Recent Developments in Slippery Liquid-Infused Porous Surface Coatings for Biomedical Applications.

Slippery liquid-infused porous surface (SLIPS), inspired by the Nepenthes pitcher plant, exhibits excellent performances as it has a smooth surface and extremely low contact angle hysteresis. Biomimetic SLIPS attracts considerable attention from the researchers for different applications in self-cleaning, anti-icing, anticorrosion, antibacteria, antithrombotic, and other fields. Hence, SLIPS has shown promise for applications across both the biomedical and industrial fields. However, the manufacturing of SLIPS with strong bonding ability to different substrates and powerful liquid locking performance remains highly challenging. In this review, a comprehensive overview of research on SLIPS for medical applications is conducted, and the design parameters and common fabrication methods of such surfaces are summarized. The discussion extends to the mechanisms of interaction between microbes, cells, proteins, and the liquid layer, highlighting the typical antifouling applications of SLIPS. Furthermore, it identifies the potential of utilizing the controllable factors provided by SLIPS to develop innovative materials and devices aimed at enhancing human health.

Comparative Study on the Lubrication Mechanism and Performance of Two Representative Ionic and Nonionic Self-Adhesive Polymer Coatings.

Surface modification of lubricating coatings on biomedical devices is a pivotal strategy to improve the overall performance and clinical efficacy, significantly reducing friction between devices and human tissues and mitigating tissue damage during intervention and long-term implantation. Recently, various hydrophilic polymeric materials have been used for achieving surface functionalization, endowing the biomedical device with excellent superlubrication performance. N-Vinylpyrrolidone (NVP) and 2-methacryloyloxyethyl phosphorylcholine (MPC) are two typical representatives of nonionic and zwitterionic materials. However, there is still a research gap in a comparative study of the lubrication mechanisms and properties between them. In this study, a bioinspired and dopamine-assisted codeposition technique was used to fabricate biomimetic hydrophilic coatings, including P(DMA-NVP) and P(DMA-MPC), on polyurethane. To achieve a thorough comparative analysis of the self-adhesive coating performance, 3 M ratios of the copolymers were synthesized and comprehensive material evaluations were conducted. Additionally, surface morphology, hydrophilicity, and lubrication at both the microscale and macroscale were performed. It was found that both hydrophilic coatings exhibited good stability. The P(DMA-MPC) coating, due to the ability to attract and bind a large number of water molecules, demonstrated superior lubrication effects compared to the P(DMA-NVP) coating. The study provides an in-depth understanding of the lubrication behavior of the self-adhesive coatings to enhance the functionality and application in biomedical engineering.

Impacts of rainfall and lakeshore soil properties on microplastics in inland freshwater: A case study in Donghu Lake, China.

Microplastic (MP) pollution has garnered global attention in recent years. Although anthropogenic factors have been extensively studied for their impacts on MP pollution, there is still a lack of research on the relationship between non-anthropogenic factors and MP occurrence in inland freshwater. This study investigated MP pollution in Donghu Lake, the largest urban freshwater lake in China, to examine the effects of rainfall and lakeshore soil properties on MP pollution. The MP abundance in the surface water of Donghu Lake was 5.84 ± 2.95 items per L under the equilibrium state. However, during and after rainfall, the MP abundances significantly increased to 8.27 ± 5.65 items per L and 7.60 ± 4.04 items per L, respectively (p < 0.05). This increase could be attributed to an increase in the amount of MPs transported to the lake via atmospheric deposition and rainfall runoff, as well as the re-suspension of MP debris in sediment during stronger hydrodynamics. A statistically significant negative correlation was observed between MP abundance and lakeshore soil particle size. It suggested that a high proportion of large-sized soil particles created large pores that enabled MPs to be deposited in the surface layer of soil to migrate to deeper layers. As a result, the amount of MPs in the surface soil and transported to the lake via surface runoff was low. It is of practical significance to understand the sources and distribution impact factors of MPs in urban lakes. The fate and effects of MPs retained in the inland freshwater environments should receive more attention.

Solid Additive Dual-Regulates Spectral Response Enabling High-Performance Semitransparent Organic Solar Cells.

Semi-transparent organic solar cells (ST-OSCs) possess significant potential for applications in vehicles and buildings due to their distinctive visual transparency. Conventional device engineering strategies are typically used to optimize photon selection and utilization at the expense of power conversion efficiency (PCE); moreover, the fixed spectral utilization range always imposes an unsatisfactory upper limit to its light utilization efficiency (LUE). Herein, a novel solid additive named 1,3-diphenoxybenzene (DB) is employed to dual-regulate donor/acceptor molecular aggregation and crystallinity, which effectively broadens the spectral response of ST-OSCs in near-infrared region. Besides, more visible light is allowed to pass through the devices, which enables ST-OSCs to possess satisfactory photocurrent and high average visible transmittance (AVT) simultaneously. Consequently, the optimal ST-OSC based on PP2+DB/BTP-eC9+DB achieves a superior LUE of 4.77%, representing the highest value within AVT range of 40-50%, which also correlates with the formation of multi-scale phase-separated morphology. Such results indicate that the ST-OSCs can simultaneously meet the requirements for minimum commercial efficiency and plant photosynthesis when integrated with the roofs of agricultural greenhouses. This work emphasizes the significance of additives to tune the spectral response in ST-OSCs, and charts the way for organic photovoltaics in economically sustainable agricultural development.

Survival of Patients with Hepatitis B-Related Hepatocellular Carcinoma with Concomitant Metabolic Associated Fatty Liver Disease.

Purpose: Metabolic associated fatty liver disease is a novel concept defined as fatty liver associated with metabolic disorders. We investigated the effect of metabolic associated fatty liver disease on hepatocellular carcinoma patient mortality. Patients and Methods: A total of 624 patients with hepatocellular carcinoma between 2012 and 2020 were enrolled in this retrospective study. Hepatic steatosis was diagnosed using computed tomography or magnetic resonance imaging. Metabolic associated fatty liver disease was defined based on the proposed criteria in 2020. Propensity score matching was performed for patients with metabolic associated fatty liver disease and those without the condition. A Cox proportional hazards regression model was used to evaluate the association between metabolic associated fatty liver disease and hepatocellular carcinoma patient outcomes. Results: Patients with hepatocellular carcinoma and metabolic associated fatty liver disease tended to achieve better outcomes than did those without metabolic associated fatty liver disease after matching (p<0.001). Metabolic associated fatty liver disease was significantly associated with better prognosis in patients with concurrent hepatitis B infection (p<0.001). Moreover, high levels of hepatitis B viral DNA in serum samples was associated with a significantly increased risk of death in patients without non-metabolic associated fatty liver disease (p=0.045). Additionally, the association between metabolic associated fatty liver disease and survival in hepatitis B virus-related hepatocellular carcinoma was similar in all subgroups based on metabolic traits. Conclusion: Metabolic associated fatty liver disease increases the survival rate of patients with hepatocellular carcinoma and hepatitis B virus infection. The potential interaction of steatosis and virus replication should be considered for future research and clinical treatment strategies.

Long-term antibody response to inactivated SARS-CoV-2 vaccination in patients with chronic liver disease: A multicenter study.

Patients with chronic liver disease (CLD) are at a greater risk of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection. This study investigated the antibody response to inactivated SARS-CoV-2 vaccination in a long-term prospective cohort of CLD patients. The seropositivity rates and antibody concentrations of anti-SARS-CoV-2 NAbs were similar among patients with different severity of CLD 6 months after the third vaccination. In addition, older CLD patients appeared to have lower antibody responses. These data might be helpful to inform vaccine decisions for patients with chronic liver disease.

Directly Cross-Linked Conjugated Polymer Donor Enables Efficient Polymer Solar Cells with Extraordinary Mechanical Robustness.

A cross-linking strategy can result in a three-dimensional network of interconnected chains for the copolymers, thereby improving their mechanical performance. In this work, a series of cross-linked conjugated copolymers, named PC2, PC5, and PC8, constructed with different ratios of monomers are designed and synthesized. For comparison, a random linear copolymer, PR2 is also synthesized based on the similar monomers. When blended with Y6 acceptor, the cross-linked polymers PC2, PC5, and PC8-based polymer solar cells (PSCs) achieve superior power conversion efficiencies (PCEs) of 17.58%, 17.02%, and 16.12%, respectively, which are higher than that (15.84%) of the random copolymer PR2-based devices. Moreover, the PCE of PC2:Y6-based flexible PSC retains ≈88% of the initial efficiency value after 2000 bending cycles, overwhelming the PR2:Y6-based device with the remaining 12.8% of the initial PCE. These results demonstrate that the cross-linking strategy is a feasible and facile approach to developing high-performance polymer donors for the fabrication of flexible PSCs.

Longitudinal Through-Hole Architecture for Efficient and Thickness-Insensitive Semitransparent Organic Solar Cells.

Semi-transparent organic solar cells (ST-OSCs) have great potential for application in vehicle- or building-integrated solar energy harvesting. Ultrathin active layers and electrodes are typically utilized to guarantee high power conversion efficiency (PCE) and high average visible transmittance (AVT) simultaneously; however, such ultrathin parts are unsuitable for industrial high-throughput manufacturing. In this study, ST-OSCs are fabricated using a longitudinal through-hole architecture to achieve functional region division and to eliminate the dependence on ultrathin films. A complete circuit that vertically corresponds to the silver grid is responsible for obtaining high PCE, and the longitudinal through-holes embedded in it allow most of the light to pass through,where the overall transparency is associated with the through-hole specification rather than the thicknesses of active layer and electrode. Excellent photovoltaic performance over a wide range of transparency (9.80-60.03%), with PCEs ranging from 6.04% to 15.34% is achieved. More critically, this architecture allows printable 300-nm-thick devices to achieve a record-breaking light utilization efficiency (LUE) of 3.25%, and enables flexible ST-OSCs to exhibit better flexural endurance by dispersing the extrusion stress into the through-holes. This study paves the way for fabricating high-performance ST-OSCs and shows great promise for the commercialization of organic photovoltaics.

Draft Genome Sequence of an Epibiotic Bacterium, Bacillus cereus, Isolated from Cyanobacterial Blooms in Lake Taihu, China.

Here, we report the draft genome sequence of Bacillus cereus strain THSB-6-2, which was isolated from cyanobacterial blooms in Lake Taihu, China. The 5,496,658-bp genome assembly of Bacillus cereus consists of 28 contigs, with a GC content of 35% and with 5,587 protein-coding sequences and 58 RNA genes.

Observation on the Efficacy of a Combined Treatment for Moderate and Severe Androgenetic Alopecia Incorporating Electric Microneedles.

Objective: To evaluate the effectiveness and safety of a combined treatment for moderate and severe androgenetic alopecia (AGA) involving the use of electric microneedles. Methods: A total of 83 patients with moderate to severe AGA in the Department of Dermatology at Beijing Jishuitan Hospital were included in this study. The male patients were administered finasteride orally and 5% minoxidil for external use, while the female patients were given spironolactone orally or Diane-35 and 2% minoxidil for external use. All the patients were then treated via electric microneedle therapy alongside the YUFA ®medical care package (Foshan, China) once a week for 1-28 weeks. The seven-point method and root hair measurement using a hair mirror were adopted to evaluate the efficacy and any adverse reactions of the combined treatment. Results: Eleven patients were treated for 1-3 weeks, 60 for 4-12 weeks, and 12 for more than 12 weeks. The efficacy evaluation using the seven-point method for 12 weeks of treatment indicated a 100% response rate, specifically, a 42.1% mild improvement rate, a 38.6% moderate improvement rate, and a 19.3% marked improvement rate. Besides, the efficacy assessment was also completed with root hair count method and the number of hair roots measured at fixed points were 148.67±11.15, 158.13±5.11 and 169.75±2.06 after treatment time at 16, 20 and 24 weeks, respectively. Of note, a statistical difference in the number of hair roots could be observed during the period of week 20-week 24 (P < 0.01). Conclusion: The combined treatment of moderate to severe AGA using the electric microneedle technique has a clear effect and can effectively increase the hair density. With a simple operation and mild side effects, the technique has wide application prospects.

Diastereoselective Indole-Dearomative Cope Rearrangements by Compounding Minor Driving Forces.

Reported herein is the discovery of a diastereoselective indole-dearomative Cope rearrangement. A suite of minor driving forces promote dearomatization: (i) steric congestion in the starting material, (ii) alkylidene malononitrile and stilbene conjugation events in the product, and (iii) an unexpected intramolecular π-π* stack on the product side of the equilibrium. The key substrates are rapidly assembled from simple starting materials, resulting in many successful examples. The products are structurally complex and bear vicinal stereocenters generated by the dearomative Cope rearrangement. They also contain a variety of functional groups for interconversion to complex architectures.

Anticancer Agents Derived from Cyclic Thiosulfonates: Structure-Reactivity and Structure-Activity Relationships.

Reported are structure-property-function relationships associated with a class of cyclic thiosulfonate molecules-disulfide-bond disrupting agents (DDAs)-with the ability to downregulate the Epidermal Growth Factor Receptor (HER) family in parallel and selectively induce apoptosis of EGFR+ or HER2+ breast cancer cells. Recent findings have revealed that the DDA mechanism of action involves covalent binding to the thiol(ate) from the active site cysteine residue of members of the protein disulfide isomerase (PDI) family. Reported is how structural modifications to the pharmacophore can alter the anticancer activity of cyclic thiosulfonates by tuning the dynamics of thiol-thiosulfonate exchange reactions, and the studies reveal a correlation between the biological potency and thiol-reactivity. Specificity of the cyclic thiosulfonate ring-opening reaction by a nucleophilic attack can be modulated by substituent addition to a parent scaffold. Lead compound optimization efforts are also reported, and have resulted in a considerable decrease of the IC50 /IC90 values toward HER-family overexpressing breast cancer cells.

Construction of vicinal 4°/3°-carbons via reductive Cope rearrangement.

Herein reported is a strategy for constructing vicinal 4°/3° carbons via reductive Cope rearrangement. Substrates have been designed which exhibit Cope rearrangement kinetic barriers of ∼23 kcal mol-1 with isoenergetic favorability (ΔG ∼ 0). These fluxional/shape-shifting molecules can be driven forward by chemoselective reduction to useful polyfunctionalized building blocks.

CD44 deficiency represses neuroinflammation and rescues dopaminergic neurons in a mouse model of Parkinson's disease.

CD44 is a transmembrane protein that transduces extracellular stimuli to immune response. Neuroinflammation is a causative factor in neurodegenerative diseases, such as Parkinson's disease (PD). Owing to its role in inflammation, this study investigated whether CD44 is involved in the pathological progression of PD. Our data showed that CD44 deficiency largely abolished proinflammatory cytokine expression in primary microglia and astrocytes. In PD model mice, CD44 knockout improved behavioral defects, prevented TH loss in the SNpc and striatum, and blocked activation of microglia and astrocytes. Moreover, CD44 neutralization by anti-CD44 antibody recapitulated the phenotypes observed in CD44 knockout mice. Mechanistically, CD44 neutralization blocked TLR4 expression and NF-κB p65 nuclear translocation induced by lipopolysaccharide in BV2 cells. Overall, our results indicate that CD44 deficiency has a beneficial role against PD, which is likely due to repression of the TLR4/NF-κB axis, leading to reduced neuroinflammation. Therefore, CD44 might be a therapeutic target for the development of anti-PD agents.

SIRT1 attenuates neuroinflammation by deacetylating HSPA4 in a mouse model of Parkinson's disease.

As a deacetylase, SIRT1 plays essential roles in various physiological events, from development to lifespan regulation. SIRT1 has been shown neuroprotective effects in neurodegeneration disorders such as Parkinson's disease (PD). However, the underlying molecular mechanisms are still not well understood. Here, we generated transgenic mice with increased expression of Sirt1 in the brain and examined the potential roles of SIRT1 in PD. Our data showed that SIRT1 repressed proinflammatory cytokine expression both in microglia and astrocytes. In MPTP induced PD model mice, lower levels of microglia and astrocyte activation were observed in SIRT1 transgenic mice. Moreover, the tyrosine hydroxylase (TH) loss in the substantia nigra pars compacta (SNpc) and striatum induced by MPTP was also attenuated by SIRT1. As a consequence, the behavioral defects induced by MPTP were largely prevented in SIRT1 transgenic mice. Mechanistically, SIRT1 interacts with heat shock 70 kDa protein 4 (HSPA4) and deacetylates it at 305, 351 and 605 lysine residues. This deacetylation modification induces the nuclear translocation of HSPA4 and thus to repress proinflammatory cytokine expression. On the contrary, mutated HSPA4, in which 305/351/605 lysine residues were replaced with arginine, was mainly localized in the cytoplasm and losses its repression on proinflammatory cytokine expression. Taken together, our data indicate that SIRT1 plays beneficial roles in PD model mice, which is likely due to, at least in part, its anti-inflammation activity in glial cells by deacetylating HSPA4. Furthermore, HSPA4 might be a druggable target for developing novel agents for treating neuroinflammation associated disorders such as PD.

Facile Transformations of a Binuclear Cp*Co(II) Diamidonaphthalene Complex to Mixed-Valent Co(II)Co(III), Co(III)(µ-H)Co(III), and Co(III)(µ-OH)Co(III) Derivatives.

A diamido-bridged dicobalt complex supported by a diamidonaphthalene ligand, Cp*2Co2(µ-1,8-C10H8(NH)2) (1), was synthesized, and the reactivity relevant to redox transformations of the Co2N2 core was investigated. It was found that the Co(II)-Co(II) bond allows for protonation by [HPPh3][BF4] resulting in a bridging hydride, [1H]+, with pKa ∼ 7.6 in CH2Cl2. The diamidonaphthalene ligand can stabilize the binuclear system in the Co(II)Co(III) mixed-valent state (1+), which is capable of binding CO to afford [1-CO]+. Surprisingly, the mixed-valent complex also activates H2O to furnish a Co(III)Co(III) hydroxy complex [1-OH]+ accompanied by release of H2. The hydroxy ligand in [1-OH]+ is exchangeable, as demonstrated by 18O-labeling experiments on [1-OH]+ with H218O that led to the heavier isotopolog [1-18OH]+.

A novel non-invasive identification of genome editing mutants from insect exuviae.

With the wide application of genome editing in insects, a simple and efficient identification method is urgently needed to meet the increasing demand for mutation detection. Here, taking migratory locusts as a model system, we developed a non-invasive method to accurately identify genome-edited mutants by using DNA from insect exuviae. We compared the quantity and quality of genomic DNA from exuviae in five instar hoppers and found that the 1st instar exuviae had the highest DNA yield and content, while the 3rd instar exuviae had the best quality. Consensus genotypes were identified from genomic DNA of hoppers at different developmental stages in the same individuals. Moreover, we demonstrated that the amplification products from DNA extracted from locust exuviae are the consensus sequences with those from the hemolymph and foreleg pre-tarsus. Therefore, non-invasive samples provide the same genotyping results as minimally invasive and invasive samples of the same individuals. Furthermore, this identification method that uses genomic DNA from exuviae can be used for early screening of positive genome-edited individuals in each generation for adult crossing. In our study, the non-invasive identification method was not only simpler and provided results earlier than existing methods, but also had a better reproducibility and accuracy. This non-invasive identification approach using genomic DNA from exuviae can be adapted to meet the growing demand for genetic analysis and will find wide application in insect genome editing research.

SIRT1 Protects Dopaminergic Neurons in Parkinson's Disease Models via PGC-1α-Mediated Mitochondrial Biogenesis.

SIRT1 is a deacetylase with multiple physiological functions by targeting histones and non-histone proteins. It has been shown that SIRT1 activation is involved in neuroprotection in Parkinson's disease (PD) models. In the present study, we provided direct evidences showing the neuroprotective roles of SIRT1 in dopaminergic neurons. Our data showed that increased expression of SIRT1 plays beneficial roles against MPP+ insults in SH-SY5Y cells and primary dopaminergic neurons, including increased cell viability, reduced LDH release, improved the mitochondrial membrane potential (MMP), and attenuated cell apoptosis. On the contrary, knockdown of SIRT1 further aggravated cell injuries induced by MPP+. Moreover, mutated SIRT1 without deacetylase activity (SIRT1 H363Y) failed to protect dopaminergic neurons from MPP+ injuries. Mechanistically, SIRT1 improved PGC-1α expression and mitochondrial biogenesis. Knockdown of PGC-1α almost completely abolished the neuroprotective roles of SIRT1 in SH-SY5Y cells. Collectively, our data indicate that SIRT1 has neuroprotective roles in dopaminergic neurons, which is dependent upon PGC-1α-mediated mitochondrial biogenesis. These findings suggest that SIRT1 may hold great therapeutic potentials for treating dopaminergic neuron loss associated disorders such as PD.

Acetylation of NDUFV1 induced by a newly synthesized HDAC6 inhibitor HGC rescues dopaminergic neuron loss in Parkinson models.

It has been shown that histone deacetylase (HDAC) inhibitors hold considerable therapeutic potentials for treating neurodegeneration-related diseases including Parkinson disease (PD). Here, we synthesized an HDAC inhibitor named as HGC and examined its neuroprotective roles in PD models. Our results showed that HGC protects dopaminergic neurons from 1-methyl-4-phenylpyridinium (MPP+)-induced insults. Furthermore, in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD model mice, HGC application rectifies behavioral defects, improves tyrosine hydroxylase-positive neurons in the midbrain, and maintains mitochondrial integrity and functions. Mechanistically, mass spectrometry data revealed that HGC stimulates acetylation modification at lysine 28 of NDUFV1. Inhibition of HDAC6 by HGC is responsible for this acetylation modification. Functional tests showed that, as well as HGC, NDUFV1 exhibits beneficial roles against MPP+ injuries. Moreover, knockdown of NDUFV1 abolishes the neuroprotective roles of HGC. Taken together, our data indicate that HGC has a great therapeutic potential for treating PD and NDUFV1 might be a target for developing drugs against PD.