Intramedullary schwannomas in the conus medullaris are very rare and are usually not associated with syringomyelia. We report a unique case of intramedullary schwannoma in the conus medullaris with long-segment syringomyelia. The patient was a 60-year-old male, initially presenting with left dorsalgia, subsequently developing weakness in the right lower extremity. As the symptoms progressed, the patient exhibited ataxia in gait, accompanied by sphincter insufficiency and voiding dysfunction. Lumbar MRI revealed the presence of two tumors at the L3 and T11-L1 levels, accompanied by syringomyelia extending from T4 to T10. During surgery, it was determined that the tumor located at the T11-L1 vertebral level was intramedullary, whereas the tumor situated at the L3 level exhibited an extramedullary intradural configuration. Pathological examination conclusively identified both the intramedullary and extramedullary tumors as schwannomas. Although intramedullary schwannomas at the conus medullaris are very rare, schwannoma remains a diagnosis that cannot be ignored when facing patients with intramedullary tumors with syringomyelia. Intramedullary schwannoma can have a good neurological prognosis after surgical treatment.

Development of B cell memory is a conundrum that scientists are still exploring. Studies have been conducted in vitro and using advanced animal models to elucidate the mechanism underlying the generation of memory B cells (MBCs), the precise roles of MBCs against pathogens, and their protective functions against repeated infections throughout life. Lifelong immunity against invading diseases is mainly the result of overcoming a single infection. This protection is largely mediated by the two main components of B cell memory—MBCs and long-lived plasma cells (PCs). The chemical and cellular mechanisms that encourage fat selection for MBCs or long-lived PCs are an area of active research. Despite the fact that nearly all available vaccinations rely on the capacity to elicit B-cell memory, we have yet to develop successful vaccines that can induce broad-scale protective MBCs against some of the deadliest diseases, including malaria and AIDS. A deeper understanding of the specific cellular and molecular pathways that govern the generation, function, and reactivation of MBCs is critical for overcoming the challenges associated with vaccine development. Here, we reviewed literature on the development of MBCs and their reactivation, interaction with other cell types, strategies against invading pathogens, and function throughout life and discussed the recent advances regarding the key signals and transcription factors which regulate B cell memory and their relevance to the quest for vaccine development.

IntroductionThe incidence of hemangioblastoma is low, constituting only 1-5% of all spinal cord tumors. Specifically, intradural extramedullary hemangioblastoma without Von Hippel-Lindau syndrome represents an exceedingly rare condition.MethodsWe report the first documented case of cervical intradural extramedullary hemangioblastoma in China. A 53-year-old male patient presented with a 3-year history of mild right hemiplegia, segmental muscle strength and sensation impairment, and a positive pyramidal tract sign. MRI showed an abnormal oval signal focus in the intradural and extramedullary region at the C6-C7 vertebral level. Before surgery, angiography was performed to identify the supplying arteries and draining veins. Subsequent interventional therapy achieved over 90% occlusion of blood vessels, creating optimal conditions for complete resection of the spinal tumor.ResultsThe patient demonstrated satisfactory postoperative recovery with significant restoration of sensory and motor functions. Pathological examination showed a significant upregulation of CD31 in tumor cells and a substantial presence of the neuro-specific marker S100 in the tumor stroma, consistent with the diagnostic criteria for spinal hemangioblastoma.ConclusionThe rarity of cervical intradural extramedullary hemangioblastoma without Von Hippel-Lindau syndrome was reaffirmed by a comprehensive review of the existing literature. Complete tumor resection remains the optimal approach for managing this uncommon condition, generally resulting in a favorable prognosis. Traditional open fenestration surgery is linked to elevated risks of bleeding and trauma. Meanwhile, endovascular injection of embolic agents may lead to residual lesions and an increased risk of recurrence. Therefore, we recommend a one-time combined treatment conducted in a hybrid operating room to achieve complete resection and effectively reduce intraoperative bleeding risk. Despite presenting challenges and requiring high proficiency, we still recommend this type of combined surgery as a suitable therapeutic option for such diseases.

Patients with bladder cancer (BLCA) still show high recurrence after surgery and chemotherapy. Hesperetin (HE), as a natural compound, has attracted researchers’ attention due to its low toxicity and easy access. However, the inhibitory effect of HE on BLCA remains unknown. The hub genes and enrichment pathways regulated by HE in the treatment of BLCA were predicted by network pharmacology. The molecular docking of HE and hub proteins was visualized. Colony and CCK8 assays were used to test cell proliferation, and BLCA migration was confirmed by transwell and wound healing assays. In addition, the occurrence of apoptosis and ferroptosis was demonstrated by Hoechst staining, transmission electron microscopy (TEM) and ROS (reactive oxygen species) assay. Western Blotting was performed to validate the hub proteins, target functions and pathways. SRC, PIK3R1 and MAPK1 were identified as hub targets for HE in BLCA, involving the PI3k/AKT pathway. Furthermore, HE inhibited the proliferation and migration of BLCA cells. The MMP2/MMP9 proteins were significantly inhibited by HE. The increased expression of Bax and cleaved caspase-3 indicated that HE could promote BLCA cell apoptosis. In addition, Hoechst staining revealed concentrated and illuminated apoptotic nuclei. The activation of ROS and the decline of GPX4 expression suggested that HE might induce ferroptosis as an anti-BLCA process. Shrunk mitochondria and apoptotic bodies were observed in BLCA cells treated with HE, with reduced or absent mitochondrial cristae. We propose for the first time that HE could inhibit the proliferation and migration of BLCA cells and promote apoptosis and ferroptosis. HE may act by targeting proteins such as SRC, PIK3R1 and MAPK1 and the PI3K/AKT pathway.

ObjectiveTo summarize the clinical effect of a single-center retrospective analysis of the contralateral approach with a microscope and tubular retractor system for ipsilateral decompression in patients with lumbar lateral recess stenosis and a narrow spinal canal.MethodsA total of 25 patients who underwent ipsilateral decompression surgery via a contralateral approach with microscope and tubular retractor system, performed by one surgeon at a single center were retrospectively examined. The width of the lamina fenestration was compared with the preoperative distance from the root of the spinous process to the dorsal articular facet, the bilateral articular facet change in the suprapedicle notch section on CT scan, and with the changes in transverse and sagittal diameters of the canal area on MRI. Clinical efficacy was assessed using the Japanese Orthopedic Association (JOA), Visual Analog Scale (VAS), and Oswestry Disability Index (ODI) scores.ResultsIn total, 25 patients were treated and the mean intraoperative time was 82.04 ± 12.48 min. There was no nerve injury, cerebrospinal fluid leakage, and infection complications. The postoperative CT revealed that the width of the contralateral laminar fenestration was less than the distance from the root of the spinous process to the dorsal articular facet. The residual widths of the ipsilateral articular facet and contralateral articular facet were greater than 2/3 of the preoperative articular facet width. The transverse and sagittal diameter of canal were significantly increased. The mean follow-up period was 12–16 months, and no recurrence or reoperation incidence were found at the last follow-up. When compared to pre-surgery, the ODI, VAS, and JOA scores were significantly improved after surgery (p < 0.05).ConclusionBased on our single-center retrospective observation of 25 cases and combined with previous literature, the contralateral approach with a microscope and tubular retractor system for ipsilateral decompression in patients with lumbar lateral recess stenosis and a narrow spinal canal can reduce damage to the articular processes, and probably more conducive to the postoperative stability of the lumbar spine. This was a single center retrospective analysis with a small sample size and lacked randomized controlled trials (RCTs). However, larger-scale, multicenter RTCs are required for additional validation.

Objective: Primary spinal cord glioblastoma (PSCGBM) is a rare malignancy with a poor prognosis. To date, no prognostic nomogram for this rare disease was established. Hence, we aimed to develop a nomogram to predict overall survival (OS) of PSCGBM.Methods: Clinical data of patients with PSCGBM was retrospectively collected from the neurosurgery department of Soochow University Affiliated Second Hospital and the Surveillance Epidemiology and End Results database. Information including age, sex, race, tumor extension, extent of resection, adjuvant treatment, marital status, income, year of diagnosis and months from diagnosis to treatment were recorded. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors for PSCGBM. A nomogram was constructed to predict 1-year, 1.5-year, and 2-year OS of PSCGBM.Results: A total of 132 patients were included. The 1-year, 1.5-year, and 2-year OS were 45.5%, 29.5%, and 18.9%, respectively. Four variables: age groups, tumor extension, extent of resection, and adjuvant therapy, were identified as independent prognostic factors. The nomogram showed robust discrimination with a C-index value for the prediction of 1-year OS, 1.5-year OS, and 2-year of 0.71 (95% confidence interval [CI], 0.61–0.70), 0.72 (95% CI, 0.62–0.70), and 0.70 (95% CI, 0.61–0.70), respectively. The calibration curves exhibited high consistencies between the predicted and observed survival probability in this cohort.Conclusion: We have developed and internally validated a nomogram for predicting the survival outcome of PSCGBM for the first time. The nomogram has the potential to assist clinicians in making individualized predictions of survival outcome of PSCGBM.

ObjectiveSpinal schwannomas are the most common intradural extramedullary tumors, and their complete removal is recommended to avoid tumor recurrence. Although laminoplasty provides a sufficient window for tumor resection, this approach may increase tissue trauma and cause postoperative instability compared with unilateral hemilaminectomy. This study aimed to compare the efficacy and clinical outcomes of the two approaches.Materials and methodsWe included 100 consecutive patients who underwent unilateral hemilaminectomy or laminoplasty for resection of spinal schwannomas between January 2015 and February 2023. The patients' baseline characteristics, including sex, age, tumor location, percentage of tumor occupying the intradural space, operative time, postoperative length of hospital stay, intraoperative bleeding volume, visual analog scale score, and neurologic results, were retrospectively analyzed.ResultsHemilaminectomy patients who underwent unilateral hemilaminectomy had smaller intraoperative bleeding (p = 0.020) volume, shorter operative time (p = 0.012), and shorter postoperative length of hospital stay (p = 0.044). The mean VAS scores at the last follow-up were similar between the two groups (p = 0.658). Although the postoperative McCormick and Karnofsky Performance scores were not significantly different between the laminoplasty and unilateral hemilaminectomy groups (p = 0.687 and p = 0.649, respectively), there was a statistically significant improvement based on postoperative neurological results compared to preoperative neurological results for both groups. The incidence of postoperative complications was 5% and 11.7% in the unilateral hemilaminectomy and laminoplasty groups, respectively (p = 0.308).ConclusionsFor spinal schwannoma resection, unilateral hemilaminectomy has more advantages than laminoplasty, including a shorter postoperative hospital stay, faster procedure, and less intraoperative blood loss while achieving the same desired result.

Traumatic brain injuries (TBI) and stroke are major causes of morbidity and mortality in both developing and developed countries. The complex and heterogeneous pathophysiology of TBI and cerebral ischemia-reperfusion injury (CIRI), in addition to the blood-brain barrier (BBB) resistance, is a major barrier to the advancement of diagnostics and therapeutics. Clinical data showed that the severity of TBI and stroke is positively correlated with the number of neutrophils in peripheral blood and brain injury sites. Furthermore, neutrophil extracellular traps (NETs) released by neutrophils correlate with worse TBI and stroke outcomes by impairing revascularization and vascular remodeling. Therefore, targeting neutrophils to deliver NETs inhibitors to brain injury sites and reduce the formation of NETs can be an optimal strategy for TBI and stroke therapy. Herein, the study designs and synthesizes a reactive oxygen species (ROS)-responsive neutrophil-targeting delivery system loaded with peptidyl arginine deiminase 4 (PAD4) inhibitor, GSK484, to prevent the formation of NETs in brain injury sites, which significantly inhibited neuroinflammation and improved neurological deficits, and improved the survival rate of TBI and CIRI. This strategy may provide a groundwork for the development of targeted theranostics of TBI and stroke.

Macrophage infiltration and polarization during lumbar intervertebral disc herniation (LDH) have attracted increased attention but their role remains unclear. To explore macrophage polarization in herniated nucleus pulposus (NP) tissue of patients with LDH and investigate the association between cell frequency and different clinical characteristics or symptoms, we conducted a retrospective study by analyzing NP tissue samples from 79 patients. Clinical features and symptoms, using the visual analog scale (VAS) and Oswestry disability index (ODI), were collected. The macrophage markers CD68, CCR7, CD163, and CD206; pro‐inflammatory cytokine TNF‐α; and anti‐inflammatory factor IL‐4 were analyzed by immunohistochemistry. The frequency of polarized macrophages and positivity rate of pro‐ and anti‐inflammatory cytokines showed significant differences in some of clinical characteristics. Specifically, higher CCR7+ and TNF‐α + proportions were identified in the high‐intensity zone (HIZ) and the type of extrusion and sequestration NP tissue than in non‐HIZ and protrude NP tissue. Higher CD206+ and IL‐4+ proportion were detected in Modic changes. However, no differences in gender, age, smoking status, Pfirrmann grade, analgesic use, leg pain duration, and segments were found between groups. CD68+, CCR7+, and CD206+ cell proportions, and TNF‐α and IL‐4 showed positive associations with VAS scores preoperation. Associations between ODI and the macrophages markers were weak/insignificant. Our results indicated that macrophage polarization or macrophage‐like cells contribute to LDH pathological features. Macrophage populations displaying significant associations with VAS score reflected continuous M1/M2 transition contributing to pain during LDH. These findings may contribute to enhanced/personalized pharmacological interventions for patients with LDH considering pain heterogeneity.

Abstract Background  Spinal cord hemangioblastomas are rare benign and highly vascular tumors that develop either sporadically or as part of von Hippel–Lindau (VHL) disease. Generally, complete resection without significant neurologic deficit remains considerably challenging due to the risk of massive bleeding. The current study therefore aimed to describe en bloc resection of spinal cord hemangioblastomas according to the typical anatomical structures of peripheral lesions and evaluate the neurofunctional prognosis of this technique. Methods  A total of 39 spinal cord hemangioblastomas from a series of 19 patients who underwent en bloc resection were retrospectively analyzed. In all cases, clinical and radiologic characteristics, as well as surgical tenets, were retrospectively determined and analyzed. Short- and long-term outcomes were analyzed using the McCormick grade and Odom's criteria. Factors significantly associated with poor neurologic function after en bloc resection were also determined. Results  All 39 spinal cord hemangioblastomas, including 28 intramedullary, 2 intramedullary–extramedullary, and 9 extramedullary lesions, were located dorsally or dorsolaterally (100.0%). The most common lesion location was the thoracic segment (53.8%), with most of the lesions being accompanied by syringomyelia (94.7%). Long-term follow-up (mean: 103 ± 50.4 months) for prognosis determination revealed that 88.2% (15/17) of all cases had stable or improved neurofunctional outcomes according to the McCormick grade and Odom's criteria. Only one case with VHL disease developed recurrence 4 years after surgery. Additionally, statistical analysis showed that VHL disease was an independent prognostic factor associated with deteriorating neurologic function ( p  = 0.015). Conclusions  En bloc resection facilitated satisfactory long-term functional outcomes in patients with spinal cord hemangioblastomas. Given that VHL disease was identified as a predictor of poor long-term outcomes, regular long-term follow-up of patients with VHL-associated spinal cord hemangioblastoma seems necessary.

Glioma is the most common primary craniocerebral tumor caused by the cancerous growth of glial cells in the brain and spinal cord. Currently, standard treatment is the surgical resection followed by concurrent radiation and chemotherapy. However, the blood-brain barrier (BBB) prevents most antitumor drugs from entering the brain and reduces their efficacy, especially in low-grade glioma. Since L-type amino acid transporter 1 (LAT1) is highly expressed in glioma cells and mediates drug transport across the BBB, it is a promising target for drug delivery and treatment of glioma. Temozolomide (TMZ) is the first-line treatment for glioma, however, patients often exhibit drug resistance at advanced stage. A multikinase inhibitor and inducer of ferroptosis, sorafenib can improve the therapeutic effects of TMZ. Therefore, to optimize the glioma treatment and cross the BBB, we designed LAT1-targeting nanoparticles co-loaded with TMZ and sorafenib. Our results from both in vitro and in vivo studies confirmed that LAT1-targeting nanoparticles significantly increased the cellular uptake, cytotoxicity, accumulation at tumor site, and the anti-tumor efficacy compared to the non-target nanoparticles. Therefore, LAT1 can be used as a potential target for brain-targeted drug delivery, and sorafenib-induced ferroptosis can aid the anti-glioma efficacy of TMZ.

Ischemic stroke is a refractory disease that endangers human health and safety owing to cerebral ischemia. Brain ischemia induces a series of inflammatory reactions. Neutrophils migrate from the circulatory system to the site of cerebral ischemia and accumulate in large numbers at the site of inflammation across the blood-brain barrier. Therefore, hitchhiking on neutrophils to deliver drugs to ischemic brain sites could be an optimal strategy. Since the surface of neutrophils has a formyl peptide receptor (FPR), this work modifies a nanoplatform surface by the peptide cinnamyl-F-(D)L-F-(D)L-F (CFLFLF), which can specifically bind to the FPR receptor. After intravenous injection, the fabricated nanoparticles effectively adhered to the surface of neutrophils in peripheral blood mediated by FPR, thereby hitchhiking with neutrophils to achieve higher accumulation at the inflammatory site of cerebral ischemia. In addition, the nanoparticle shell is composed of a polymer with reactive oxygen species (ROS)-responsive bond breaking and is encased in ligustrazine, a natural product with neuroprotective properties. In conclusion, the strategy of hitching the delivered drugs to neutrophils in this study could improve drug enrichment in the brain, thereby providing a general delivery platform for ischemic stroke or other inflammation-related diseases.

Background and Objectives: Intracranial hemorrhage following spinal surgery is an infrequent but severe complication. Due to its rarity, the etiology, clinical characteristics, and treatment have not yet been fully elucidated. This literature review analyzed the incidence, clinical manifestations, hemorrhage location, current therapeutic strategies, location of operation, and interval time between surgery and bleeding. The objectives of the article were to provide insights for clinicians to promptly identify and prevent potential cases of intracranial hemorrhage. Methods: The authors queried PubMed and Web of Science databases using predefined keywords and included published literature reporting on intracranial hemorrhage after spinal surgery. Relevant case reports, case series, and reviews describing the mechanism of intracranial hemorrhage after spinal surgery and meeting diagnostic criteria for intracranial hemorrhage related to spinal surgery were included. Clinicodemographc data, presentations symptoms, location, index surgery type, and neurological outcomes after brain hemorrhage. Oxford Centre Level of Evidence guidelines was used to evaluate the quality of included studies. Descriptive statistics were used to synthesize the results. Key Content and Findings: A total of 80 publications of level of evidence IV involving 108 patients with median age at diagnosis was 58.5 years (inter- quartile range: 6-85) were analyzed. The incidence of intracranial hemorrhage was 0.08-0.37% among patients who underwent spinal surgery, and this complication occurred predominantly within 48 hours postoperatively. The initial presentation included headache, reduced level of consciousness, dysarthria, nausea, vomiting, hearing loss, blurred vision, neck rigidity, and delayed recovery from anesthesia. More than half (58.3%) of patients improved, while 23.1% still experienced neurological dysfunctions, and 7.4% died. Conclusions: The present study is limited by the levels of evidence of the included studies. There is heterogeneity among cases with respect to patient demographics and medical history. Angiography is critical in assessing the presence and extent of underlying vascular diseases. Intracranial hemorrages may be caused by intraoperative or postoperative cerebrospinal fluid leakage that will lead to intracranial pressure change and induced by intracranial venous or arterial bleeding. The treatment strategies include conservative medical management and surgical treatment. Individualized treatment should be emphasized.

Stroke is a serious acute cerebrovascular disease attributable to disruptions in the blood supply to the brain tissue as a result of vascular obstruction or sudden rupture of blood vessels in the brain, which further result in hypoxia of the brain and reduction of necessary nutrients, apoptosis of neurons, and damage to brain tissue. The majority of stroke patients are ischemic stroke. The main clinical treatments for ischemic stroke include medical thrombolysis in the early stage of onset and surgical thrombectomy or stent implantation in the late stage of onset, all of which have their own indications, advantages, and disadvantages, and show limited clinical application. For cerebral ischemia-reperfusion injury with an extremely poor prognosis, there is currently no effective prevention and treatment method in the clinic. Therefore, timely and effective treatment is needed to treat cerebral ischemia-reperfusion injury. An increasing number of studies have shown that natural products have a good curative effect on cerebral ischemia-reperfusion injury. However, due to their low solubility, low bioavailability, and short half-life, many natural products cannot optimally exert their curative effects on cerebral ischemia-reperfusion injury. Natural products-based nanoparticles modified with specific ligands have attracted much attention because of their high-efficiency permeation through the blood–brain barrier, targeted delivery abilities, and the protection of the active components from degradation. Therefore, this review focused on the prevention and treatment of cerebral ischemia-reperfusion injury in the natural product-based nanoparticles.

Background and Objective: Ischemic cerebrovascular disease is one of the main diseases threatening human health and survival and is a commonly occurring disease in neurology. Due to its high disability rate, ischemic cerebrovascular disease is one of the most important diseases to be prevented and treated at present. The risk factors of cerebral ischemia include atherosclerosis, hypertension, hyperlipidemia, and blood viscosity caused by thrombocytosis. After cerebral ischemia, cerebral ischemia-reperfusion injury may be induced by oxidative stress (OS), inflammatory reaction, nitric oxide damage, apoptosis, excitatory amino acid toxicity, calcium (Ca2+) overload, and other mechanisms. Hesperidin is a flavanone compound and is a key component in citrus plants. It is a kind of traditional Chinese medicine extract with high levels of Pericarpium, shell, fruit, and green peel. In recent years, Hesperidin has received great attention, compelling evidence has indicated Hesperidin plays a beneficial role in cerebral ischemia. Methods: We conducted a literature search for published manuscripts hesperidin in ischemia/reperfusion up to December 2021 in common English databases (i.e., PubMed, EMBASE, Web of Science, SpringerLink, Wiley, Cochrane Library) and Chinese databases [Chinese BioMedical Literature Service System (CBM), WANFANG database, China Knowledge Resource Integrated Database (CNKI)]. Key Content and Findings: In this article, we reviewed the mechanisms of action of hesperidin in the treatment of cerebral ischemia, including antioxidant stress, anti-inflammatory reaction, anti-atherosclerosis, anti-thrombosis, anti-apoptosis, and nitric oxide regulation. Conclusions: In this narrative review, Hesperidin exhibits antioxidant stress, anti-platelet aggregation, vasodilation, anti-atherosclerotic, anti-inflammatory, anti-apoptotic, hypolipidemic, anti-tumor, cardiovascular protection, and nitric oxide-release regulatory properties Such a comprehension of the recent progress of hesperidin will help identify biomarkers for diagnosis and therapeutic targets to cerebral ischemia.

Background:Glioma is a common primary craniocerebral malignant tumor, due to the lack of specificity of imaging examination and clinical manifestations, its diagnostic accuracy is relatively low, which may result in misdiagnosis and missed diagnosis. The apparent diffusion coefficient (ADC) in magnetic resonance diffusion weighted imaging (DWI) can reflect the histological characteristics of gliomas, which can be widely applied to classify gliomas and evaluate the extent of metastasis of glioma. The present study aimed to assess the clinical value of magnetic resonance DWI in the pathological grading of glioma and its therapeutic application in clinical surgery.Methods:This article retrospectively analyzed the clinical data of 41 patients with glioma confirmed by surgical pathology results from January 1, 2019 to March 31, 2020 in the People's Hospital of Gaozhou. Among them, 16 patients had low-grade gliomas [World Health Organization (WHO) grade I-II] and 25 patients had high-grade gliomas (WHO grade III-IV). They were subjected to conventional T1WI and T2WI plain scans, along with DWI and enhanced scans before surgery. The ADC values of the glioma parenchyma, the peritumoral edema area, the surrounding white matter, and the contralateral normal white matter were measured. We selected some tumor tissues for pathological analysis as well, and conducted pathological grading according to WHO grading standards.Results:We compared and evaluated the ADC values of the observed areas for low-grade gliomas and high-grade gliomas. The ADC values of low-grade gliomas in the tumor parenchyma, peritumoral edema, and white matter around the edema area were significantly lower than those of high-grade gliomas, and the differences were statistically significant (P<0.05). The difference in ADC values of normal white matter between the two groups of patients was not statistically significant (P=0.125).Conclusions:DWI has prognostic predictive value in the preoperative differential diagnosis and pathological classification of gliomas. This advanced technology can verify the extent of glioma infiltration in the surrounding brain tissue. It can help clinicians formulate a safer and more effective therapeutic strategy by providing accurate information on prognostic evaluation before the successful surgical intervention of gliomas.

Due to the aggregation-caused quenching effect and near-infrared I poor penetration capabilities of common fluorescent molecules, their applications in visualized imaging and photoactivated treatment are limited. Therefore, new near-infrared II (NIR-II) molecule (named TST), which had the abilities of aggregation-induced emission (AIE) and photothermal therapy are synthesized. Moreover, in order to further improve its fluorescent yield and therapeutic effect, camptothecin prodrug (CPT-S-PEG) and novel immune checkpoint inhibitor AZD4635 are used to co-assemble with TST into nanoparticles for drug delivery. On account of the strong interaction of camptothecin and TST, the intramolecular rotation of TST is limited, thereby inhibiting non-radiation attenuation and promoting fluorescence generation when the nanoparticles are intact. As nanoparticles uptake by cancer cells, redox sensitive CPT-S-PEG is degraded and the nanoparticles disintegrate. The released TST enhances non-radiative attenuation and expedites photothermal conversion because of the removal of the constraint of camptothecin. Furthermore, photothermal therapy induces immunogenic cell death of cancer cells and releases abundant ATP into the tumor microenvironment to recruit immune cells. However, superfluous ATP is converted into immunosuppressive adenosine through the CD39-CD73-A2AR pathway. The AZD4635 released by photothermal disintegration of the nanoparticles just blocks this pathway timely, achieving favorable synergistic effect of photothermal therapy, chemotherapy, and immunotherapy.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Emerging therapies, such as ferroptosis mediated cancer therapy and phototherapy, offer new opportunities for HCC treatment. The combination of multiple treatments is often more effective than monotherapy, but many of the current treatments are prone to serious side effects, resulting in a serious decline in patients' quality of life. Therefore, the combination therapy of tumor in situ controllable activation will improve the efficacy and reduce side effects for precise treatment of tumor. Herein, we synthesized a GSH-activatable nanomedicine to synergize photothermal therapy (PTT) and ferrotherapy. We utilized a near-infrared dye SQ890 as both an iron-chelating and a photothermal converter agent, which was encapsulated with a GSH-sensitive polymer (PLGA-SS-mPEG), to attain the biocompatible SQ890@Fe nanoparticles (NPs). In the tumor microenvironment (TME), SQ890@Fe NPs showed a GSH-activated photothermal effect that could increase the Fenton reaction rate. Meanwhile, the depletion of GSH could further increase ferroptosis effect. In turn, the increasing radical generated by ferrotherapy could impair the formation of heat shock proteins (HSPs) which could amplify PTT effects by limiting the self-protection mechanism. Overall, the intelligent nanomedicine SQ890@Fe NPs combines ferrotherapy and PTT to enhance the efficacy and safety of cancer treatment through the mutual promotion of the two treatment mechanisms, providing a new dimension for tumor combination therapy.

In order to determine the relationship between the most recently isolated bluetongue virus serotype (BTV-2), and other US serotypes, the complete nucleotide sequence was determined from cDNA clones representing the L2 dsRNA of BTV-2, the gene that codes for the outer capsid neutralization antigen (VP2). The predicted amino acid sequence of the protein was compared with the VP2 sequences of the US serotypes BTV-10, BTV-11, BTV-13 and BTV-17. The VP2 protein of BTV-2 was found to exhibit 47% homology with the VP2 species of BTV-13, but only 40–41% homology with the VP2 species of earlier US isolates, BTV-10, -11 and -17. However, Diagon comparisons and hydropathic plots of all five VP2 species indicated that all of them are structurally very similar.

Traumatic brain injury (TBI) is the main cause of death and disability in people of all ages worldwide. Neuroinflammation plays beneficial and harmful roles in secondary brain injury. Neutrophils play an important role in chemically mediated inflammatory responses through myeloperoxidase (MPO) and inflammation triggered by TBI. Herein, a nanodrug targeting neutrophils and MPO through chemical and biological functions after TBI is designed to enhance the retention and sustained release of drug cargos for improved TBI therapy. 5‐Hydroxytryptamide (5‐HT) is modified on nanoparticles (NPs) loaded with an anti‐inflammatory and antioxidant natural product, hesperetin, to obtain MPO‐ and neutrophil‐targeting NPs, denoted as T‐Hes. In a mouse TBI model, it is confirmed that neutrophil‐targeting NPs can quickly accumulate and remain in the brain tissue, reduce the secretion of inflammatory factors, and the level of microglia and astrocytes, subsequently inducing the transformation of microglia from pro‐inflammatory M1 to anti‐inflammatory M2 cells and promoting the infiltration of regulatory T cells (Tregs). T‐Hes significantly inhibits neuroinflammation and improves neurological deficits through the sustained release of hesperetin in the brain. The findings may open up new avenues for designing clinically translatable probes for TBI treatment.