Identification of a new species of Gyrodactylus von Nordmann, 1832 (Monogenoidea Gyrodactylidae) isolated from Diptychus maculatus in Yarkand River, Xinjiang, China.

To investigate Gyrodactylus infection of fish in the river system of Xinjiang (China), Gyrodactylus individuals were isolated from specimens of Diptychus maculatus. Morphological characterization and phylogenetic analysis based on ITS1-5.8S-ITS2 rDNA locus revealed that the gyrodactylids belong to new species. Gyrodactylus diptychi n. sp. differs significantly in the morphology of the haptoral structures from 12 known species of Gyrodactylus found in fishes of the subfamily Schizothoracinae. In particular, G. diptychi n. sp. has a relatively short dorsal bar with thick and large ends, flat and straight hamuli roots, and small ventral bar processes. Furthermore, G. diptychi n. sp. is the only representative of Gyrodactylus found on D. maculatus. Using the BLASTn search of ITS1-5.8S-ITS2 rDNA sequences in GenBank and the Bayesian Information and Maximum Likelihood methods, we constructed phylogenetic trees for G. diptychi n. sp. As a result, our studies clearly identified that G. diptychi n. sp. was the first Gyrodactylus monogenean isolated from D. maculatus and a new species belonged to the subgenus Limnonephrotus.

Cytarabine prevents neuronal damage by enhancing AMPK to stimulate PINK1 / Parkin-involved mitophagy in Parkinson's disease model.

Parkinson's disease (PD) is a common age-related neurodegenerative disorder, which may be largely due to the mitochondrial dysfunction and impaired mitophagy. Thus, it is of great importance to seek novel therapeutic strategies for PD targeting mitochondrial function and mitophagy. Cytarabine is a marine-derived antimetabolite used in the treatment of acute leukemia, which is also used in the study of the nervous system. In this study, we found that cytarabine pretreatment significantly inhibited the apoptosis and necrosis in the ROT-induced SH-SY5Y cell PD model and reduced the oxidative stress, as evidenced by the reduced MDA levels and the increased levels of SOD, GSH, and total antioxidant capacity. Cytarabine can also enhance mitochondrial vitality, improve mitochondrial respiratory function, and preserve mitochondrial morphology. Cytarabine also enhanced the expression of the mitophagy-related proteins PINK1, Parkin, VDAC1, and DJ-1, and its actions can be reversed by treatment with AMPK inhibitor - Compound C (CC), suggesting that AMPK activation may be involved in cytarabine-enhanced mitophagy. Furthermore, cytarabine can also ameliorate the motor symptoms in the MPTP-induced PD-like mice model, and attenuate the neuropathy in the substantia nigra (SN) of PD mice, while Compound C antagonized cytarabine's beneficial effects. In summary, marine-derived compound cytarabine could resist neurological damage both in vitro and in vivo by activating AMPK to increase PINK1/Parkin-induced mitophagy, serving as a promising disease modulator for treating neurodegenerative disease.

Neuroprotective effects of polyphyllin VI against rotenone-induced toxicity in SH-SY5Y cells.

BACKGROUND: A substantial body of evidence is drawing connections between Parkinson's disease (PD) and the phenomena of oxidative stress and mitochondrial dysfunction. Polyphyllin VI (PPVI), an active compound found in Rhizoma Paridis-commonly known as Chonglou (CL) in China, has been identified for its various pharmacological properties, including anti-tumor and anti-inflammatory effects. OBJECTIVE: In the present study, an in vitro model of PD was established by treating SH-SY5Y cells with rotenone (ROT), to evaluate the potential neuroprotective effects of polyphyllin VI and its underlying mechanism. METHODS: SH-SY5Y cells were treated with ROT to establish an in vitro model of PD. The effects of polyphyllin VI on cell viability were assessed using the resazurin assay. Cell morphology was examined using a microscope. The YO-PRO-1/PI was used to detect apoptosis. Mito-Tracker Red CMXRos, Mito-Tracker Green, and JC-1 were used to detect the effects of polyphyllin Ⅵ on mitochondrial viability, morphology, and function. Oxidative stress-related marker detection kits were used to identify the effects of polyphyllin VI on oxidative stress. Western blot analysis was employed to investigate the signaling pathways associated with neuroprotection. RESULTS: PPVI increased ROT-induced SH-SY5Y cell viability and improved ROT-induced cellular morphological changes. PPVI ameliorated ROT-induced oxidative stress status, and attenuated mitochondrial function and morphological changes. PPVI may exert neuroprotective effects through FOXO3α/CREB1/DJ-1-related signaling pathways. CONCLUSION: These preliminary findings suggested that PPVI possesses neuroprotective attributes in vitro, and it may be a potential candidate for PD treatment. However, extensive research is necessary to fully understand the mechanisms of PPVI and its effectiveness both in vitro and in vivo.

Prognostic value of red blood cell distribution width combined with chloride in predicting short- and long-term mortality in critically ill patients with congestive heart failure: Findings from the MIMIC-IV database.

Background: Hypochloremia and red blood cell distribution width (RDW) play important roles in congestive heart failure (CHF) pathophysiology, and they were associated with the prognosis of CHF. However, the prognostic value of chloride combined with RDW in patients with CHF remains unknown. Methods: We retrospectively analyzed critically ill patients with CHF. The database was derived from the Medical Information Mart for Intensive Care IV v2.0 (MIMIC-IV-v2.0) database. Results: In the final analysis, 5376 critically ill patients with CHF were included, and 2428 patients (45.2 %) experienced 5-year mortality. The restricted cubic spline model revealed a positive correlation between RDW and 5-year mortality, whereas chloride showed a U-shaped correlation with 5-year mortality. The median values of RDW and chloride were used to classify patients into four groups: high chloride/low RDW, low chloride/low RDW, high chloride/high RDW, and low chloride/high RDW. We observed the prognostic value of RDW combined with chloride in the Cox proportional hazard model, in predicting 5-year mortality, in-hospital mortality and 1-year mortality. Furthermore, we discovered that patients with chronic kidney disease (CKD) had a higher 5-year mortality risk than patients without CKD. Conclusion: We found the translational potential role of chloride combined with RDW in prioritizing patients at high risk for short- and long-term mortality in a cohort of critically ill patients with CHF. Prospective multicenter investigations are warranted to validate our results.

Myosin 9 and N-glycans jointly regulate human papillomavirus entry.

Persistent high-risk HPV infection is closely associated with cervical cancer development, and there is no drug targeting HPV on the market at present, so it is particularly important to understand the interaction mechanism between HPV and the host which may provide the novel strategies for treating HPV diseases. HPV can hijack cell surface heparan sulfate proteoglycans (HSPGs) as primary receptors. However, the secondary entry receptors for HPV remain elusive. We identify myosin-9 (NMHC-IIA) as a host factor that interacts with HPV L1 protein and mediates HPV internalization. Efficient HPV entry required myosin-9 redistribution to the cell surface regulated by HPV-hijacked MEK-MLCK signaling. Myosin-9 maldistribution by ML-7 or ML-9 significantly inhibited HPV pseudoviruses infection in vitro and in vivo. Meanwhile, N-glycans, especially the galactose chains, may act as the decoy receptors for HPV, which can block the interaction of HPV to myosin-9 and influence the way of HPV infection. Taken together, we identify myosin-9 as a novel functional entry receptor for high-risk HPV both in vitro and in vivo, and unravel the new roles of myosin-9 and N-glycans in HPV entry, which provides the possibilities for host targets of antiviral drugs.

SIRT1-dependent mitochondrial biogenesis supports therapeutic effects of vidarabine against rotenone-induced neural cell injury.

Parkinson's disease (PD) is the second most common neurodegenerative disease in the world, which is distinguished by the loss of dopaminergic (DA) neurons in the substantia nigra and the formation of intraneuronal. Numerous studies showed that the damage and dysfunction of mitochondria may play key roles in DA neuronal loss. Thus, it is necessary to seek therapeutic measures for PD targeting mitochondrial function and biogenesis. In this study, through screening the purchased compound library, we found that marine derived vidarabine had significant neuroprotective effects against rotenone (ROT) induced SH-SY5Y cell injury. Further studies indicated that vidarabine pretreatment significantly protected ROT-treated SH-SY5Y cells from toxicity by preserving mitochondrial morphology, improving mitochondrial function, and reducing cell apoptosis. Vidarabine also reduced the oxidative stress and increased the expression levels of PGC-1α, NRF1, and TFAM proteins, which was accompanied by the increased mitochondrial biogenesis. However, the neuroprotective effects of vidarabine were counteracted in the presence of SIRT1-specific inhibitor Ex-527. Besides, vidarabine treatment attenuated the weight loss, alleviated the motor deficits and inhibited the neuronal injury in the MPTP induced mouse model. Thus, vidarabine may exert neuroprotective effects via a mechanism involving specific connections between the SIRT1-dependent mitochondrial biogenesis and its antioxidant capacity, suggesting that vidarabine has potential to be developed into a novel therapeutic agent for PD.

New species of Gyrodactylus von Nordmann, 1832 (Monogenoidea: Gyrodactylidae) from Gymnodiptychus dybowskii (Kessler, 1874) (Schizothoracinae) in the Kunes River (Yili River basin), China.

Yili River system hosts a diverse fauna of fishes and parasites. Gymnodiptychus dybowskii is a rare and endangered aboriginal cold-water fish inhabit in the Yili river system. Our research identified a new species Gyrodactylus gymnodiptychi n. sp. isolated from G. dybowskii in the Kunes River (Yili River, China). Morphological comparison revealed identifiable differences between the new species and other parasites, including Gyrodactylus aksuensis, and Gyrodactylus tokobaevi, which are two known parasites living in G. dybowskii inhabit in the Aksu River west of Frunze (Kyrgyzstan), as well as Gyrodactylus montanus living in Shizothorax intermedius inhabited in the Tadzhikistan or Uzbekistan. Especially, the dorsal bar of G. gymnodiptychi n. sp. was raised at both ends with a hollow, and its hamulus roots were curved inward. The BLASTN search of GenBank did not detect any other ITS1-5.8S-ITS2 rDNA sequences same as G. gymnodiptychi's. Using the Bayesian Information and Maximum Likelihood methods to analyze the ITS1-5.8S-ITS2 rDNA gene sequences, we constructed phylogenetic trees for G. gymnodiptychi n. sp. Accordingly, our morphological and molecular research indicated that G. gymnodiptychi n. sp. was not only a new species of parasites but also the first Gyrodactylus member identified in the Yili River in China.

Inhibition of herpes simplex virus by wedelolactone via targeting viral envelope and cellular TBK1/IRF3 and SOCS1/STAT3 pathways.

OBJECTIVES: Development of novel antiherpes simplex virus (HSV) agents with active mechanisms different from nucleoside analogues is of high importance. Herein, we investigated the anti-HSV activities and mechanisms of wedelolactone (WDL) both in vitro and in vivo. METHODS: Cytopathic effect (CPE) inhibition assay, plaque assay, and western blot assay were used to evaluate the anti-HSV effects of WDL in vitro. The immunofluorescence assay, RT-PCR assay, plaque reduction assay, sandwich ELISA assay, syncytium formation assay, tanscriptome analysis and western blot assay were used to explore the anti-HSV mechanisms of WDL. The murine encephalitis and vaginal models of HSV infection were performed to evaluate the anti-HSV effects of WDL in vivo. RESULTS: WDL possessed inhibitory effects against both HSV-1 and HSV-2 in different cells with low toxicity, superior to the effects of acyclovir. WDL can directly inactivate the HSV particle via destruction of viral envelope and block HSV replication process after virus adsorption, different from the mechanisms of acyclovir. WDL may influence the host genes and signaling pathways related to HSV infection and immune responses. WDL can mainly interfere with the TBK1/IRF3 and SOCS1/STAT3 pathways to reduce HSV infection and inflammatory responses. Importantly, WDL treatment markedly improved mice survival, attenuated inflammatory symptoms, and reduced the virus titres in both HSV-1 and HSV-2 infected mice. CONCLUSIONS: Thus, the natural compound WDL has the potential to be developed into a novel anti-HSV agent targeting both viral envelope and cellular TBK1/IRF3 and SOCS1/STAT3 pathways.

Inhibition of influenza a virus infection by natural stilbene piceatannol targeting virus hemagglutinin.

BACKGROUND: Given the magnitude of influenza pandemics as a threat to the global population, it is crucial to have as many prevention and treatment options as possible. Piceatannol (PIC) is a tetrahydroxylated stilbenoid (trans-3,4,3',5'-tetrahydroxystilbene), also known as 3'- hydroxy resveratrol, which has demonstrated many different biological activities such as anti-inflammatory and antiviral activities. PURPOSE: In this study, the anti-influenza A virus (IAV) activities and mechanisms of PIC in vitro and in vivo were investigated in order to provide reference for the development of novel plant-derived anti-IAV drugs. METHODS: The viral plaque assay, RT-PCR and western blot assay were used to evaluate the anti-IAV effects of PIC in vitro. The anti-IAV mechanism of PIC was determined by HA syncytium assay, DARTS assay and Surface Plasmon Resonance assay. The mouse pneumonia model combined with HE staining were used to study the anti-IAV effects of PIC in vivo. RESULTS: PIC shows inhibition on the multiplication of both H1N1 and H3N2 viruses, and blocks the infection of H5N1 pseudovirus with low toxicity. PIC may directly act on the envelope of IAV to induce the rupture and inactivation of IAV particles. PIC can also block membrane fusion via binding to HA2 rather than HA1 and cleavage site of HA0. PIC may interact with the two residues (HA2-T68 and HA2-I75) of HA2 to block the conformational change of HA so as to inhibit membrane fusion. Importantly, oral therapy of PIC also markedly improved survival and reduced viral titers in IAV-infected mice. CONCLUSION: PIC possesses significant anti-IAV effects both in vitro and in vivo and may block IAV infection mainly through interaction with HA to block membrane fusion. Thus, PIC has the potential to be developed into a new broad-spectrum anti-influenza drug for the prevention and treatment of influenza.

Chronic cough relief by allosteric modulation of P2X3 without taste disturbance.

P2X receptors are cation channels that sense extracellular ATP. Many therapeutic candidates targeting P2X receptors have begun clinical trials or acquired approval for the treatment of refractory chronic cough (RCC) and other disorders. However, the present negative allosteric modulation of P2X receptors is primarily limited to the central pocket or the site below the left flipper domain. Here, we uncover a mechanism of allosteric regulation of P2X3 in the inner pocket of the head domain (IP-HD), and show that the antitussive effects of quercetin and PSFL2915 (our nM-affinity P2X3 inhibitor optimized based on quercetin) on male mice and guinea pigs were achieved by preventing allosteric changes of IP-HD in P2X3. While being therapeutically comparable to the newly licensed P2X3 RCC drug gefapixant, quercetin and PSFL2915 do not have an adverse effect on taste as gefapixant does. Thus, allosteric modulation of P2X3 via IP-HD may be a druggable strategy to alleviate RCC.

Effect of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers on In-Hospital Outcomes Based on Renal Function Among Critically Ill Patients: Findings From the Medical Information Mart for Intensive Care IV Database.

Renal dysfunction is associated with increased mortality and length of hospital stay in critically ill patients. However, it remains unclear whether the early administration of an angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) for intensive care unit patients with renal dysfunction is associated with reduced in-hospital mortality. We conducted a retrospective analysis of critically ill patients who received early administration of an ACEI/ARB within 72 hours after being hospitalized. Patients were selected from the Medical Information Mart for Intensive Care IV database. We included 18,986 critically ill patients in our analysis. After propensity score matching, our final study cohort of 4974 patients consisted of patients who received early administration of an ACEI/ARB (n = 2487) and nonusers (n = 2487). Results of logistic regression showed that early administration of an ACEI/ARB was associated with reduced risk of in-hospital mortality (odds ratio, 0.64; 95% confidence interval, 0.53-0.77; P < .001) and intensive care unit death (odds ratio, 0.56; 95% confidence interval, 0.45-0.70; P < .001) when compared to nonusers. There was no meaningful interaction for early administration of an ACEI/ARB versus nonusers across estimated glomerular filtration rate in outcomes. Sensitivity analysis showed there was no difference in the outcomes between early administration of ACEI and that of ARB. In this study, we found that early administration of an ACEI/ARB was associated with a reduced risk of in-hospital adverse outcomes based on renal function among critically ill patients. There was no interaction between early administration of an ACEI/ARB and in-hospital adverse outcomes across estimated glomerular filtration rate.

The neuroprotective effects of peracetylated chitosan oligosaccharides against ß-amyloid-induced cognitive deficits in rats.

Chitosan oligosaccharides (COSs) have been reported to possess a broad range of activities such as antitumor, antioxidant and neuroprotective activities. In this study, the protective effects and mechanisms of peracetylated chitosan oligosaccharides (PACOs) against Aß-induced cognitive deficits were investigated in Sprague-Dawley (SD) rats. PACOs treatment significantly improved the learning and memory function of Alzheimer's disease (AD) rats and attenuated the neuron cell damage caused by Aß. PACOs also markedly reduced the levels of lactate dehydrogenase (LDH) and Malondialdehyde (MDA) and decreased the phosphorylation of Tau protein to inhibit oxidative injury and inflammatory responses in AD rats. Further studies indicated that PACOs may promote the repair of Aß induced nerve damage and inhibit neuronal apoptosis mainly through regulating PI3K/Akt/GSK3ß signaling pathway. Consistently, the transcriptome analysis verified that the differentially expressed genes (DEGs) were mainly involved in neuron development and the PI3K-Akt signaling pathway. Taken together, peracetylated chitosan oligosaccharides (PACOs) have the potential to be developed into novel anti-AD agents targeting the cellular PI3K/Akt/GSK3ß signaling pathway. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00172-3.

Altered Membrane Expression and Function of CD11b Play a Role in the Immunosuppressive Effects of Morphine on Macrophages at the Nanomolar Level.

Morphine, one of the most efficacious analgesics, is effective in severe pain, especially in patients with concomitant painful cancers. The clinical use of morphine may be accompanied by increased immunosuppression, susceptibility to infection and postoperative tumor metastatic recurrence, and the specific mechanisms and clinical strategies to alleviate this suppression remain to be investigated. Expression of CD11b is closely associated with the macrophage phagocytosis of xenobiotic particles, bacteria or tumor cells. Here, we find that morphine at 0.1-10 nM levels inhibited CD11b expression and function on macrophages via a µ-opioid receptor (MOR)-dependent mechanism, thereby reducing macrophage phagocytosis of tumor cells, a process that can be reversed by thymopentin (TP5), a commonly used immune-enhancing adjuvant in clinical practice. By knocking down or overexpressing MOR on macrophages and using naloxone, an antagonist of the MOR receptor, and LA1, a molecule that promotes macrophage CD11b activation, we suggest that morphine may regulate macrophage phagocytosis by inhibiting the surface expression and function of macrophage CD11b through the membrane expression and activation of MOR. The CD47/SIRPα axis, which is engaged in macrophage-tumor immune escape, was not significantly affected by morphine. Notably, TP5, when combined with morphine, reversed the inhibition of macrophage phagocytosis by morphine through mechanisms that promote membrane expression of CD11b and modulate its downstream signaling (e.g., NOS2, IFNG, IL1B and TNFA, as well as AGR1, PDGFB, IL6, STAT3, and MYC). Thus, altered membrane expression and function of CD11b may mediate the inhibition of macrophage phagocytosis by therapeutic doses of morphine, and the reversal of this process by TP5 may provide an effective palliative option for clinical immunosuppression by morphine.

Inhibition Effects and Mechanisms of Marine Polysaccharide PSSD against Herpes Simplex Virus Type 2.

Genital herpes is a common sexually transmitted disease mainly caused by herpes simplex virus type 2 (HSV-2), which can increase the risk of HIV transmission and is a major health problem in the world. Thus, it is of great significance to develop new anti-HSV-2 drugs with high efficiency and low toxicity. In this study, the anti-HSV-2 activities of PSSD, a marine sulfated polysaccharide, was deeply explored both in vitro and in vivo. The results showed that PSSD had marked anti-HSV-2 activities in vitro with low cytotoxicity. PSSD can directly interact with virus particles to inhibit the adsorption of virus to the cell surface. PSSD may also interact with virus surface glycoproteins to block virus-induced membrane fusion. Importantly, PSSD can significantly attenuate the symptoms of genital herpes and weight loss in mice after gel smear treatment, as well as reducing the titer of virus shedding in the reproductive tract of mice, superior to the effect of acyclovir. In summary, the marine polysaccharide PSSD possesses anti-HSV-2 effects both in vitro and in vivo, and has potential to be developed into a novel anti-genital herpes agent in the future.

Mitochondrial phylogenomics provides conclusive evidence that the family Ancyrocephalidae is deeply paraphyletic.

BACKGROUND: Unresolved taxonomic classification and paraphyly pervade the flatworm class Monogenea: the class itself may be paraphyletic and split into Polyopisthocotylea and Monopisthocotylea; there are some indications that the monopisthocotylean order Dactylogyridea may also be paraphyletic; single-gene markers and some morphological traits indicate that the family Ancyrocephalidae is paraphyletic and intertwined with the family Dactylogyridae. METHODS: To attempt to study the relationships of Ancyrocephalidae and Monopisthocotylea using a phylogenetic marker with high resolution, we sequenced mitochondrial genomes of two fish ectoparasites from the family Dactylogyridae: Dactylogyrus simplex and Dactylogyrus tuba. We conducted phylogenetic analyses using three datasets and three methods. Datasets were ITS1 (nuclear) and nucleotide and amino acid sequences of almost complete mitogenomes of almost all available Monopisthocotylea mitogenomes. Methods were maximum likelihood (IQ-TREE), Bayesian inference (MrBayes) and CAT-GTR (PhyloBayes). RESULTS: Both mitogenomes exhibited the ancestral gene order for Neodermata, and both were compact, with few and small intergenic regions and many and large overlaps. Gene sequences were remarkably divergent for nominally congeneric species, with only trnI exhibiting an identity value > 80%. Both mitogenomes had exceptionally low A + T base content and AT skews. We found evidence of pervasive compositional heterogeneity in the dataset and indications that base composition biases cause phylogenetic artefacts. All six mitogenomic analyses produced unique topologies, but all nine analyses produced topologies that rendered Ancyrocephalidae deeply paraphyletic. Mitogenomic data consistently resolved the order Capsalidea as nested within the Dactylogyridea. CONCLUSIONS: The analyses indicate that taxonomic revisions are needed for multiple Polyopisthocotylea lineages, from genera to orders. In combination with previous findings, these results offer conclusive evidence that Ancyrocephalidae is a paraphyletic taxon. The most parsimonious solution to resolve this is to create a catch-all Dactylogyridae sensu lato clade comprising the current Ancyrocephalidae, Ancylodiscoididae, Pseudodactylogyridae and Dactylogyridae families, but the revision needs to be confirmed by another marker with a sufficient resolution.

Inhibitory effects and mechanisms of proanthocyanidins against enterovirus 71 infection.

Proanthocyanidins (PC), a natural flavonoid compound, was reported to possess a variety of pharmacological activities such as anti-tumor and anti-viral effects. In this study, the anti-Enterovirus 71 (EV71) activities and mechanisms of PC were investigated both in vitro and in vivo. The results showed that PC possessed anti-EV71 activities in different cell lines with low toxicity. PC can block both the adsorption and entry processes of EV71 via directly binding to virus VP1 protein. PC may competitively interfere with the binding of VP1 to its receptor SCARB2. PC can also regulate three different MAPK signaling pathways to reduce EV71 infection and attenuate virus induced inflammatory responses. Importantly, intramuscular therapy of EV71-infected mice with PC markedly improved their survival and attenuated the severe clinical symptoms. Therefore, the natural compound PC has potential to be developed into a novel anti-EV71 agent targeting viral VP1 protein and MAPK pathways.

Inhibition of influenza A virus replication by a marine derived quinolone alkaloid targeting virus nucleoprotein.

Owing to the emergence of drug resistance and high morbidity and mortality, the need for novel anti-influenza A virus (IAV) drugs with divergent targets is highly sought after. Herein, a novel quinolone alkaloid (QLA) derived from marine fungus was discovered with broad-spectrum anti-IAV activities with low toxicity. Distinct from current anti-IAV drugs, QLA may block virus replication and viral RNA (vRNA) export from the nucleus by targeting virus nucleoprotein (NP). QLA can block the binding of chromosome region maintenance 1 to nuclear export signal 3 of NP to inhibit the nuclear export of NP and vRNP. QLA may also affect vRNP assembly by interfering with the binding of NP to RNA rather than NP oligomerization. Arg305 and Phe488-Gly490 may be required for the interaction between QLA and NP, and the binding pocket around these amino acids may be a promising target for anti-IAV drugs. Importantly, oral administration of QLA can protect the mice against IAV-induced death and weight loss, superior to the effects of the clinical drug oseltamivir. In summary, the marine derived compound QLA has the potential to be developed into a novel anti-IAV agent targeting virus NP protein in the future.

Cell Membrane-Derived Nanovehicles for Targeted Therapy of Ischemic Stroke: From Construction to Application.

Ischemic stroke (IS) is a prevalent form of stroke and a leading cause of mortality and disability. Recently, cell membrane-derived nanovehicles (CMNVs) derived from erythrocytes, thrombocytes, neutrophils, macrophages, neural stem cells, and cancer cells have shown great promise as drug delivery systems for IS treatment. By precisely controlling drug release rates and targeting specific sites in the brain, CMNVs enable the reduction in drug dosage and minimization of side effects, thus significantly enhancing therapeutic strategies and approaches for IS. While there are some reviews regarding the applications of CMNVs in the treatment of IS, there has been limited attention given to important aspects such as carrier construction, structural design, and functional modification. Therefore, this review aims to address these key issues in CMNVs preparation, structural composition, modification, and other relevant aspects, with a specific focus on targeted therapy for IS. Finally, the challenges and prospects in this field are discussed.

Anti-herpes simplex virus activities and mechanisms of marine derived compounds.

Herpes simplex virus (HSV) is the most widely prevalent herpes virus worldwide, and the herpetic encephalitis and genital herpes caused by HSV infection have caused serious harm to human health all over the world. Although many anti-HSV drugs such as nucleoside analogues have been ap-proved for clinical use during the past few decades, important issues, such as drug resistance, toxicity, and high cost of drugs, remain unresolved. Recently, the studies on the anti-HSV activities of marine natural products, such as marine polysaccharides, marine peptides and microbial secondary metabolites are attracting more and more attention all over the world. This review discusses the recent progress in research on the anti-HSV activities of these natural compounds obtained from marine organisms, relating to their structural features and the structure-activity relationships. In addition, the recent findings on the different anti-HSV mechanisms and molecular targets of marine compounds and their potential for therapeutic application will also be summarized in detail.

Use of specific contrast-enhanced CT regions of interest to differentiate renal oncocytomas from small clear cell and chromophobe renal cell carcinomas.

PURPOSE We aimed to examine the usefulness of utilizing a specific contrast-enhanced computed tomog raphy (CT) region of interest (ROI) to differentiate renal oncocytoma (RO) from small clear cell renal cell carcinoma (ccRCC) and chromophobe renal cell carcinoma (chRCC). METHODS A retrospective analysis of pre-contrast phase (PCP), corticomedullary phase (CMP), and nephro graphic phase (NP) contrast-enhanced CT images of the histopathologically confirmed initial cohort (27 ROs, 74 ccRCCs, and 36 chRCCs) was conducted. Small, medium, large, and whole ROIs (S-ROI, M-ROI, L-ROI, and W-ROI, respectively) were utilized for CT attenuation value of tumor (AVT), lesion-to-cortex attenuation (L/C), and heterogeneous degree of tumor (HDT) calcula tions. Differences in these parameters were then compared between RO and ccRCC/chRCC, with receiver operating characteristic (ROC) curves being utilized to gauge the diagnostic utility of the statistically significant parameters. Logistic regression analyses were employed to identify key factors capable of differentiating RO and ccRCC/chRCC, with predictive models further being established. A validation cohort (6 ROs, 30 ccRCCs, and 12 chRCCs) was then employed to vali date the performance of the predictive models. RESULTS Of the parameters evaluated using different ROIs, L/C-CMP (S-ROI) (0.88 ± 0.15 vs. 1.13 ± 0.25, P < .001) and HDT-CMP (W-ROI) (23.02 (12.00-51.21) vs. 37.81 (16.09-89.45), P < .001) were best suited to differentiating RO and ccRCC, yielding respective area under the curve (AUC) values of 0.803 and 0.834. AVT-NP (S-ROI) (122.85 ± 18.87 vs. 86.50 ± 18.65, P < .001) and AVT-NP (M-ROI) (119 (86-167) vs. 81.5 (53-142), P < .001) were better able to differentiate RO and chRCC, yielding respective AUC values of 0.918 and 0.906. Logistic regression analyses revealed that L/C-CMP (S-ROI) and HDT-PCP, as well as AVT-NP (S-ROI) and HDT-CMP, were the primary factors capable of differentiating RO from ccRCC and chRCC, respectively. The predictive model developed to dif ferentiate between RO and ccRCC exhibited a sensitivity of 66.67% and 55.14% in the initial and validation cohorts, respectively, with corresponding specificity of 94.59% and 93.55%, accuracy of 87.13% and 86.84%, and AUC of 0.908 and 0.876. The predictive model developed to differ entiate between RO and chRCC exhibited a sensitivity of 85.19% and 100.00% in the initial and validation cohorts, respectively, with corresponding specificity of 94.59% and 92.86%, accuracy of 87.30% and 95.24%, and AUC of 0.944 and 0.959. CONCLUSION These data demonstrate that a combination of quantitative parameters measured with particu lar ROIs can enable the efficient and reliable differentiation of RO from ccRCC and chRCC for use in routine patient differential diagnosis.