Unveiling microbial dynamics in lung adenocarcinoma and adjacent nontumor tissues: insights from nicotine exposure and diverse clinical stages via nanopore sequencing technology.

Background: Lung is the largest mucosal area of the human body and directly connected to the external environment, facing microbial exposure and environmental stimuli. Therefore, studying the internal microorganisms of the lung is crucial for a deeper understanding of the relationship between microorganisms and the occurrence and progression of lung cancer. Methods: Tumor and adjacent nontumor tissues were collected from 38 lung adenocarcinoma patients and used nanopore sequencing technology to sequence the 16s full-length sequence of bacteria, and combining bioinformatics methods to identify and quantitatively analyze microorganisms in tissues, as well as to enrich the metabolic pathways of microorganisms. Results: the microbial composition in lung adenocarcinoma tissues is highly similar to that in adjacent tissues, but the alpha diversity is significantly lower than that in adjacent tissues. The difference analysis results show that the bacterial communities of Streptococcaceae, Lactobacillaceae, and Neisseriales were significantly enriched in cancer tissues. The results of metabolic pathway analysis indicate that pathways related to cellular communication, transcription, and protein synthesis were significantly enriched in cancer tissue. In addition, clinical staging analysis of nicotine exposure and lung cancer found that Haemophilus, paralinfluenzae, Streptococcus gordonii were significantly enriched in the nicotine exposure group, while the microbiota of Cardiobactereae and Cardiobacterales were significantly enriched in stage II tumors. The microbiota significantly enriched in IA-II stages were Neisseriaeae, Enterobacteriales, and Cardiobacterales, respectively. Conclusion: Nanopore sequencing technology was performed on the full length 16s sequence, which preliminarily depicted the microbial changes and enrichment of microbial metabolic pathways in tumor and adjacent nontumor tissues. The relationship between nicotine exposure, tumor progression, and microorganisms was explored, providing a theoretical basis for the treatment of lung cancer through microbial targets.

hFcγRIIa: a double-edged sword in osteoclastogenesis and bone balance in transgenic mice.

Rheumatoid arthritis (RA) is a chronic autoimmune disease accompanied by local and systemic bone loss. FcγRs, especially FcγRIIa (hFcγRIIa), have been implicated in the pathogenesis of RA. However, the contribution of hFcγRIIa to bone loss has not been fully elucidated. In the present study, we demonstrated the double-edged sword role of hFcγRIIa on osteoclast differentiation through investigations involving hFcγRIIa-transgenic (hFcγRIIa-Tg) mice. Our findings reveal that hFcγRIIa-Tg mice, previously shown to exhibit heightened susceptibility to collagen-induced arthritis (CIA), displayed increased osteoporosis during CIA or at advanced ages (40 weeks), accompanied by heightened in vivo osteoclast differentiation. Notably, bone marrow cells from hFcγRIIa-Tg mice exhibited enhanced efficiency in differentiating into osteoclasts and bone resorption in vitro compared to wild-type mice when stimulated with receptor activators of NF-κB ligand (RANKL). Additionally, hFcγRIIa-Tg mice exhibited augmented sensitivity to RANKL-induced bone loss in vivo, highlighting the osteoclast-promoting role of hFcγRIIa. Mechanistically, bone marrow cells from hFcγRIIa-Tg mice displayed heightened Syk self-activation, leading to mTOR-pS6 pathway activation, thereby promoting RANKL-driven osteoclast differentiation. Intriguingly, while hFcγRIIa crosslinking hindered RANKL-induced osteoclast differentiation, it activated the kinase cAbl, subsequently triggering STAT5 activation and inhibiting the expression of osteoclast-associated genes. This study provides novel insights into hFcγRIIa-mediated osteoclast biology, suggesting promising therapeutic targets for managing bone remodeling disorders.

The ICF2 gene Zbtb24 specifically regulates the differentiation of B1 cells via promoting heme synthesis.

BACKGROUND: Loss-of-function mutations of ZBTB24 cause immunodeficiency, centromeric instability, and facial anomalies syndrome 2 (ICF2). ICF2 is a rare autosomal recessive disorder with immunological defects in serum antibodies and circulating memory B cells, resulting in recurrent and sometimes fatal respiratory and gastrointestinal infections. The genotype-phenotype correlation in patients with ICF2 indicates an essential role of ZBTB24 in the terminal differentiation of B cells. METHODS: We used the clustered regularly interspaced short palindromic repeats (CRISPER)/Cas9 technology to generate B cell specific Zbtb24-deficient mice and verified the deletion specificity and efficiency by quantitative polymerase chain reaction (Q-PCR) and western blotting analyses in fluorescence-activated cell sorting (FACS)-sorted cells. The development, phenotype of B cells and in vivo responses to T cell dependent or independent antigens post immunization were analyzed by flow cytometry and enzyme-linked immunosorbent assay (ELISA). Adoptive transfer experiment in combination with in vitro cultures of FACS-purified B cells and RNA-Seq analysis were utilized to specifically determine the impact of Zbtb24 on B cell biology as well as the underlying mechanisms. RESULTS: Zbtb24 is dispensable for B cell development and maintenance in naive mice. Surprisingly, B cell specific deletion of Zbtb24 does not evidently compromise germinal center reactions and the resulting primary and secondary antibody responses induced by T cell dependent antigens (TD-Ags), but significantly inhibits T cell independent antigen-elicited antibody productions in vivo. At the cellular level, Zbtb24-deficiency specifically impedes the plasma cell differentiation of B1 cells without impairing their survival, activation and proliferation in vitro. Mechanistically, Zbtb24-ablation attenuates heme biosynthesis partially through mTORC1 in B1 cells, and addition of exogenous hemin abrogates the differentiation defects of Zbtb24-null B1 cells. CONCLUSIONS: Zbtb24 seems to regulate antibody responses against TD-Ags B cell extrinsically, but it specifically promotes the plasma cell differentiation of B1 cells via heme synthesis in mice. Our study also suggests that defected B1 functions contribute to recurrent infections in patients with ICF2.

Olfactory Ecto-Mesenchymal Stem Cells in Modeling and Treating Alzheimer's Disease.

Alzheimer's disease (AD) is a condition in the brain that is marked by a gradual and ongoing reduction in memory, thought, and the ability to perform simple tasks. AD has a poor prognosis but no cure yet. Therefore, the need for novel models to study its pathogenesis and therapeutic strategies is evident, as the brain poorly recovers after injury and neurodegenerative diseases and can neither replace dead neurons nor reinnervate target structures. Recently, mesenchymal stem cells (MSCs), particularly those from the human olfactory mucous membrane referred to as the olfactory ecto-MSCs (OE-MSCs), have emerged as a potential avenue to explore in modeling AD and developing therapeutics for the disease due to their lifelong regeneration potency and facile accessibility. This review provides a comprehensive summary of the current literature on isolating OE-MSCs and delves into whether they could be reliable models for studying AD pathogenesis. It also explores whether healthy individual-derived OE-MSCs could be therapeutic agents for the disease. Despite being a promising tool in modeling and developing therapies for AD, some significant issues remain, which are also discussed in the review.

Spinal nerve transection-induced upregulation of KDM4A in the dorsal root ganglia contributes to the development and maintenance of neuropathic pain via promoting CCL2 expression in rats.

Studies indicate that the lysine-specific demethylase 4A (KDM4A), acts as a key player in neuropathic pain, driving the process through its involvement in promoting neuroinflammation. Emerging evidence reveals that C-C Motif Chemokine Ligand 2 (CCL2) participates in neuroinflammation, which plays an important role in the development and maintenance of neuropathic pain. However, it remains unclear if KDM4A plays a role in regulating CCL2 in neuropathic pain. This study found that following spinal nerve transection (SNT) of the lumbar 5 nerve root in rats, the expression of KDM4A and CCL2 increased in the ipsilateral L4/5 dorsal root ganglia (DRG). Injecting KDM4A siRNA into the DRGs of rats post-SNT resulted in a higher paw withdrawal threshold (PWT) and paw-withdrawal latency (PWL) compared to the KDM4A scRNA group. In addition, prior microinjection of AAV-EGFP-KDM4A shRNA also alleviates the decrease in PWT and PWL caused by SNT. Correspondingly, microinjection of AAV-EGFP-KDM4A shRNA subsequent to SNT reduced the established mechanical and thermal hyperalgesia. Furthermore, AAV-EGFP-KDM4A shRNA injection decreased the expression of CCL2 in DRGs. ChIP-PCR analysis revealed that increased binding of p-STAT1 with the CCL2 promoter induced by SNT was inhibited by AAV-EGFP-KDM4A shRNA treatment. These findings suggest that KDM4A potentially influences neuropathic pain by regulating CCL2 expression in DRGs.

Consensus for antifungal stewardship in China (2024 edition).

Background: Invasive fungal disease (IFD) has become a serious threat to human health in China and around the world, with high mortality and morbidity. Currently, the misdiagnosis rate of IFD is extremely high, compounded with the low quality of prescription antifungals and the high incidence of adverse events associated with IFD treatment, resulting in lengthy hospitalization, low clinical response, and high disease burden, which have become serious challenges in clinical practice. Antifungal stewardship (AFS) can not only significantly increase the early diagnosis rate of IFD, reduce inappropriate utilization of antifungal drugs, improve patient prognosis, but can also improve therapeutic safety and reduce healthcare expenses. Thus, it is urgent to identify key AFS metrics suitable for China's current situation. Methods: Based on metrics recommended by international AFS consensuses, combined with the current situation of China and the clinical experience of authoritative experts in various fields, several metrics were selected, and experts in the fields of respiratory diseases, hematology, intensive care units (ICUs), dermatology, infectious diseases, microbiology laboratory and pharmacy were invited to assess AFS metrics by the Delphi method. Consensus was considered to be reached with an agreement level of ≥80% for the metric. Results: Consensus was reached for 24 metrics, including right patient metrics (n=4), right time metrics (n=3), and right use metrics (n=17). Right use metrics were further subdivided into drug choice (n=8), drug dosage (n=4), drug de-escalation (n=1), drug duration (n=2), and drug consumption (n=2) metrics. Forty-six authoritative experts assessed and reviewed the above metrics, and a consensus was reached with a final agreement level of ≥80% for 22 metrics. Conclusions: This consensus is the first to propose a set of AFS metrics suitable for China, which helps to establish AFS standards in China and is also the first AFS consensus in Asia, and may improve the standard of clinical diagnosis and treatment of IFD, and guide hospitals to implement AFS, ultimately promoting the rational use of antifungal drugs and improving patient prognosis.

Simple Framework for Simultaneous Analysis of Both Electrodes in Stoichiometric Lithium-Sulfur Batteries.

A battery is composed of two electrodes that depend on and interact with each other. However, galvanostatic charging-discharging measurement, the most widely used method for battery evaluation, cannot simultaneously reflect performance metrics [capacity, Coulombic efficiency (CE), and cycling stability] of both electrodes because the result is generally governed by the lower-capacity electrode of the cell, namely the limiting reagent of the battery reaction. In studying stoichiometric Li-S cells operating under application-relevant high-mass-loading and lean-electrolyte conditions, we take advantage of the two-stage discharging behavior of sulfur to construct a simple framework that allows us to analyze both electrodes simultaneously. The cell capacity and its decay are anode performance descriptors, whereas the first plateau capacity and cell CE are cathode performance descriptors. Our analysis within this frame identifies Li stripping/plating and polysulfide shuttling to be the limiting factors for the cycling performance of the stoichiometric Li-S cell. Using our newly developed framework, we examine various previously reported strategies to mitigate these bottleneck problems and find modifying the separator with a reduced graphene oxide layer to be an effective means, which improves the capacity retention rate of the cell to 99.7% per cycle.

Screening of co-expressed genes in hypopharyngeal carcinoma with esophageal carcinoma based on RNA sequencing and Clinical Research.

To explore the hub comorbidity genes and potential pathogenic mechanisms of hypopharyngeal carcinoma with esophageal carcinoma, and evaluate their diagnostic value for hypopharyngeal carcinoma with co-morbid esophageal carcinoma. We performed gene sequencing on tumor tissues from 6 patients with hypopharyngeal squamous cell carcinoma with esophageal squamous cell carcinoma (hereafter referred to as "group A") and 6 patients with pure hypopharyngeal squamous cell carcinoma (hereafter referred to as "group B"). We analyzed the mechanism of hub genes in the development and progression of hypopharyngeal squamous cell carcinoma with esophageal squamous cell carcinoma through bioinformatics, and constructed an ROC curve and Nomogram prediction model to analyze the value of hub genes in clinical diagnosis and treatment. 44,876 genes were sequenced in 6 patients with group A and 6 patients with group B. Among them, 76 genes showed significant statistical differences between the group A and the group B.47 genes were expressed lower in the group A than in the group B, and 29 genes were expressed higher. The top five hub genes were GABRG2, CACNA1A, CNTNAP2, NOS1, and SCN4B. GABRG2, CNTNAP2, and SCN4B in the hub genes have high diagnostic value in determining whether hypopharyngeal carcinoma patients have combined esophageal carcinoma (AUC: 0.944, 0.944, 0.972). These genes could possibly be used as potential molecular markers for assessing the risk of co-morbidity of hypopharyngeal carcinoma combined with esophageal carcinoma.

Ice sheet and precession controlled subarctic Pacific productivity and upwelling over the last 550,000 years.

The polar oceans play a vital role in regulating atmospheric CO2 concentrations (pCO2) during the Pleistocene glacial cycles. However, despite being the largest modern reservoir of respired carbon, the impact of the subarctic Pacific remains poorly understood due to limited records. Here, we present high-resolution, 230Th-normalized export productivity records from the subarctic northwestern Pacific covering the last five glacial cycles. Our records display pronounced, glacial-interglacial cyclicity superimposed with precessional-driven variability, with warm interglacial climate and high boreal summer insolation providing favorable conditions to sustain upwelling of nutrient-rich subsurface waters and hence increased export productivity. Our transient model simulations consistently show that ice sheets and to a lesser degree, precession are the main drivers that control the strength and latitudinal position of the westerlies. Enhanced upwelling of nutrient/carbon-rich water caused by the intensification and poleward migration of the northern westerlies during warmer climate intervals would have led to the release of previously sequestered CO2 from the subarctic Pacific to the atmosphere. Our results also highlight the significant role of the subarctic Pacific in modulating pCO2 changes during the Pleistocene climate cycles, especially on precession timescale ( ~ 20 kyr).

[Correlation study of NCF2 in chronic rhinosinusitis with nasal polyps].

Objective:After selecting NCF2 based on bioinformatics, clinical experiments were conducted to verify the expression of NCF2 in chronic rhinosinusitis with nasal polyps to study its correlation. Methods:The differentially expressed genes（DEGs） between CRSwNP and non-CRS patients were explored using the CRS-related dataset from the gene expression omnibus GEO database. The weighted gene co-expression network（WGCNA） was used for cluster analysis. The expression and cell distribution of NCF2 in the tissues were determined by single gene enrichment analysis（GSEA）, immune inflammatory infiltration analysis, and principal component（PCA） analysis. The expression degree of NCF2 in the tissues of the subjects was determined by immunohistochemistry, and the percentage of EOS in the peripheral blood of the subjects was detected and the correlation was analyzed. EOS in the tissues of the subjects were counted under a microscope and compared. Results:①The Venn diagram was obtained by crossing the module with the highest correlation between DEGs and WGCNA to determine the core gene NCF2. ②GSEA analysis showed that NCF2 was significantly related to the immunological processes such as allogeneic rejection and asthma. ③The area under the ROC curve was 1, indicating that NCF2 had diagnostic value for CRSwNP. ④NCF2 was highly expressed in nasal polyps, mainly distributed in monocytes and eosinophils. ⑤HE staining showed that the number of EOS in ECRSwNP tissues and the percentage of eosinophils in peripheral blood were higher than those in nonECRSwNP and control groups. ⑥The immunohistochemistry results showed that NCF2 was significantly expressed in the nasal polyps of ECRSwNP patients, which was higher than that in the nasal mucosa of nonECRSwNP group and control group. ⑦The expression of NCF2 in tissues was positively correlated with EOS count in ECRSwNP group and EOS expression in peripheral blood. Conclusion:The expression of NCF2 is increased in eosinophilic chronic rhinosinusitis with nasal polyps, and it is significantly correlated with the expression of eosinophils in peripheral blood and tissues, suggesting that NCF2 may be used as a basis for the intrinsic classification of ECRSwNP and a reference index for clinical diagnosis and treatment.

Correlation analysis between cerebral microangiopathy and autonomic nervous dysfunction.

OBJECTIVE: Our study was conducted aimed at investigating the potential correlation between cerebral microangiopathy and autonomic nervous dysfunction. METHODS: We initially included 164 hospitalized patients with cerebral microangiopathy at our hospital from November 2019 to January 2021. Based on the inclusion and exclusion criteria, a final total of 162 patients with cerebral microangiopathy were selected. According to the patient's Autonomic Symptom Profile (ASP) score, patients with a score greater than 22 were categorized into a group with concomitant autonomic dysfunction (71 cases, combined group), while those with a score below 22 were categorized into a group of isolated cerebral microangiopathy (83 cases, cerebral microangiopathy group). The general data and laboratory examination results of the two groups were analyzed, and Pearson correlation analysis was performed to evaluate the correlation between cerebral microangiopathy and autonomic dysfunction, as well as the influencing factors of cerebral microangiopathy patients combined with autonomic dysfunction. RESULTS: There were no significant differences between the two groups in terms of sex, BMI, smoking, drinking, family dementia history, diabetes, hypothyroidism, carotid atherosclerosis, obstructive sleep apnea hypopnea syndrome, hyperuricemia, hyperlipidemia, chronic obstructive pulmonary disease, Hamilton Anxiety Scale score, Hamilton Depression Scale score, 24-h mean systolic blood pressure (SBP), 24-h mean diastolic blood pressure DBP, daytime mean systolic blood pressure (dSBP), daytime mean diastolic blood pressure, nighttime mean systolic blood pressure (nSBP), nighttime mean diastolic blood pressure, 24-h systolic blood pressure standard deviation (SBPSD), 24-h diastolic blood pressure standard deviation, daytime diastolic blood pressure standard deviation, nighttime diastolic blood pressure standard deviation (nDBPSD), nDBPSD (p > .05). However, significant differences were observed between the two groups regarding age, history of coronary heart disease, hypertension, leukoaraiosis, cognitive function, ASP score, SSR, 24-h SBPSD, daytime systolic blood pressure standard deviation (dSBPSD), nighttime systolic blood pressure standard deviation (nSBPSD), standard deviation of RR interval (SDNN), root mean square value of successive RR interval difference (RMSSD), high-frequency component (HF), and low-frequency component (LF) (p < .05). Moreover, the levels of TG, TC, HDL-C, and LDL-C did not show significant differences between the two groups (p > .05), but there were significant differences in blood uric acid and homocysteine (Hcy) levels (p < .05). Age, history of leukoaraiosis, cognitive function assessment, blood uric acid, Hcy levels, 24-h SBPSD, dSBPSD, and nSBPSD showed positive correlations with ASP scores and SSR in patients with cerebral microangiopathy (p < .001). In contrast, hypertension, SDNN, RMSSD, HF, and LF showed negative correlations with ASP scores and SSR (p < .001). Moreover, coronary heart disease was negatively correlated with ASP scores but positively correlated with SSR (p < .001). The independent variables included age, history of leukoaraiosis, cognitive function assessment, ASP score, SSR, blood uric acid, Hcy, bradykinin, coronary heart disease, hypertension, 24-h SBPSD, dSBPSD, nSBPSD, SDNN, RMSSD, HF, and LF, which were indicators with differences in general data and laboratory indicators. The dependent variable was patients with cerebral microangiopathy combined with autonomic nervous dysfunction. The analysis results showed that age, history of leukoaraiosis, ASP score, SSR, 24-h SBPSD, dSBPSD, nSBPSD, SDNN, RMSSD, HF, and LF were the influencing factors of patients with cerebral microangiopathy complicated with autonomic nervous dysfunction. CONCLUSION: We demonstrates that age, history of leukoaraiosis, cognitive function assessment, blood uric acid, Hcy level, 24-h SBPSD, dSBPSD, nSBPSD, blood pressure, SDNN, RMSSD, HF, LF, and coronary heart disease were highly associated with cerebral microangiopathy with autonomic dysfunction. Furthermore, the influencing factors of cerebral microangiopathy with autonomic dysfunction are age, history of leukoaraiosis, ASP score, SSR, blood pressure variability, and HRV.

Impaired 26S proteasome causes learning and memory deficiency and induces neuroinflammation mediated by NF-κB in mice.

A reduction in proteasome activity, loss of synapses and increased neuroinflammation in the brain are hallmarks of aging and many neurodegenerative disorders, including Alzheimer's disease (AD); however, whether proteasome dysfunction is causative to neuroinflammation remains less understood. In this study, we investigated the impact of 26S proteasome deficiency on neuroinflammation in the Psmc1 knockout (KO) mice deficient in a 19S proteasome subunit limited to the forebrain region. Our results revealed that impaired 26S proteasome led to reduced learning and memory capability and overt neuroinflammation in the synapses of the Psmc1 KO brain at eight weeks of age. Moreover, pronounced neuroinflammation was also found in the whole brain cortex, which was confirmed by increased levels of several key immune response-related proteins, including Stat1, Trem2 and NF-κB, and by activation of astrocytes and microglia in the KO brain. To validate NF-κB mediating neuroinflammation, we administered a selective NF-κB inhibitor to the KO animals at 5 weeks of age for three weeks, and then, animal behaviors and neuroinflammation were assessed when they reached eight weeks of age. Following the treatment, the KO mice exhibited improved behaviors and reduced neuroinflammation compared to the control animals. These data indicate that impaired 26S proteasome causes AD-like cognitive deficiency and induces neuroinflammation mediated largely by NF-κB. These results may aid development of effective therapeutics and better understanding of the pathogenesis of AD and many other neurodegenerative disorders where impaired proteasome is consistently coupled with neuroinflammation.

Development and Validation of a Nomogram for Predicting the Severity of Coronary Artery Disease Based on Cardiopulmonary Exercise Testing.

As a major global health concern, coronary artery disease (CAD) demands precise, noninvasive diagnostic methods like cardiopulmonary exercise testing (CPET) for effective assessment and management, balancing the need for accurate disease severity evaluation with improved treatment decision-making. Our objective was to develop and validate a nomogram based on CPET parameters for noninvasively predicting the severity of CAD, thereby assisting clinicians in more effectively assessing patient conditions. This study analyzed 525 patients divided into training (367) and validation (183) cohorts, identifying key CAD severity indicators using least absolute shrinkage and selection operator (LASSO) regression. A predictive nomogram was developed, evaluated by average consistency index (C-index), the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA), confirming its reliability and clinical applicability. In our study, out of 25 variables, 6 were identified as significant predictors for CAD severity. These included age (OR = 1.053, P < .001), high-density lipoprotein (HDL, OR = 0.440, P = .002), hypertension (OR = 2.050, P = .007), diabetes mellitus (OR = 3.435, P < .001), anaerobic threshold (AT, OR = 0.837, P < .001), and peak kilogram body weight oxygen uptake (VO2/kg, OR = 0.872, P < .001). The nomogram, based on these predictors, demonstrated strong diagnostic accuracy for assessing CAD severity, with AUC values of 0.939 in the training cohort and 0.840 in the validation cohort, and also exhibited significant clinical utility. The nomogram, which is based on CPET parameters, was useful for predicting the severity of CAD and assisted in risk stratification by offering a personalized, noninvasive diagnostic approach for clinicians.

Genome analysis of vB_SupP_AX, a novel N4-like phage infecting Sulfitobacter.

Sulfitobacter is a bacterium recognized for its production of AMP-independent sulfite oxidase, which is instrumental in the creation of sulfite biosensors. This capability underscores its ecological and economic relevance. In this study, we present a newly discovered phage, Sulfitobacter phage vB_SupP_AX, which was isolated from Maidao of Qingdao, China. The vB_SupP_AX genome is linear and double-stranded and measures 75,445 bp with a GC content of 49%. It encompasses four transfer RNA (tRNA) sequences and 79 open reading frames (ORFs), one of which is an auxiliary metabolic gene encoding thioredoxin. Consistent with other N4-like phages, vB_SupP_AX possesses three distinct RNA polymerases and is characterized by the presence of four tRNA molecules. Comparative genomic and phylogenetic analyses position vB_SupP_AX and three other viral genomes from the Integrated Microbial Genomes/Virus v4 database within the Rhodovirinae virus subfamily. The identification of vB_SupP_AX enhances our understanding of virus-host interactions within marine ecosystems.

Shewanella phage encoding a putative anti-CRISPR-like gene represents a novel potential viral family.

Shewanella is a prevalent bacterial genus in deep-sea environments including marine sediments, exhibiting diverse metabolic capabilities that indicate its significant contributions to the marine biogeochemical cycles. However, only a few Shewanella phages were isolated and deposited in the NCBI database. In this study, we report the isolation and characterization of a novel Shewanella phage, vB_SbaS_Y11, that infects Shewanella KR11 and was isolated from the sewage in Qingdao, China. Transmission electron microscopy revealed that vB_SbaS_Y11 has an icosahedral head and a long tail. The genome of vB_SbaS_Y11 is a linear, double-stranded DNA with a length of 62,799 bp and a G+C content of 46.9%, encoding 71 putative open reading frames. No tRNA genes or integrase-related feature genes were identified. An uncharacterized anti-CRISPR AcrVA2 gene was detected in its genome. Phylogenetic analysis based on the amino acid sequences of whole genomes and comparative genomic analyses indicate that vB_SbaS_Y11 has a novel genomic architecture and shares low similarity to Pseudomonas virus H66 and Pseudomonas phage F116. vB_SbaS_Y11 represents a potential new family-level virus cluster with eight metagenomic assembled viral genomes named Ranviridae.IMPORTANCEThe Gram-negative Shewanella bacterial genus currently includes about 80 species of mostly aquatic Gammaproteobacteria, which were isolated around the globe in a multitude of environments, such as freshwater, seawater, coastal sediments, and the deepest trenches. Here, we present a Shewanella phage vB_SbaS_Y11 that contains an uncharacterized anti-CRISPR AcrVA2 gene and belongs to a potential virus family, Ranviridae. This study will enhance the knowledge about the genome, diversity, taxonomic classification, and global distribution of Shewanella phage populations.

Study of electronic biofeedback combined with nursing intervention in the treatment of vascular cognitive impairment-no dementia.

OBJECTIVE: To investigate the effects of electronic biofeedback combined with nursing intervention and conventional drug treatment on cognitive function in patients with vascular cognitive impairment-no dementia (VCIND). METHODS: A total of 102 patients with VCIND treated in the Department of Neurology from January 2021 to May 2022 were enrolled and divided into the routine treatment group and biofeedback group according to different treatment methods. The routine treatment group was given conventional drug therapy and nursing intervention; for the biofeedback group, electronic biofeedback therapy was added, based on the routine treatment group. The Montreal Cognitive Assessment, (MoCA), Alzheimer's Disease Assessment Scale-Cognitive Subscale, (ADAS-cog), and Hamilton Depression Scale (HAMD) were checked before treatment, 2 weeks after treatment, and 3 months after treatment. RESULTS: At 3 months of treatment, the scores of the MoCA and ADAS-cog scales in the biofeedback group were better than those in the routine treatment group, while no difference was detected in the HAMD scores before and after treatment and between the two groups. CONCLUSION: Electronic biofeedback therapy for VCIND can significantly improve the MoCA score, reduce the ADAS-cog score and improve the cognitive level of patients and can be used as a complementary treatment for VCIND.

Pathogenic and therapeutic role of exosomes in neurodegenerative disorders.

Neurodegenerative disorders affect millions of people worldwide, and the prevalence of these disorders is only projected to rise as the number of people over 65 will drastically increase in the coming years. While therapies exist to aid in symptomatic relief, effective treatments that can stop or reverse the progress of each neurodegenerative disease are lacking. Recently, research on the role of extracellular vesicles as disease markers and therapeutics has been intensively studied. Exosomes, 30-150 nm in diameter, are one type of extracellular vesicles facilitating cell-to-cell communication. Exosomes are thought to play a role in disease propagation in a variety of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Accordingly, the exosomes derived from the patients are an invaluable source of disease biomarkers. On the other hand, exosomes, especially those derived from stem cells, could serve as a therapeutic for these disorders, as seen by a rapid increase in clinical trials investigating the therapeutic efficacy of exosomes in different neurological diseases. This review summarizes the pathological burden and therapeutic approach of exosomes in neurodegenerative disorders. We also highlight how heat shock increases the yield of exosomes while still maintaining their therapeutic efficacy. Finally, this review concludes with outstanding questions that remain to be addressed in exosomal research.

Abdominal lymph node metastasis in non-surgical esophageal squamous cell carcinoma: prognostic significance and a novel staging strategy.

Purpose: This study aimed to evaluate the feasibility of a combination of abdominal lymph node (LN) metastasis and the number of LNs in esophageal squamous cell carcinoma (ESCC) patients to optimize its clinical nodal staging. Methods: A retrospective study, including a total of 707 ESCC patients treated with definitive radiotherapy, was conducted at two participating institutes. Different combinations of LN variables, including abdominal LN metastasis (R1: no-abdominal LN metastasis; R2: abdominal LN metastasis), were further analyzed to propose a potential revised nodal (rN) staging. Results: The multivariate analyses showed that the number of metastatic LN and abdominal LN metastasis were independent prognostic factors for the overall survival (OS). The results showed no significant differences in the OS between the N2 patients with abdominal LN metastasis and N3 patients. The OS of the stage III patients with abdominal LN metastasis was not significantly different from those with stage IVa. The N3R1 and N1-2R2 had similar hazard ratios (HRs). The N1R1 subset was defined as rN1, the N2R1 subset was defined as rN2, and the N3R1-2 and N1-2R2 subsets were defined as rN3. The HRs of OS of the rN2 and rN3 groups increased subsequently. The rN stage could identify the differences in the OS times of each subgroup based on the 8th AJCC cN staging or the 11th JES N staging. Conclusions: The rN staging, including the number of metastatic LNs and abdominal LN metastasis, might serve as a potential prognostic predictor for non-surgical patients with ESCC.

Identification and genomic analysis of temperate Halomonas bacteriophage vB_HmeY_H4907 from the surface sediment of the Mariana Trench at a depth of 8,900 m.

Viruses play crucial roles in the ecosystem by modulating the host community structure, mediating biogeochemical cycles, and compensating for the metabolism of host cells. Mariana Trench, the world's deepest hadal habitat, harbors a variety of unique microorganisms that have adapted to its extreme conditions of low temperatures, high pressure, and nutrient scarcity. However, our knowledge about isolated hadal phage strains in the hadal trench is still limited. This study reported the discovery of a temperate phage, vB_HmeY_H4907, infecting Halomonas meridiana H4907, isolated from surface sediment from the Mariana Trench at a depth of 8,900 m. To our best knowledge, it is the deepest isolated siphovirus from the ocean. Its 40,452 bp linear dsDNA genome has 57.64% GC content and 55 open reading frames, and it is highly homologous to its host. Phylogenetic analysis and average nucleotide sequence identification reveal that vB_HmeY_H4907 is separated from the isolated phages and represents a new family, Suviridae, with eight predicted proviruses and six uncultured viral genomes. They are widely distributed in the ocean, suggesting a prevalence of this viral family in the deep sea. These findings expand our understanding of the phylogenetic diversity and genomic features of hadal lysogenic phages, provide essential information for further studies of phage-host interactions and evolution, and may reveal new insights into the lysogenic lifestyles of viruses inhabiting the hadal ocean. IMPORTANCE Halomonas phage vB_HmeY_H4907 is the deepest isolated siphovirus from the ocean, and it represents a novel abundant viral family in the ocean. This study provides insights into the genomic, phylogenetic, and ecological characteristics of the new viral family, namely, Suviridae.

Characterization and genomic analysis of a novel lytic phage vB_PstM_ZRG1 infecting Stutzerimonas stutzeri, representing a new viral genus, Elithevirus.

Stutzerimonas stutzeri is an opportunistic pathogen widely distributed in the environment and displays diverse metabolic capabilities. In this study, a novel lytic S. stutzeri phage, named vB_PstM_ZRG1, was isolated from the seawater in the East China Sea (29°09'N, 123°39'E). vB_PstM_ZRG1 was stable at temperatures ranging from -20°C to 65°C and across a wide range of pH values from 3 to 10. The genome of vB_PstM_ZRG1 was determined to be a double-stranded DNA with a genome size of 52,767 bp, containing 78 putative open reading frames (ORFs). Three auxiliary metabolic genes encoded by phage vB_PstM_ZRG1 were predicted, including Toll/interleukin-1 receptor (TIR) domain, proline-alanine-alanine-arginine (PAAR) protein and SGNH (Ser-Gly-Asn-His) family hydrolase, especially TIR domain is not common in isolated phages. Phylogenic and network analysis showed that vB_PstM_ZRG1 has low similarity to other phage genomes in the GenBank and IMG/VR database, and might represent a novel viral genus, named Elithevirus. Additionally, the distribution map results indicated that vB_PstM_ZRG1 could infect both extreme colds- and warm-type hosts in the marine environment. In summary, our finding provided basic information for further research on the relationship between S. stutzeri and their phages, and expanded our understanding of genomic characteristics, phylogenetic diversity and distribution of Elithevirus.