Synergistic effects of the bimetallic Ni-Fe systems and their application in the reductive amination of polyether polyols.

We report the synthesis of xNi-yFe/γ-Al2O3 catalysts which were applied to the reductive amination of polypropylene glycol (PPG) for the preparation of polyether amine (PEA). The catalysts were characterized by N2-sorption, X-ray diffraction, H2-temperature programmed reduction, energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy to reveal the synergistic effect of the bimetallic Ni-Fe-loaded catalysts. It was found that in the reductive amination of PPG to PEA, the conversion and product selectivity of the reaction were closely related to the types of active centers of the catalyst. In particular, the surface Ni0 content increased by adding Fe as a promoter, with a maximum Ni0 content on the 15Ni-7.5Fe/Al2O3 catalyst, which also led to the highest conversion rate (>99%). In addition, no deactivation was observed after three cycles of reaction carried out by the catalyst.

Identification of a novel HIV-1 third-generation circulating recombinant form (CRF126_0755) in Guangdong, China.

The genetic recombination patterns and genetic distribution of HIV-1 are valuable for elucidating the epidemic and genetic diversity of HIV. Numerous HIV-1 circulating recombinant forms (CRFs) have recently emerged and disseminated rapidly. In China, at least 32 CRFs have been reported to account for more than 80% of all HIV infections. However, CRFs derived from the CRF07_BC and CRF55_01B lineages have never been recorded. Here, a novel third-generation CRF involving HIV-1 was identified in four HIV-1-infected patients in Guangdong, China, who had no epidemiological association with each other. Phylogenetic and recombinant analyses confirmed that these strains shared highly similar recombination patterns, with the CRF07_BC backbone substituted by a CRF55_01B segment; therefore, these strains were classified as CRF126_0755. This is the first study of a CRF derived from CRF07_BC and CRF55_01B. Bayesian phylogenetic inference suggested that CRF126_0755 originated in approximately 2005-2007. The present findings reveal that the genotype composition of HIV-1 has become more complex than that of other viruses and highlight the urgent need for continuous molecular screening and epidemic surveillance within HIV-1-infected populations to advance our understanding of viral transmission mechanisms.

Drug Resistance Profile Among HIV-1 Infections Experiencing ART with Low-Level Viral Load in Guangdong China During 2011-2022: A Retrospective Study.

Background: Antiretroviral therapy (ART) efficiently reduces the morbidities and mortalities caused by HIV-1 infection and prevents the HIV epidemic. However, virologic failure (VF) occurs in some patients receiving ART experience, especially increases in those patients with intermittent or persistent low-level viremia (LLV). The presence of drug resistance mutations (DRMs) in LLV was a strong predictor of subsequent VF. The data on drug resistance (DR) or DRMs for HIV-1 infections at low-level viral load (LLVL) are limited in China. Objective: To monitor the prevalence of HIV-1 drug resistance and to evaluate the risk factors associated with drug resistance in LLVL HIV-1 infections during ART in Guangdong, China. Methods: Plasma samples with LLVL during ART in Guangdong Province between Jan 2011 and Dec 2022 were subjected to a modified reverse-transcription PCR with a pre-step of virus concentration by ultracentrifugation before extraction and the Sanger sequencing. Then, the genotypic resistance test was performed and DR was analyzed by the Stanford HIVDB program. Finally, DR-associated factors were identified by logistic regression analysis. Results: We found that CRF01_AE (53.57%) and CRF07_BC (25.07%) were the dominant HIV-1 genotypes in LLVL in Guangdong between 2011 and 2022 but that the percentage of CRF01_AE showed a trend of decrease over time. M46 (1.49%), M184 (30.91%), and K103 (21.46%) were the dominant PI-, NRTI-, and NNRTI-associated mutations, respectively. The total DR rate was 47.06%. Specifically, PI (3.71%) showed a significantly lower DR rate than NNRTI (40.74%) and NRTI (34.14%). Duration of ART, initial ART regimen, ethnicity, and WHO clinical stages were associated with DR. Conclusion: The drug resistance rate among the LLVL during ART in Guangdong, China is high. The risk factors associated with HIV drug resistance should be seriously considered for better control.

HIV-1 tropism in low-level viral load HIV-1 infections during HAART in Guangdong, China.

Background: Since only a few studies have been conducted on the factors associated with different HIV-1 tropisms in low-level viral load HIV-1 infections in China, we investigated the sequences of HIV-1 V3 loop in prevalent HIV-1 subtypes and factors related to HIV-1 tropism and immune recovery in HIV-1 infections after 6 months of highly active antiretroviral therapy (HAART) in Guangdong, China. Methods: Plasma samples with HIV-1 RNA of 400-999 copies/mL were collected. We analyzed the amino acid sequence of the V3 loop by in silico prediction algorithms. Mann-Whitney and Chi-square tests were used for statistical comparison. Furthermore, logistic regression and multiple linear regression were used, respectively, for factors associated with 351 HIV-1 tropism and immune recovery of 67 cases with continued CD4+ T cell count during HAART. Results: There was a lower percentage of HIV-1 R5-tropic virus in CRF01_AE (66.3%) (p < 0.0001) and CRF55_01B (52.6%) (p < 0.0001) compared with both CRF07_BC (96.1%) and CRF08_BC (97.4%), respectively. Compared with the R5-tropic virus, higher proportions of IIe8/Val8, Arg11/Lys11, and Arg18/His18/Lys18 were observed in the X4-tropic virus of CRF01_AE and CRF07_BC (p < 0.0001). The baseline CD4+ T cell count (p < 0.0001) and baseline CD4+ T/CD8+ T ratio (p = 0.0006) of all R5-tropic infections were higher than those in the X4-tropic infection. The baseline CD4+ T cell count (odds ratio [OR] 0.9963, p = 0.0097), CRF07_BC (OR 0.1283, p = 0.0002), and CRF08_BC (OR 0.1124, p = 0.0381) were associated with less HIV-1 X4-tropism. The baseline CD4+ T cell count was a positive factor (p < 0.0001) in the recovery of CD4+ T cell count during HAART. Conclusion: R5-tropism represented the majority in low-level viral load HIV-1 infections receiving HAART for more than 6 months in Guangdong, China. The baseline immune level in the HIV-1 R5-tropic infections was higher than that in the X4-tropic infections. The amino acids of the 8th, 11th, and 18th of the HIV-1 V3 loop were more variable in the X4-tropic HIV-1. CRF01_AE, CRF55_01B, and lower baseline CD4+ T cell count were associated with more HIV-1 X4-tropism. The immune recovery during HAART was positively related to baseline CD4+ T cell count.

Osteoimmunomodulatory Nanoparticles for Bone Regeneration.

Treatment of large bone fractures remains a challenge for orthopedists. Bone regeneration is a complex process that includes skeletal cells such as osteoblasts, osteoclasts, and immune cells to regulate bone formation and resorption. Osteoimmunology, studying this complicated process, has recently been used to develop biomaterials for advanced bone regeneration. Ideally, a biomaterial shall enable a timely switch from early stage inflammatory (to recruit osteogenic progenitor cells) to later-stage anti-inflammatory (to promote differentiation and terminal osteogenic mineralization and model the microstructure of bone tissue) in immune cells, especially the M1-to-M2 phenotype switch in macrophage populations, for bone regeneration. Nanoparticle (NP)-based advanced drug delivery systems can enable the controlled release of therapeutic reagents and the delivery of therapeutics into specific cell types, thereby benefiting bone regeneration through osteoimmunomodulation. In this review, we briefly describe the significance of osteoimmunology in bone regeneration, the advancement of NP-based approaches for bone regeneration, and the application of NPs in macrophage-targeting drug delivery for advanced osteoimmunomodulation.

Current Advances in 3D Dynamic Cell Culture Systems.

The traditional two-dimensional (2D) cell culture methods have a long history of mimicking in vivo cell growth. However, these methods cannot fully represent physiological conditions, which lack two major indexes of the in vivo environment; one is a three-dimensional 3D cell environment, and the other is mechanical stimulation; therefore, they are incapable of replicating the essential cellular communications between cell to cell, cell to the extracellular matrix, and cellular responses to dynamic mechanical stimulation in a physiological condition of body movement and blood flow. To solve these problems and challenges, 3D cell carriers have been gradually developed to provide a 3D matrix-like structure for cell attachment, proliferation, differentiation, and communication in static and dynamic culture conditions. 3D cell carriers in dynamic culture systems could primarily provide different mechanical stimulations which further mimic the real in vivo microenvironment. In this review, the current advances in 3D dynamic cell culture approaches have been introduced, with their advantages and disadvantages being discussed in comparison to traditional 2D cell culture in static conditions.

K. ZHENG ET AL.Gold-nanoparticle-based multistage drug delivery system for antitumor therapy.

Nanoparticles can promote the accumulation of drugs in tumors. However, they find limited clinical applications because they cannot easily penetrate the stroma of cancer tissues, and it is difficult to control drug release. We developed a multiresponse multistage drug-delivery nanogel with improved tumor permeability and responsiveness to the tumor microenvironment for the controlled delivery of anticancer agents. For this purpose, ∼100 nm multistage drug delivery nanogels with pH, redox, near-infrared stimulation, and enzyme responsiveness were grown in situ using 20 nm gold nanoparticles (AuNPs) via an emulsion-aiding crosslinking technique with cysteine crosslinker. An alginate cysteine AuNP (ACA) nanocarrier can efficiently load the cationic drug doxorubicin (DOX) to produce a multistage drug delivery nanocarrier (DOX@ACA). DOX@ACA can maintain the slow release of DOX and reduce its toxicity. In cancer tissues, the high pH and reductase microenvironment combined with the in vitro delivery of alginate and near-infrared light drove drug release. The developed nanoparticles effectively inhibited cancer cells, and in vivo evaluations showed that they effectively enhanced antitumor activity while having negligible in vivo toxicity to major organs.

Kinetics of Severity Biomarkers and Immunological Features of Methylprednisolone Therapy for Severe COVID-19 Patients.

In contrast to dexamethasone, the clinical efficacy of methylprednisolone (MP) remains controversial, and a systems biology study on its mechanism is lacking. In this study, a total of 38 severe COVID-19 patients were included. The demographics, clinical characteristics, and severity biomarkers including C-reactive protein (CRP), d-dimer, albumin, and Krebs von den Lungen 6 of patients receiving MP (n=26, 40 mg or 80 mg daily for 3-5 days) and supportive therapy (n=12) were compared. Longitudinal measurements of 92 cytokines in MP group from admission to over six months after discharge were performed by multiplex Proximity Extension Assay. The results showed that demographics, baseline clinical characteristics were similar in MP and non-MP groups. No death occurred and the hospital stays between the two groups were similar. Kinetics studies showed that MP was not better than supportive therapy at improving the four severity biomarkers. Cytokines in MP group were characterized by five clusters according to their baseline levels and responses to MP. The immunological feature of severe COVID-19 could be defined by the "core signature" cytokines in cluster 2: MCP-3, IL-6, IFN-γ, and CXCL10, which strongly correlated with each other and CRP, and are involved in cytokine release storm. The "core signature" cytokines were significantly upregulated at baseline and remained markedly elevated after MP treatment. Our work showed a short course of MP therapy could not rapidly improve the immune disorders among severe COVID-19 patients or clinical outcomes, also confirmed "core signature" cytokines, as severity biomarkers similar to CRP, could be applied to evaluate clinical treatment effect.

Chlorella vulgaris Extract-Decorated Gold Nanoparticle Hybridized Antimicrobial Hydrogel as a Potential Dressing.

This study reports a novel design of a moisturizing and antimicrobial hydrogel with injectable properties, using a green solvent (glycerol) as a cross-linking agent and gold nanoparticle reduced by Chlorella extract as an antimicrobial approach. We have synthesized gold nanoparticles (AuNPs) with environmentally friendly and bio-safe properties using Chlorella aqueous extracts (AuNPs@Chlorella). Characterization of the nanoparticles by ultraviolet-visible spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FTIR), Raman spectrum, and transmission electron microscope (TEM) confirmed that spherical AuNPs with the particle size of 10-20 nm were successfully synthesized. An analysis of the enhancement of the stability of gelatin hydrogels by the addition of glycerol and AuNPs was performed by rheometry. In addition, we also used Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) to confirm the good antibacterial activity. Therefore, the as-prepared gelatin-glycerol hydrogels containing AuNPs@Chlorella are most likely promising alternatives for wound healing dressings.

COVID-19 induces new-onset insulin resistance and lipid metabolic dysregulation via regulation of secreted metabolic factors.

Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism. In this study, we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases, and found new-onset insulin resistance, hyperglycemia, and decreased HDL-C in these patients. Mechanistically, SARS-CoV-2 infection increased the expression of RE1-silencing transcription factor (REST), which modulated the expression of secreted metabolic factors including myeloperoxidase, apelin, and myostatin at the transcriptional level, resulting in the perturbation of glucose and lipid metabolism. Furthermore, several lipids, including (±)5-HETE, (±)12-HETE, propionic acid, and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation, especially in insulin resistance. Taken together, our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19, and further illustrated the underlying mechanisms, providing potential therapeutic targets for COVID-19-induced metabolic complications.

Prognostic roles of KL-6 in disease severity and lung injury in COVID-19 patients: A longitudinal retrospective analysis.

To investigate the dynamic changes of Krebs von den Lungen-6 (KL-6) among patients with coronavirus disease 2019 (COVID-19) and the role of KL-6 as a noninvasive biomarker for predicting long-term lung injury, the clinical information and laboratory tests of 166 COVID-19 patients were collected, and a correlation analysis between KL-6 and other parameters was conducted. There were 17 (10.2%, 17/166) severe/critical and 149 (89.8%, 149/166) mild COVID-19 patients in our cohort. Serum KL-6 was significantly higher in severe/critical COVID-19 patients than in mild patients (median 898.0 vs. 451.2 U/ml, p < .001). KL-6 was next confirmed to be a sensitive and specific biomarker for distinguishing mild and severe/critical patients and correlate to computed tomography lung lesions areas. Serum KL-6 concentration during the follow-up period (>100 days postonset) was well correlated to those concentrations within 10 days postonset (Pearson r = .867, p < .001), indicating the prognostic value of KL-6 levels in predicting lung injury after discharge. Finally, elevated KL-6 was found to be significantly correlated to coagulation disorders, and T cells subsets dysfunctions. In summary, serum KL-6 is a biomarker for assessing COVID-19 severity and predicting the prognosis of lung injury of discharged patients.

Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity.

The novel coronavirus (2019-nCoV) infection caused pneumonia. we retrospectively analyzed the virus presence in the pharyngeal swab, blood, and the anal swab detected by real-time PCR in the clinical lab. Unexpectedly, the 2109-nCoV RNA was readily detected in the blood (6 of 57 patients) and the anal swabs (11 of 28 patients). Importantly, all of the 6 patients with detectable viral RNA in the blood cohort progressed to severe symptom stage, indicating a strong correlation of serum viral RNA with the disease severity (p-value = 0.0001). Meanwhile, 8 of the 11 patients with annal swab virus-positive was in severe clinical stage. However, the concentration of viral RNA in the anal swab (Ct value = 24 + 39) was higher than in the blood (Ct value = 34 + 39) from patient 2, suggesting that the virus might replicate in the digestive tract. Altogether, our results confirmed the presence of virus RNA in extra-pulmonary sites.

[Semen quality and HIV RNA level in HIV/AIDS male patients after treated by highly active antiretroviral therapy].

OBJECTIVE: To evaluate the semen quality of the HIV/AIDS male patients after treated by the highly active antiretroviral therapy (HAART) and their potential of transmitting HIV/AIDS and provide some evidence for this cohort of males who wish for parenthood. METHODS: We collected semen samples from 20 HIV/AIDS male patients who had been treated by HAART for over 6 months and wished for parenthood. We examined sperm concentration, viability and total motility and the percentage of morphologically normal sperm (MNS) using the computer-assisted semen analysis system, measured the HIV-1 RNA loads in the semen by the Cobas Amplicor Monitor test, and counted CD4+ T cells in the peripheral blood by flow cytometry. RESULTS: The patients were aged 25－40 (30.7 ± 5.05) years. After treated by HAART for 6－26 (14.24 ± 12.26) months, the count of blood CD4+ T cells was significantly increased (341－1 058 ï¼»535.76 ± 212.021ï¼½ /µl) in comparison with the baseline (226－965 ï¼»422.38 ± 200.86ï¼½ /µl). Compared with the normal value, the semen volume was increased except in 1 case (≥2 ml) while total sperm motility was decreased in 13 cases (≥40%), and so were sperm concentration in 2 cases (≥15 × 106 / ml), sperm viability in 5 (58%), the percentage of progressively motile sperm in 18 (≥32%), and the percentage of MNS in 6 (≤4%). HIV-1 RNA in the peripheral blood was <20 copies/mL in all the cases and that in the seminal plasma was also <20 copies/ml in 18 cases but >20 copies/mL in the other 2 (ï¼»4.70 × 101ï¼½ and ï¼»2.2 × 102ï¼½ copies/ml, respectively). Of the 4 couples that had sex without protective measures for over 6 months, all the 4 female partners exhibited negative HIV antibodies in regular follow-up examinations and 1 achieved spontaneous pregnancy and healthy birth, with negative HIV-1 RNA in both the mother and the baby. CONCLUSIONS: The HIV RNA level is higher in the semen than in the blood of the HIV/AIDS male patients after HAART, which indicates the potential risk of their semen transmitting HIV/AIDS to their female partners. Their sperm concentration and total sperm motility are lower than the normal value, which suggests a decreased fertility.

Experimental performance evaluation of software defined networking (SDN) based data communication networks for large scale flexi-grid optical networks.

Software defined networking (SDN) has become the focus in the current information and communication technology area because of its flexibility and programmability. It has been introduced into various network scenarios, such as datacenter networks, carrier networks, and wireless networks. Optical transport network is also regarded as an important application scenario for SDN, which is adopted as the enabling technology of data communication networks (DCN) instead of general multi-protocol label switching (GMPLS). However, the practical performance of SDN based DCN for large scale optical networks, which is very important for the technology selection in the future optical network deployment, has not been evaluated up to now. In this paper we have built a large scale flexi-grid optical network testbed with 1000 virtual optical transport nodes to evaluate the performance of SDN based DCN, including network scalability, DCN bandwidth limitation, and restoration time. A series of network performance parameters including blocking probability, bandwidth utilization, average lightpath provisioning time, and failure restoration time have been demonstrated under various network environments, such as with different traffic loads and different DCN bandwidths. The demonstration in this work can be taken as a proof for the future network deployment.