Use of the Tubridge flow diverter in the treatment of intracranial aneurysms: a single center experience.

To investigate the safety and effect of Tubridge flow diverter deployment for the treatment of intracranial aneurysms, 85 patients with intracranial aneurysms treated with the Tubridge flow diverter were retrospectively enrolled. The clinical data including the baseline data, aneurysm parameters before and after treatment, and follow-up outcomes were assessed. Among 85 patients, there were 35 (41.2%) males and 50 females (58.8%) aged 17-77 (mean 56.7 ± 11.1) years with 110 aneurysms. Five (5.9%) patients initially presented with subarachnoid hemorrhage from aneurysm rupture. The aneurysm size was 2-30 (mean 8.6) mm, and the aneurysm neck was 2-10.6 (mean 5.7 ± 2.3) mm. Ninety-three Tubridge stents were deployed. Twenty-five (29.4%) patients experienced adjunctive loose coiling. Blood flow was significantly reduced from entering the aneurysm after stent deployment. Periprocedural complications occurred in three (3.5%) patients, including in-stent thrombosis during embolization in one patient (1.2%), conjunctiva edema on the right in one patient (1.2%), and acute multiple cerebral infarctions in one patient (1.2%). Angiographic follow-up was conducted in 67 (78.8%) patients 3-36 (mean 15.3 ± 5.6) months later. In 11 (16.4% or 11/67) patients, blood flow still entered the aneurysm with the O'Kelly-Marotta (OKM) grade B in two (3.0%) patients and grade C in nine (13.4%), whereas complete occlusion (OKM grade D) was achieved in the other 56 (83.6% or 56/67) aneurysms. In-stent stenosis was present in five (7.5%) patients with approximately 25% stenosis in three (4.5%) patients and 50% in two (3.0%). In conclusion, the Tubridge flow diverter can be safely and efficiently applied in the treatment of small and large intracranial aneurysms, with a low periprocedural complication rate, a high occlusion degree, and a low in-stent stenosis rate at follow-up even though large aneurysms may necessitate a longer surgical time and adjunctive coiling.

Quantitative assessment of multiple pathogen exposure and immune dynamics at scale.

IMPORTANCE: Serology reveals exposure to pathogens, as well as the state of autoimmune and other clinical conditions. It is used to evaluate individuals and their histories and as a public health tool to track epidemics. Employing a variety of formats, studies nearly always perform serology by testing response to only one or a few antigens. However, clinical outcomes of new infections also depend on which previous infections may have occurred. We developed a high-throughput serology method that evaluates responses to hundreds of antigens simultaneously. It can be used to evaluate thousands of samples at a time and provide a quantitative readout. This tool will enable doctors to monitor which pathogens an individual has been exposed to and how that changes in the future. Moreover, public health officials could track populations and look for infectious trends among large populations. Testing many potential antigens at a time may also aid in vaccine development.

Unraveling False Positives in Unsupervised Defect Detection Models: A Study on Anomaly-Free Training Datasets.

Unsupervised defect detection methods have garnered substantial attention in industrial defect detection owing to their capacity to circumvent complex fault sample collection. However, these models grapple with establishing a robust boundary between normal and abnormal conditions in intricate scenarios, leading to a heightened frequency of false-positive predictions. Spurious alerts exacerbate the work of reconfirmation and impede the widespread adoption of unsupervised anomaly detection models in industrial applications. To this end, we delve into the sole available data source in unsupervised defect detection models, the unsupervised training dataset, to introduce a solution called the False Alarm Identification (FAI) method aimed at learning the distribution of potential false alarms using anomaly-free images. It exploits a multi-layer perceptron to capture the semantic information of potential false alarms from a detector trained on anomaly-free training images at the object level. During the testing phase, the FAI model operates as a post-processing module applied after the baseline detection algorithm. The FAI algorithm determines whether each positive patch predicted by the normalizing flow algorithm is a false alarm by its semantic features. When a positive prediction is identified as a false alarm, the corresponding pixel-wise predictions are set to negative. The effectiveness of the FAI method is demonstrated by two state-of-the-art normalizing flow algorithms on extensive industrial applications.

Middle cerebral artery bifurcation aneurysms are associated with patient age, sex, bifurcation angle, and vascular diameters.

To investigate the relationship of the middle cerebral artery (MCA) bifurcation aneurysms with patients' age and sex, vascular angles at the bifurcation, and diameters of the M1 and two M2 arteries, patients with and without MCA aneurysms were retrospectively enrolled. The lateral angles, MCA bifurcation angle and arterial diameter were measured and analyzed. Totally, 121 (19.0%) patients with and 517 (81.0%) without MCA aneurysms were enrolled. Most (n = 88 or 72.7%) aneurysms were present in the age range of 40-70 years, and significantly (P = 0.01) more women than men had the bifurcation aneurysms. The MCA bifurcation angle was significantly greater (149.2° ± 32.6° vs. 107.2° ± 26.3°; P < 0.0001) while both the smaller and larger lateral (M1/M2) angles were significantly smaller in patients with than without aneurysms (82.0° ± 23.7° vs. 109.1° ± 22.7° with P < 0.001 for the smaller and 123.2° ± 25.2° vs. 139.5° ± 16.9° with P < 0.001 for the larger lateral angle). 109 (90.1%) bifurcation aneurysms deviated towards the smaller lateral angle, and 103 (85.1%) aneurysms deviated towards the thinner M2 branch. The maximal aneurysm diameter ranged 1.6-13.8 (mean 5.4 ± 2.4) mm and was significantly (P < 0.05) positively correlated with the diameter of both M2 arterial branches (R = 0.57 and P = 0.01 for the smaller M2, and R = 0.69 and P = 0.002 for the larger M2) or the MCA bifurcation angle. A significant (P < 0.0001) negative correlation was detected between age and the smaller lateral angle but a significant (P < 0.0001) positive correlation between age and the MCA bifurcation angle in patients without MCA bifurcation aneurysms or in the total patients. MCA bifurcation angle was the only significant (P = 0.0001, odds ratio 2.7, 95% confidence interval 1.6-3.8) independent risk factor for MCA bifurcation aneurysm presence, with the bifurcation angle threshold of 124.1° and an area under the ROC curve of 0.86. In conclusion, significantly more MCA bifurcation aneurysms are present in older patients, females, and patients with a wider MCA bifurcation angle, and deviate towards the smaller lateral angle and the thinner M2 segment. MCA bifurcation angle is the only independent risk factor for presence of MCA bifurcation aneurysms with the threshold of 124.1°.

Nanotheranostics in cancer lymph node metastasis: The long road ahead.

Lymph node metastasis (LNM) significantly impacts the prognosis of cancer patients. Despite significant advancements in diagnostic techniques and treatment modalities, clinical challenges continue to persist in the realm of LNM. These include difficulties in early diagnosis, limited treatment efficacy, and potential side effects and injuries associated with treatment. Nanotheranostics, a field within nanotechnology, seamlessly integrates diagnostic and therapeutic functionalities. Its primary goal is to provide precise and effective disease diagnosis and treatment simultaneously. The development of nanotheranostics for LNM offers a promising solution for the stratified management of patients with LNM and promotes the advancement of personalized medicine. This review introduces the mechanisms of LNM and challenges in its diagnosis and treatment. Furthermore, it demonstrates the advantages and development potential of nanotheranostics, focuses on the challenges nanotheranostics face in its application, and provides an outlook on future trends. We consider nanotheranostics a promising strategy to improve clinical effectiveness and efficiency as well as the prognosis of cancer patients with LNM.

Use of the Neuroform Atlas stent for wide-necked cerebral aneurysms.

To investigate the effect and safety of the Neuroform Atlas (NFA) stent in stent-assisted coiling of wide-necked intracranial aneurysms, patients with wide-necked intracranial aneurysms were retrospectively enrolled and treated with the NFA stent-assisted coiling. The modified Rankin scale (mRS) grades and Raymond grades were used to assess the clinical outcomes and aneurysm occlusion degrees, respectively, after embolization and at follow-up. Totally, 122 patients were enrolled with 129 wide-necked aneurysms, and forty-nine (40.2%) patients experienced subarachnoid hemorrhage. A total of 134 NFA stents were deployed in all patients. Immediately after endovascular embolization, the Raymond grade was I in 112 (86.8%), II in 8 (6.2%), and III in 9 (7.0%). Complications occurred in 7 (5.7%) patients, including stent displacement in 2 (1.6%) patients, thrombosis and cerebral infarction in 4 (3.3%), and death in 1 (0.8%). Clinical follow-up was performed in 113 (92.6%) patients 6-30 (mean 21) months after embolization, with the mRS grade 0 in 99 (87.6%) patients, 1 in 7 (6.2%), 2 in 5 (4.4%), and 3 in 2 (1.8%). Good prognosis (mRS ≤ 2) was achieved in 111 (98.2%) patients while poor prognosis (mRS > 2) in two (1.8%). Digital subtraction angiography was conducted in 98 (80.3%) patients with 104 (80.6%) aneurysms 6-30 (mean 21) months after embolization. The Raymond grade was grade I in 94 (90.4%) aneurysms, II in 4 (3.8%), and III in 6 (5.8%). Compared with the Raymond grades immediately after embolization, 93 (89.4%) aneurysms disappeared, 9 (8.7%) remained unchanged in the occlusion status, and 2 (1.9%) were recurrent. In conclusion, the NFA stent may have a high aneurysm occlusion rate and a low complication rate in assisting coiling of wide-necked intracranial aneurysms even though further studies are necessary to prove this.

Comparative Analysis of Antimicrobial Antibodies between Mild and Severe COVID-19.

Patients with 2019 coronavirus disease (COVID-19) exhibit a broad spectrum of clinical presentations. A person's antimicrobial antibody profile, as partially shaped by past infection or vaccination, can reflect the immune system health that is critical to control and resolve the infection. We performed an explorative immunoproteomics study using microbial protein arrays displaying 318 full-length antigens from 77 viruses and 3 bacteria. We compared antimicrobial antibody profiles between 135 patients with mild COVID-19 disease and 215 patients with severe disease in 3 independent cohorts from Mexico and Italy. Severe disease patients were older with higher prevalence of comorbidities. We confirmed that severe disease patients elicited a stronger anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) response. We showed that antibodies against HCoV-229E and HcoV-NL63 but not against HcoV-HKU1 and HcoV-OC43 were also higher in those who had severe disease. We revealed that for a set of IgG and IgA antibodies targeting coronaviruses, herpesviruses, and other respiratory viruses, a subgroup of patients with the highest reactivity levels had a greater incidence of severe disease compared to those with mild disease across all three cohorts. On the contrary, fewer antibodies showed consistent greater prevalence in mild disease in all 3 cohorts. IMPORTANCE The clinical presentations of COVID-19 range from asymptomatic to critical illness that may lead to intensive care or even death. The health of the immune system, as partially shaped by past infections or vaccinations, is critical to control and resolve the infection. Using an innovative protein array platform, we surveyed antibodies against hundreds of full-length microbial antigens from 80 different viruses and bacteria in COVID-19 patients from different geographic regions with mild or severe disease. We not only confirmed the association of severe COVID-19 disease with higher reactivity of antibody responses to SARS-CoV-2 but also uncovered known and novel associations with antibody responses against herpesviruses and other respiratory viruses. Our study represents a significant step forward in understanding the factors contributing to COVID-19 disease severity. We also demonstrate the power of comprehensive antimicrobial antibody profiling in deciphering risk factors for severe COVID-19. We anticipate that our approach will have broad applications in infectious diseases.

Comparison of pipeline classic and flex embolization devices in endovascular performance for intracranial aneurysms.

To investigate the endovascular performance of the Pipeline Classic embolization device (PED Classic) and PED Flex device (PED Flex) in the treatment of intracranial aneurysms. Fifty-three patients with intracranial aneurysms treated with the PED Classic were retrospectively enrolled into the PED Classic group, and 118 patients with intracranial aneurysms treated with the PED Flex were enrolled into the PED Flex group. The Procedure time, contrast dosage, fluoroscopy time, and perioperative complications were analyzed. The success rate of the stenting procedure was 100% in both groups. In the PED Classic group, 58 PED Classic devices were implanted, and 26 aneurysms underwent coil embolization. In the PED Flex group, 126 PED Flex devices were implanted, and 35 aneurysms underwent concomitant coil embolization. The procedure time was significantly (P < .001) greater in the PED Classic (159.0 ±â€…42.0 minutes) than in the PED Flex (121.9 ±â€…4.0 minutes) group. The dosage of contrast agent (156.4 ±â€…39.4 vs 110.1 ±â€…38.5 mL) and the total fluoroscopic time (34.7 ±â€…5.7 minutes vs 22.8 ±â€…7.6 minutes) were significantly (P < .001) greater in the PED Classic than in the PED Flex group. Peri-procedural complications occurred in 5 (9.4%) patients in the PED Classic group and in 3 (2.5%) patients in the Flex group, without a statistically significant (P = .11) difference. The performance of the PED Flex device may be safer and easier than that of the PED Classic device in the treatment of intracranial aneurysms despite some serious complications which remain to be prevented.

Scaling eukaryotic cell-free protein synthesis achieved with the versatile and high-yielding tobacco BY-2 cell lysate.

Eukaryotic cell-free protein synthesis (CFPS) can accelerate expression and high-throughput analysis of complex proteins with functionally relevant post-translational modifications (PTMs). However, low yields and difficulties scaling such systems have prevented their widespread adoption in protein research and manufacturing. Here, we provide detailed demonstrations for the capabilities of a CFPS system derived from Nicotiana tabacum BY-2 cell culture (BY-2 lysate; BYL). BYL is able to express diverse, functional proteins at high yields in 48 h, complete with native disulfide bonds and N-glycosylation. An optimized version of the technology is commercialized as ALiCE® and advances in scaling of BYL production methodologies now allow scaling of eukaryotic CFPS reactions. We show linear, lossless scale-up of batch mode protein expression from 100 µL microtiter plates to 10 and 100 mL volumes in Erlenmeyer flasks, culminating in preliminary data from a litre-scale reaction in a rocking-type bioreactor. Together, scaling across a 20,000x range is achieved without impacting product yields. Production of multimeric virus-like particles from the BYL cytosolic fraction were then shown, followed by functional expression of multiple classes of complex, difficult-to-express proteins using the native microsomes of the BYL CFPS. Specifically: a dimeric enzyme; a monoclonal antibody; the SARS-CoV-2 receptor-binding domain; a human growth factor; and a G protein-coupled receptor membrane protein. Functional binding and activity are demonstrated, together with in-depth PTM characterization of purified proteins through disulfide bond and N-glycan analysis. Taken together, BYL is a promising end-to-end R&D to manufacturing platform with the potential to significantly reduce the time-to-market for high value proteins and biologics.

Safety and effect of pipeline flex embolization device for complex unruptured intracranial aneurysms.

To investigate the safety and short-term effect of Pipeline Flex devices in the treatment of complex unruptured intracranial aneurysms, a retrospective study was performed for patients with complex unruptured intracranial aneurysms who were treated with the Pipeline Flex embolization device (PED Flex device) combined with or without coiling. The clinical, endovascular, and follow-up data were analyzed. One hundred and thirty-one patients with 159 complex unruptured cerebral aneurysms were treated with the PED Flex device, with 144 Flex devices deployed. Periprocedural complications occurred in four patients, resulting in the complication rate of 3.1%, including ischemic complications in three patients (2.3%) and hemorrhagic complication in one (0.8%). At discharge, the mRS was 0 in 101 (77.1%) patients, 1 in 25 (19.1%), 2 in four (3.1%), and 4 in one (0.8%), with the good prognosis rate (mRS 0-2) of 99.2%. Clinical follow-up was carried out in 87 (66.4%) patients 3-42 months after the procedure, with the mRS of 0 in 78 (89.7%), 1 in five (5.7%), 2 in three (3.4%), and 4 in one (1.1%). No significant (P = 0.16) difference existed in the mRS at discharge compared with that at clinical follow-up. Angiographic follow-up was performed in 61 (46.7%) patients with 80 (50.3%) aneurysms at 3-40 months, with the OKM grade of D in 57 (71.3%) aneurysms, C in eight (10%), and B in 15 (18.8%). Asymptomatic instent stenosis occurred in four patients (6.6%). In conclusion: The treatment of complex intracranial aneurysms with the Pipeline Flex embolization device may be safe and effective, with a high complete occlusion rate, a decreased complication rate, and a good prognosis rate at medium follow-up.

Multifunctional Organic-Inorganic Hybrid Perovskite Microcrystalline Engineering and Electromagnetic Response Switching Multi-Band Devices.

High-efficiency electromagnetic (EM) functional materials are the core building block of high-performance EM absorbers and devices, and they are indispensable in various fields ranging from industrial manufacture to daily life, or even from national defense security to space exploration. Searching for high-efficiency EM functional materials and realizing high-performance EM devices remain great challenges. Herein, a simple solution-process is developed to rapidly grow gram-scale organic-inorganic (MAPbX3 , X = Cl, Br, I) perovskite microcrystals. They exhibit excellent EM response in multi bands covering microwaves, visible light, and X-rays. Among them, outstanding microwave absorption performance with multiple absorption bands can be achieved, and their intrinsic EM properties can be tuned by adjusting polar group. An ultra-wideband bandpass filter with high suppression level of -71.8 dB in the stopband in the GHz band, self-powered photodetectors with tunable broadband or narrowband photoresponse in the visible-light band, and a self-powered X-ray detector with high sensitivity of 3560 µC Gyair -1  cm-2  in the X-ray band are designed and realized by precisely regulating the physical features of perovskite and designing a novel planar device structure. These findings open a door toward developing high-efficiency EM functional materials for realizing high-performance EM absorbers and devices.

Evaluating Fe-Site and Vacancy Dependent Intrinsic Activity of NiFe Layered Double Hydroxides through Cavity Microelectrodes.

We report evaluating the intrinsic activity of Ni(OH)2, NiFe layered double hydroxides (LDHs), and NiFe-LDH having vacancies for oxygen evolution reaction (OER) by the use of cavity microelectrodes (CMEs) with controllable mass loading. The number of active Ni sites (NNi-sites) ranging from 1 × 1012 to 6 × 1012 is quantitatively correlated with OER current, which reveals that the introduction of Fe-sites and vacancies increases the turnover frequency (TOF) from 0.027 to 0.118 and 0.165 s-1, respectively. Electrochemical surface area (ECSA) is further quantitatively correlated with NNi-sites, which indicates that NNi-sites per unit ECSA (NNi-per-ECSA) is decreased by the introduction of Fe-sites and vacancies. Therefore, the difference of OER current per unit ECSA (JECSA) is reduced compared with that of TOF. The results demonstrate that CMEs provide a good platform to evaluate intrinsic activity with TOF, NNi-per-ECSA, and JECSA more reasonably.

Proteomic analysis identifies Stomatin as a biological marker for psychological stress.

Psychological stress emerges to be a common health burden in the current society for its highly related risk of mental and physical disease outcomes. However, how the quickly-adaptive stress response process connects to the long-observed organismal alterations still remains unclear. Here, we investigated the profile of circulatory extracellular vesicles (EVs) after acute stress (AS) of restraint mice by phenotypic and proteomic analyses. We surprisingly discovered that AS-EVs demonstrated significant changes in size distribution and plasma concentration compared to control group (CN) EVs. AS-EVs were further characterized by various differentially expressed proteins (DEPs) closely associated with biological, metabolic and immune regulations and were functionally important in potentially underlying multiple diseases. Notably, we first identified the lipid raft protein Stomatin as an essential biomarker expressed on the surface of AS-EVs. These findings collectively reveal that EVs are a significant function-related liquid biopsy indicator that mediate circulation alterations impinged by psychological stress, while also supporting the idea that psychological stress-associated EV-stomatin can be used as a biomarker for potentially predicting acute stress responses and monitoring psychological status. Our study will pave an avenue for implementing routine plasma EV-based theranostics in the clinic.

Identification of anti-Helicobacter pylori antibody signatures in gastric intestinal metaplasia.

BACKGROUND: Chronic Helicobacter pylori infection may induce gastric intestinal metaplasia (IM). We compared anti-H. pylori antibody profiles between IM cases and non-atrophic gastritis (NAG) controls. METHODS: We evaluated humoral responses to 1528 H. pylori proteins among a discovery set of 50 IM and 50 NAG using H. pylori protein arrays. Antibodies with ≥ 20% sensitivity at 90% specificity for either group were selected and further validated in an independent set of 100 IM and 100 NAG using odds ratios (OR). A validated multi-signature was evaluated using the area under the receiver operating characteristics curve (AUC) and net reclassification improvement (NRI). RESULTS: Sixty-two immunoglobulin (Ig) G and 11 IgA antibodies were detected in > 10%. Among them, 22 IgG and 6 IgA antibodies were different between IM and NAG in the discovery set. Validated antibodies included 11 IgG (anti-HP1177/Omp27/HopQ [OR = 8.1, p < 0.001], anti-HP0547/CagA [4.6, p < 0.001], anti-HP0596/Tipα [4.0, p = 0.002], anti-HP0103/TlpB [3.8, p = 0.001], anti-HP1125/PalA/Omp18 [3.1, p = 0.001], anti-HP0153/RecA [0.48, p = 0.03], anti-HP0385 [0.41, p = 0.006], anti-HP0243/TlpB [0.39, p = 0.016], anti-HP0371/FabE [0.37, p = 0.017], anti-HP0900/HypB/AccB [0.35, p = 0.048], and anti-HP0709 [0.30, p = 0.003]), and 2 IgA (anti-HP1125/PalA/Omp18 [2.7, p = 0.03] and anti-HP0596/Tipα [2.5, p = 0.027]). A model including all 11 IgG antibodies (AUC = 0.81) had better discriminated IM and NAG compared with an anti-CagA only (AUC = 0.77) model (NRI = 0.44; p = 0.001). CONCLUSIONS: Our study represents the most comprehensive assessment of anti-H. pylori antibody profiles in IM. The target antigens for these novel antibodies may act together with CagA in the progression to IM. Along with other biomarkers, specific H. pylori antibodies may identify IM patients, who would benefit from surveillance.

Comparative Microbiomics Analysis of Antimicrobial Antibody Response between Patients with Lung Cancer and Control Subjects with Benign Pulmonary Nodules.

BACKGROUND: CT screening can detect lung cancer early but suffers a high false-positive rate. There is a need for molecular biomarkers that can distinguish malignant and benign indeterminate pulmonary nodules (IPN) detected by CT scan. METHODS: We profiled antibodies against 901 individual microbial antigens from 27 bacteria and 29 viruses in sera from 127 lung adenocarcinoma (ADC), 123 smoker controls (SMC), 170 benign nodule controls (BNC) individuals using protein microarrays to identify ADC and BNC specific antimicrobial antibodies. RESULTS: Analyzing fourth quartile ORs, we found more antibodies with higher prevalence in the three BNC subgroups than in ADC or SMC. We demonstrated that significantly more anti-Helicobacter pylori antibodies showed higher prevalence in ADC relative to SMC. We performed subgroup analysis and found that more antibodies with higher prevalence in light smokers (≤20 pack-years) compared with heavy smokers (>20 pack-years), in BNC with nodule size >1 cm than in those with ≤1 cm nodules, and in stage I ADC than in stage II and III ADC. We performed multivariate analysis and constructed antibody panels that can distinguish ADC versus SMC and ADC versus BNC with area under the ROC curve (AUC) of 0.88 and 0.80, respectively. CONCLUSIONS: Antimicrobial antibodies have the potential to reduce the false positive rate of CT screening and provide interesting insight in lung cancer development. IMPACT: Microbial infection plays an important role in lung cancer development and the formation of benign pulmonary nodules.

Atypical stromal herpes simplex keratitis: clinical features and diagnosis.

PURPOSE: To report atypical clinical features and diagnosis of stromal herpes simplex keratitis (HSK) and to evaluate the diagnostic efficiency of tear HSV-sIgA in atypical HSK. STUDY DESIGN: Prospective observational study. METHODS: Records of keratitis' patients with tear herpes simplex virus (HSV)-sIgA test results acquired between May 2019 and November 2021 were evaluated retrospectively. Positive tear HSV-sIgA test was used to identify herpes simplex virus (HSV) infection. Patients with typical presentations and histories of HSV keratitis (HSK) were excluded. RESULTS: Eleven eyes of 11 patients initially diagnosed as keratitis caused by other etiology were confirmed as having HSV infection by positive results of tear HSV-sIgA. Clinical features of atypical stromal HSK were variable. Antiviral treatment was effective in all patients. CONCLUSION: The appearance of an atypical stromal HSK represents a diagnostic challenge. Tear HSV-sIgA test could help provide a quick diagnosis.

The MocR family transcriptional regulator DnfR has multiple binding sites and regulates Dirammox gene transcription in Alcaligenes faecalis JQ135.

Microbial ammonia oxidation is vital to the nitrogen cycle. A biological process, called Dirammox (direct ammonia oxidation, NH3 →NH2 OH→N2 ), has been recently identified in Alcaligenes ammonioxydans and Alcaligenes faecalis. However, its transcriptional regulatory mechanism has not yet been fully elucidated. The present study characterized a new MocR-like transcription factor DnfR that is involved in the Dirammox process in A. faecalis strain JQ135. The entire dnf cluster was composed of 10 genes and transcribed as five transcriptional units, that is, dnfIH, dnfR, dnfG, dnfABCDE and dnfF. DnfR activates the transcription of dnfIH, dnfG and dnfABCDE genes, and represses its own transcription. The intact 1506-bp dnfR gene was required for activation of Dirammox. Electrophoretic mobility shift assays and DNase I footprinting analyses showed that DnfR has one binding site in the dnfH-dnfR intergenic region and two binding sites in the dnfG-dnfA intergenic region. Three binding sites of DnfR shared a 6-bp repeated conserved sequence 5'-GGTCTG-N17 -GGTCTG-3' which was essential for the transcription of downstream target genes. Cysteine and glutamate act as possible effectors of DnfR to activate the transcription of transcriptional units of dnfG and dnfABCDE, respectively. This study provided new insights in the transcriptional regulation mechanism of Dirammox by DnfR in A. faecalis JQ135.

Evaluation of peripheral blood T-lymphocyte subpopulations features in patients with hepatitis B virus-related acute-on-chronic liver failure based on single-cell sequencing technology / 中华肝脏病杂志

Objective: T lymphocyte exhaustion is an important component of immune dysfunction. Therefore, exploring peripheral blood-exhausted T lymphocyte features in patients with hepatitis B virus-related acute-on-chronic liver failure may provide potential therapeutic target molecules for ACLF immune dysfunction. Methods: Six cases with HBV-ACLF and three healthy controls were selected for T-cell heterogeneity detection using the single-cell RNA sequencing method. In addition, exhausted T lymphocyte subpopulations were screened to analyze their gene expression features, and their developmental trajectories quasi-timing. An independent sample t-test was used to compare the samples between the two groups. Results: Peripheral blood T lymphocytes in HBV-ACLF patients had different differentiation trajectories with different features distinct into eight subpopulations. Among them, the CD4(+)TIGIT(+) subsets (P = 0.007) and CD8(+)LAG3(+) (P = 0.010) subsets with highly exhausted genes were significantly higher than those in healthy controls. Quasi-time analysis showed that CD4(+)TIGIT(+) and CD8(+)LAG3(+) subsets appeared in the late stage of T lymphocyte differentiation, suggesting the transition of T lymphocyte from naïve-effector-exhausted during ACLF pathogenesis. Conclusion: There is heterogeneity in peripheral blood T lymphocyte differentiation in patients with HBV-ACLF, and the number of exhausted T cells featured by CD4(+)TIGIT(+)T cell and CD8(+)LAG3(+) T cell subsets increases significantly, suggesting that T lymphocyte immune exhaustion is involved in the immune dysfunction of HBV-ACLF, thereby identifying potential effective target molecules for improving ACLF patients' immune function.

Effect and safety of Tubridge flow diverter in the treatment of unruptured intracranial aneurysms.

The effect and safety of the Tubridge flow diverting device are unknown in the treatment of intracranial aneurysms after optimization of the device, improvement in the deployment of the device, and accumulation of experience of using the device. This retrospective one-center study was performed to investigate the clinical effect and safety of the Tubridge flow diverting device in the treatment of unruptured intracranial aneurysms. Twenty-three patients with 33 unruptured intracranial aneurysms which were treated with the Tubridge device were retrospectively enrolled. The clinical data, endovascular procedure, complications, and follow-up were analyzed. Twenty-seven Tubridge devices were deployed to treat the 33 aneurysms, and the deployment was failed in 1 case, resulting in the success stenting rate of 96.3%. In 5 (15.2%) aneurysms, coils were loosely packed. Peri-procedural complications occurred in 2 patients (8.7%), including 1 procedure-related complication in which the distal end of a Tubridge device herniated into the aneurysm cavity. In another case, weakness of left upper limb occurred on the second day post procedure, with instent thrombosis being suspected, which was recovered after medication. No other complications occurred. Twenty-three (100%) patients had clinical follow-up 6 months later, with the mRS of 0 in 21 patients, 1 in 1, and 2 in 1. Five (21.7%) patients with 11 aneurysms underwent digital subtraction angiography at 6-month follow-up, with 8 aneurysms being completely occluded (Raymond grade I) and 3 aneurysms still visible (Raymond grade III). The Tubridge flow diverter may be safe and effective in the treatment of unruptured intracranial aneurysms with low perioperative complications and good follow-up outcomes even though multi-center and prospective clinical studies with a large size sample are still needed to validate these results.