[Evaluation of the feasibility of endoscopic tympanoplasty in two-person three-hand operation].

Objective:To study the difference of postoperative efficacy between two-person three-hand ear endoscopy and microscopic tympanoplasty in patients with chronic suppurative otitis media, and to explore the advantages and disadvantages of two-person three-hand ear endoscopy. Methods:A retrospective study was conducted on 100 patients who underwent tympanoplasty in the Department of Otolaryngology and Head and Neck Surgery of Hunan People's Hospital from April 2019 to March 2023, and they were divided into 2 groups with 50 cases each according to random number table method. Among them, 50 cases underwent endoscopic tympanoplasty in two-person three-hand（group A） and 50 cases underwent routine microscopic tympanoplasty（group B）. The operation and postoperative conditions of the two groups were followed up. Results:In group A, the mean operation time was（65.78±18.21） min, the mean intraoperative blood loss was（12.94±4.46） mL, the postoperative pain score was（1.82±0.60） points, and the mean postoperative hospital stay was（2.76±0.72） d. The mean operation time of group B was（89.45±20.38） min, the mean intraoperative blood loss was（22.78±5.74） mL, the postoperative pain score was（2.98±0.85） points, and the mean postoperative hospital stay was（3.82±0.75） d, which with statistical significance between the two groups（P<0.05）. Hearing in both groups was significantly improved 6 months after surgery, and the difference was statistically significant before and after surgery（P<0.05）, but there was no significant difference between the two groups before surgery and 6 months after surgery（P>0.05）. There were 2 cases in group A（4%） and 1 case in group B（2%） complicated with tympanic cord injury during operation, and the difference was not statistically significant（P>0.05）. There were 47 cases of A group（94%） of one-time healing of tympanic membrane after operation, 48 cases（96%） of group B, and the difference was not statistically significant（P>0.05）. Conclusion:There is no significant difference in cure rate and hearing improvement between two-person three-hand ear endoscopic tympanoplasty and conventional microscope surgery, and the operation time is significantly shortened, the amount of blood loss is less, and the postoperative recovery is faster. It has the advantages of clear operating field, two-person three-hand operation, minimally invasive, and can reach the range of middle ear tympanic sinus and mastoid apex, and the surgical complications are seldom, which is worth promoting.

Dynamic Cortical Connectivity During Propofol Sedation in Glioma Patients.

BACKGROUND: The behavioral manifestations and neurophysiological responses to sedation can assist in understanding brain function after neurological damage, and can be described by cortical functional connectivity. Glioma patients may experience neurological deficits that are not clinically detectable before sedation. We hypothesized that patients with gliomas exhibit distinct cortical connectivity patterns compared to non-neurosurgical patients during sedation. METHODS: This is a secondary analysis of a previously published prospective observational study. Patients scheduled for resection of supratentorial glioma (n=21) or a non-neurosurgical procedure (n=21) under general anesthesia were included in this study. Frontal electroencephalography (EEG) signals were recorded at different sedation levels as assessed by the Observer Assessment of Alertness/Sedation (OAA/S) score. Kernel principal component analysis and k-means clustering were used to determine possible temporal dynamics from the weighted phase lag index characteristics. RESULTS: Ten EEG connectivity states were identified by clustering (76% consistency), each with unique properties. At OAA/S 3, the median (Q1, Q3) occurrence rates of state 6 (glioma group, 0.110 [0.083, 0.155] vs. control group, 0.070 [0.030, 0.110]; P=0.008) and state 7 (glioma group, 0.105 [0.083, 0.148] vs. control group: 0.065 [0.038, 0.090]; P=0.001), which are dominated by beta connectivity, were significantly different between the 2 groups, reflecting differential conversion of the beta band between the left and right brain regions. In addition, the temporal dynamics of the brain's functional connectivity was also reflected in the transition relationships between metastable states. CONCLUSIONS: There were differences in EEG functional connectivity, which is dynamic, between the glioma and nonglioma groups during sedation.

Morphology, Not Only Volume: A Study on Empty Nose Syndrome and Inferior Turbinates.

OBJECTIVES: Empty nose syndrome (ENS) is an underdiagnosed but burdensome clinical condition. Studies that have addressed the impact of remnant inferior turbinate volume (ITV) on ENS are scarce. We aimed to evaluate the impact of ITV and phenotyping on the severity and presentation of ENS. METHODS: All the enrolled patients underwent the following subjective assessments: the ENS 6-Item Questionnaire (ENS6Q), Sino-Nasal Outcome Test-25 (SNOT-25), Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI). The ITV was obtained from finely cut (1-mm-thick slices) sino-nasal computed tomography scan images and analyzed using ImageJ. The correlation between ITV, subjective measurements, and morphology of inferior turbinates was evaluated. ENS was categorized as torpedo type (balanced tissue volume) or pistol type (posterior dominance) based on the morphology. RESULTS: Overall, 54 patients met the inclusion criteria. The ITV was positively correlated with the ENS6Q score and domain of ENS symptoms in SNOT-25. Neither BDI-II nor BAI scores had a significant correlation with ITV. Based on their morphological classification, the torpedo type exhibited diverse manifestations in the SNOT-25 analysis in response to changes in ITV, while the pistol type demonstrated an elevated rhinologic symptom burden and ENS-specific symptoms as their ITV increased. Nasal resistance did not correlate with the ITV in either type of ENS. CONCLUSIONS: Symptoms were paradoxically worse in ENS patients with greater remnant ITV, and distinct morphological phenotypes in the nasal cavities may result in different presentations. Further investigation into the correlation between remnant inferior turbinates and nerve function is warranted. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Disinfection by-products control in wastewater effluents treated with ozone and biological activated carbon followed by UV/Chlor(am)ine processes.

Sequential utilization of ozone (O3) and biological activated carbon (BAC) followed by UV/chlor(am)ine advanced oxidation process (AOP) has drawn attention in water reuse. However, the formation of disinfection by-products (DBPs) in this process is less evaluated. This study investigated the DBP formation and the relevant toxicity during the O3-BAC-UV/chlor(am)ine treatment of sand-filtered municipal secondary effluent. DBP formation in UV/chlorine and UV/dichloramine (NHCl2) processes were compared, where the impact of key operational parameters (e.g., UV wavelength, pH) on DBP formation were comprehensively evaluated. O3-BAC significantly reduced DBP formation potential (DBPFP) (58.2 %). Compared to UV/chlorine AOP, UV/NHCl2 AOP reduced DBP formation by 29.7 % in short-time treatment, while insignificantly impacting on DBPFP (p > 0.05). UV/NHCl2 AOP also led to lower calculated cytotoxicity (67.7 %) and genotoxicity (55.9 %) of DBPs compared to UV/chlorine AOP. Compared to 254 nm UV light, the utilization of 285 nm UV light decreased the formation of DBPs in wastewater treated with the UV/chlorine AOP and UV/NHCl2 AOP by 31.3 % and 19.2 %, respectively. However, the cytotoxicity and genotoxicity in UV/NHCl2 AOP using 285 nm UV light increased by 83.4 % and 58.5 %, respectively, compared to 254 nm. The concentration of DBPs formed in the UV/NHCl2 AOP at pH 8 was 54.3 % lower than that at pH 7, suggesting a better control of DBPs at alkaline condition. In the presence of bromide, UV/NHCl2 AOP tended to generate more brominated DBPs than UV/chlorine AOP. Overall, UV/NHCl2 AOP resulted in lower concentration and toxicity of DBPs compared to UV/chlorine AOP.

Microbes translocation from oral cavity to nasopharyngeal carcinoma in patients.

The presence of oral microbes in extra-oral sites is linked to gastrointestinal cancers. However, their potential ectopically colonization in the nasopharynx and impact on local cancer development remains uncertain. Our study involving paired nasopharyngeal-oral microbial samples from nasopharyngeal carcinoma (NPC) patients and controls unveils an aberrant oral-to-nasopharyngeal microbial translocation associated with increased NPC risk (OR = 4.51, P = 0.012). Thirteen species are classified as oral-translocated and enriched in NPC patients. Among these, Fusobacterium nucleatum and Prevotella intermedia are validated through culturomics and clonal strain identification. Nasopharyngeal biopsy meta-transcriptomes confirm these microbes within tumors, influencing local microenvironment and cytokine response. These microbes correlate significantly with the Epstein-Barr virus (EBV) loads in the nasopharynx, exhibiting an increased dose-response relationship. Collectively, our study identifies oral microbes migrating to the nasopharynx, infiltrating tumors, impacting microenvironments and linking with EBV infection. These results enhance our understanding of abnormal microbial communication and their roles in carcinogenesis.

Haemolysin Ahh1 secreted from Aeromonas dhakensis activates the NLRP3 inflammasome in macrophages and mediates severe soft tissue infection.

Severe soft tissue infections caused by Aeromonas dhakensis, such as necrotizing fasciitis or cellulitis, are prevalent in southern Taiwan and around the world. However, the mechanism by which A. dhakensis causes tissue damage remains unclear. Here, we found that the haemolysin Ahh1, which is the major virulence factor of A. dhakensis, causes cellular damage and activates the NLR family pyrin domain containing 3 (NLRP3) inflammasome signalling pathway. Deletion of ahh1 significantly downregulated caspase-1, the proinflammatory cytokine interleukin 1ß (IL-1ß) and gasdermin D (GSDMD) and further decreased the damage caused by A. dhakensis in THP-1 cells. In addition, we found that knockdown of the NLRP3 inflammasome confers resistance to A. dhakensis infection in both THP-1 NLRP3-/- cells and C57BL/6 NLRP3-/- mice. In addition, we demonstrated that severe soft-tissue infections treated with antibiotics combined with a neutralizing antibody targeting IL-1ß significantly increased the survival rate and alleviated the degree of tissue damage in model mice compared control mice. These findings show that antibiotics combined with therapies targeting IL-1ß are potential strategies to treat severe tissue infections caused by toxin-producing bacteria.

Causal Relationships Between Screen Use, Reading, and Brain Development in Early Adolescents.

The rise of new media has greatly changed the lifestyles, leading to increased time on these platforms and less time spent reading. This shift has particularly profound impacts on early adolescents, who are in a critical stage of brain development. Previous studies have found associations between screen use and mental health, but it remains unclear whether screen use is the direct cause of the outcomes. Here, the Adolescent Brain Cognitive Development (ABCD) dataset is utlized to examine the causal relationships between screen use and brain development. The results revealed adverse causal effects of screen use on language ability and specific behaviors in early adolescents, while reading has positive causal effects on their language ability and brain volume in the frontal and temporal regions. Interestingly, increased screen use is identified as a result, rather than a cause, of certain behaviors such as rule-breaking and aggressive behaviors. Furthermore, the analysis uncovered an indirect influence of screen use, mediated by changes in reading habits, on brain development. These findings provide new evidence for the causal influences of screen use on brain development and highlight the importance of monitoring media use and related habit change in children.

Calreticulin, a potential coregulator of immune checkpoints and biomarker associated with tumor microenvironment and clinical prognostic significance in breast invasive carcinoma.

As a promising immune checkpoint of immunogenic cell death (ICD) and multifunctional calcium-binding molecular chaperone, calreticulin (CALR) has been attracting increasing attention. CALR mainly locates in cellular endoplasmic reticulum and significantly affects cell proliferation, invasion, induction of apoptosis, and angiogenesis in breast invasive carcinoma (BRCA). CALR overexpression might be correlated with a worse outcome. Nonetheless, it remains obscure how CALR correlates with immune infiltration and survival prognosis of BRCA. In this study, we investigated CALR expression utilizing RNAseq data from the cancer genome atlas (TCGA) and genotype-tissue expression (GTEx) database. The prognostic value of CALR was analyzed using clinical survival data. Enrichment analysis was conducted using the R package "clusterProfiler." We downloaded the immune cell infiltration score of TCGA samples from published articles and online databases and performed a correlation analysis between immune cell infiltration levels and CALR expression. We further assessed the association between CALR and immunomodulators. Moreover, we also evaluated the expression of CALR in 100 formalin-fixed and paraffin-embedded breast cancer and adjacent normal breast tissue specimens. Our results found that CALR was highly expressed in BRCA, and CALR expression levels differed in pathological stages, T stages, and N stages. Besides, these results suggested that CALR overexpression may have adverse effects on the progression-free interval (PFI) and disease-free interval (DFI), which may be related to tumor proliferation, invasion, and metastasis, leading to tumor deterioration. Meanwhile, immune cell infiltration analysis revealed a correlation between the expression of CALR and the number of neutrophils and dendritic cells, suggesting that CALR was highly correlated with many immunomodulators in BRCA. Our results provide potential biomarkers of CALR in BRCA. CALR may interact synergistically with other immunomodulators to regulate the immune microenvironment, which could be utilized to develop new immunotherapy drugs.

The use of multicomponent reactions in the development of bis-boronic acids for the detection of ß-sialic acid.

Sialic acid (SA) is a naturally occurring monosaccharide found in glycoproteins and glycolipids. Changes in the expression of SA are associated with several diseases; thus, the detection of SA is of great significance for biological research, cancer diagnosis, and treatment. Boronic acid analogs have emerged as a promising tool for detecting sugars such as SA due to its reversible covalent bonding ability. In this study, 11 bis-boronic acid compounds and 2 mono-boronic acid compounds were synthesized via a highly efficient Ugi-4CR strategy. The synthesized compounds were subjected to affinity fluorescence binding experiments to evaluate their binding capability to SA. Compound A1 was shown to have a promising binding constant of 2602 ± 100 M-1 at pH = 6.0. Density Functional Theory (DFT) calculations examining the binding modes between A1 and SA indicated that the position of the boronic acid functional group was strongly correlated with its interaction with SA's α-hydroxy acid unit. The DFT calculations were consistent with the observations from the fluorescence experiments, demonstrating that the number and relative positions of the boronic acid functional groups are critical factors in enhancing the binding affinity to SA. DFT calculations of both S and R configuration of A1 indicated that the effect of the S/R configuration of A1 on its binding with ß-sialic acid was insignificant as the Ugi-4CR generated racemic products. A fluorine atom was incorporated into the R2 substituent of A1 as an electron-withdrawing group to produce A5, which possessed a significantly higher capability to bind to SA (Keq = 7015 ± 5 M-1 at pH = 6.0). Finally, A1 and A5 were shown to possess exceptional binding selectivity toward ß-sialic acid under pH of 6.0 and 6.5 while preferring to bind with glucose, fructose, and galactose under pH of 7.0 and 7.5.

The respiratory enzyme complex Rnf is vital for metabolic adaptation and virulence in Fusobacterium nucleatum.

IMPORTANCE: This paper illuminates the significant question of how the oral commensal Fusobacterium nucleatum adapts to the metabolically changing environments of several extra-oral sites such as placenta and colon to promote various diseases as an opportunistic pathogen. We demonstrate here that the highly conserved Rhodobacter nitrogen-fixation complex, commonly known as Rnf complex, is key to fusobacterial metabolic adaptation and virulence. Genetic disruption of this Rnf complex causes global defects in polymicrobial interaction, biofilm formation, cell growth and morphology, hydrogen sulfide production, and ATP synthesis. Targeted metabolomic profiling demonstrates that the loss of this respiratory enzyme significantly diminishes catabolism of numerous amino acids, which negatively impacts fusobacterial virulence as tested in a preterm birth model in mice.

Antidepressant effect of licorice total flavonoids and liquiritin: A review.

With the development of society and changes in lifestyle, major depressive disorder (MDD) has become a significant disease that plagues many people. Licorice, an excellent natural medicine with a long history of cultivation and application, is found in classical antidepressant prescriptions such as Chaihu Shugan Powder, Ganmai Dazao Decoction, Suanzaoren Decoction, etc. Licorice mainly contains triterpenoids and flavonoids, among which licorice total flavonoids (LF) and liquiritin are the main active components with good antidepressant effects. The pharmacological effects of licorice have been extensively investigated in current studies. However, a review of the antidepressant effects of LF and liquiritin has not been conducted. This article reviews the antidepressant effects of LF and liquiritin, including the biological characteristics of licorice and the pharmacological mechanism of LF and liquiritin in treating MDD. Studies have shown that LF and liquiritin can exert their antidepressant effects by improving depressive behavior, regulating endocrine and hypothalamic-pituitary-adrenal (HPA) axis function, affecting the brain-derived neurotrophic factor (BDNF)/tyrosine kinase B (TrkB) signaling pathway, enhancing synaptic plasticity, increasing monoamine neurotransmitter levels, protecting nerve cells, reducing inflammation, preventing apoptosis, reducing oxidation and other ways. This lays a theoretical foundation for the development of antidepressant drugs.

Chemical composition, sources, and health risks of PM2.5 in small cities with different urbanization during 2020 Chinese Spring Festival.

To investigate the impact of quarantine measures and fireworks banning policy on chemical composition and sources of PM2.5 and associated health risks in small, less developed cities, we sampled in Guigang (GG), Shaoyang (SY), and Tianshui (TS), located in eastern, central, and north-western China, in 2020 Spring Festival (CSF). Mass concentration, carbonaceous, metals, and WSIIs of PM2.5 were analyzed. The study found high levels of PM2.5 pollution with the average concentration of 168.05 µg/m3 in TS, 134.59 µg/m3 in SY, and 125.71 µg/m3 in GG. A negative correlation was found between the urbanization level and PM2.5 pollution. Lockdown measures reduced PM2.5 mass and industrial elements. In non-control period (NCP), combustion and fireworks were the major sources of PM2.5 in GG and TS, and industry source accounted for a significant proportion in the relatively more urbanized SY. Whereas on control period (CP), soil dust, combustion, and road dust were the main source in GG, secondary aerosols dominated in SY and TS. Our health risk assessment showed unacceptable levels of non-carcinogenic and carcinogenic risks over the study areas, despite lockdown measures reducing health risks. As and Cr(VI), as the major pollutants, their associated sources, industry sources, and fireworks sources, posed the greatest risk to people at the sampling sites after exposure to PM2.5. This work supports the improvement of PM2.5 control strategies in small Chinese cities during the CSF.

Hydrogenated silicene nanosheet functionalized scaffold enables immuno-bone remodeling.

An ideal implant needs to have the ability to coordinate the foreign body response and tissue regeneration. Here, Hydrogenated-silicon nanosheets (H-Si NSs) with favorable biodegradability are integrated and functionalized into a ß-tricalcium phosphate scaffold (H-Si TCP) for bone defect healing. H-Si TCP can greatly improve bone regeneration through osteoimmunomodulation-guided biodegradation in vivo. The spatiotemporal regulation of degradation products replenishes sufficient nutrients step by step for the entire process of bone repair. Extracellular and intracellular reactive oxygen species (ROS) are first downregulated by reaction with H-Si NSs, followed by marked M2 polarization, remodeling the micro-environment timely for immune-bone regeneration. The release of primary reaction products awakened bone marrow mesenchymal stem cells (BMSCs), which are converted into osteoblasts anchored on scaffolds. Subsequently, biomineralization is promoted by the final degradation products. The intrinsic ROS-responsive, immunoregulatory, and osteo-promotive capability of 2D H-Si NSs makes such composite H-Si TCP scaffold a highly potential alternative for the treatment of critical bone defect.

Butyrate protects against MRSA pneumonia via regulating gut-lung microbiota and alveolar macrophage M2 polarization.

IMPORTANCE: Pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) continues to carry a high burden in terms of mortality. With the roles of gut microbiota in mediating lung diseases being gradually uncovered, the details of the molecular mechanism of the "gut-lung axis" mediated by beneficial microorganisms and small-molecule metabolites have gradually attracted the attention of researchers. However, further studies are still necessary to determine the efficacy of microbial-based interventions. Our findings indicate that sodium butyrate (NaB) alleviates MRSA-induced pulmonary inflammation by improving gut-lung microbiota and promoting M2 polarization of alveolar macrophages. Therefore, the preventive administration of NaB might be explored as an effective strategy to control MRSA pneumonia.

Organocatalytic Si-CAryl Bond Functionalization-Enabled Atroposelective Synthesis of Axially Chiral Biaryl Siloxanes.

Chiral organosilanes are valuable chemical entities in the development of functional organic materials, asymmetric catalysis, and medicinal chemistry. As an important strategy for constructing chiral organosilanes, the asymmetric functionalization of the Si-CAryl bond typically relies on transition-metal catalysis. Herein, we present an efficient method for atroposelective synthesis of biaryl siloxane atropisomers via organocatalytic Si-C bond functionalization of dinaphthosiloles with silanol nucleophiles. The reaction proceeds through an asymmetric protonation and simultaneous Si-C bond cleavage/silanolysis sequence in the presence of a newly developed chiral Brønsted acid catalyst. The versatile nature of the Si-C bond streamlines the derivatization of axially chiral products into other functional atropisomers, thereby expanding the applicability of this method.

Proteomic analysis of high and low-motility frozen-thawed spermatozoa in yak provides important insights into the molecular mechanisms underlying sperm cryodamage.

Sperm cryodamage caused by cryopreservation limits the use of frozen yak spermatozoa in artificial insemination (AI). However, the proteomic changes involved in the cryodamage of yak spermatozoa have not been investigated to date. Therefore, this study aimed to identify proteins related to freezing tolerance. Tandem mass tag (TMT) were used in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for identifying differentially expressed proteins (DEPs) between high-motility (HM) and low-motility (LM) frozen-thawed yak spermatozoa. A total of 116 DEPs were identified (>1.5-fold, P < 0.05); of which, 104 proteins were upregulated in HM spermatozoa and 12 proteins were upregulated in LM spermatozoa. The results of functional annotation analysis revealed that the DEPs were mainly involved in metabolic processes. A total of 20 DEPs that were abundantly expressed in HM spermatozoa were strongly associated with carbohydrate metabolism. The results of KEGG analysis revealed that the DEPs were enriched in glycolysis/gluconeogenesis, PPAR signaling pathway, and Ras signaling pathway. In addition, many antioxidant enzymes such as superoxide dismutase (SOD1), peroxiredoxin-6 (PRDX6), and Parkinson disease protein 7 (PARK7) were upregulated in HM spermatozoa, suggesting that these enzymes affect the motility of spermatozoa by regulating the levels of reactive oxygen species (ROS) in frozen-thawed spermatozoa. Altogether, the findings of this study elucidate the mechanisms through which cryopreservation affects the movement of yak spermatozoa and offer a novel basis for refining freezing techniques and modifying cryopreservation extender components.

Research progress of sophoridine's pharmacological activities and its molecular mechanism: an updated review.

Background: Sophoridine, the major active constituent of Sophora alopecuroides and its roots, is a bioactive alkaloid with a wide range of pharmacological effects, including antitumor, anti-inflammatory, antiviral, antibacterial, analgesic, cardioprotective, and immunoprotective activities. Sophora flavescens Aiton is a traditional Chinese medicine that is bitter and cold. Additionally, it also exhibits the effects of clearing heat, eliminating dampness, and expelling insects. Aims of the study: To summarize the pharmacological research and associated mechanisms of sophoridine, we compiled this review by combining a huge body of relevant literature. Materials and methods: The information related to this article was systematically collected from the scientific literature databases including PubMed, Google Scholar, Web of Science, Science Direct, Springer, China National Knowledge Infrastructure, published books, PhD and MS dissertations. Results: Its antitumor activity is particularly remarkable, as it can inhibit cancer cell proliferation, invasion, and metastasis while inducing cell cycle arrest and apoptosis. Additionally, sophoridine also holds therapeutic potential for myocardial ischemia, osteoporosis, arrhythmias, and neurological disorders, primarily through the suppression of related inflammatory factors and cell apoptosis. However, sophoridine has also exhibited adverse effects such as hepatotoxicity and neurotoxicity. The antidisease effect and mechanism of sophoridine are diverse, so it has high research value. Conclusion: As an important traditional Chinese medicine alkaloid, modern pharmacological studies have demonstrated that sophoridine has prominent bioactivities, especially on anti-tumor anti-inflammation activities, and cardiovascular system protection. These activities provide prospects for novel drug development for cancer and some chronic diseases. Nevertheless, the understanding of the multitarget network pharmacology, long-term in vivo toxicity, and clinical efficacy of sophoridine require further detailed research.

The respiratory enzyme complex Rnf is vital for metabolic adaptation and virulence in Fusobacterium nucleatum.

A prominent oral commensal and opportunistic pathogen, Fusobacterium nucleatum can traverse to extra-oral sites such as placenta and colon, promoting adverse pregnancy outcomes and colorectal cancer, respectively. How this anaerobe sustains many metabolically changing environments enabling its virulence potential remains unclear. Informed by our genome-wide transposon mutagenesis, we report here that the highly conserved Rnf complex, encoded by the rnfCDGEAB gene cluster, is key to fusobacterial metabolic adaptation and virulence. Genetic disruption of the Rnf complex via non-polar, in-frame deletion of rnfC (Δ rnfC ) abrogates polymicrobial interaction (or coaggregation) associated with adhesin RadD and biofilm formation. The defect in coaggregation is not due to reduced cell surface of RadD, but rather an increased level of extracellular lysine, which binds RadD and inhibits coaggregation. Indeed, removal of extracellular lysine via washing Δ rnfC cells restores coaggregation, while addition of lysine inhibits this process. These phenotypes mirror that of a mutant (Δ kamAΔ ) that fails to metabolize extracellular lysine. Strikingly, the Δ rnfC mutant is defective in ATP production, cell growth, cell morphology, and expression of the enzyme MegL that produces hydrogen sulfide from cysteine. Targeted metabolic profiling demonstrated that catabolism of many amino acids, including histidine and lysine, is altered in Δ rnfC cells, thereby reducing production of ATP and metabolites including H2S and butyrate. Most importantly, we show that the Δ rnfC mutant is severely attenuated in a mouse model of preterm birth. The indispensable function of Rnf complex in fusobacterial pathogenesis via modulation of bacterial metabolism makes it an attractive target for developing therapeutic intervention.

Brain and Spinal Tumors Originating from the Germ Line Cells.

Primary central nervous system germ cell tumors (CNS GCTs) are part of the GCTs in children and adults. This tumor entity presents with geographic variation, age, and sex predilection. There are two age peaks of incidence distribution at the first few months of life and in adolescence. CNS GCTs are heterogeneous in histopathological subtypes, locations, and tumor marker (AFP, ß-hCG) secretions. In the WHO CNS tumor classification, GCTS are classified as germinoma and nongerminomatous GCT (NGGCT) with different subtypes (including teratoma). Excluding mature teratoma, the remaining NGGCTs are malignant (NGMGCT). In teratoma, growing teratoma syndrome and teratoma with somatic-type malignancy should be highlighted. The common intracranial locations are pineal region, neurohypophysis (NH), bifocal pineal-NH, basal ganglia, and cerebral ventricle. Above 50% of intracranial GCTs (IGCTs) present obstructive hydrocephalus. Spinal tumors are rare. Age, locations, hydrocephalus, and serum/CSF titer of ß-hCG correlate with clinical manifestations. Delayed diagnosis is common in tumors arising in neurohypophysis, bifocal, and basal ganglia resulting in the increasing of physical dysfunction and hormonal deficits. Staging work-up includes CSF cytology for tumor cells and contrast-enhanced MRI of brain and spine for macroscopic metastasis before treatment commences. The therapeutic approach of CNS GCTs integrates locations, histopathology, staging, tumor marker level, and therapeutic classification. Treatment strategies include surgical biopsy/excision, chemotherapy, radiotherapy (single or combination). Secreting tumors with consistent imaging may not require histopathological diagnosis. Primary germinomas are highly radiosensitive and the therapeutic aim is to maintain high survival rate using optimal radiotherapy regimen with/without chemotherapy combination. Primary NGNGCTs are less radiosensitive. The therapeutic aim is to increase survival utilizing more intensive chemotherapy and radiotherapy. The negative prognostic factors are residue disease at the end of treatment and serum or CSF AFP level >1000 ng/mL at diagnosis. In refractory or recurrent NMGGCTs, besides high-dose chemotherapy, new therapy is necessary. Molecular profiling and analysis help for translational research. Survivors of pediatric brain tumors frequently experience cancer-related cognitive dysfunction, physical disability, pituitary hormone deficiency, and other CNS complications after cranial radiotherapy. Continuous surveillance and assessment may lead to improvements in treatment protocols, transdisciplinary interventions, after-treatment rehabilitation, and quality of life.