Moxibustion improves motor function by down-regulating SNX5 and inhibiting ferroptosis in neurons of corpus striatum in mice with Parkinson's disease. / 艾灸调控SNX5å¯¹å¸•é‡‘æ£®ç— æ¨¡åž‹å°é¼ ç¥žç»å ƒé“æ­»äº¡çš„å½±å“.

OBJECTIVES: To explore the effect of moxibustion on the expression of sorting nexin 5 (SNX5), glutathione peroxidase (GPX4) and ferritin heavy chain (FTH1) in the corpus striatum in mice with Parkinson's disease (PD), so as to explore its mechanisms underlying improvement of PD by ameliorating ferroptosis in the substantia nigra striatum. METHODS: C57BL/6J mice were randomly divided into normal, sham operation, model, and moxibustion groups, with 10 mice in each group. The PD model was established by unilateral injection of 6-hydroxydopamine (3.5 µL) into the right medial forebrain bundle (AP=-1.2 mm, ML=-1.3 mm, DV=-4.75 mm). The mice in the moxibustion group received moxibustion at "Baihui"(GV20) and "Sishencong"(EX-HN1) for 20 min each time, once a day, 6 times a week for 4 weeks. After the intervention, mice received apomorphine rotation behavior detection and pole climbing test. The expression of tyrosine hydroxylase (TH) in the substantia nigra was detected by immunofluorescence, the contents of Fe2+, malondialdehyde (MDA), the ratio of glutathione/oxidized glutathione (GSH/GSSG) in the corpus striatum were detected by using photocolorimetric method, and the expression levels of SNX5 (endocytosomal protein), GPX4 (one of the key targets for inhibiting ferroptosis) and FTH1 proteins and mRNAs in the corpus striatum were detected by Western blot and qPCR, respectively. RESULTS: Behavior tests showed that the pole climbing time and number of body rotation were significantly increased in the model group relevant to the sham operation group (P<0.01), and strikingly decreased in the moxibustion group relevant to the model group (P<0.01). The immunofluorescence intensity of TH in the substantia nigra, the ratio of GSH/GSSG, and the expression levels of GPX4 and FTH1 mRNAs and proteins in the corpus striatum were markedly decreased (P<0.01, P<0.05), while the contents of Fe2+ and MDA and the expression levels of SNX5 mRNA and protein in the corpus striatum significantly increased in the model group relevant to the sham operation group (P<0.01, P<0.05). Compared with the model group, the decreased immunofluorescence intensity of TH, GSH/GSSH, and the expression levels of GPX4 and FTH1 mRNAs and proteins, and the increased contents of Fe2+ and MDA and the expression levels of SNX5 mRNA and protein were reversed in the moxibustion group relevant to the model group (P<0.01, P<0.05). CONCLUSIONS: Moxibustion may improve motor dysfunction in PD mice, which may be related to its effects in down-regulating the expression of SNX5, promoting the synthesis of GSH, decreasing the contents of Fe2+ and MDA, up-regulating the ratio of GSH/GSSG and the expression of GPX4 and FTH1 mRNAs and proteins in the corpus striatum, and inhibiting the occurrence of ferroptosis.

Antimicrobial peptide LL37 and regulatory T cell associated with late-onset sepsis in very preterm infants.

Stem cell therapy may prevent late-onset sepsis (LOS) via antimicrobial peptide LL37 secretion and regulatory T cell (Treg) regulation. The early prediction of LOS is still a challenge. This study evaluated whether immunological state of LL37 or Tregs precedes LOS. We firstly analyzed the LL37 level, Treg proportion, and LOS incidence in very preterm infants treated with autologous cord blood mononuclear cells (ACBMNCs) in our previous trial. Then, we constructed a prediction model and built validation cohort. We found ACBMNC intervention reduced the incidence of LOS from 27.3% to 6.9% (p = 0.021). LL37 and Treg abundances were higher in the ACBMNCs group. The nomogram demonstrated that early-life Treg and LL37 characteristics were closely associated with LOS (area under the curve, AUC 0.936), with implications for early prediction and timely clinical management. This composite model was also helpful to evaluate the beneficial effect of ACBMNCs intervention on LOS, thus promoting translational research.

Molecular mechanism of infectious spleen and kidney necrosis virus in manipulating the hypoxia-inducible factor pathway to augment virus replication.

Infectious spleen and kidney necrosis virus (ISKNV), a member of the genus Megalocytivirus in the family Iridoviridae, can infect over 50 fish species and cause significant economic losses in Asia. Our previous study showed that hypoxia triggers the hypoxia-inducible factor pathway (HIF-pathway), leading to increased replication of ISKNV through promoting the upregulation of viral hypoxic response genes like orf077r. This study delved into the molecular mechanism of how ISKNV manipulates the HIF-pathway to enhance its replication. In vitro and in vivo experiments confirmed that ISKNV infection activated the HIF-pathway, which in turn promoted ISKNV replication. These findings suggest that ISKNV actively manipulates the HIF-pathway. Co-immunoprecipitation experiments revealed that the ISKNV-encoded protein VP077R interacts with the Von Hippel-Lindau (VHL) protein at the HIF-binding region, competitively inhibiting the interaction of HIF-1α with VHL. This prevents HIF degradation and activates the HIF-pathway. Furthermore, VP077R interacts with factor-inhibiting HIF (FIH), recruiting FIH and S-phase kinase-associated protein 1 (Skp1) to form an FIH - VP077R - Skp1 complex. This complex promotes FIH protein degradation via ubiquitination, further activating the HIF-pathway. These findings indicated that ISKNV takes over the HIF-pathway by releasing two "brakes" on this pathway (VHL and FIH) via VP077R, facilitating virus replication. We speculate that hypoxia initiates a positive feedback loop between ISKNV VP077R and the HIF pathway, leading to the outbreak of ISKNV disease. This work offers valuable insights into the complex interactions between the environment, host, and virus.

Umbilical cord blood cell characteristics in very preterm neonates for autologous cell therapy of preterm-associated complications.

BACKGROUND: There are emerging clinical evidence for umbilical cord blood mononuclear cells (UCBMNCs) intervention to improve preterm complications. The first critical step in cell therapy is to obtain high-quality cells. This retrospective study aimed to investigate the quantity and quality of UCBMNCs from very preterm infants (VPIs) for the purpose of autologous cell therapy in prevention and treatment of preterm complications. METHODS: Very preterm infants (VPIs) born in Guangdong Women and Children Hospital from January 1, 2017, to December 8, 2022, from whom cord blood was successfully collected and separated for public or private banking, were enrolled. The UCBMNCs characters from route cord blood tests performed in cord blood bank, impact of perinatal factors on UCBMNCs, the relationship between UCBMNCs characteristics and preterm outcomes, and the correlation of UCBMNCs characteristics and peripheral blood cells in VPIs were analyzed. RESULTS: Totally, 89 VPIs underwent UCB collection and processing successfully. The median cell number post processing was 2.6 × 108. To infuse a dose of 5 × 107 cells/kg, only 3.4% of infants required a volume of more than 20 mL/kg, which exceeded the maximum safe volume limit for VPIs. However, when infusing 10 × 107 cells/kg, 25.8% of infants required a volume of more than 20 ml/kg volume. Antenatal glucocorticoids use and preeclampsia was associated with lower original UCBMNCs concentration. Both CD34+ hematopoietic stem cells (HSC) frequency and colony forming unit - granulocyte and macrophage (CFU-GM) number correlated negatively with gestational age (GA). UCBMNCs characters had no significant effect on preterm outcomes, whereas a significant positive correlation was observed between UCBMNCs concentration and total white blood cell, neutrophil, lymphocyte and PLT counts in peripheral blood. CONCLUSION: UCBMNCs collected from VPIs was feasible for autologous cell therapy in improving preterm complications. Setting the infusion dose of 5 × 107 cells/kg guaranteed a safe infusion volume in more than 95% of the targeted infants. UCBMNCs characters did not affect preterm complications; however, the effect of UCBMNCs concentration on peripheral blood classification count should be considered when evaluating the immunomodulation of UCBMNCs transfusion.

Cucurbitacin B suppresses hepatocellular carcinoma progression through inducing DNA damage-dependent cell cycle arrest.

BACKGROUND: The mortality rate of liver cancer ranks third in the world, and hepatocellular carcinoma (HCC) is a malignant tumor of the digestive tract. Cucurbitacin B (CuB), a natural compound extracted from Cucurbitaceae spp., is the main active component of Chinese patent medicine the Cucurbitacin Tablet, which has been widely used in the treatment of various malignant tumors in clinics, especially HCC. PURPOSE: This study explored the role and mechanism of CuB in the suppression of liver cancer progression. METHODS: Cell Counting Kit-8 (CCK-8) and colony formation assays were used to detect the inhibitory function of CuB in Huh7, Hep3B, and Hepa1/6 hepatoma cells. Calcein-AM/propidium iodide (PI) staining and lactate dehydrogenase (LDH) measurement assays were performed to determine cell death. Mitochondrial membrane potential (Δψm) was measured, and flow cytometry was performed to evaluate cell apoptosis and cell cycle. Several techniques, such as proteomics, Western blotting (WB), and ribonucleic acid (RNA) interference, were utilized to explore the potential mechanism. The animal experiment was performed to verify the results of in vitro experiments. RESULTS: CuB significantly inhibited the growth of Huh7, Hep3B, and Hepa1/6 cells and triggered the cell cycle arrest in G2/M phage without leading to cell death, especially apoptosis. Knockdown of insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), a target of CuB, did not reverse CuB elicited cell cycle arrest. CuB enhanced phosphorylated ataxia telangiectasia mutated (p-ATM) and phosphorylated H2A histone family member X (γ-H2AX) levels. Moreover, CuB increased p53 and p21 levels and decreased cyclin-dependent kinase 1 (CDK1) expression, accompanied by improving phosphorylated checkpoint kinase 1 (p-CHK1) level and suppressing cell division cycle 25C (CDC25C) protein level. Interestingly, these phenomena were partly abolished by a deoxyribonucleic acid (DNA) protector methylproamine (MPA). Animal studies showed that CuB also significantly suppressed tumor growth in BALB/c mice bearing Hepa1/6 cells. In tumor tissues, CuB reduced the expression levels of proliferating cell nuclear antigen (PCNA) and γ-H2AX but did not change the terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL) level. CONCLUSION: This study demonstrated for the first time that CuB could effectively impede HCC progression by inducing DNA damage-dependent cell cycle arrest without directly triggering cell death, such as necrosis and apoptosis. The effect was achieved through ataxia telangiectasia mutated (ATM)-dependent p53-p21-CDK1 and checkpoint kinase 1 (CHK1)-CDC25C signaling pathways. These findings indicate that CuB may be used as an anti-HCC drug, when the current findings are confirmed by independent studies and after many more clinical phase 1, 2, 3, and 4 testings have been done.

Association between testosterone levels and RigiScan parameters of patients with erectile dysfunction.

Background: It is difficult to diagnose hypogonadism because of the lack of objective assessments of erectile dysfunction (ED), which is caused by hypogonadism. Aim: To provide a new approach for diagnosing hypogonadism, this study evaluated the efficacy of nocturnal penile tumescence and rigidity (NPTR) testing with RigiScan for patients with ED with and without hypogonadism. Methods: From June 2021 to February 2023, 133 patients with ED (62 with hypogonadism and 71 without) underwent NPTR testing at the Department of Andrology. A detailed history of all participants was obtained. All participants also underwent a physical examination, sex hormone testing, and ultrasound examination of the cavernous vessels of the penis. Outcomes: Patient characteristics, sex hormone serum levels, and RigiScan Plus data of NPTR testing of patients with ED were obtained and evaluated. Results: Between the groups, there were no significant differences in age, body mass index, or erectile function score or in the prevalence of smoking, drinking, diabetes, hypertension, and hyperlipidemia. RigiScan data revealed differences in erection episodes per night, average event rigidity, erection durations, and percentage of tumescence greater than baseline, which were significantly lower in the testosterone-deficient group than in the normal testosterone group. The average event rigidity of the tip displayed the largest area under the curve value, with a sensitivity of 67.6%, a specificity of 85.5%, and a cutoff value of 52.50. Clinical Implications: Our findings may allow appropriate patients to receive testosterone replacement therapy, which has been shown to be an effective treatment for hypogonadism. Strengths and Limitations: This is the first study of its kind to perform a comprehensive review of the association between hypogonadism and RigiScan parameters. This study was limited by its small sample size. Conclusion: RigiScan parameters of patients with ED and testosterone deficiency were significantly lower than those of patients with normal testosterone; therefore, RigiScan is useful for the differential diagnosis of patients with ED caused by hypogonadism.

Biosurfactants-based mixed polycyclic aromatic hydrocarbon degradation: From microbial community structure toward non-targeted metabolomic profile determination.

Biosurfactants-based bioremediation is considered an efficient technology to eliminate environmental pollutants including polycyclic aromatic hydrocarbons (PAHs). However, the precise role of rhamnolipids or lipopeptide-biosurfactants in mixed PAH dissipation, shaping microbial community structure, and influencing metabolomic profile remained unclear. In this study, results showed that the maximum PAH degradation was achieved in lipopeptide-assisted treatment (SPS), where the pyrene and phenanthrene were substantially degraded up to 74.28 % and 63.05 % respectively, as compared to rhamnolipids (SPR) and un-aided biosurfactants (SP). Furthermore, the high throughput sequencing analysis revealed a significant change in the PAH-degrading microbial community, with Proteobacteria being the predominant phylum (>98 %) followed by Bacteroidota and Firmicutes in all the treatments. Moreover, Pseudomonas and Pannonibacter were found as highly potent bacterial genera for mixed PAH degradation in SPR, SPS, and SP treatments, nevertheless, the abundance of the genus Pseudomonas was significantly enhanced (>97 %) in SPR treatment groups. On the other hand, the non-targeted metabolomic profile through UHPLC-MS/MS exhibited a remarkable change in the metabolites of amino acids, carbohydrates, and lipid metabolisms by the input of rhamnolipids or lipopeptide-biosurfactants whereas, the maximum intensities of metabolites (more than two-fold) were observed in SPR treatment. The findings of this study suggested that the aforementioned biosurfactants can play an indispensable role in mixed PAH degradation as well as seek to offer new insights into shifts in PAH-degrading microbial communities and their metabolic function, which can guide the development of more efficient and targeted strategies for complete removal of organic pollutants such as PAH from the contaminated environment.

Efficacy of Tounongsan decoction on pyogenic liver abscess: network pharmacology and clinical trial validation.

OBJECTIVE: To elucidate the molecular mechanisms governing the effect of Tounongsan decoction (, TNS) on the pyogenic liver abscess. METHODS: Based on oral bioavailability and drug-likeness, the main active components of TNS were screened using the Traditional Chinese Medicine Systems Pharmacology platform. The GeneCard and UniProt databases were used to establish a database of pyogenic liver abscess targets. The interactive network map of drug-ingredients-target-disease was constructed using Cytoscape software (Version 3.7.2). A protein-protein interaction network was constructed using the STRING database, and the related protein interaction relationships were analyzed. biological process of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed for the core targets. Finally, a clinical trial was performed to verify the reliability of the network pharmacology. RESULTS: Forty active components of TNS decoction were obtained, and 61 potential targets and 11 proteins were identified. Pathways involved in the treatment of pyogenic liver abscess include the phosphatidylinositide 3-kinases-protein kinase B (PI3K-AKT), advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE), and tumor necrosis factor (TNF) signaling pathways. The results of network pharmacology analysis combined with clinical trials validated that TNS decoction could alleviate the inflammatory response of pyogenic liver abscesses by decreasing interleukin 6 (IL-6) levels. CONCLUSIONS: TNS decoction has the characteristics of being multi-system, multi-component, and multi-target. Active ingredients in TNS, such as quercetin, kaempferol, fisetin, and ß-sitosterol, have strong potential to be candidate drugs for treating pyogenic liver abscesses. The possible mechanism of TSN decoction includes regulating immune and inflammatory responses and reducing IL-6 production to control inflammatory development.

Compound-composed Chinese medicine of Huachansu triggers apoptosis of gastric cancer cells through increase of reactive oxygen species levels and suppression of proteasome activities.

BACKGROUND: Huachansu (HCS), a known Chinese patent drug extracted from the Chinese toad skin, is frequently used for the treatment of various advanced cancers, especially gastric cancer, due to the good therapeutic effect. However, it is rather difficult to clarify the active substances and molecular mechanisms involved owing to the lack of appropriate research strategies. We recently proposed the concept and research ideas of compound-composed Chinese medicine formula. PURPOSE: To discover compound-composed Chinese medicine from Huachansu and to explore its mechanism of action in inducing apoptosis of gastric cancer cells. METHOD: Network pharmacology combined with serum pharmacochemistry was utilized to screen the predominant active constituents from HCS against gastric cancer. Then, the compound-composed Chinese medicine of HCS (CCMH) was prepared according to their relative contents in serum. The pharmacological effects and potential mechanisms for CCMH were investigated by assays for cell viability, cell cycle, apoptosis, mitochondrial membrane potential (MMP), proteomics, reactive oxygen species (ROS), N-Acetylcysteine (NAC) antagonism, proteasome activity, and western blot. RESULTS: CCMH was comprised of arenobufagin (11.14%), bufalin (18.67%), bufotalin (7.33%), cinobufagin (16.67%), cinobufotalin (16.74%), gamabufotalin (8.45%), resibufogenin (12.03%), and telocinobufagin (8.97%). CCMH evidently induced proliferation inhibition, cell cycle arrest, apoptosis, and MMP collapse in gastric cancer cells, possessing the better activities than HCS. Proteomic analysis showed that CCMH influenced ROS pathway, ubiquitin proteasome system, and PI3K/Akt and MAPK signaling pathways. CCMH markedly enhanced intracellular ROS levels in gastric cancer cells, which was reversed by NAC. Accordingly, NAC antagonized the apoptosis-inducing effect of CCMH. Significantly decreased proteasome 20S activity by CCMH was observed in gastric cancer cells. CCMH also regulated the expression of key proteins in PI3K/Akt and MAPK signaling pathways. CONCLUSION: CCMH possesses more significant apoptotic induction effects on gastric cancer cells than HCS, which is achieved primarily through suppression of proteasome activities and increase of ROS levels, followed by regulating PI3K/Akt and MAPK signaling pathways. Network pharmacology combined with serum pharmacochemistry is an effective strategy for discovering compound-composed Chinese medicine from traditional Chinese medicine, which can help clarify the pharmacological substances and mechanisms of action for traditional Chinese medicine.

Neurological complications during the Omicron COVID-19 wave in China: A cohort study.

BACKGROUND AND PURPOSE: The aim was to investigate the neurological complications associated with coronavirus disease 19 (COVID-19) during the 2022 Omicron wave. METHODS AND ANALYSIS: The medical records of a cohort of people admitted to neurological wards of three participating tertiary centres in Sichuan from 12 December 2022 to 12 January 2023 were reviewed. Demographics and clinical data were obtained and analysed with an interest in COVID-19-related new-onset or worse neurological symptoms. The current data were also compared in two centres with similar data from the same period 12 months earlier. RESULTS: In all, 790 people were enrolled, of whom 436 were positive for COVID-19. Ninety-nine had new onset COVID-related neurological problems, or their known neurological condition deteriorated during the wave. There was a significant difference in demographics from the findings amongst admissions 12 months earlier as there was an increase in the average age, the incidence of encephalitis and encephalopathy, and mortality rates. One hundred and one received COVID-specific antivirals, intravenous glucocorticoids and intravenous immunoglobulin therapy. No differences were seen between these and those who did not use them. CONCLUSION: New-onset neurological conditions, particularly encephalitis and encephalopathy, increased significantly during this period. Deterioration of existing neurological conditions, such as seizure exacerbation, was also observed. A large-scale treatment trial of people with COVID-19 infection presenting with neurological disorders is still needed.

A novel technique for lymphadenectomy along the left recurrent laryngeal nerve during minimally invasive esophagectomy: a retrospective cohort study.

BACKGROUND: In the context of esophageal cancers, lymph nodes located along the left recurrent laryngeal nerve (RLN) exhibit significant involvement, posing significant challenges for lymphadenectomy. The objective of this study is to assess the safety and efficacy of a novel technique for lymphadenectomy called "elastic suspension of left RLN" method, comparing it with the conventional approach. METHODS: Between January 2016 and June 2020, a total of 393 patients who underwent minimally invasive esophagectomy with gastroplasty and cervical esophagogastric anastomosis were enrolled in the study. Among them, 291 patients underwent the "elastic suspension of left RLN" method, while 102 patients underwent the conventional method. We compared the number of harvested lymph nodes along the left RLN and assessed postoperative complications between these two groups. Additionally, the overall survival (OS) rate was calculated and analyzed for the entire cohort. RESULTS: In comparison to the conventional group, the elastic suspension group exhibited a higher yield of harvested lymph nodes along the left RLN (5.36 vs 3.07, P < 0.001). Moreover, the incidence of postoperative hoarseness was lower in the elastic suspension group (10.65% vs 18.63%, P = 0.038). The average duration of lymphadenectomy along the left RLN was 11.85 min in the elastic suspension group and 11.51 min in the conventional group, although this difference was not statistically significant (P = 0.091). Notably, the overall 5-year OS was markedly higher in the elastic suspension group compared to the conventional group (64.1% vs. 50.1%, P = 0.020). CONCLUSIONS: The findings suggest that the novel "elastic suspension of left RLN" method for lymphadenectomy along the left RLN in minimally invasive esophagectomy is both safe and effective. This technique holds promise for widespread adoption in esophagectomy procedures.

Artesunate, as an Hsp90 inhibitor, inhibits the proliferation of Burkitt's lymphoma cells by inhibiting AKT and ERK.

Introduction: Artesunate, a derivative of artemisinin, has anti-malarial effects, and in recent years has also been reported to have anti-tumor activity. However, its anti-tumor mechanisms are not well understood. Methods: In this study, we focused on the targeting of Hsp90 by artesunate to inhibit tumor cell proliferation, which we examined using immunoprecipitation, a proliferation assay, flow cytometry, western blotting, a tumor xenograft animal model, and immunohistochemistry. Furthermore, to examine the tumor-suppressive effects of artesunatein nude mice, we used artesunate-loaded PLGA-PEG nanoparticles. Results: The binding of artesunate to Hsp90 was found to reduce the expression of its client proteins AKT, ERK, p-AKT, p-ERK, and EGFR, thereby blocking the cell cycle at the G0/G1 → S stage in lymphoma cells and inducing apoptosis. In addition, the results of tumor xenograft experiments revealed that artesunate reduced the expression of AKT and ERK proteins in tumor tissues, inhibited tumor proliferation, and reduced tumor size and weight. Furthermore, nanoparticle encapsulation was demonstrated to enhance the anti-cancer activity of artesunate. Discussion: We thus established that artesunate inhibits the proliferation of lymphoma cells by targeting the Hsp90 protein, and we accordingly believe that this compound has potential for development as a novelanti-tumor drug.

Physalis pubescens L. branch and leaf extracts inhibit lymphoma proliferation by inducing apoptosis and cell cycle arrest.

Physalis pubescens L. is an annual or perennial plant in the family Solanaceae It is used in traditional medicine for treating sore throats, coughs, urinary discomfort, and astringent pain, and externally for pemphigus and eczema in northern China. The proliferation inhibitory activity and mechanisms of the ethyl acetate extract (PHY-EA) from the leaves of Physalis pubescens were investigated. High performance liquid chromatography was used to identify the chemical composition of PHY-EA; sulforhodamine B was used to detect the proliferation inhibitory effect of PHY-EA on MCF-7, CA-46, Hela, HepG2, B16, and other tumor cells; flow cytometry was used to detect the effect of PHY-EA on the lymphoma cell cycle and apoptosis; Western blot was used to detect the expression of the cycle- and apoptosis-related proteins. The expression of Ki-67 and cleaved caspase 3 was detected by immunohistochemistry. The results showed that PHY-EA contained physalin B, physalin O, and physalin L. PHY-EA blocked the cell cycle of G2/M→G0/G1 in lymphoma cells and induced apoptosis in tumor cells. Mouse transplantation tumor experiments showed that PHY-EA had a significant inhibitory effect on mouse transplantation tumors, and the tumor volume and weight were significantly reduced. In conclusion, PHY-EA has a good antiproliferative effect on Burkkit lymphoma, indicating its potential medicinal value.

Reusable SERS Substrates Based on Gold Nanoparticles for Peptide Detection.

Raman spectroscopy is a powerful analytical technique widely used for quantitative and qualitative analysis. However, the development of inexpensive, reproducible, and reusable enhancing substrates remains a challenge for material scientists and analytical chemists. In this study, we address this challenge by demonstrating the deposition of core-shell nanoparticles consisting of a gold core and a thin inert SiO2 shell within a confined space, resulting in the formation of a highly efficient Raman-enhancing structure. Nanoparticles were characterized by UV-vis spectroscopy, dynamic light scattering, and total reflectance X-ray fluorescence spectroscopy, whereas the prepared substrates were characterized by scanning electron microscopy and Raman spectroscopy with a model molecule, malachite green. The relationship between Raman intensity and the loading of malachite green dye exhibited linearity, indicating the uniform spatial distribution of hotspots across the substrate. The limit of detection was determined as 2.9 µM of malachite green when 10 uL was distributed over a ca. 25 mm2 surface area. Moreover, the same substrate, after thorough washing in ethanol, was successfully employed for the detection of bovine serum albumin at a concentration level of 55 µg mL-1, demonstrating its reusability and versatility. Our findings highlight the potential of these substrates for various applications in biomedical research, clinical diagnosis, and beyond.

Rapid and sensitive smartphone non-enzymatic colorimetric assay for the detection of glucose in food based on peroxidase-like activity of Fe3O4@Au nanoparticles.

A low-cost and reliable analytical method based on the combination of a newly designed Fe3O4@Au as peroxidase mimetics, supported on smartphone analysis software package was proposed for the determination of glucose content in food samples. The nanocomposite was prepared by self-assembling technique, and the characterization was carried out using transmission electron microscopy (TEM), Fourier transforms infrared, and X-ray diffractometer. Record the color change of the solution with a smartphone camera and optimize the operation parameters and reaction conditions. A smartphone with a free self-developed app was accustomed live the RGB (red-greenblue) values of color intensity within the Fe3O4@Au system and were processed with Image J software before computationally convert them glucose concentrations. At the optimization experiment, reaction temperature of 60 °C, reaction time of 50 min and the amount of addition of Fe3O4@Au 0.0125 g was the optimal combination of detecting glucose smartphone color detection system. Hereon, the accuracy of the proposed method was evaluated by comparison between smartphone colorimetry and UV-vis spectrophotometer, a linear calibration in the range of 0.25 âˆ¼ 15 mmol/L glucose was obtained with minimum detection limit of 1.83 and 2.25 µmol/L, respectively. The proposed method was applied effectively to the detection of glucose in actual samples. The results were in accordance with the conventional UV-vis spectrophotometer method.

Treatment effectiveness and side effects of patients with hepatitis C in the prisons of Southern Taiwan: a real-life retrospective analysis.

OBJECTIVE: Hepatitis C is an important risk factor for cirrhosis and liver cancer in the Taiwanese population. Domestic prisons reported a higher rate of hepatitis C infection than the national average. Efficient and effective treatment of patients with hepatitis C in prisons is required to decrease the number of infections. This study analysed the effectiveness of hepatitis C treatment and its side effects in prison patients. DESIGN: This retrospective analysis included adult patients with hepatitis C who received direct-acting antiviral agents between 2018 and 2021. SETTING: The special hepatitis C clinics in the two prisons were run by a medium-sized hepatitis C treatment hospital in Southern Taiwan. Three direct-acting antiviral agents, sofosbuvir/ledipasvir for 12 weeks, glecaprevir/pibrentasvir for 8 or 12 weeks and sofosbuvir/velpatasvir for 12 weeks, were adopted based on patient characteristics. PARTICIPANTS: 470 patients were included. OUTCOME MEASURE: The sustained virological response at 12 weeks after the end of treatment was compared between the different groups. RESULTS: Most of the patients were men (70.0%) with a median age of 44 years. The most prevalent hepatitis C virus genotype was genotype 1 (44.26%). A total of 240 patients (51.06%) had a history of injectable drug use; 44 (9.36%) and 71 (15.11%) patients were coinfected with hepatitis B virus and HIV, respectively. Only 51 patients (10.85%) had liver cirrhosis. Most patients (98.30%) had normal renal function or no history of kidney disease. The patients had a sustained virological response achievement rate of 99.2%. The average incidence of adverse reactions during treatment was approximately 10%. Many of the adverse reactions were mild and resolved spontaneously. CONCLUSION: Direct-acting antiviral agents are effective for treating hepatitis C in Taiwanese prisoners. These therapeutics were well-tolerated by the patient population.

Heat shock protein 90 facilitates SARS-CoV-2 structural protein-mediated virion assembly and promotes virus-induced pyroptosis.

Inhibition of heat shock protein 90 (Hsp90), a prominent molecular chaperone, effectively limits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection but little is known about any interaction between Hsp90 and SARS-CoV-2 proteins. Here, we systematically analyzed the effects of the chaperone isoforms Hsp90α and Hsp90ß on individual SARS-CoV-2 viral proteins. Five SARS-CoV-2 proteins, namely nucleocapsid (N), membrane (M), and accessory proteins Orf3, Orf7a, and Orf7b were found to be novel clients of Hsp90ß in particular. Pharmacological inhibition of Hsp90 with 17-DMAG results in N protein proteasome-dependent degradation. Hsp90 depletion-induced N protein degradation is independent of CHIP, a ubiquitin E3 ligase previously identified for Hsp90 client proteins, but alleviated by FBXO10, an E3 ligase identified by subsequent siRNA screening. We also provide evidence that Hsp90 depletion may suppress SARS-CoV-2 assembly partially through induced M or N degradation. Additionally, we found that GSDMD-mediated pyroptotic cell death triggered by SARS-CoV-2 was mitigated by inhibition of Hsp90. These findings collectively highlight a beneficial role for targeting of Hsp90 during SARS-CoV-2 infection, directly inhibiting virion production and reducing inflammatory injury by preventing the pyroptosis that contributes to severe SARS-CoV-2 disease.

Facile synthesis of Ni3Se4/Ni0.6Zn0.4O/ZnO nanoparticle as high-performance electrode materials for electrochemical energy storage device.

To enhance the performance of transition metal chalcogenide composite electrode material, a key point is a composite design and preparation based on the synergistic effect between the oxide and selenide materials. With a facile 'one step template-annealing' step, Ni3Se4, Ni0.6Zn0.4O and ZnO are simultaneously synthesized, by 500 °C annealing. With the increase of annealing temperature from 350 °C to 600 °C, nickel selenides change from NiSe2to Ni3Se4to NiSe. The charge storage capacity increases first and then decreases with the increase of annealing temperature, and the 500 °C annealing obtained three compound composite Ni3Se4/Ni0.6Zn0.4O/ZnO (NNZ-500) nanoparticle material displayed a high specific capacitance of 1089.2 F g-1at 1 A g-1, and excellent cycle stability of 99.8% capacitance retention after 2000 cycles at 5 A g-1. Moreover, an asymmetric supercapacitor was assembled with NNZ-500 as the positive electrode material and activated carbon as the negative electrode material. This kind of asymmetric supercapacitor demonstrated a high energy density of 53.4 Wh kg-1at 819.0 W kg-1, and cycle stability with 98.6% capacitance retention after 2000 cycles. This material preparation approach provides great potential for the future development of high performance transition metal composite electrode materials in energy storage applications.

Chicken or Porcine Aminopeptidase N Mediates Cellular Entry of Pseudoviruses Carrying Spike Glycoprotein from the Avian Deltacoronaviruses HKU11, HKU13, and HKU17.

Members of deltacoronavirus (DCoV) have mostly been identified in diverse avian species as natural reservoirs, though the porcine DCoV (PDCoV) is a major swine enteropathogenic virus with global spread. The important role of aminopeptidase N (APN) orthologues from various mammalian and avian species in PDCoV cellular entry and interspecies transmission has been revealed recently. In this study, comparative analysis indicated that three avian DCoVs, bulbul DCoV HKU11, munia DCoV HKU13, and sparrow DCoV HKU17 (Chinese strain), and PDCoV in the subgenera Buldecovirus are grouped together at whole-genome levels; however, the spike (S) glycoprotein and its S1 subunit of HKU17 are more closely related to night heron DCoV HKU19 in Herdecovirus. Nevertheless, the S1 protein of HKU11, HKU13, or HKU17 bound to or interacted with chicken APN (chAPN) or porcine APN (pAPN) by flow cytometry analysis of cell surface expression of APN and by coimmunoprecipitation in APN-overexpressing cells. Expression of chAPN or pAPN allowed entry of pseudotyped lentiviruses with the S proteins from HKU11, HKU13 and HKU17 into nonsusceptible cells and natural avian and porcine cells, which could be inhibited by the antibody against APN or anti-PDCoV-S1. APN knockdown by siRNA or knockout by CRISPR/Cas9 in chicken or swine cell lines significantly or almost completely blocked infection of these pseudoviruses. Hence, we demonstrate that HKU11, HKU13, and HKU17 with divergent S genes likely engage chAPN or pAPN to enter the cells, suggesting a potential interspecies transmission from wild birds to poultry and from birds to mammals by certain avian DCoVs. IMPORTANCE The receptor usage of avian deltacoronaviruses (DCoVs) has not been investigated thus far, though porcine deltacoronavirus (PDCoV) has been shown to utilize aminopeptidase N (APN) as a cell receptor. We report here that chicken or porcine APN also mediates cellular entry by three avian DCoV (HKU11, HKU13, and HKU17) spike pseudoviruses, and the S1 subunit of three avian DCoVs binds to APN in vitro and in the surface of avian and porcine cells. The results fill the gaps in knowledge about the avian DCoV receptor and elucidate important insights for the monitoring and prevention of potential interspecies transmission of certain avian DCoVs. In view of the diversity of DCoVs, whether this coronavirus genus will cause novel virus to emerge in other mammals from birds, are worthy of further surveillance and investigation.