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Abstract Background and aim Depression in Parkinson’s disease (DPD) has a high incidence rate among patients with Parkinson’s disease (PD). It is a common nonmotor symptom of PD that seriously affects the quality of life of patients. Thus, improving DPD is important for improving the quality of life of patients. Psychotherapy for depression is limited for many reasons, and only a few patients are able to benefit from this therapy. Several studies have demonstrated that relaxation therapy, playing, and exercise therapy are effective treatments for depression. In recent years, virtual reality (VR) has rapidly developed as a form of rehabilitation due to its immersive characteristics and accessibility. It has also been applied in the psychological treatment of phobia and anxiety. However, no relevant research on the treatment of DPD has been conducted using VR. This study aims to assess the effects of immersive VR-assisted training on patients with DPD. Methods This single-blind randomized controlled trial will recruit 74 patients with DPD. The patients will then be randomly allocated into two groups. The patients in the VR group (n = 37) will receive VR-assisted training (40 min) three times a week for 8 weeks. The patients in the non-VR training group (n = 37) will receive treatment as usual. The outcome measures will be assessed before intervention, and after 8 weeks, 3 months, and 6 months of the intervention. The primary outcomes will include the Hamilton Depression Scale-24. The secondary outcomes will include the 36-Item Short-Form Health Survey questionnaire, neuroinflammation factors (brain-derived neurotrophic factor, interleukin-6, and C-reactive protein), and functional magnetic resonance imaging. Discussion The traditional treatment of depression has limited resources and requires a lot of time and energy. It is not suitable for patients with PD having mobility difficulties and residing in remote areas. VR can make up for limitations in traditional treatment methods. An advantage of VR is that it makes patients more invested in active participation. This study may provide an improved method for the clinical treatment of patients with DPD, which is suitable for clinical decision-making and future practice. Trial registration The study has been registered in the Chinese Clinical Trial Registry ChiCTR2200065843, November 16, 2022. https://www.chictr.org.cn/showproj.html?proj=174551 {2a and 2b}

BackgroundConstitution is a valuable part of traditional Chinese medicine theory; it is defined as the internal foundation for the occurrence, development, transformation and outcome of diseases, and has its characteristic gut microbiota. Previous study showed that deficiency constitution was related to lower Hb counts. However, no research has examined how alterations in the gut microbiome induced by deficiency constitution may increase the tendency for anemia.MethodsWe used a multiomics strategy to identify and quantify taxonomies and compounds found under deficient constitution individuals and further explore the possible pathological factors that affect red blood cell indices.Results① People with deficient constitution showed lower hemoglobin (Hb), more Firmicutes, less Bacteroidetes, and higher α diversity. ② We identified Escherichia coli, Clostridium bolteae, Ruminococcus gnavus, Streptococcus parasanguinis and Flavonifractor plautii as potential biomarkers of deficient constitution. ③ Slackia piriformis, Clostridium_sp_L2_50 and Bacteroides plebeius were enriched in balanced-constitution individuals, and Parabacteroides goldsteinii was the key bacterial marker of balanced constitution. ④ Flavonifractor plautii may be a protective factor against the tendency for anemia among deficient individuals. ⑤ Ruminococcus gnavus may be the shared microbe base of deficiency constitution-related the tendency for anemia. ⑥ The microorganism abundance of the anaerobic phenotype was lower in deficient constitution group. ⑦ Alterations in the microbiome of deficient-constitution individuals were associated with worse health status and a greater risk of anemia, involving intestinal barrier function, metabolism and immune responses, regulated by short-chain fatty acids and bile acid production.ConclusionThe composition of the gut microbiome was altered in people with deficient constitution, which may explain their poor health status and tendency toward anemia.

Abstract The development of dietary fibers as safe and effective food additives or nutrients for preventing and alleviating inflammatory bowel disease (IBD) is increasingly important. β‐glucans, renowned prebiotics, have shown promise in alleviating IBD symptoms by modulating gut flora diversity and repairing the intestinal barrier. Auricularia auricula‐judae, an edible fungus, contains a β‐glucan with a triple‐helical structure polysaccharide from black fungus Auricularia auricula‐judae (BFP), which exhibits unique sol–gel properties. This study revealed that BFP forms weak gels or sols at increasing concentrations, enhancing swallow ability and extending intestinal transit time, beneficial for patients with dysphagia requiring targeted intestinal administration. The impact of BFP on dextran sulfate sodium (DSS)‐induced ulcerative colitis was examined, showing that BFP sols maintain intestinal barrier integrity by up‐regulating MUC2, ZO‐1, Occludin, and Claudin expressions and reducing inflammatory factors. Furthermore, BFP sols augmented probiotics abundance, decreased harmful bacteria, and restored Bacteroidetes/Firmicutes balance. These findings suggest BFP sols’ potential as functional food or alternative IBD treatment.

Abstract The E3 ligase-degron interaction determines the specificity of the ubiquitin‒proteasome system. We recently discovered that FEM1B, a substrate receptor of Cullin 2-RING ligase (CRL2), recognizes C-degrons containing a C-terminal proline. By solving several cryo-EM structures of CRL2FEM1B bound to different C-degrons, we elucidate the dimeric assembly of the complex. Furthermore, we reveal distinct dimerization states of unmodified and neddylated CRL2FEM1B to uncover the NEDD8-mediated activation mechanism of CRL2FEM1B. Our research also indicates that, FEM1B utilizes a bipartite mechanism to recognize both the C-terminal proline and an upstream aromatic residue within the substrate. These structural findings, complemented by in vitro ubiquitination and in vivo cell-based assays, demonstrate that CRL2FEM1B-mediated polyubiquitination and subsequent protein turnover depend on both FEM1B-degron interactions and the dimerization state of the E3 ligase complex. Overall, this study deepens our molecular understanding of how Cullin-RING E3 ligase substrate selection mediates protein turnover.

Differential synthetic aperture radar tomography (D-TomoSAR) uses multiple SAR acquisitions at different times to form an elevation-time 2-D synthetic aperture, enabling recovery of the target's 3-D structure and deformation velocity. However, the imaging performance of D-TomoSAR is influenced by the spatial-temporal baseline distribution, which is one of the crucial factors. Due to the difference in orbit altitude, the effects of various perturbation forces on geosynchronous SAR (GEO SAR) are significantly different from those on low Earth orbit SAR (LEO SAR), leading to different geometries in the spatial-temporal baseline distributions of GEO SAR and LEO SAR in the repeat-pass acquisitions. The spatial-temporal baseline distribution of LEO SAR is random, while that of GEO SAR is coupled. Although GEO SAR obtains a large number of acquisitions due to the short repeat-pass time, using data under all spatial-temporal baselines for D-TomoSAR does not necessarily provide the best imaging results. Therefore, how to select spatial-temporal baselines that can improve the estimation accuracy is important. In this article, the Cramér–Rao lower bound of GEO D-TomoSAR estimation accuracy is determined by considering multiple factors, including baseline decorrelation and spatial-temporal coupling. The optimal spatial-temporal baseline selection is modeled as a multiobjective problem and solved by the Nondominated Sorting Genetic Algorithm II (NSGA-II). Given the absence of in-orbit GEO SAR and the orbital similarity between GEO SAR and BeiDou Inclined Geosynchronous Orbit (IGSO) satellite, the real ephemeris of BeiDou IGSO satellite is used to simulate the baseline distribution of GEO SAR and verify the baseline optimization method.

Geosynchronous synthetic aperture radar (GEO SAR) has the advantages of a short revisit time and a large beam footprint. Enhancing spatial resolution has become a hotspot in spaceborne SAR research areas. The existing designs of GEO SAR suffer from the problem of poor resolution (greater than 10 m) and cause low-precision observation in urban areas. First time, this article points out that GEO SAR has the ability to improve the two-dimensional (2-D) resolution of SAR images by spatial spectrum synthesis based on 2-D baselines, and proposes models and a signal processing method involved in GEO SAR spectrum synthesis. The 2-D spatial baselines of GEO SAR are analyzed and evaluated first based on satellite software and real ephemeris from Beidou Inclined Geosynchronous Orbit (IGSO) navigation satellites to demonstrate the potential of 2-D resolution improvement. Then the analytical models of the spectral shape and relative spectral shift between GEO SAR images are derived. Furthermore, a 2-D spectrum synthesis algorithm suitable for GEO SAR is also proposed, where we use deramping operation instead of the traditional spectrum shifting process. Nonideal factors are considered in the processing of synthesized. In addition, performances of the proposed algorithm, including the resolution improvement factor, the amplitude fluctuation, and the critical baseline, are constructed. Finally, computer simulations and equivalent experiments based on Beidou IGSO navigation satellites verify the proposed algorithm.

The improvement of mitochondrial function is described as a strategy for alleviating oxidative stress and intervening in the aging process. 2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG) is one of the major bioactive components isolated from Polygonum multiflorum Thunb, and it exhibits multiple activities, including antioxidant and anti-inflammatory effects. In this study, we found that 200 μM TSG significantly extended the mean lifespan of Caenorhabditis elegans by 16.48% and improved health status by delaying age-associated physiological decline in worms. The longevity prolongation effect of TSG depended on the regulation of the mitochondrial quality control process mediated by DAF-16/FOXO, SKN-1/Nrf2 and SIR-2.1/SIRT1 to improve mitochondrial function. Moreover, TSG treatment obviously alleviated the proteotoxicity of β-amyloid and tau proteins in worms. Our findings indicated that TSG is a promising natural product for preventing aging and treating aging-associated neurodegenerative diseases by regulating the mitochondrial quality control process to improve mitochondrial function.

Considering that the precise delivery of Celastrol (Cst) into mitochondria to induce mitochondrial dysfunction may be a potential approach to improve the therapeutic outcomes of Cst on TNBC, a novel tumor mitochondria dual-targeted mixed-micelle nano-system was fabricated via self-synthesized triphenylphosphonium-modified cholesterol (TPP-Chol) and hyaluronic acid (HA)-modified cholesterol (HA-Chol). The Cst-loaded mixed micelles (Cst@HA/TPP-M) exhibited the characteristics of a small particle size, negative surface potential, high drug loading of up to 22.8%, and sustained drug release behavior. Compared to Cst-loaded micelles assembled only by TPP-Chol (Cst@TPP-M), Cst@HA/TPP-M decreased the hemolysis rate and upgraded the in vivo stability and safety. In addition, a series of cell experiments using the triple-negative breast cancer cell line MDA-MB-231 as a cell model proved that Cst@HA/TPP-M effectively increased the cellular uptake of the drug through CD44-receptors-mediated endocytosis, and the uptake amount was three times that of the free Cst group. The confocal results demonstrated successful endo-lysosomal escape and effective mitochondrial transport triggered by the charge converse of Cst@HA/TPP-M after HA degradation in endo-lysosomes. Compared to the free Cst group, Cst@HA/TPP-M significantly elevated the ROS levels, reduced the mitochondrial membrane potential, and promoted tumor cell apoptosis, showing a better induction effect on mitochondrial dysfunction. In vivo imaging and antitumor experiments based on MDA-MB-231-tumor-bearing nude mice showed that Cst@HA/TPP-M facilitated drug enrichment at the tumor site, attenuated drug systemic distribution, and polished up the antitumor efficacy of Cst compared with free Cst. In general, as a target drug delivery system, mixed micelles co-constructed by TPP-Chol and HA-Chol might provide a promising strategy to ameliorate the therapeutic outcomes of Cst on TNBC.

Using data from three automatic weather stations (LGB69, Eagle and Dome A) from distinctly different climatological zones along the CHINARE (Chinese National Antarctic Research Expedition) traverse route from Zhongshan Station to Dome A, we investigated the characteristics of meteorological conditions and subsurface heat conduction. Spatial analysis indicated decreasing trends in air temperature, relative humidity and wind speed from the coastal katabatic wind zone to the inland plateau region, and air temperatures clearly showed a strong daily variability in winter, suggesting the effect from the fluctuation in the Antarctic atmospheric system. We also analyzed the optimal response time of the 1 and 3 m depth snow temperatures to the 0.1 m depth snow temperature for each site under clear/overcast and day/night situations. This showed an important enhancement to the heat transfer from shortwave radiation penetration. Using an iterative optimization method, we estimated the subsurface heat conduction variations along the transect. This was ~3–5 W m–2. Multiple maxima in daily mean subsurface fluxes were found in winter, with a typical value above 2 W m–2, while a single minimum value under –2 W m–2 was found in summer. On an annual scale, a larger mean loss of subsurface heat conduction was observed in the inland plateau compared to in the coastal katabatic area. Finally, we discussed the possible influences of turbulent and radiant transport on the vertical heat response and confirmed the wind enhancement on the growth of thermal conductivity. This preliminary study provides a brief perspective and an important reference for studying subsurface heat conduction in inland areas of Antarctica.

ObjectiveEvidence on the individual and combined relationship of physical activity (PA) and fish oil supplement use on the incidence of Parkinson’s disease (PD) risk remains lacking.Materials and methodsThis UK population-based prospective cohort study, involving 385,275 UK Biobank participants, collected PA and fish oil supplement data via touchscreen questionnaires. Using Cox proportional hazards models and restricted cubic splines to examined the associations between use of fish oil supplements, PA and PD risk.ResultsDuring a median 12.52-year follow-up, 2,131 participants incident PD. Analysis showed that fish oil supplement users had a lower PD risk [hazard ratio (HR), 0.89; 95% confidence interval (CI), 0.82–0.98]. The adjusted HRs for the PD incidence were 0.96 (95% CI, 0.95–0.98) for total PA; 0.93 (95% CI, 0.90–0.96) for moderate PA; 0.95 (95% CI, 0.91–0.99) for vigorous PA and 0.93 (95% CI, 0.89–0.98) for walking activity. Significant interactions were found between fish oil supplement use and total PA (P for interaction = 0.011), moderate PA (P for interaction = 0.015), and walking activity (P for interaction = 0.029) in relation to PD incidence.ConclusionBoth fish oil supplement use and PA were associated with a reduced risk of PD, and the effect of PA in reducing the risk of PD was more pronounced when fish oil supplement was used.

AbstractIn order to precisely deliver celastrol into mitochondria of tumor cells, improve antitumor efficacy of celastrol and overcome its troublesome problems in clinical application, a novel multistage-targeted celastrol delivery system (C-TL/HA) was developed via electrostatic binding of hyaluronic acid (HA) to celastrol-loaded cationic liposomes composed of natural soybean phosphatidylcholine and cholesterol modified with mitochondrial targeting molecular TPP. Study results in this article showed that C-TL/HA successfully transported celastrol into mitochondria, effectively activated apoptosis of mitochondrial pathway, exerted higher tumor inhibition efficiency and lower toxic side effects compared with free celastrol. More importantly, HA coating not only enabled this delivery system to have good stability and safety in vivo, but also increased drug uptake and facilitated tumor targeting through recognizing CD44 receptors rich on the surface of tumor cells. Conclusively, this HA-coated mitochondrial targeting liposomes may provide a prospect for the clinical application of celastrol in tumor therapy.

In winter and spring, for greenhouses with larger areas and stereoscopic cultivation, distributed light environment regulation based on photosynthetic rate prediction model can better ensure good crop growth. In this paper, strawberries at flowering-fruit stage were used as the test crop, and the LI-6800 portable photosynthesis system was used to control the leaf chamber environment and obtain sample data by nested photosynthetic rate combination experiments under temperature, light and CO2 concentration conditions to study the photosynthetic rate prediction model construction method. For a small-sample, nonlinear real experimental data set validated by grey relational analysis, a photosynthetic rate prediction model was developed based on Support vector regression (SVR), and the particle swarm algorithm (PSO) was used to search the influence of the empirical values of parameters, such as the penalty parameter C, accuracy ε and kernel constant g, on the model prediction performance. The modeling and prediction results show that the PSO-SVR method outperforms the commonly used algorithms such as MLR, BP, SVR and RF in terms of prediction performance and generalization on a small sample data set. The research in this paper achieves accurate prediction of photosynthetic rate of strawberry and lays the foundation for subsequent distributed regulation of greenhouse strawberry light environment.

Abstract Prolonged activation of nuclear factor (NF)-кB signaling significantly contributes to the development of colorectal cancer (CRC). New therapeutic opportunities are emerging from targeting this distorted cell signaling transduction. Here, we discovered the critical role of RING finger 138 (RNF138) in CRC tumorigenesis through regulating the NF-кB signaling, which is independent of its Ubiquitin-E3 ligase activity involved in DNA damage response. RNF138−/− mice were hyper-susceptible to the switch from colitis to aggressive malignancy, which coincided with sustained aberrant NF-кB signaling in the colonic cells. Furthermore, RNF138 suppresses the activation of NF-кB signaling pathway through preventing the translocation of NIK and IKK-Beta Binding Protein (NIBP) to the cytoplasm, which requires the ubiquitin interaction motif (UIM) domain. More importantly, we uncovered a significant correlation between poor prognosis and the downregulation of RNF138 associated with reinforced NF-кB signaling in clinical settings, raising the possibility of RNF138 dysregulation as an indicator for the therapeutic intervention targeting NF-кB signaling. Using the xenograft models built upon either RNF138-dificient CRC cells or the cells derived from the RNF138-dysregulated CRC patients, we demonstrated that the inhibition of NF-кB signaling effectively hampered tumor growth. Overall, our work defined the pathogenic role of aberrant NF-кB signaling due to RNF138 downregulation in the cascade events from the colitis switch to colonic neoplastic transformation and progression, and also highlights the possibility of targeting the NF-кB signaling in treating specific subtypes of CRC indicated by RNF138-ablation.

Polygonum cuspidatum (PC) extract has been listed in the “Catalog of Used Cosmetic Ingredients (2021 Edition)”, which can inhibit melanogenesis, thus exerting a whitening effect, and has been widely used in cosmetics. However, there are currently no quality standards for PC extract used in cosmetics, and the bioactive components associated with anti-melanogenesis remain unclear. In view of this, the present study was the first to investigate the spectrum-effect relationship between fingerprints of PC extract and melanogenesis inhibition. Ten batches of PC extract fingerprints were established by HPLC. Pearson’s correlation analysis, gray correlation analysis (GRA) and orthogonal partial least squares regression analysis (OPLSR) were used to screen out resveratrol, emodin and physcion as the main whitening active ingredients using the inhibition of tyrosinase in B16F10 cells as the pharmacological index. Then, the melanogenesis inhibitory effects of the above three components were verified by tyrosinase inhibition and a melanin content assay in B16F10 cells. The interaction between small molecules and proteins was investigated by the molecular docking method, and it was confirmed by quantitative real-time PCR (qRT-PCR) that resveratrol, emodin and physcion significantly down-regulated the transcript levels of melanogenesis-related factors. In conclusion, this study established a general model combining HPLC fingerprinting and melanogenesis inhibition and also analyzed the spectrum–effect relationship of PC extract, which provided theoretical support for the quality control of PC extract in whitening cosmetics.

As a prospective visible-light-responsive photochemical material, graphitic carbon nitride (g-C3N4) has become a burgeoning research hot topics and aroused a wide interest as a metal-free semiconductor in the area of energy utilization and conversion, environmental protection due to its unique properties, such as facile synthesis, high physicochemical stability, excellent electronic band structure, and sustainability. However, the shortcomings of high recombination rate of charge carriers, relatively low electrical conductivity and visible light absorption impede its practical application. Various strategies, such as surface photosensitization, heteroatom deposition, semiconductor hybridization, etc., have been applied to overcome the barriers. Among all the strategies, functional nanocarbon materials with various dimensions (0D∼3D) attract much attention as modifiers of g-C3N4 due to their unique electronic properties, optical properties, and easy functionalization. More importantly, the properties of these functional nanocarbon materials can be tuned by various dimensions and thus there will be a way to overcome the defects of g-C3N4 by choosing different dimensional carbon materials. Distinguishing from some present reviews, this review starts with the fundamental physicochemical characteristics of g-C3N4 materials, followed by analyzing the advantages of functional nanocarbon materials modifying g-C3N4. Then, we present a systematic introduction to various dimensional carbon materials.The design philosophy of carbon/g-C3N4 composites and the advanced studies are exemplified in detail. Finally, a nichetargeting summary and outlook on the major challenges, opportunities for future research in high-powered carbon/g-C3N4 composites was proposed.

Background. The coronary artery calcium score (CACS) is commonly employed to quantify the degree of calcification in coronary atherosclerosis. Indeed, increased coronary stenosis severity is associated with a progressive increase in CACS. Objectives. This study sought to explore the association between CACS and coronary stenosis of ≥50% and ≥70%. Methods. We conducted a retrospective analysis of patient data collected between July 1, 2017, and March 3, 2022, at Jiangmen Central Hospital. A total of 208 patients, presenting with both symptomatic and asymptomatic manifestations and suspected coronary artery disease (CAD), were included. Statistical analyses included ROC curve assessments, subgroup analyses based on age, and comparisons of CACS values against the presence of coronary stenosis ≥50% and ≥70%. Results. Ultimately, 208 patients were included, with a median age of 65.0 years and a median CACS of 115.7 (interquartile range: 13.7–369.4). A CACS threshold of ≥1300 demonstrated a specificity of 100% for coronary stenosis of ≥50%. Notably, the percentage of patients with obstructive CAD showing CACS = 0 was significantly higher in those under 65 years (15.1%) compared to patients over 65 years (3.8%) (P=0.005). The inflection point, at which the risk probability for coronary stenosis of ≥50% shifted from being a protective factor to a risk factor, was observed when CACS fell within the range of 63.3 to 66.0. Conclusion. CACS demonstrates good performance for the detection of coronary artery stenosis.

Abstract Hepatocellular carcinoma (HCC) is the sixth most common primary cancer with an unsatisfactory long-term survival. Gain of function mutations of PIK3CA occur in a subset of human HCC. Alpelisib, a selective PIK3CA inhibitor, has been approved by the FDA to treat PIK3CA mutant breast cancers. In this manuscript, we evaluated the therapeutic efficacy of alpelisib, either alone or in combination, for the treatment of HCC. We tested alpelisib in mouse HCC induced by hydrodynamic injection of c-Met/PIK3CA(H1047R) (c-Met/H1047R), c-Met/PIK3CA(E545K) (c-Met/E545K), and c-Met/sgPten gene combinations. Alpelisib slowed down the growth of c-Met/H1047R and c-Met/E545K HCC but was ineffective in c-Met/sgPten HCC. Mechanistically, alpelisib inhibited p-ERK and p-AKT in c-Met/H1047R and c-Met/E545K HCC progression but did not affect the mTOR pathway or genes involved in cell proliferation. In human HCC cell lines transfected with PIK3CA(H1047R), alpelisib synergized with the mTOR inhibitor MLN0128 or the CDK4/6 inhibitor palbociclib to suppress HCC cell growth. In c-Met/H1047R mice, alpelisib/MLN0128 or alpelisib/palbociclib combination therapy caused tumor regression. Our study demonstrates that alpelisib is effective for treating PIK3CA-mutated HCC by inhibiting MAPK and AKT cascades. Furthermore, combining alpelisib with mTOR or CDK4/6 inhibitors has a synergistic efficacy against PIK3CA-mutated HCC, providing novel opportunities for precision medicine against HCC.

Alkaline pH can induce triacylglyceride accumulation in microalgae, however its molecular mechanism remains elusive. Here, we investigated the effect of 2-[N-cyclohexylamino]-ethane-sulfonic acid (CHES) -induced intracellular alkalization on the lipid production in Phaeodactylum tricornutum. Intracellular pH was increased upon CHES treatment, displaying a high BCECF fluorescence ratio. CHES treatment significantly induced lipid accumulation but had no change in cell density and biomass. The expression of genes involved in photoreaction, carbon fixation, glycolysis, pentose phosphate pathway, amino acid catabolism, GS/GOGAT cycle, TCA cycle, triacylglyceride assembly, de novo fatty acid synthesis were up-regulated, while that in amino acid biosynthesis were down-regulated under CHES conditions. Correspondingly, the activity of phosphoribulokinase, carbonic anhydrase, pyruvate dehydrogenase and acetaldehyde dehydrogenase were enhanced by CHES treatment. Chloroplast-specific biological processes were activated by CHES treatment in P. tricornutum, which redirects the flux of carbon into lipid biosynthesis, meanwhile stimulates de novo fatty acid biosynthesis, leading to lipid accumulation under CHES conditions. These indicate an enhancement of intermediate metabolism, resulting in lipid accumulation by CHES.

Sec-O-glucosylhamaudol (SOG), an active flavonoid compound derived from the root of Saposhnikovia divaricata (Turcz. ex Ledeb.) Schischk., exhibits analgesic, anti-inflammatory, and high 5-lipoxygenase (5-LO) inhibitory effects. However, its effect on osteoclastogenesis was unclear. We demonstrated that SOG markedly attenuated RANKL-induced osteoclast formation, F-actin ring formation, and mineral resorption by reducing the induction of key transcription factors NFATc1, c-Fos, and their target genes such as TRAP, CTSK, and DC-STAMP during osteoclastogenesis. Western blotting showed that SOG significantly inhibited the phosphorylation of AKT and GSK3β at the middle–late stage of osteoclastogenesis without altering calcineurin catalytic subunit protein phosphatase-2β-Aα expression. Moreover, GSK3β inhibitor SB415286 partially reversed SOG-induced inhibition of osteoclastogenesis, suggesting that SOG inhibits RANKL-induced osteoclastogenesis by activating GSK3β, at least in part. 5-LO gene silencing by small interfering RNA in mouse bone marrow macrophages markedly reduced RANKL-induced osteoclastogenesis by inhibiting NFATc1. However, it did not affect the phosphorylation of AKT or GSK3β, indicating that SOG exerts its inhibitory effects on osteoclastogenesis by suppressing both the independent 5-LO pathway and AKT-mediated GSK3β inactivation. In support of this, SOG significantly improved bone destruction in a lipopolysaccharide-induced mouse model of bone loss. Taken together, these results suggest a potential therapeutic effect for SOG on osteoclast-related bone lysis disease.

Background: An unprecedented coronavirus disease 2019 (COVID-19) wave occurred in China between December 2022 and January 2023, challenging the efficacy of the primary series of COVID-19 vaccines. The attitudes toward future COVID-19 booster vaccines (CBV) after the massive breakthrough infection among healthcare workers remain unknown. This study aimed to explore the prevalence and determinants of future CBV refusal after the unprecedented COVID-19 wave among healthcare workers. Methods: Between 9 and 19 February 2023, a cross-sectional nationwide online survey was conducted using a self-administered questionnaire vaccine among healthcare workers in China. Sociodemographics, profession, presence of chronic medical conditions, previous COVID-19 infection, attitudes towards future CBV, and reasons for future CBV refusal were collected. We estimated odds ratio [OR] with 95% confidence interval [CI] using a multivariable logistic regression model to explore the factors associated with future CBV refusal. Results: Among the 1618 participants who completed the survey, 1511 respondents with two or more doses of COVID-19 vaccines were analyzed. A total of 648 (41.8%) of respondents were unwilling to receive a future CBV. Multivariable logistic regression analysis revealed the association of CBV refusal with profession (vs. other staff, physician-adjusted OR 1.17, 95%CI 0.79–1.72, nurse-adjusted OR 1.88, 95%CI 1.24−2.85, p = 0.008), history of allergy (adjusted OR 1.72, 95%CI 1.05–2.83, p = 0.032), a lower self-perceived risk of future COVID-19 infection (p < 0.001), and a lower belief in CBV effectiveness (p = 0.014), safety (p < 0.001), and necessities for healthcare workers and the public (p < 0.001, respectively). Conclusions: Our findings highlight that a considerable proportion of healthcare workers were against a future booster dose after an unprecedented COVID-19 wave. Self-perception of future COVID-19 risk, and potential harm or doubtful efficacy of vaccines are the main determinants. Our findings may help public health authorities to establish future COVID-19 vaccination programs.

To improve the fresh-keeping of highly perishable fruits with high commercial value, a novel starch-based foam packaging material was developed in this study. The foam incorporated the antiseptic ingredient Na2S2O5, which chemically interacted with environmental moisture to release SO2 as an antifungal agent. Scanning electron microscopy (SEM), moisture absorption and mechanical measurements were used to characterize the unique sandwich-like inner structure of the foam which allowed for the modulable release of SO2. The starch-based foam exhibited sufficient resilience (~100%) to provide ideal cushioning to prevent physical damage to fresh fruits during transportation. When 25 g/m2 of Na2S2O5 was applied, the foam stably released over 100 ppm SO2 and demonstrated satisfactory antifungal performance (inhibition over 60%) in terms of maintaining the appearance and nutritional values (such as soluble solids 14 vs. 11%, total acidity 0.45 vs. 0.30%, and Vitamin C 3.4 vs. 2.5 mg/100 g) of fresh grapes during a 21 day storage period. Additionally, the residual SO2 (14 mg/kg) also meets the safety limits (

Laccase immobilization is a promising method that can be used for the recyclable treatment of refractory phenolic pollutants (e.g., chlorophenols) under mild conditions, but the method is still hindered by the trade-off limits of supports in terms of their high specific surface area and rich functional groups. Herein, confined polymerization was applied to create abundant amino-functionalized polymeric ionic liquids (PILs) featuring a highly specific surface area and mesoporous structure for chemically immobilizing laccase. Benefiting from this strategy, the specific surface area of the as-synthesized PILs was significantly increased by 60-fold, from 5 to 302 m2/g. Further, a maximum activity recovery of 82% towards laccase was recorded. The tolerance and circulation of the immobilized laccase under harsh operating conditions were significantly improved, and the immobilized laccase retained more than 84% of its initial activity after 15 days. After 10 cycles, the immobilized laccase was still able to maintain 80% of its activity. Compared with the free laccase, the immobilized laccase exhibited enhanced stability in the biodegradation of 2,4-dichlorophenol (2,4-DCP), recording around 80% (seven cycles) efficiency. It is proposed that the synergistic effect between PILs and laccase plays an important role in the enhancement of stability and activity in phenolic pollutant degradation. This work provides a strategy for the development of synthetic methods for PILs and the improvement of immobilized laccase stability.

Glyphosate-resistant crops developed by the CP4-EPSPS gene from Agrobacterium have been planted on a massive scale globally, which benefits from the high efficiency and broad spectrum of glyphosate in weed control. Some glyphosate-resistant (GR) genes from microbes have been reported, which might raise biosafety concerns. Most of them were obtained through a hygromycin-HPT transformation system. Here we reported the plant source with 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene from goosegrass endowed rice with high resistance to glyphosate. The integrations and inheritability of the transgenes in the rice genome were investigated within two generations. The EiEPSPS transgenic plants displayed similar growth and development to wild type under no glyphosate selection pressure but better reproductive performance under lower glyphosate selection pressure. Furthermore, we reconstructed a binary vector pCEiEPSPS and established the whole stage glyphosate selection using the vector. The Glyphosate-pCEiEPSPS selection system showed a significantly higher transformation efficiency compared with the hygromycin-HPT transformation system. Our results provided a promising alternative gene resource to the development of GR plants and also extended the plant transformation toolbox.

Abstract Background Corneal biomechanical properties are important for the diagnosis of corneal diseases, individualized design and prognosis of corneal surgery. Clinical available devices such as Ocular Response Analyzer (ORA) and Corneal Visualization Scheimpflug Technology (Corvis ST) can provide corneal biomechanics related parameters, while corneal elastic modulus cannot be extracted directly from them at present. The aim of this study is to suggest a method to determine corneal elastic modulus based on the results of Corvis ST test according to Reissner’s theory on the relation between stress and small displacement in shallow spherical shell. Results Five rabbits (10 eyes) and 10 healthy humans (20 eyes) were measured with Corvis ST to obtain the normal range of corneal elastic modulus. Results showed Corneal elastic modulus of rabbit was 0.16 MPa to 0.35 MPa, human corneal elastic modulus was 0.16–0.30 MPa. Rabbit corneas were also measured at different intraocular pressures (IOP), and results showed corneal elastic modulus, first applanation time (A1T) and stiffness parameter (SP-A1) were positively correlated with IOP. Deformation amplitude (DA), the second applanations time (A2T), and peak distance (PD) were negatively correlated with IOP. Finite element method was used to simulate the Corvis measurements according to the calculated elastic modulus and the simulated corneal apical displacements were agreement with experimental results in general. Conclusions The method to determine corneal elastic modulus based on Corvis test according to the relationship between force and displacements of shallow spherical shell is convenient and effective.

‘Don't eat me’ signal of CD47 is activated via its interaction with SIRPα protein on myeloid cells, especially phagocytic cells, and prevents malignant cells from anti-tumor immunity in which pyroglutamate modification of CD47 by glutaminyl-peptide cyclotransferase-like protein (isoQC) takes an important part evidenced by our previous report that isoQC is an essential regulator for CD47-SIRPα axis with a strong inhibition on macrophage-mediated phagoctyosis. Therefore, we screened for potential isoQC inhibitors by fluorescence-activated cell sorting assay and identified luteolin as a potent compound that blocked the pyroglutamation of CD47 by isoQC. We further demonstrated that luteolin directly bound to isoQC using pull-down assay and isothermal calorimetric (ITC) assay. In consistency, we showed that luteolin markedly abrogated the cell-surface interaction between CD47 and SIRPα in multiple myeloma H929 cells and consequently promoted the macrophage-mediated phagocytosis. Collectively, our study discovered a promising lead compound targeting isoQC, luteolin, which functions distinctly from current CD47 antibody-based drugs and therefore may potentially overcome the clinical side effects associated with CD47 antibody treatment-induced anemia.

Facile construction of functional nanomaterials with laccase-like activity is important in sustainable chemistry since laccase is featured as an efficient and promising catalyst especially for phenolic degradation but still has the challenges of high cost, low activity, poor stability and unsatisfied recyclability. In this paper, we report a simple method to synthesize nanozymes with enhanced laccase-like activity by the self-assembly of copper ions with various imidazole derivatives. In the case of 1-methylimidazole as the ligand, the as-synthesized nanozyme (denoted as Cu-MIM) has the highest yield and best activity among the nanozymes prepared. Compared to laccase, the Km of Cu-MIM nanozyme to phenol is much lower, and the vmax is 6.8 times higher. In addition, Cu-MIM maintains excellent stability in a variety of harsh environments, such as high pH, high temperature, high salt concentration, organic solvents and long-term storage. Based on the Cu-MIM nanozyme, we established a method for quantitatively detecting phenol concentration through a smartphone, which is believed to have important applications in environmental protection, pollutant detection and other fields.

Abstract Fiber microactuators are interesting in wide variety of emerging fields, including artificial muscles, biosensors, and wearable devices. In the present study, a robust, fast‐responsive, and humidity‐induced silk fiber microactuator is developed by integrating force‐reeling and yarn‐spinning techniques. The shape gradient, together with hierarchical rough surface, allows these silk fiber microactuators to respond rapidly to humidity. The silk fiber microactuator can reach maximum rotation speed of 6179.3° s−1 in 4.8 s. Such a response speed (1030 rotations per minute) is comparable with the most advanced microactuators. Moreover, this microactuator generates 2.1 W kg−1 of average actuation power, which is twice higher than fiber actuators constructed by cocoon silks. The actuating powers of silk fiber microactuators can be precisely programmed by controlling the number of fibers used. Lastly, theory predicts the observed performance merits of silk fiber microactuators toward inspiring the rational design of water‐induced microactuators.

BackgroundMetformin plays an important role in diabetes treatment. Studies have shown that the combined use of oral hypoglycemic medications is more effective than metformin monotherapy. In this double-blind, randomized, placebo-controlled, multicenter trial, we evaluated whether Jinlida, a Chinese herbal medicine, enhances the glycemic control of metformin in type 2 diabetes patients whose HbA1c was ineffectively controlled with metformin alone.MethodsA total of 186 diabetes patients were enrolled in this double-Blind, randomized, placebo-controlled, multicenter trial. Subjects were randomly allocated to receive either Jinlida (9 g) or the placebo TID for 12 consecutive weeks. All subjects in both groups also continuously received their metformin without any dose change. During this 12-week period, the HbA1c, FPG, 2 h PG, body weight, BMI were assessed. HOMA insulin resistance (HOMA-IR) and β-cell function (HOMA-β) were also evaluated.ResultsAt week 12, compared to the HbA1c level from week 0, the level of the Jinlida group was reduced by 0.92 ± 1.09% and that of the placebo group was reduced by 0.53 ± 0.94%. The 95% CI was 0.69-1.14 for the Jinlida group vs. 0.34-0.72 for the placebo group. There was a very significant HbA1c reduction between the two groups after 12 weeks (p < 0.01). Both FG and 2 h PG levels of the Jinlida group and placebo group were reduced from week 0. There were a very significant FG and 2 h PG level reductions between the two groups after 12 weeks (both p < 0.01). The Jinlida group also showed improved β-cell function with a HOMA-β increase (p < 0.05). No statistical significance was observed in the body weight and BMI changes. No serious adverse events were reported.ConclusionJinlida significantly enhanced the hypoglycemic action of metformin when the drug was used alone. This Chinese herbal medicine may have a clinical value as an add-on medication to metformin monotherapy.Trial registrationChinese Clinical Trial Register ChiCTR-TRC-13003159.