients were determined by single-cell RNA sequencing. Key hub genes expression were validated by the Nephroseq v5 platform. The HTN endothelium upregulated cellular adhesion genes (ICAM2 and CEACAM1), inflammatory genes (ETS2 and IFI6) and apoptosis related genes (CNN3). Proximal tubules in HTN highly expressed hub genes including BBOX1, TPM1, TMSB10, SDC4, and NUP58, which might be potential novel targets for proximal tubular injury. The upregulated genes in tubules of HTN were mainly participating in inflammatory signatures including IFN-γ signature, NF-κB signaling, IL-12 signaling and Wnt signaling pathway. Receptor-ligand interaction analysis indicated potential cell-cell crosstalk between endothelial cells or mesangial cells with other renal resident cells in HTN. Together, our data identify a distinct cell-specific gene expression profile, pathogenic inflammatory signaling and potential cell-cell communications between endothelial cells or mesangial cells with other renal resident cells in HTN. These findings may provide a promising novel landscape for mechanisms and treatment of human HTN.