Endovascular treatment of symptomatic severe intracranial atherosclerotic stenosis with a novel intracranial dedicated drug-eluting stent: a more effective treatment approach.

Background: Endovascular treatment of severe intracranial atherosclerotic stenosis (ICAS) using coronary drug-eluting stents (DESs) significantly reduces the risk of in-stent restenosis (ISR) and stroke recurrence. However, there are few reports regarding the treatment of ICAS with intracranial dedicated DES. Herein, we present our experience with the feasibility, safety, and medium-term follow-up outcomes of a novel intracranial DES, named NOVA stent, in patients with symptomatic severe ICAS (≥70%). Methods: From December 2021 to May 2022, patients with symptomatic severe ICAS who underwent implantation of the NOVA stent in our institution were retrospectively analyzed for procedural results, perioperative complications, imaging and clinical follow-up outcomes. Results: Twenty-four patients, 16 (66.7%) with anterior circulation lesions and 8 (33.3%) with posterior circulation lesions, were enrolled. All patients with intracranial ICA (n = 6), middle cerebral artery (n = 10), basilar artery (n = 3), intracranial vertebral artery (n = 3), and the vertebrobasilar junction (n = 2) stenosis were treated successfully using NOVA stents. The severity of stenosis ranged from 75 to 96% (mean 85.9%) before treatment and this was reduced to 0 to 20% (mean 8.6%) immediately after stent placement. Symptomatic distal embolism occurred in one case; however, there were no other perioperative complications. The mean follow-up duration was 12.2 ± 1.06 months. No symptomatic ischemic events occurred during follow-up. Follow-up cerebral angiography was performed in 22 of 24 patients (91.7%), and significant ISR occurred in one patient (4.2%). Conclusion: Our results demonstrate that implantation of the novel intracranial DES NOVA in severe ICAS is feasible, safe, and effective in selected cases, reducing the incidence of ISR, and showing excellent midterm clinical outcomes, providing a promising option for ICAS treatment.

Cancer on motors: How kinesins drive prostate cancer progression?

Prostate cancer causes numerous male deaths annually. Although great progress has been made in the diagnosis and treatment of prostate cancer during the past several decades, much about this disease remains unknown, especially its pathobiology. The kinesin superfamily is a pivotal group of motor proteins, that contains a microtubule-based motor domain and features an adenosine triphosphatase activity and motility characteristics. Large-scale sequencing analyses based on clinical samples and animal models have shown that several members of the kinesin family are dysregulated in prostate cancer. Abnormal expression of kinesins could be linked to uncontrolled cell growth, inhibited apoptosis and increased metastasis ability. Additionally, kinesins may be implicated in chemotherapy resistance and escape immunologic cytotoxicity, which creates a barrier to cancer treatment. Here we cover the recent advances in understanding how kinesins may drive prostate cancer progression and how targeting their function may be a therapeutic strategy. A better understanding of kinesins in prostate cancer tumorigenesis may be pivotal for improving disease outcomes in prostate cancer patients.

Biocontrol activity of an endophytic Alternaria alternata Aa-Lcht against apple Valsa canker.

Apple Valsa canker (AVC), caused by Valsa mali, is the most serious branch disease for apples in East Asia. Biocontrol constitutes a desirable alternative strategy to alleviate the problems of orchard environment pollution and pathogen resistance risk. It is particularly important to explore efficient biocontrol microorganism resources to develop new biocontrol technologies and products. In this study, an endophytic fungus, which results in the specific inhibition of the growth of V. mali, was isolated from the twig tissue of Malus micromalus with a good tolerance to AVC. The fungus was identified as Alternaria alternata, based on morphological observations and phylogenetic analysis, and was named Aa-Lcht. Aa-Lcht showed a strong preventive effect against AVC, as determined with an in vitro twig evaluation method. When V. mali was inhibited by Aa-Lcht, according to morphological and cytological observations, the hyphae was deformed and it had more branches, a degradation in protoplasm, breakages in cell walls, and then finally died completely due to mycelium cells. Transcriptome analysis indicated that Aa-Lcht could suppress the growth of V. mali by inhibiting the activity of various hydrolases, destroying carbohydrate metabolic processes, and damaging the pathogen membrane system. It was further demonstrated that Aa-Lcht could colonize apple twig tissues without damaging the tissue's integrity. More importantly, Aa-Lcht could also stimulate the up-regulated expression of defense-related genes in apples together with the accumulation of reactive oxygen species and callose deposition in apple leaf cells. Summarizing the above, one endophytic biocontrol resource was isolated, and it can colonize apple twig tissue and play a biocontrol role through both pathogen inhibition and resistance inducement.

USP14 negatively regulates IFN signaling by dampening K63-linked ubiquitination of TBK1 in black carp.

USP14 regulates the immune related pathways by deubiquitinating the signaling molecules in mammals. In teleost, USP14 is also reported to inhibit the antiviral immune response through TBK1, but its regulatory mechanism remains obscure. To elucidate the role of USP14 in the RLR/IFN antiviral pathway in teleost, the homolog USP14 (bcUSP14) of black carp (Mylopharyngodon piceus) has been cloned and characterize in this paper. bcUSP14 contains 490 amino acids (aa), and the sequence is well conserved among in vertebrates. Over-expression of bcUSP14 in EPC cells attenuated SVCV-induced transcription activity of IFN promoters and enhanced SVCV replication. Knockdown of bcUSP14 in MPK cells led to the increased transcription of IFNs and decreased SVCV replication, suggesting the improved antiviral activity of the host cells. The interaction between bcUSP14 and bcTBK1 was identified by both co-immunoprecipitation and immunofluorescent staining. Co-expressed bcUSP14 obviously inhibited bcTBK1-induced IFN production and antiviral activity in EPC cells. K63-linked polyubiquitination of bcTBK1 was dampened by co-expressed bcUSP14, and bcTBK1-mediated phosphorylation and nuclear translocation of IRF3 were also inhibited by this deubiquitinase. Thus, all the data demonstrated that USP14 interacts with and inhibits TBK1 through deubiquitinating TBK1 in black carp.

Crystalline metal phosphide-coated amorphous iron oxide-hydroxide (FeOOH) with oxygen vacancies as highly active and stable oxygen evolution catalyst in alkaline seawater at high current density.

In this study, we employed a straightforward phosphorylation approach to achieve a dual objective: constructing c-a heterostructures consisting of crystalline Ni12P5 and amorphous FeOOH, while simultaneously enhancing oxygen vacancies. The resulting oxygen evolution reaction (OER) catalyst, Ni12P5/FeOOH/NF, exhibited remarkable performance with current densities of 500 mA cm-2 in both 1 M KOH and 1 M KOH + seawater, requiring low overpotentials of only 288 and 365 mV, respectively. Furthermore, Ni12P5/FeOOH/NF exhibited only a slight increase in overpotential, with increments of 18 mV and 70 mV in 1 M KOH after 15 and 150 h, and 32 mV and 108 mV in 1 M KOH + seawater at 500 mA cm-2 after 15 and 150 h, respectively. This minimal change can be attributed to the stabilized c-a structure, the protective coating of Ni12P5, and superhydrophilic. Through in-situ Raman and ex-situ XPS analysis, we discovered that Ni12P5/FeOOH/NF can undergo a reconfiguration into an oxygen vacancy-rich (Fe/Ni)OOH phase during OER process. The elevated OER activity is mainly due to the contribution of the oxygen vacancy-rich (Fe/Ni)OOH phase from the reconfigure of the Ni12P5/FeOOH/NF. This finding emphasizes the critical role of oxygen vacancies in facilitating the production of OO species and overcoming the limitations associated with OOH formation, ultimately enhancing the kinetics of the OER.

Mircrofabricating double-sided polydimethylsiloxane (PDMS) artificial phylloplane for microbial food safety research.

Leafy green surface microbiology studies often experience significant variations in results due to the heterogeneous nature of leaf surfaces. To provide a precise and controllable substitute, we microfabricated double-sided artificial leafy green phylloplanes using polydimethylsiloxane (PDMS) with a vinyl-terminated polyethylene glycol chain-based hydrophobicity modifier (PDMS-PEG) to modify PDMS hydrophobicity. We further tested the properties and applications of these artificial leaves, by examining the function of epicuticular wax, growth and survival of E. coli O157:H7 87-23 on the surface, and removal of attached E. coli cells via sanitation. The double-sided PDMS-PDMS-PEG leaves well-replicated their natural counterparts in macroscopic and microscopic structure, hydrophobicity, and E. coli O157:H7 87-23 attachment. After depositing natural epicuticular wax onto artificial leaves, the leaf surface wetting ability decreased, while E. coli O157:H7 87-23 surface retention increased. The artificial leaves supplied with lettuce lysate or bacterial growth media supported E. coli O157:H7 87-23 growth and survival similarly to those on natural leaves. In the sanitation test, the artificial lettuce leaves also displayed patterns similar to those of natural leaves regarding sanitizer efficiency. Overall, this study showcased the microfabrication and applications of double-sided PDMS-PDMS-PEG leaves as a replicable and controllable platform for future leafy green food safety studies.

Turtle peptide and its derivative peptide ameliorated DSS-induced ulcerative colitis by inhibiting inflammation and modulating the composition of the gut microbiota.

Ulcerative colitis (UC) is a recurrent intestinal disease with an increasing incidence worldwide that seriously affects the life of patients. Turtle peptide (TP) is a bioactive peptide extracted from turtles that has anti-inflammatory, antioxidant and anti-aging properties. However, studies investigating the effect of TP on the progression of UC are lacking. The aim of this study was to investigate effects and underlying mechanisms of TP and its derivative peptide GPAGPIGPV (GP-9) in alleviating UC in mice. The results showed that 500 mg/kg TP treatment significantly ameliorated colitis symptoms and oxidative stress in UC mice. TP alleviated intestinal barrier damage in UC mice by promoting mucosal repair and increasing the expression of tight junction proteins (ZO1, occludin and claudin-1). TP also modulated the composition of the gut microbiota by increasing the abundance of the beneficial bacteria Anaerotignum, Prevotellaceae_UCG-001, Alistipes, and Lachno-spiraceae_NK4A136_group and decreasing the abundance of the harmful bacteria Prevotella_9 and Parasutterella. Furthermore, we characterized the peptide composition of TP and found that GP-9 ameliorated the symptoms of dextran sodium sulfate (DSS)-induced colitis in mice by inhibiting the TLR4/NF-κB signaling pathway. In conclusion, TP and its derivative peptides ameliorated DSS-induced ulcerative colitis by inhibiting the expression of inflammatory factors and modulating the composition of the intestinal microbiota; this study provides a theoretical basis for the application of TP and its derivative peptides for their anti-inflammatory activity.

Itaconate alleviates anesthesia/surgery-induced cognitive impairment by activating a Nrf2-dependent anti-neuroinflammation and neurogenesis via gut-brain axis.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common neurological complication of anesthesia and surgery in aging individuals. Neuroinflammation has been identified as a hallmark of POCD. However, safe and effective treatments of POCD are still lacking. Itaconate is an immunoregulatory metabolite derived from the tricarboxylic acid cycle that exerts anti-inflammatory effects by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. In this study, we investigated the effects and underlying mechanism of 4-octyl itaconate (OI), a cell-permeable itaconate derivative, on POCD in aged mice. METHODS: A POCD animal model was established by performing aseptic laparotomy in 18-month-old male C57BL/6 mice under isoflurane anesthesia while maintaining spontaneous ventilation. OI was intraperitoneally injected into the mice after surgery. Primary microglia and neurons were isolated and treated to lipopolysaccharide (LPS), isoflurane, and OI. Cognitive function, neuroinflammatory responses, as well as levels of gut microbiota and their metabolites were evaluated. To determine the mechanisms underlying the therapeutic effects of OI in POCD, ML385, an antagonist of Nrf2, was administered intraperitoneally. Cognitive function, neuroinflammatory responses, endogenous neurogenesis, neuronal apoptosis, and Nrf2/extracellular signal-related kinases (ERK) signaling pathway were evaluated. RESULTS: Our findings revealed that OI treatment significantly alleviated anesthesia/surgery-induced cognitive impairment, concomitant with reduced levels of the neuroinflammatory cytokines IL-1ß and IL-6, as well as suppressed activation of microglia and astrocytes in the hippocampus. Similarly, OI treatment inhibited the expression of IL-1ß and IL-6 in LPS and isoflurane-induced primary microglia in vitro. Intraperitoneal administration of OI led to alterations in the gut microbiota and promoted the production of microbiota-derived metabolites associated with neurogenesis. We further confirmed that OI promoted endogenous neurogenesis and inhibited neuronal apoptosis in the hippocampal dentate gyrus of aged mice. Mechanistically, we observed a decrease in Nrf2 expression in hippocampal neurons both in vitro and in vivo, which was reversed by OI treatment. We found that Nrf2 was required for OI treatment to inhibit neuroinflammation in POCD. The enhanced POCD recovery and promotion of neurogenesis triggered by OI exposure were, at least partially, mediated by the activation of the Nrf2/ERK signaling pathway. CONCLUSIONS: Our findings demonstrate that OI can attenuate anesthesia/surgery-induced cognitive impairment by stabilizing the gut microbiota and activating Nrf2 signaling to restrict neuroinflammation and promote neurogenesis. Boosting endogenous itaconate or supplementation with exogenous itaconate derivatives may represent novel strategies for the treatment of POCD.

Analysis on time delay of tuberculosis among adolescents and young adults in Eastern China.

Background: Tuberculosis (TB) is recognized as a significant global public health concern. Still, there remains a dearth of comprehensive evaluation regarding the specific indicators and their influencing factors of delay for adolescents and young adults. Methods: All notified pulmonary TB (PTB) patients in Jiaxing City were collected between 2005 and 2022 from China's TB Information Management System. Logistic regression models were conducted to ascertain the factors that influenced patient and health system delays for PTB cases, respectively. Furthermore, the impact of the COVID-19 pandemic on local delays has been explored. Results: From January 1, 2005 to December 31, 2022, a total of 5,282 PTB cases were notified in Jiaxing City, including 1,678 adolescents and 3,604 young adults. For patient delay, female (AOR: 1.18, 95%CI: 1.05-1.32), PTB complicated with extra-pulmonary TB (AOR: 1.70, 95% CI: 1.28-2.26), passive case finding (AOR: 1.46, 95% CI: 1.07-1.98) and retreatment (AOR: 1.52, 95% CI: 1.11-2.09) showed a higher risk of delay. For health system delay, minorities (AOR: 0.69, 95% CI: 0.53-0.90) and non-students (AOR: 0.83, 95% CI: 0.71-0.98) experienced a lower delay. Referral (AOR: 1.46, 95% CI: 1.29-1.65) had a higher health system delay compared with clinical consultation. Furthermore, county hospitals (AOR: 1.47, 95% CI: 1.32-1.65) and etiological positive results (AOR: 1.46, 95% CI: 1.30-1.63) were associated with comparatively high odds of patient delay. Contrarily, county hospitals (AOR: 0.88, 95% CI: 0.78-1.00) and etiological positive results (AOR: 0.67, 95% CI: 0.59-0.74) experienced a lower health system delay. Besides, the median of patient delay, health system delay, and total delay during the COVID-19 pandemic were significantly lower than that before. Conclusion: In general, there has been a noteworthy decline in the notification rate of PTB among adolescents and young adults in Jiaxing City while the declining trend was not obvious in patient delay, health system delay, and total delay, respectively. It also found factors such as gender, case-finding method, and the hospital level might influence the times of seeking health care and diagnosis in health agencies. These findings will provide valuable insights for refining preventive and treatment strategies for TB among adolescents and young adults.

USP46 promotes the interferon antiviral signaling in black carp by deubiquitinating TBK1.

Ubiquitin-specific peptidase 46 (USP46) functions as a deubiquitinating enzyme, facilitating the removal of ubiquitin molecules attached to substrate proteins and playing a critical role in cancer and neurodegenerative diseases. However, its function in innate antiviral immunity is unknown. In this study we cloned and identified bcUSP46, a homolog of USP46 from black carp. We discovered that overexpression of bcUSP46 enhanced the transcription of interferon (IFN) promoters and increased the expression of IFN, PKR, and Mx1. In addition, bcUSP46 knockdown significantly inhibited the expression of ISG genes, as well as the antiviral activity of the host cells. Interestingly, when bcUSP46 was co-expressed with the RLR factors, it significantly enhanced the activity of the IFN promoter mediated by these factors, especially TANK-binding kinase 1 (TBK1). The subsequent co-immunoprecipitation (co-IP) and immunofluorescence (IF) assay confirmed the association between bcUSP46 and bcTBK1. Noteworthily, co-expression of bcUSP46 with bcTBK1 led to an elevation of bcTBK1 protein level. Further analysis revealed that bcUSP46 stabilized bcTBK1 by eliminating the K48-linked ubiquitination of bcTBK1. Overall, our findings highlight the unique role of USP46 in modulating TBK1/IFN signaling and enrich our knowledge of the function of deubiquitination in regulating innate immunity in vertebrates.

Realization of sextuple polarization states and interstate switching in antiferroelectric CuInP2S6.

Realization of higher-order multistates with mutual interstate switching in ferroelectric materials is a perpetual drive for high-density storage devices and beyond-Moore technologies. Here we demonstrate experimentally that antiferroelectric van der Waals CuInP2S6 films can be controllably stabilized into double, quadruple, and sextuple polarization states, and a system harboring polarization order of six is also reversibly tunable into order of four or two. Furthermore, for a given polarization order, mutual interstate switching can be achieved via moderate electric field modulation. First-principles studies of CuInP2S6 multilayers help to reveal that the double, quadruple, and sextuple states are attributable to the existence of respective single, double, and triple ferroelectric domains with antiferroelectric interdomain coupling and Cu ion migration. These findings offer appealing platforms for developing multistate ferroelectric devices, while the underlining mechanism is transformative to other non-volatile material systems.

Hematoporphyrin injection mediated photodynamic therapy for secondary squamous cell carcinoma of arsenical keratosis: A case report.

Hematoporphyrin injection (HpD) mediated photodynamic therapy (PDT) has demonstrated efficacy in treating various types of Bowen's disease, including basal-cell carcinoma, squamous cell carcinoma, extramammary Paget's disease, and actinic keratosis. We present a case of a male patient who developed squamous cell carcinoma as a result of repeated instances of arsenic-induced keratosis on both his hands and feet. Due to the involvement of the joint in both hands, the patient declined the conventional surgical resection treatment since it could potentially impact normal physiological function. Instead, the patient chose to undergo hemoporphyrin photodynamic therapy. After the treatment, the rash was entirely eliminated and there were no restrictions in the movement of the joint. Nevertheless, a local recurrence was detected throughout the two-year monitoring period. Arsenical keratosis carries a substantial likelihood of recurring. However, we believe that hemoporphyrin photodynamic therapy is effective in treating this condition.

STAT2 negatively regulates RIG-I in the antiviral innate immunity of black carp.

The signal transducer and activator of transcription 2 (STAT2), a downstream factor of type I interferons (IFNs), is a key component of the cellular antiviral immunity response. However, the role of STAT2 in the upstream of IFN signaling, such as the regulation of pattern recognition receptors (PRRs), remains unknown. In this study, STAT2 homologue of black carp (Mylopharyngodon piceus) has been cloned and characterized. The open reading frame (ORF) of bcSTAT2 comprises 2523 nucleotides and encodes 841 amino acids, which presents the conserved structure to that of mammalian STAT2. The dual-luciferase reporter assay and the plaque assay showed that bcSTAT2 possessed certain IFN-inducing ability and antiviral ability against both spring viremia of carp virus (SVCV) and grass carp reovirus (GCRV). Interestingly, we detected the association between bcSTAT2 and bcRIG-I through co-immunoprecipitation (co-IP) assay. Moreover, when bcSTAT2 was co-expressed with bcRIG-I, bcSTAT2 obviously suppressed bcRIG-I-induced IFN expression and antiviral activity. The subsequent co-IP assay and immunoblotting (IB) assay further demonstrated that bcSTAT2 inhibited K63-linked polyubiquitination but not K48-linked polyubiquitination of bcRIG-I, however, did not affect the oligomerization of bcRIG-I. Thus, our data conclude that black carp STAT2 negatively regulates RIG-I through attenuates its K63-linked ubiquitination, which sheds a new light on the regulation of the antiviral innate immunity cascade in vertebrates.

Effector enrichment by Candidatus Liberibacter promotes Diaphorina citri feeding via Jasmonic acid pathway suppression.

BACKGROUND: Citrus huanglongbing (HLB) is a devastating disease caused by Candidatus Liberibacter asiaticus (CLas) that affects the citrus industry. In nature, CLas relies primarily on Diaphorina citri Kuwayama as its vector for dissemination. After D. citri ingests CLas-infected citrus, the pathogen infiltrates the insect's body, where it thrives, reproduces, and exerts regulatory control over the growth and metabolism of D. citri. Previous studies have shown that CLas alters the composition of proteins in the saliva of D. citri, but the functions of these proteins remain largely unknown. RESULTS: In this study, we detected two proteins (DcitSGP1 and DcitSGP3) with high expression levels in CLas-infected D. citri. Quantitative PCR and Western blotting analysis showed that the two proteins were highly expressed in the salivary glands and delivered into the host plant during feeding. Silencing the two genes significantly decreased the survival rate for D. citri, reduced phloem nutrition sucking and promoted jasmonic acid (JA) defenses in citrus. By contrast, after overexpressing the two genes in citrus, the expression levels of JA pathway-associated genes decreased. CONCLUSION: Our results suggest that CLas can indirectly suppress the defenses of citrus and support feeding by D. citri via increasing the levels of effectors in the insect's saliva. This discovery facilitates further research into the interaction between insect vectors and pathogens. © 2024 Society of Chemical Industry.