Cell migration is an essential bioactive ceramics property and critical for bone induction, clinical application, and mechanism research. Standardized cell migration detection methods have many ...limitations, including a lack of dynamic fluid circulation and the inability to simulate cell behavior in vivo. Microfluidic chip technology, which mimics the human microenvironment and provides controlled dynamic fluid cycling, has the potential to solve these questions and generate reliable models of cell migration in vitro. In this study, a microfluidic chip is reconstructed to integrate the bioactive ceramic into the microfluidic chip structure to constitute a ceramic microbridge microfluidic chip system. Migration differences in the chip system are measured. By combining conventional detection methods with new biotechnology to analyze the causes of cell migration differences, it is found that the concentration gradients of ions and proteins adsorbed on the microbridge materials are directly related to the occurrence of cell migration behavior, which is consistent with previous reports and demonstrates the effectiveness of the microfluidic chip model. This model provides in vivo environment simulation and controllability of input and output conditions superior to standardized cell migration detection methods. The microfluidic chip system provides a new approach to studying and evaluating bioactive ceramics.
Nonalcoholic steatohepatitis (NASH), as one of the key stages in the development of nonalcoholic fatty liver disease (NAFLD), can directly progress to HCC, but the underlying mechanism is not fully ...understood.
Differentially expressed genes (DEGs) in each stage of disease development were studied through a GEO dataset deriving from a Stelic Animal Model (STAM), which can simulate the evolution of NAFLD/NASH to HCC in humans. GSVA analysis was performed to analyze the differentially expressed oncogenic signatures in each stage. A human NAFLD-related dataset from GEO database was utilized for gene expression verification and further validated in the protein level in STAM mice. Small molecule inhibitors were applied to STAM mice for investigating whether inhibition of the LPL/FABP4/CPT1 axis could prevent the occurrence of NASH-related HCC
. Microsphere formation and clonal formation assays
were applied to study if inhibition of the LPL/FABP4/CPT1 axis can reduce the viability of liver cancer stem cells (LCSCs).
We found that upregulation of the LPL/FABP4/CPT1 molecular axis, as a fatty acid metabolic reprogramming process, occurred specifically during the NASH phase. GSVA analysis showed widespread activation of a large number of oncogenic signals, which may contribute to malignant transformation during NASH. Furthermore, inhibition of the LPL/FABP4/CPT1 axis could effectively delay the tumor growth in STAM mice. Cell assays revealed inhibitors targeting this axis can significantly reduce the sphere-forming, proliferation, and clonality of LCSCs.
These results suggest that activation of the LPL/FABP4/CPT1 axis is essential for LCSCs maintenance, which acts synergistically with a variety of up-regulated oncogenic signals that drive the hepatocyte-LCSCs transdifferentiation during NASH to HCC progression. Thus, targeting the LPL/FABP4/CPT1 axis may provide a potential direction for NASH-related HCC prevention.
Wound management requires the preparation of controllable, safe and effective dressings to isolate the wound from the external environment. Currently, widely used commercial dressings focus on the ...isolation effect rather than an environment conducive to wound healing. To provide the dressing with beneficial properties such as wetting and antioxidant and antibacterial activity, this study used polyvinyl alcohol (PVA) hydrogel as the base material and introduced chitosan (CS) and vanillin (V) to design a PVA/CS/V three-phase hydrogel dressing. The dressings were prepared using a freeze-thaw cycle to achieve properties. We conducted a comparative analysis of PVA/V and PVA/CS two-phase hydrogels. The PVA/CS/V (PCV) hydrogel dressing maintaining an elastic modulus at >5 kPa at 15–40 °C. An in vitro antibacterial assay showed the potent antibacterial ability of hydrogels against gram-positive and -negative bacteria, and cells in some PCV groups showed higher activity. The antioxidant results showed that PCV hydrogel had a potent scavenging effect on DPPH, ABTS+, and PTIO free radical. The antibacterial and antioxidant properties of three-phase hydrogel showed the best performance in all experimental groups. These results suggest that PCV hydrogel has value in commercial applications due to its simple preparation process and excellent biological properties.
•The PVA hydrogels have excellent antibacterial properties and potent antioxidant properties.•The preparation process of PVA hydrogels are straightforward and its quality is controllable.•PVA hydrogels are cost-effective and have the potential for large-scale commercial applications.
Background. As K13 propeller mutations have been recently reported to serve as molecular markers, assessment of K13 propeller polymorphisms in multidrug-resistant gene in isolates from Myanmar, ...especially the eastern and western border areas, is crucial if we are to understand the spread of artemisinin resistance. Methods. A 3-day surveillance study was conducted in the eastern and western border areas in Myanmar, and K13 propeller and Plasmodium falciparum multidrug resistance-associated protein 1 (pfmrp1) mutations were analyzed. Results. Among the 1761 suspected malaria cases screened, a total of 42 uncomplicated falciparum cases from the eastern border and 49 from the western border were subjected to 3 days of surveillance after artemether-lumefantrine treatment. No parasitemic case showing positivity on day 3 was noted from the western border, but 26.2% (11/42) of cases were positive in the eastern border. Although we found no marked difference in the prevalence of the pfmrp1 mutation in the eastern and western borders (36% vs 31%, respectively), K13 mutations were more frequent in the eastern border area (where the 3-day persistent cases were detected; 48% vs 14%). C580Y, M476I, A481V, N458Y, R539T, and R516Y accounted for 68.9% of all K13 mutations significantly associated with day 3 parasitaemia. Conclusions. The K13 mutations were significantly associated with day 3 parasitaemia, emphasizing the importance of K13 surveillance. The low prevalence of K13 mutations and the absence of day 3 parasitaemic cases indicate that artemisinin resistance may not have spread to the western Myanmar border region. Although analysis of multiple K13 mutations is challenging, it should be done at various sentinel sites in Myanmar.
Pre-exposure prophylaxis (PrEP) is effective for human immunodeficiency virus (HIV) prevention in risk groups. We assessed PrEP uptake and 12-month retention among men who have sex with men (MSM) and ...transgender women (TGW) in Myanmar during the coronavirus disease 2019 pandemic and a political crisis.
Using prospectively collected data, we assessed the proportion of persons eligible, initiated and retained 12 months on PrEP. We calculated HIV and syphilis incidence among those initiated on PrEP. Predictors of compliance to scheduled visits were assessed with fractional logistic regression.
Among 652 persons screened between July and December 2020, 85.3% were eligible and 38.8% initiated PrEP. The daily pill burden was the main reason (86.5%) for refusing PrEP. A history of HIV post-exposure prophylaxis (PEP) and having an HIV-positive partner not on anti-retroviral therapy (ART) was associated with PrEP uptake (p<0.05). The 12-month retention among those initiating PrEP was 43.0%. Age ≥25 y, a history of PEP and having an HIV-positive partner not on ART predicted better compliance with scheduled visits (p<0.05). HIV incidence among PrEP initiators was 3.1 per 100 person-years (95% confidence interval CI 1.3 to 7.4) and syphilis incidence was 17.6 per 100 person-years (95% CI 12.3 to 25.1).
A PrEP program for MSM and TGW in Myanmar was implemented successfully under difficult circumstances. Alternative strategies are needed addressing PrEP uptake and retention.
Despite recent advances in antidepressants in treating major depression (MDD), their usage is marred by adverse effects and social stigmas. Probiotics may be an efficacious adjunct or standalone ...treatment, potentially circumventing the aforementioned issues with antidepressants. However, there is a lack of head-to-head clinical trials between these 2 interventions.
A systematic review and network meta-analysis was conducted to compare the efficacy and acceptability of these 2 interventions in treating MDD.
Six databases and registry platforms for the clinical trial were systematically searched to identify the eligible double-blinded, randomized controlled trials published between 2015 and 2022.
Two authors selected independently the placebo-controlled trials of antidepressants and microbiota-targeted interventions (prebiotics, probiotics, and synbiotics) used for the treatment of MDD in adults (≥18 years old). Standardized mean differences (SMDs) of depressive symptom scores from individual trials were pooled for network meta-analysis (PROSPERO no. CRD42020222305).
Forty-two eligible trials covering 22 interventions were identified, of which 16 were found to be effective in MDD treatment and the certainty of evidence was moderate to very low. When all trials were considered, compared with placebo, SMDs of interventions ranged from -0.16 (95% credible interval: -0.30, -0.04) for venlafaxine to -0.81 (-1.06, -0.52) for escitalopram. Probiotics were superior to brexpiprazole (SMD 95% credible interval: -0.42 -0.68, -0.17), cariprazine (-0.44 -0.69, -0.24), citalopram (-0.37 -0.66, -0.07), duloxetine (-0.26, -0.51, -0.04), desvenlafaxine (-0.38 -0.63, -0.14), ketamine (-0.32 -0.66, -0.01), venlafaxine (-0.47 -0.73, -0.23), vilazodone (-0.37 -0.61, -0.12), vortioxetine (-0.39 -0.63, -0.15), and placebo (-0.62 -0.86, -0.42), and were noninferior to other antidepressants. In addition, probiotics ranked the second highest in the treatment hierarchy after escitalopram. Long-term treatment (≥8 weeks) using probiotics showed the same tolerability as antidepressants.
Probiotics, compared with antidepressants and placebo, may be efficacious as an adjunct or standalone therapy for treating MDD.
PROSPERO registration no. CRD42020222305.
Design and fabrication of collagen-based injectable and self-crosslinkable hydrogels for cell delivery. （CSsNHS: activated chondroitin sulfate; NH2: amino groups; COsNHS: activated carboxyl groups; ...CONH: amide groups
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•ColI/CS-sNHS hydrogels were injectable and self-crosslinkable.•The gelation occurred without the addition of any crosslinking agent.•The physical properties of hydrogels were tuned by regulating the DS of CS-sNHS.•ColI/CS-sNHS hydrogels supported the survival and ECM secretion of chondrocytes.•The hydrogels exhibited acceptable inflammatory responses.
Injectable and self-crosslinkable hydrogels have drawn much attention for their potential application as cell delivery carriers to deliver cells to the injury site of arbitrary shape. In this study, injectable and self-crosslinkable hydrogels were designed and fabricated based on collagen type I (Col I) and activated chondroitin sulfate (CS-sNHS) by physical and chemical crosslinking without the addition of any catalysts. The physical properties of hydrogels, including mechanical properties, swelling and degradation properties, were investigated. The results demonstrated that the physical properties of hydrogels, especially the stiffness of hydrogels, were readily tuned by varying the degree of substitution (DS) of CS-sNHS without changing the concentration of collagen-based precursor. Chondrocytes were encapsulated into hydrogels to investigate the effects of hydrogels on the survival, proliferation and extracellular matrix (ECM) secretion of cells by FDA/PI staining, CCK-8 test and histological staining. The results suggested that all of these hydrogels supported the survival and ECM secretion of chondrocytes, while there was more ECM secretion around chondrocytes encapsulated in hydrogel Col I/CS-sNHS56% in which the DS of CS-sNHS was 56%. When the neutral precursor solution for hydrogel of Col I or Col I/CS-sNHS56% was subcutaneously injected into SD rats, hydrogels both displayed acceptable biocompatibility in vivo. These results imply that these injectable and self-crosslinkable hydrogels are suitable candidates for applications in the fields of cell delivery and tissue engineering.
Oil and gas seismic exploration have to adopt irregular seismic acquisition due to the increasingly complex exploration conditions to adapt to complex geological conditions and environments. However, ...the irregular seismic acquisition is accompanied by the lack of acquisition data, which requires high-precision regularization. The sparse signal feature in the transform domain in compressed sensing theory is used in this paper to recover the missing signal, involving sparse transform base optimization and threshold modeling. First, this paper analyzes and compares the effects of six sparse transformation bases on the reconstruction accuracy and efficiency of irregular seismic data and establishes the quantitative relationship between sparse transformation and reconstruction accuracy and efficiency. Second, an adaptive threshold modeling method based on sparse coefficient is provided to improve the reconstruction accuracy. Test results show that the method has good adaptability to different seismic data and sparse transform bases. The f-x domain reconstruction method of effective frequency samples is studied to address the problem of low computational efficiency. The parallel computing strategy of curvelet transform combined with OpenMP is further proposed, which substantially improves the computational efficiency under the premise of ensuring the reconstruction accuracy. Finally, the actual acquisition data are used to verify the proposed method. The results indicate that the proposed method strategy can solve the regularization problem of irregular seismic data in production and improve the imaging quality of the target layer economically and efficiently.
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