Thinking Outside the Energetic Box: Stabilizing and Greening High-Energy Materials with Reticular Chemistry.

ConspectusReticular chemistry has provided intriguing opportunities for systematically designing porous materials with different pores by adjusting the building blocks. Among them, framework materials have demonstrated outstanding performance for the design of new functional materials used in a broad range of fields, including energetic materials. Energetic materials are widely used for rockets, satellites, mining, and tunneling. In terms of energetic materials, explosophores and nitrogen-rich heterocycles are fundamental building blocks for high-energy compounds. However, the traditional strategy of synthesizing HEDMs (high energy density materials) at the molecular level has faced the long-term challenge of balancing energy and stability. Inspired by reticular chemistry, nitrogen-rich heterocycles offer diverse nitrogen sites for designing diversified coordination interactions. Ionic bond interactions exist in a wide range of energetic salts. Furthermore, most metastable explosophores, e.g., nitro, nitramino, and amino groups, can form strong hydrogen-bonding networks. Based on these noncovalent interactions (such as coordination, ionic, and/or hydrogen bonds (HBs)) and/or covalent interactions can determine intermolecular packing/linkage of the energetic fuel and oxidizer components, reticular chemistry provides a new platform evolving from single-molecular design to various energetic frameworks (E of the energetic frameworks with superior comprehensive properties. For example, to achieve coordination with metals or introduce sufficient hydrogen bond donor/acceptor structural units, the host structure of energetic framework materials usually contains less oxygen-rich substituents such as nitro, so the host molecules of the framework, F) at the crystal level, which can enhance the integrated stabilities of EFs.Along with growing concerns about the environment and safety issues, considerable effort has been devoted to pursuing environmentally friendly and insensitive energetic materials. The newly emerging EFs are conducive to introducing explosophores into a green chemical pathway. Benefiting from these cross-disciplinary achievements, taming metastable energetic molecules in specific porous frameworks is a green strategy to desensitize energetic materials while concomitantly retaining excellent energetic properties, which has become one of the most forward and promising investigations. In the past decade, EFs have achieved further results in stabilizing and greening energetic materials using HBs, covalent bonds, and alkaline earth metal-involving coordination bonds to avoid heavy metal toxicity and to employ halogen-free oxidizers. Because this field is still expanding rapidly, it is of great value for researchers and possible users of the work to be able to view all the progress.Through this Account, we intend that more readers will become knowledgeable about EFs, including their definition, history, synthesis, properties, and possible applications. The aim of this Account is to present the latest advances in EFs in recent years and to offer a perspective on the future direction of this field.

Hypomethylation-associated LINC00987 downregulation induced lung adenocarcinoma progression by inhibiting the phosphorylation-mediated degradation of SND1.

DNA methylation, an epigenetic regulatory mechanism dictating gene transcription, plays a critical role in the occurrence and development of cancer. However, the molecular underpinnings of LINC00987 methylation in the regulation of lung adenocarcinoma (LUAD) remain elusive. This study investigated LINC00987 expression in LUAD patients through analysis of The Cancer Genome Atlas data sets. Quantitative real-time polymerase chain reaction (RT-qPCR) and fluorescence in situ hybridization assays were used to assess LINC00987 expression in LUAD. The bisulfite genomic sequence PCR (BSP) assay was used to determine the methylation levels of the LINC00987 promoter. The interaction between LINC00987 and SND1 was elucidated via immunoprecipitation and RNA pull-down assays. The functional significance of LINC00987 and SND1 in Calu-3 and NCI-H1688 cells was evaluated in vitro through CCK-8, EdU, Transwell, flow cytometry, and vasculogenic mimicry (VM) tube formation assays. LINC00987 expression decreased in LUAD concomitant with hypermethylation of the promoter region, while hypomethylation of the LINC00987 promoter in LUAD tissues correlated with tumor progression. Treatment with 5-Aza-CdR augmented LINC00987 expression and inhibited tumor growth. Mechanistically, LINC00987 overexpression impeded LUAD progression and VM through direct binding with SND1, thereby facilitating its phosphorylation and subsequent degradation. Additionally, overexpression of SND1 counteracted the adverse effects of LINC00987 downregulation on cell proliferation, apoptosis, cell migration, invasion, and VM in LUAD in vitro. In conclusion, this pioneering study focuses on the expression and function of LINC00987 and reveals that hypermethylation of the LINC00987 gene may contribute to LUAD progression. LINC00987 has emerged as a potential tumor suppressor gene in tumorigenesis through its binding with SND1 to facilitate its phosphorylation and subsequent degradation.

Myelin oligodendrocyte glycoprotein antibody and N-methyl-d-aspartate receptor antibody overlapping syndrome: insights from the recent case reports.

The overlapping of two or more types of neural autoantibodies in one patient has increasingly been documented in recent years. The coexistence of myelin oligodendrocyte glycoprotein (MOG) and N-methyl-d-aspartate receptor (NMDAR) antibodies is most common, which leads to a unique condition known as the MOG antibody and NMDAR antibody overlapping syndrome (MNOS). Here, we have reviewed the pathogenesis, clinical manifestations, paraclinical features, and treatment of MNOS. Forty-nine patients with MNOS were included in this study. They were young males with a median onset age of 23 years. No tumors were observed in the patients, and 24 of them reported prodromal symptoms. The most common clinical presentations were psychiatric symptoms (35/49) and seizures (25/49). Abnormalities on magnetic resonance imaging involved the brainstem (11/49), cerebellum (9/49), and parietal lobe (9/49). Most patients mostly responded to immunotherapy and had a good long-term prognosis. However, the overall recurrence rate of MNOS was higher than that of mono antibody-positive diseases. The existence of concurrent NMDAR antibodies should be suspected in patients with MOG antibody-associated disease having psychiatric symptoms, seizures, movement disorders, or autonomic dysfunction. Similarly, serum MOG antibody testing should be performed when patients with anti-NMDAR encephalitis present with atypical clinical manifestations, such as visual impairment and limb weakness, and neuroradiological findings, such as optic nerve, spinal cord, or infratentorial involvement or meningeal enhancement. Early detection of the syndrome and prompt treatment can be beneficial for these patients, and maintenance immunosuppressive therapy is recommended due to the high overall recurrence rate of the syndrome.

Type 2 herpes simplex virus-induced anti-N-methyl-D-aspartate receptor encephalitis responsive to immunoglobulin monotherapy.

Herpes simplex virus-2 encephalitis (HSV2E) in immunocompetent adults is exceptionally rare, and the subsequent onset of autoimmune encephalitis after HSV2E is even less common. This report presents the inaugural Chinese case of anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) induced by HSV2E, confirmed via metagenomic next-generation sequencing (mNGS). The patient demonstrated a favorable response to intravenous immunoglobulin (IVIG) monotherapy. This case emphasizes the importance of considering autoimmune encephalitis in patients exhibiting new or recurrent neurological symptoms after HSV2E recovery. Comprehensive mNGS and neuronal antibody testing are essential for timely diagnosis. Moreover, IVIG monotherapy can serve as an effective treatment for NMDARE induced by HSV2, providing a viable alternative, particularly when steroid therapy is contraindicated.

Identifying Genetic Factors of Polycystic Ovary Syndrome in Women with Epilepsy: A Whole-Genome Sequencing Study.

INTRODUCTION: Women with epilepsy (WWE) are more likely to develop reproductive endocrine disorders, especially polycystic ovary syndrome (PCOS). This study aimed to explore the genetic factors of PCOS in WWE in hope of improving individual precision diagnosis and treatment. METHODS: WWE registered at West China Hospital between January 2022 and October 2022 were enrolled in this study. Demographic and epilepsy-related characteristics were recorded, and blood samples were collected for hormones, glucose metabolism testing, and whole-genome sequencing. RESULTS: After sample sequencing, quality control, and variants selection, association analyses were performed. Pathway analysis was performed to identify involved biological pathways. The overall and PCOS "burden score" of each individual were calculated to count the deleterious variants. A total of 95 WWE were included in this study and 19 patients were diagnosed with PCOS. WWE with PCOS showed a significantly different hormone profiles and a tendency of impaired glucose metabolism. The most commonly associated genes were ZFYVE28, COL19A1, SIK3, ANKK1, PPIG, and REPIN1. The top 3 canonical pathways are adipogenesis pathway, epoxysqualene biosynthesis signaling, and glutamate degradation signaling. The most significant common variant was rs11914038 located in gene CELSR1 and rs651748 located in gene ZBTB16. In human gene connectome prioritizations, ITGA9, PNPLA2, and DAB2 are the top 3 genes having the shortest distance to known PCOS genes. CONCLUSION: Genetic factors involved in the abnormal regulation of glucose and insulin metabolism are likely to be associated with the comorbidity of PCOS in WWE. Interventions targeting these processes should be given more priority in clinical practice.

Effects of Hypertension on Alzheimer's Disease: Updates in Pathophysiological and Neuroimaging Findings.

Alzheimer's disease (AD) is recognized as the leading cause of dementia, imposing a significant economic toll on society. Despite the emergence of novel therapeutic approaches for AD, their efficacy and safety mandates further validation through rigorous clinical trials. In this context, hypertension (HTN) has garnered considerable attention as an amendable risk factor for AD. Research indicates that hypertension during midlife is associated with an elevated risk of AD in later years, influencing both the onset and progression of the disease. Nevertheless, the relationship between AD and hypertension in the later stages of life remains a subject of debate. Moreover, the consequences of blood pressure reduction on cognitive function, along with the optimal pharmacological interventions and therapeutic thresholds for hypertension, have emerged as pivotal areas of inquiry. This review synthesizes findings on epidemiology, neuroimaging, and biomarkers, and the effects of antihypertensive medications to elucidate the link between hypertension and cognitive performance. We particularly investigate how hypertension and AD are related by plasma sulfide dysregulation, offering possible indicators for future diagnosis and therapy.

A Machine-Learning Strategy to Detect Mura Defects in a Low-Contrast Image by Piecewise Gamma Correction.

A detection and classification machine-learning model to inspect Thin Film Transistor Liquid Crystal Display (TFT-LCD) Mura is proposed in this study. To improve the capability of the machine-learning model to inspect panels' low-contrast grayscale images, piecewise gamma correction and a Selective Search algorithm are applied to detect and optimize the feature regions based on the Semiconductor Equipment and Materials International Mura (SEMU) specifications. In this process, matching the segment proportions to gamma values of piecewise gamma is a task that involves derivative-free optimization which is trained by adaptive particle swarm optimization. The detection accuracy rate (DAR) is approximately 93.75%. An enhanced convolutional neural network model is then applied to classify the Mura type through using the Taguchi experimental design method that identifies the optimal combination of the convolution kernel and the maximum pooling kernel sizes. A remarkable defect classification accuracy rate (CAR) of approximately 96.67% is ultimately achieved. The entire defect detection and classification process can be completed in about 3 milliseconds.

Phenotyping the late- and younger-onset neuronal surface antibody-mediated autoimmune encephalitis: a multicenter study.

Neuronal surface antibody-mediated autoimmune encephalitis (NSAE) occurs across a wide age range. However, few studies focused on the onset age and their related characteristics. We aimed to explore the age-dependent profile of NSAE. A total of 134 patients with a definite diagnosis of NSAE were retrospectively enrolled from 3 tertiary hospitals between July 2014 and August 2020. Demographic, clinical, therapeutic, and prognostic data were collected and compared between the late- (≥45) and younger-onset (<45) groups. The results showed that 56 (41.8%) patients were classified as late-onset NSAE, and 78 (58.2%) as younger-onset NSAE. There were more males, especially in the late-onset group (P = 0.036). Prodromal symptoms were more common in the younger-onset group (P = 0.004). Among the onset symptoms, more late-onset patients presented as seizures, while more younger-onset patients presented as psychiatric symptoms. Throughout the disease course, the late-onset patients were more likely to have memory dysfunction (P < 0.001), but less likely to have central hypoventilation (P = 0.045). The late-onset patients also had a significantly lower modified Rankin Scale score on admission (P = 0.042), required intensive care unit (ICU) admission less frequently during hospitalization (P = 0.042) and had a shorter hospital stay (P = 0.014). Our study revealed that the late- and younger-onset NSAE had a distinct spectrum of demographic features, presentations, and prognoses. More attention is needed for the younger-onset patients, given a higher disease severity on admission, more frequent requirement for ICU admission and longer length of stay.

Diterpenoids with an unusual tricyclo[10.3.0.02,9]pentadecane skeleton from Pedilanthus tithymaloides as multidrug resistance modulators.

Three new diterpenoids with an unusual carbon skeleton, pedilanins A-C (1-3), and nine new jatrophane diterpenoids, pedilanins D-L (4-12), along with five known ones (13-17), were isolated from Pedilanthus tithymaloides. Compounds 1-3 characterize an unprecedented tricyclo[10.3.0.02,9]pentadecane skeleton. Compounds 4-8 are rare examples of the jatrophanes bearing a cyclic hemiketal substructure. Their structures were determined by an extensive analysis of HRESIMS, NMR, quantum-chemical calculation, DP4+ probability, and X-ray crystallographic data. In the bioassay, compounds 1-12 dramatically reversed multidrug resistance in cancer cells with the fold-reversals ranging from 17.9 to 396.8 at the noncytotoxic concentration of 10 µM. The mechanism results indicated that compounds 2 and 3 inhibited the P-glycoprotein (Pgp) transporter function, thus reversing the drug resistance.

Paracoccus onchidii sp. nov., a moderately halophilic bacterium isolated from a marine invertebrate from the South China Sea.

A novel moderately halophilic bacterial strain, designated Z330T, was isolated from the egg of a marine invertebrate of the genus Onchidium collected in the South China Sea. The 16S rRNA gene sequence of strain Z330T exhibited the highest similarity value to that of the type strain Paracoccus fistulariae KCTC 22803T (97.6%), Paracoccus seriniphilus NBRC 100798T (97.6%) and Paracoccus aestuarii DSM 19484T (97.6%). Phylogenomic and 16S rRNA phylogenetic analysis showed that strain Z330T was most closely related to P. seriniphilus NBRC 100798T and P. fistulariae KCTC 22803T. Strain Z330T grew optimally at 28-30 °C, pH 7.0-8.0 with the presence of 5.0-7.0% (w/v) NaCl. In addition, growth of strain Z330T occurred at 0.5-16% NaCl, indicated strain Z330T was a moderately halophilic and halotolerant bacterium of genus Paracoccus. The predominant respiratory quinone in strain Z330T was identified as ubiquinone-10. The major polar lipids of strain Z330T were phosphatidylcholine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmonomethylethanolamine, glycolipid and six unidentified polar lipids. The major fatty acids of strain Z330T was summed feature 8 (C18:1 ω6c and/or C18:1 ω7c). The draft genome sequence of strain Z330T includes 4,084,570 bp in total (N50 = 174,985 bp) with a medium read coverage of 463.6 × and 83 scaffolds. The DNA G + C content of strain Z330T was 60.5%. In silico DNA-DNA hybridization with the four type strains showed 20.5, 22.3, 20.1 and 20.1% relatedness to Paracoccus fistulariae KCTC 22803T, Paracoccus seriniphilus NBRC 100798T, Paracoccus aestuarii DSM 19484T and Paracoccus denitrificans 1A10901T, respectively. And the average nucleotide identity (ANIb) values between strain Z330T and these four type strains were 76.2, 80.0, 75.8 and 73.8%, respectively, lower than the 95-96% threshold value for dividing prokaryotic species. On the basis of the phenotypic, phylogenetic, phylogenomic and chemotaxonomic properties, a novel species of the genus Paracoccus, Paracoccus onchidii sp. nov. is proposed with the type strain Z330T (= KCTC 92727T = MCCC 1K08325T).

Myelin oligodendrocyte glycoprotein antibody-associated disease preceding primary central nervous system lymphoma: causality or coincidence?

INTRODUCTION: Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphomatous malignancy that affects the brain, spinal cord, leptomeninges, or eyes, in the absence of systemic diffusion. Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a newly identified benign immune-mediated CNS inflammatory disorder with specific anti-MOG antibody seropositivity. These two seemingly unrelated nosological entities both have abundant clinical and radiological manifestations, and whether there is a potential link between them is unclear. CASE REPORT: We describe a 49-year-old man who presented progressive headache, dizziness, and unsteady gait with multifocal scattered T2 hyperintensities with contrast enhancement. The serum anti-MOG antibody test was positive, and a brain biopsy showed inflammatory infiltration. Initially, he was diagnosed with MOGAD and his condition improved after corticosteroid therapy. The patient relapsed with exacerbation of symptoms and neuroimaging showed new mass-forming lesions four months later. A second brain biopsy confirmed PCNSL. DISCUSSION: This is the first report of histologically confirmed successive MOGAD and PCNSL. Our case broadens the phenotypic spectrum of sentinel lesions in PCNSL. Though rare, PCNSL should be considered in patients diagnosed with benign CNS inflammatory disorder and responding well to steroid treatment when their clinical symptoms worsen and the imaging deteriorates. A timely biopsy is critical for accurate diagnosis and appropriate therapy.

Kelch-like protein 11 antibody-associated paraneoplastic neurological syndrome: A state-of-the-art review.

The Kelch-like protein 11 antibody-associated paraneoplastic neurological syndrome (KLHL 11-PNS) was first identified in 2019. This novel antibody, targeting the intracellular KLHL 11 antigen, can be detected in serum and cerebrospinal fluid using tissue-based and cell-based assays. It is thought to be a biomarker for a T-cell autoimmunity response. The most likely immunopathogenesis of KLHL 11-PNS appears to be linked to cytotoxic T-cell-mediated neuronal injury and loss. Patients have adult-male predilection, rhombencephalitis (brainstem and / or cerebellar involvement), and a robust oncological correlation with testicular germ cell tumors (predominately seminoma). Brain magnetic resonance imaging demonstrated T2 / fluid-attenuated inversion recovery hyperintensities and atrophy of the temporal lobe, cerebellum, and brainstem. Most patients responded poorly to immunotherapy and oncotherapy and thus had a poor long-term prognosis. We review the literature and provide an update of current knowledge regarding KLHL 11-PNS, including epidemiology, underlying mechanism, clinical presentations, paraclinical and oncological findings, diagnostic workup, and treatment approaches.

Seizures and epilepsy in multiple sclerosis, aquaporin 4 antibody-positive neuromyelitis optica spectrum disorder, and myelin oligodendrocyte glycoprotein antibody-associated disease.

Seizure is one of the manifestations of central nervous system inflammatory demyelinating diseases, which mainly include multiple sclerosis (MS), aquaporin 4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Acute symptomatic seizures secondary to MS/AQP4-NMOSD/MOGAD occur in the acute phase of the diseases, and are more frequent in MOGAD. In contrast, recurrent nonprovoked seizures, mainly attributed to autoimmune-associated epilepsy, occur in the nonacute phase of the diseases. Seizures in MS/AQP4-NMOSD/MOGAD mostly have a focal onset. MS patients with concomitant systemic infections, earlier onset, and greater disease activity are more likely to have seizures, whereas factors such as greater MS severity, the presence of status epilepticus, and cortical damage indicate a greater risk of developing epilepsy. In MOGAD, cerebral cortical encephalitis and acute disseminated encephalomyelitis (ADEM)-like phenotypes (predominately ADEM and multiphasic disseminated encephalomyelitis) indicate a greater seizure risk. Multiple relapses with ADEM-like phenotypes predict epilepsy in pediatrics with MOGAD. Pathophysiologically, acute symptomatic seizures in MS are associated with neuronal hyperexcitability secondary to inflammation and demyelination. Chronic epilepsy in MS is largely due to gliosis, neuronal dysfunction, and synaptic abnormalities. The mainstay of treatment for seizures secondary to MS/AQP4-NMOSD/MOGAD consists of immunotherapy along with antiseizure medications. This critical review discusses the most-updated evidence on epidemiology, clinical correlates, and inflammatory mechanisms underlying seizures and epilepsy in MS/AQP4-NMOSD/MOGAD. Treatment cautions including drug-drug interactions and the impact of treatments on the diseases are outlined. We also highlight pitfalls and challenges in managing such patients and future research perspectives to address unsolved questions.

Long-Term Outcome of a "Mother-Child" Coaxial Dual-Catheter Technique for Percutaneous Transluminal Angioplasty of Central Vein Stenosis or Occlusion in Hemodialysis Patients.

PURPOSE: This study aims to evaluate the long-term outcome and prognostic factors of a "mother-child" coaxial dual-catheter technique for percutaneous transluminal angioplasty (PTA) in the treatment of central vein stenosis (CVS) or central vein occlusion (CVO). MATERIALS AND METHODS: During September 2017 to August 2020, totally, 76 hemodialysis patients with symptomatic CVS or CVO were treated with PTA using the mother-child technique. The success rate, complications, and follow-up information were collected. Cox proportional hazard analysis was used to explore the predicting factors of primary patency. Primary patency rates of different subgroups were generated with the Kaplan-Meier analysis and compared using the log-rank (Mantel-Cox) test. RESULTS: There were 31 CVS patients and 45 CVO patients who presented with 114 PTAs. The initial procedure success rate was 98.25%. By the end of the follow-up, 57 patients (75%) had maintained functioning fistula after initial or repeated PTAs. The primary patency rates were 88.75% at 3 months, 73.36% at 6 months, 55.83% at 12 months, and 50.75% at 18 months. The secondary patency rates were 97.14% at 6 months, 87.66% at 12 months, and 82.18% at 24 months. The predictors for primary patency were history diabetes mellitus (hazard ratio [HR] = 3.1, 95% confidence interval [CI]: 1.31-7.30, P = .010), abnormal white blood cell count (HR = 1.44, 95% CI: 1.18-1.75, P < .001), lesion at subclavian-innominate vein (HR=2.75, 95% CI: 1.34-5.63, P = .006), and occlusion (HR=0.33, 95% CI: 0.14-0.76, P = .010). The primary patency was significantly lower in the subclavian-innominate vein subgroup, with a median primary patency of 4.5 (3-12.75) months, than in the nonsubclavian-innominate vein subgroup (8.5 [5-13] months; P = .005). The median duration of each PTA was 8 months for the first PTA, 7.5 months for the second PTA, and 5 months for the third PTA. There was no significant difference in the patency duration of repeated PTAs and the primary PTA (P = .389). CONCLUSIONS: The mother-child coaxial dual-catheter technique has a good success rate and acceptable primary patency in the treatment of hemodialysis patients with CVS or CVO. Repeated PTA is as effective as the primary PTA. CLINICAL IMPACT: This is the follow up report on the "Mother-Child" coaxial dual-catheter technique for percutaneous transluminal angioplasty of central vein stenosis or occlusion in hemodialysis patients since we first presented it in 2019. In this paper, we can see that the long-term patency rate of this technique for central venous disease is satisfactory, and repeated use of this technique does not affect the patency time. Compared with other literature reports, the surgical success rate of this technique is significantly improved. Therefore, this technique is worth popularizing in the treatment of central venous disease.

Lymphomatosis cerebri: a rare diffuse leukoencephalopathy you should never miss.

INTRODUCTION: Lymphomatosis cerebri (LC) is a rare variant of primary central nervous system lymphoma that diffusely involves throughout the brain. In recent years, increasingly reported cases have notably broadened the spectrum of clinical and radiological features; however, it remains a great diagnostic challenge. CASE REPORT: We reported an atypical case of LC presented with subacute onset of focal neurological deficits and diffuse T2 hyperintensities without contrast enhancement on magnetic resonance imaging. He was initially considered as inflammatory leukoencephalopathy and received empirical corticosteroids, showing a dramatically clinical response. Three months later, the patient relapsed with deteriorating symptoms and enlarged brain lesions with mass-like enhancement. A diagnosis of LC was finally established according to the radiological and pathological findings. DISCUSSION: Though rare, LC should always be kept as a differential diagnosis of diffuse leukoencephalopathy. Neurologists should be aware of every detailed information about LC to avoid a delay of diagnostic biopsy in clinical practice.

Acremocholone, an Anti-Vibrio Steroid from the Marine Mesophotic Zone Ciocalypta Sponge-Associated Fungus Acremonium sp. NBUF150.

Mesophotic coral ecosystems (MCEs) represent an underexplored source of intriguing natural products. Efforts to discover bioactive metabolites from sponge-associated fungi in MCEs identified a new steroid, acremocholone (1) and its three known analogs (2-4), from Acremonium sp. NBUF150. The Acremonium sp. NBUF150 was isolated from a Ciocalypta sponge located 70 m deep within the South China Sea. The planar structures and absolute configuration of 1-4 were determined from NMR-derived spectroscopic data, HR-ESI-MS, and X-ray crystallography. Compound 1 exhibited antimicrobial inhibition against Vibrio scophthalmi, V. shilonii and V. brasiliensis at minimum inhibitory concentrations of 8 µg/mL; compound 2 inhibited V. shilonii and V. brasiliensis at 8 and 32 µg/mL, respectively, and compound 4 inhibited growth of V. brasiliensis at 16 µg/mL. Sponge associated fungi from MCEs represent a promising resource of anti-Vibrio drug leads for aquaculture use.

In Situ Prodrug Activation by an Affibody-Ruthenium Catalyst Hybrid for HER2-Targeted Chemotherapy.

Transition-metal catalysts exhibit great potential as therapeutic agents to inhibit tumor growth. However, the precise delivery and in situ catalysis are challenging in catalytic medicine. Herein, we report an anti-HER2 affibody-ruthenium catalyst hybrid, named Ru-HER2 for selective and effective killing of cancer cells. Ru-HER2 binds to the HER2 receptor on a tumor cell and in situ catalyzes the activation of gemcitabine prodrug, resulting in enhanced selectivity in suppression of tumor growth and reduction of side effects. Immunoblotting reveals that Ru-HER2 in combination with gemcitabine prodrug can not only induce DNA damage, but also effectively block the HER2 signaling pathway in cancer cells. Therefore, the HER2-targeted chemotherapy exhibits substantially high anticancer activity toward HER2-positive cancer cells in vitro and in vivo. In a word, we report the first affibody-ruthenium catalyst hybrid and reveal its potential for effective HER2-targeted cancer chemotherapy.

Bisphosphonate-enoxacin inhibit osteoclast formation and function by abrogating RANKL-induced JNK signalling pathways during osteoporosis treatment.

Osteoporosis is an age-related disease characterized by low mineral density, compromised bone strength and increased risk of fragility fracture. Most agents for treating osteoporosis focus primarily on anti-resorption by inhibiting osteoclast activity. Bisphosphonate (BP) is a potent anti-resorptive agent that has been used clinically for decades and is proven to be effective. However, BP has a variety of side effects and is far from being an ideal anti-osteoporosis agent. BP selectively binds to calcium crystals, which are subsequently taken up or released by osteoclasts. Based on the action of BP, we previously demonstrated the inhibitory effect of a novel bone-targeting BP derivative, bisphosphonate-enoxacin (BE). In the current study, we used bone marrow-derived osteoclast cultures to further assess the inhibitory effect of BE on osteoclastogenesis and employed reverse transcription PCR and real-time PCR to examine expression of osteoclast-specific genes. Additionally, we used bone resorption and F-actin immunofluorescence assays to evaluate the effect of BE on osteoclast function and investigated the potential mechanisms affecting osteoclast differentiation and function in vitro. Furthermore, an ovariectomized (OVX) rat model was established to evaluate the therapeutic effects of BE on preventing bone loss. Results showed that BE exerted potent inhibitory effects on osteoclast formation and bone resorption by specifically abrogating RANKL-induced JNK signalling, and that it preserved OVX rat bone mass in vivo without any notable side effects. Collectively, these results indicated that the BP derivative BE may have significant potential as a treatment for osteoporosis and other osteolytic diseases.

Efficacy of ultrasound-guided percutaneous transluminal angioplasty for arteriovenous fistula stenosis or occlusion at juxta-anastomosis: A 3-year follow-up cohort study.

OBJECTIVE: Arteriovenous fistula (AVF) is the preferred access for hemodialysis. Percutaneous transluminal angioplasty (PTA) has become a choice for AVF stenosis, and ultrasound has been used in PTA more frequently. METHODS: This single-center retrospective cohort study analyzed 129 patients who underwent PTA in the First Affiliated Hospital of Chongqing Medical University from January 2016 to December 2016. Angioplasty was performed using a noncompliant high-pressure balloon. The process was visualized by duplex scan. Our inclusion criteria were as follows: (1) stenoses or occlusions were located at the juxta-anastomosis site: the first 5 cm of the vein distal to the anastomosis; (2) stenosis was confirmed with the following conditions: (a) flow rates are <500 mL/min in the brachial artery and <200 mL/min in the fistula during dialysis, and (b) the stenosis diameter is <1.7 mm. We used the Kaplan-Meier curve to show the postintervention primary and secondary patency rates of patients with stenosis and occlusion. RESULTS: Altogether, 129 patients with 76 males were analyzed. Moreover, 104 have AVFs on the left arm, and only one patient had an ulnar-basilic AVF, whereas others had a radial-cephalic AVF. The postintervention primary patency rates are better in occlusion cases (P < .05), whereas secondary patency rates have no difference. The postintervention primary patency rates are better in patients without diabetes mellitus (P < .05), whereas the secondary patency rates had no difference. CONCLUSIONS: For juxta-anastomosis site stenosis or occlusion, PTA can be used to obtain satisfactory results.

Cupidesulfovibrio liaohensis gen. nov., sp. nov., a novel sulphate-reducing bacterium isolated from an oil reservoir and reclassification of Desulfovibrio oxamicus and Desulfovibrio termitidis as Cupidesulfovibrio oxamicus comb. nov. and Cupidesulfovibrio termitidis comb. nov.

A novel sulphate-reducing, Gram-stain-negative, anaerobic strain, isolate XJ01T, recovered from production fluid at the LiaoHe oilfield, PR China, was the subject of a polyphasic study. The isolate together with Desulfovibrio oxamicus NCIMB 9442T and Desulfovibrio termitidis DSM 5308T formed a distinct, well-supported clade in the Desulfovibrionaceae 16S rRNA gene tree. The taxonomic status of the clade was underscored by complementary phenotypic data. The three isolates comprising the clade formed distinct phyletic branches and were distinguished using a combination of physiological features and by low average nucleotide identity and digital DNA-DNA hybridization values. Consequently, it is proposed that isolate XJ01T represents a novel genus and species for which the name Cupidesulfovibrio liaohensis gen. nov., sp. nov. is proposed with the type strain XJ01T (=CGMCC 1.5227T=DSM 107637T). It is also proposed that D. oxamicus and D. termitidis be reclassified as Cupidesulfovibrio oxamicus comb. nov. and Cupidesulfovibrio termitidis comb. nov., respectively.