Novel approach to soft tissue regeneration: in vitro study of compound hyaluronic acid and horizontal platelet-rich fibrin combination.

OBJECTIVE: This study aims to develop a compound biomaterial to achieve effective soft tissue regeneration. METHODOLOGY: Compound hyaluronic acid (CHA) and liquid horizontal-platelet-rich fibrin (H-PRF) were mixed at a ratio of 1:1 to form a CHA-PRF gel. Human gingival fibroblasts (HGFs) were used in this study. The effect of CHA, H-PRF, and the CHA-PRF gel on cell viability was evaluated by CCK-8 assays. Then, the effect of CHA, H-PRF, and the CHA-PRF gel on collagen formation and deposition was evaluated by qRT‒PCR and immunofluorescence analysis. Finally, qRT‒PCR, immunofluorescence analysis, Transwell assays, and scratch wound-healing assays were performed to determine how CHA, H-PRF, and the CHA-PRF gel affect the migration of HGFs. RESULTS: The combination of CHA and H-PRF shortened the coagulation time of liquid H-PRF. Compared to the pure CHA and H-PRF group, the CHA-PRF group exhibited the highest cell proliferation at all time points, as shown by the CCK-8 assay. Col1a and FAK were expressed at the highest levels in the CHA-PRF group, as shown by qRT‒PCR. CHA and PRF could stimulate collagen formation and HGF migration, as observed by fluorescence microscopy analysis of COL1 and F-actin and Transwell and scratch healing assays. CONCLUSION: The CHA-PRF group exhibited greater potential to promote soft tissue regeneration by inducing cell proliferation, collagen synthesis, and migration in HGFs than the pure CHA or H-PRF group. CHA-PRF can serve as a great candidate for use alone or in combination with autografts in periodontal or peri-implant soft tissue regeneration.

Effects of extreme temperatures on public sentiment in 49 Chinese cities.

The rising sentiment challenges of the metropolitan residents may be attributed to the extreme temperatures. However, nationwide real-time empirical studies that examine this claim are rare. In this research, we construct a daily extreme temperature index and sentiment metric using geotagged posts on one of China's largest social media sites, Weibo, to verify this hypothesis. We find that extreme temperatures causally decrease individuals' sentiment, and extremely low temperature may decrease more than extremely high temperature. Heterogeneity analyses reveal that individuals living in high levels of PM2.5, existing new COVID-19 diagnoses and low-disposable income cities on workdays are more vulnerable to the impact of extreme temperatures on sentiment. More importantly, the results also demonstrate that the adverse effects of extremely low temperatures on sentiment are more minor for people living in northern cities with breezes. Finally, we estimate that with a one-standard increase of extremely high (low) temperature, the sentiment decreases by approximately 0.161 (0.272) units. Employing social media to monitor public sentiment can assist policymakers in developing data-driven and evidence-based policies to alleviate the adverse impacts of extreme temperatures.

A highly sensitive, long-time stable Ag/AgCl ultra-micro sensor for in situ monitoring chloride ions inside the crevice using SECM.

Tracking the variation of Cl- timely within the crevice is of great significance for comprehending the dynamic mechanism of crevice corrosion. The reported chloride ion selective electrodes are difficult to realize the long-time Cl- detection inside the confined crevice, due to their millimeter size or a relative limited lifespan. For this purpose, an Ag/AgCl ultra-micro sensor (UMS) with a radius of 12.5 µm was fabricated and optimized using laser drawing and electrodeposition techniques. Results show the AgCl film's structure is significantly impacted by the deposited current density, and further affects the linear response, life span and stability of Ag/AgCl UMS. The UMS prepared at current density of 0.1 mA/cm2 for 2 h shows a rapid response (several seconds), excellent stability and reproducibility, strong acid/alkali tolerance, sufficient linearity (R2 > 0.99), and long lifespan (86 days). Moreover, combined with the potentiometric mode of scanning electrochemical microscope (SECM), the Ag/AgCl UMS was successfully applied to monitor the in-situ radial Cl- concentration in micro-regions inside a 100 µm gap of stainless steel. The findings demonstrated that there was obvious radial difference in Cl- concentration inside the crevice, where the fastest rise in Cl- concentration was at the opening. The proposed method which combines the UMS with SECM has attractive practical applications for microzone Cl- monitoring in real time inside crevice. It may further promote the study of other localized corrosion mechanism and the development of microzone ions detection method.

ESCO2's oncogenic role in human tumors: a pan-cancer analysis and experimental validation.

PURPOSE: Establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) is involved in the mitotic S-phase adhesins acetylation and is responsible for bridging two sister chromatids. However, present ESCO2 cancer research is limited to a few cancers. No systematic pan-cancer analysis has been conducted to investigate its role in diagnosis, prognosis, and effector function. METHODS: We thoroughly examined the ESCO2 carcinogenesis in pan-cancer by combining public databases such as The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), UALCAN and Tumor Immune Single-cell Hub (TISCH). The analysis includes differential expression analysis, survival analysis, cellular effector function, gene mutation, single cell analysis, and tumor immune cell infiltration. Furthermore, we confirmed ESCO2's impacts on clear cell renal cell carcinoma (ccRCC) cells' proliferative and invasive capacities in vitro. RESULTS: In our study, 30 of 33 cancer types exhibited considerably greater levels of ESCO2 expression in tumor tissue using TCGA and GTEx databases, whereas acute myeloid leukemia (LAML) exhibited significantly lower levels. Kaplan-Meier survival analyses in adrenocortical carcinoma (ACC), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), brain lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), mesothelioma (MESO), and pancreatic adenocarcinoma (PAAD) demonstrated that tumor patients with high ESCO2 expression have short survival periods. However, in thymoma (THYM), colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ), ESCO2 was a favorable prognostic factor. Moreover, ESCO2 expression positively correlates with tumor stage and tumor size in several cancers, including LIHC, KIRC, KIRP and LUAD. Function analysis revealed that ESCO2 participates in mitosis, cell cycle, DNA damage repair, and other processes. CDK1 was identified as a downstream gene regulated by ESCO2. Furthermore, ESCO2 might also be implicated in immune cell infiltration. Finally, ESCO2'S knockdown significantly inhibited the A498 and T24 cells' proliferation, invasion, and migration. CONCLUSIONS: In conclusion, ESCO2 is a possible pan-cancer biomarker and oncogene that can reliably predict the prognosis of cancer patients. ESCO2 was also implicated in the cell cycle and proliferation regulation. In a nutshell, ESCO2 is a therapeutically viable and dependable target.

Molecular strategies of the pygmy grasshopper Eucriotettix oculatus adapting to long-term heavy metal pollution.

To study the heavy metal accumulation and its impact on insect exterior and chromosome morphology, and reveal the molecular mechanism of insects adapting to long-term heavy metal compound pollution habitats, this study, in the Diaojiang river basin, which has been polluted by heavy metals(HMs) for nearly a thousand years, two Eucriotettix oculatus populations was collected from mining and non-mining areas. It was found that the contents of 7 heavy metals (As, Cd, Pb, Zn, Cu, Sn, Sb) in E. oculatus of the mining area were higher than that in the non-mining 1-11 times. The analysis of morphology shows that the external morphology, the hind wing type and the chromosomal morphology of E. oculatus are significant differences between the two populations. Based on the heavy metal accumulation，morphological change, and stable population density, it is inferred that the mining area population has been affected by heavy metals and has adapted to the environment of heavy metals pollution. Then, by analyzing the transcriptome of the two populations, it was found that the digestion, immunity, excretion, endocrine, nerve, circulation, reproductive and other systems and lysosomes, endoplasmic reticulum and other cell structure-related gene expression were suppressed. This shows that the functions of the above-mentioned related systems of E. oculatus are inhibited by heavy metal stress. However, it has also been found that through the significant up-regulation of genes related to the above system, such as ATP2B, pepsin A, ubiquitin, AQP1, ACOX, ATPeV0A, SEC61A, CANX, ALDH7A1, DLD, aceE, Hsp40, and catalase, etc., and the down-regulation of MAPK signalling pathway genes, can enhanced nutrient absorption, improve energy metabolism, repair damaged cells and degrade abnormal proteins, maintain the stability of cells and systems, and resist heavy metal damage so that E. oculatus can adapt to the environment of heavy metal pollution for a long time.

[Effect of Biochar on NO3--N Transport in Loessial Soil and Its Simulation].

The objective of this study was to explore the effects of different amounts of biochar on the migration process and characteristics of NO3--N in loessial soil. In this study, six groups of mixed soil samples with biochar and loessial soil mass ratios of 0% (T0), 1% (T1), 2% (T2), 3% (T3), 4% (T4), and 5% (T5) were used as research objects. NO3--N was used as the tracer. Through the indoor soil column solute transport simulation tests, the effects of different biochar application amounts on the NO3--N transport process in loessial soil were simulated and studied. The results showed that the breakthrough curve of NO3--N in loessial soil shifted to the right with the increasing of biochar application, and the peak value gradually decreased. The initial penetration time, complete penetration time, and total penetration time increased with the increasing of biochar application amount. The total penetration time of NO3- in the T1, T2, T3, T4, and T5 treatments was 1.26, 2.31, 2.72, 3.22, and 3.57 times that of T0, respectively. The R2 was > 0.997 and RMSE was < 2.083 of the two-zone model (TRM). Compared with the convection-dispersion equation (CDE), the TRM model had higher fitting accuracy and could better simulate the NO3--N migration process in loessial soil after the application of different contents of biochar. The analysis of the fitting parameters of the TRM model showed that the average pore velocity, hydrodynamic dispersion coefficient, and water content ratio in the movable zone gradually decreased with the increasing of biochar application, whereas the dispersion and mass exchange coefficient showed an increasing trend. The results showed that biochar application could effectively enhance the ability of loessial soil to fix NO3--N, reduce the leakage of NO3--N to groundwater, and play an important role in maintaining soil fertility and preventing groundwater pollution.

Risk of cardiovascular death in patients with hepatocellular carcinoma based on the Fine-Gray model.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common types of cancers worldwide, ranking fifth among men and seventh among women, resulting in more than 7 million deaths annually. With the development of medical technology, the 5-year survival rate of HCC patients can be increased to 70%. However, HCC patients are often at increased risk of cardiovascular disease (CVD) death due to exposure to potentially cardiotoxic treatments compared with non-HCC patients. Moreover, CVD and cancer have become major disease burdens worldwide. Thus, further research is needed to lessen the risk of CVD death in HCC patient survivors. AIM: To determine the independent risk factors for CVD death in HCC patients and predict cardiovascular mortality (CVM) in HCC patients. METHODS: This study was conducted on the basis of the Surveillance, Epidemiology, and End Results database and included HCC patients with a diagnosis period from 2010 to 2015. The independent risk factors were identified using the Fine-Gray model. A nomograph was constructed to predict the CVM in HCC patients. The nomograph performance was measured using Harrell's concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve, and area under the ROC curve (AUC) value. Moreover, the net benefit was estimated via decision curve analysis (DCA). RESULTS: The study included 21545 HCC patients, of whom 619 died of CVD. Age (< 60) [1.981 (1.573-2.496), P < 0.001], marital status (married) [unmarried: 1.370 (1.076-1.745), P = 0.011], alpha fetoprotein (normal) [0.778 (0.640-0.946), P = 0.012], tumor size (≤ 2 cm) [(2, 5] cm: 1.420 (1.060-1.903), P = 0.019; > 5 cm: 2.090 (1.543-2.830), P < 0.001], surgery (no) [0.376 (0.297-0.476), P < 0.001], and chemotherapy(none/unknown) [0.578 (0.472-0.709), P < 0.001] were independent risk factors for CVD death in HCC patients. The discrimination and calibration of the nomograph were better. The C-index values for the training and validation sets were 0.736 and 0.665, respectively. The AUC values of the ROC curves at 2, 4, and 6 years were 0.702, 0.725, 0.740 in the training set and 0.697, 0.710, 0.744 in the validation set, respectively. The calibration curves showed that the predicted probabilities of the CVM prediction model in the training set vs the validation set were largely consistent with the actual probabilities. DCA demonstrated that the prediction model has a high net benefit. CONCLUSION: Risk factors for CVD death in HCC patients were investigated for the first time. The nomograph served as an important reference tool for relevant clinical management decisions.

Artificial Intelligence-Assisted Multiparameter Size Discrimination of Silver Nanoparticles through Electrochemical Collision.

Single particle collision is an important tool for size analysis at the individual particle level; however, due to complex dynamic behaviors of nanoparticles on the surface of an electrode, the accuracy of size discrimination is limited. A silver (Ag) nanoparticle (NP) was chosen as the research target, and the dynamic behavior of Ag NPs was simplified by enhancing adsorption between Ag NP and Au ultramicroelectrode (UME) in alkaline media. Immediately after, accurate dynamic and thermodynamic information on single Ag NP was accurately extracted from collision events, including current intensity, transferred charge, and duration time. On the basis that there were differences between parameters of different-sized Ag NPs, multiparameter size discrimination was proposed, which improved the accuracy compared to single-parameter discrimination. More intriguingly, multiparameter analysis was combined with artificial intelligence, a tool adept at processing multidimensional data, for the first time. Finally, artificial intelligence-assisted multiparameter size discrimination was successfully used to intelligently distinguish mixed Ag NPs, with an optimal accuracy of more than 95%. To sum up, the artificial intelligence-assisted multiparameter method showed an excellent ability to quickly achieve the most accurate size discrimination of nanoparticles at the level of individual particle and provide an effective guidance for the application of nanoparticles.

Ptip safeguards the epigenetic control of skeletal stem cell quiescence and potency in skeletogenesis.

Stem cells remain in a quiescent state for long-term maintenance and preservation of potency; this process requires fine-tuning regulatory mechanisms. In this study, we identified the epigenetic landscape along the developmental trajectory of skeletal stem cells (SSCs) in skeletogenesis governed by a key regulator, Ptip (also known as Paxip1, Pax interaction with transcription-activation domain protein-1). Our results showed that Ptip is required for maintaining the quiescence and potency of SSCs, and loss of Ptip in type II collagen (Col2)+ progenitors causes abnormal activation and differentiation of SSCs, impaired growth plate morphogenesis, and long bone dysplasia. We also found that Ptip suppressed the glycolysis of SSCs through downregulation of phosphoglycerate kinase 1 (Pgk1) by repressing histone H3K27ac at the promoter region. Notably, inhibition of glycolysis improved the function of SSCs despite Ptip deficiency. To the best of our knowledge, this is the first study to establish an epigenetic framework based on Ptip, which safeguards skeletal stem cell quiescence and potency through metabolic control. This framework is expected to improve SSC-based treatments of bone developmental disorders.

Immediate versus Non-immediate Loading Protocols for Reduced-diameter Implants Supporting Overdentures: A Systematic Review and Meta-analysis.

OBJECTIVE: This systematic review aimed to compare the influence of immediate and non-immediate loading protocols on overdentures retained by reduced-diameter implants(≦3.5mm). METHODS: Electronic databases, including MEDLINE (via PubMed), Embase and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) comparing clinical outcomes of immediately and nonimmediately loaded reduced-diameter implants supported overdentures. The risk of bias within and across the studies and the certainty of evidence were assessed by RoB 2.0 and GRADE, respectively. Sensitivity analysis was performed by eliminating studies at high risk of bias, and repeating the data synthesis employing the randomeffect model. Subgroup analyses were conducted based on the implant diameter and the length of follow-up. RESULTS: Six RCTs with 255 patients were included in this systematic review. The meta-analyses found similar implant survival rates between immediate and nonimmediate loaded implants in mini implant (RR=0.98; 95% CI=0.95, 1.01; p=0.12) and narrow implant subgroups (RR=0.99, 95% CI=0.94, 1.03, p =0.56), as well as in short-term (RR=0.98, 95% CI=0.97, 1.00, p =0.11) and long-term (RR=0.97, 95% CI=0.93, 1.01, p =0.09) follow-up subgroups. Additionally, marginal bone loss (MBL) showed no statistically significant difference between the loading protocols in the subgroup of long-term follow-up (MD=0.03; 95%CI=-0.16, 0.23; p=0.74). Three RCTs investigating peri-implant parameters found relatively higher modified plaque index and probing depth in reduced-diameter implant under immediate loading. CONCLUSION: Compared with non-immediate loading, the immediately loading protocol can achieve comparable survival rates and MBL in reduced-diameter implant retained overdentures.

Comparison of the osteogenic potential of fibroblasts from different sources.

OBJECTIVE: With the growing interest in the role of fibroblasts in osteogenesis, this study presents a comparative evaluation of the osteogenic potential of fibroblasts derived from three distinct sources: human gingival fibroblasts (HGFs), mouse embryonic fibroblasts (NIH3T3 cells), and mouse subcutaneous fibroblasts (L929 cells). MC3T3-E1 pre-osteoblast cells were employed as a positive control for osteogenic behavior. DESIGN: Our assessment involved multiple approaches, including vimentin staining for cell origin verification, as well as ALP and ARS staining in conjunction with RT-PCR for osteogenic characterization. RESULTS: Our findings revealed the superior osteogenic differentiation capacity of HGFs compared to MC3T3-E1 and NIH3T3 cells. Analysis of ALP staining confirmed that early osteogenic differentiation was most prominent in MC3T3-E1 cells at 7 days, followed by NIH3T3 and HGFs. However, ARS staining at 21 days demonstrated that HGFs produced the highest number of calcified nodules, indicating their robust potential for late-stage mineralization. This late-stage osteogenic potential of HGFs was further validated through RT-PCR analysis. In contrast, L929 cells displayed no significant osteogenic differentiation potential. CONCLUSIONS: In light of these findings, HGFs emerge as the preferred choice for seed cells in bone tissue engineering applications. This study provides valuable insights into the potential utility of HGFs in the fields of bone tissue engineering and regenerative medicine.

Risk of uveitis in autoimmune diseases patients treated with hydroxychloroquine: A population-based retrospective cohort study.

OBJECTIVE: Uveitis is a common manifestation of various autoimmune diseases and can lead to severe visual impairment. Hydroxychloroquine (HCQ) is an antimalarial drug that is also used to treat autoimmune diseases. The aim of this study was to investigate the association between HCQ use and the incidence of uveitis in patients with autoimmune diseases, as well as to identify potential risk factors for the development of uveitis in this study. METHODS: We conducted a population-based cohort study using a nationwide database to investigate the incidence of uveitis in patients with autoimmune diseases who received HCQ treatment. We selected non-HCQ comparison cohort at a 1:1 ratio by propensity score matching on age, sex, index date, urbanization, income, comorbidities, and medications. The data were analyzed using Cox proportional hazards models, and propensity score matching (PSM) was used to reduce selection bias. RESULTS: Our study included 15 822 patients with autoimmune diseases. After 1:1 PSM, there were 4555 individuals in both the HCQ group (n = 4555) and the non-HCQ group (n = 4555). The multiple Cox proportional hazard regression analysis was used for the estimation of adjusted hazard ratios on uveitis. After PSM, the adjusted hazard ratio for the HCQ group was 0.74 (95% CI = 0.58-0.95). These findings suggest that HCQ may play a protective role in reducing the risk of uveitis in patients with autoimmune diseases, including rheumatoid arthritis, Sjogren's syndrome, and systemic lupus erythematosus groups. The Kaplan-Meier survival curves also showed a significantly lower incidence of uveitis in the HCQ group (log-rank = 0.0229) after PSM. CONCLUSION: HCQ use is associated with a lower incidence of uveitis in patients with autoimmune diseases. Further studies are needed to confirm this association and to investigate the underlying mechanisms.

Insights into the effect mechanism of acidic pH condition on the in vitro starch digestion of black highland barley semi-dried noodles.

In this study, black highland barley semi-dried noodles (BHBSNs) were adjusted to acidic pH (5.0, 4.5, 4.0) with an acidity regulator (monosodium fumarate) for obtaining low glycemic index (GI) BHBSNs, and the changes in the in vitro starch digestion, free phenolic content, and α-amylase activity in BHBSNs were investigated. The estimated glycemic index (eGI) of BHBSNs decreased from 59.23 to 52.59, 53.89 and 53.61, respectively, as the pH was adjusted from 6.0 to 5.0, 4.5, 4.0. As the pH of BHBSNs decreased, the equilibrium hydrolysis (C∞) decreased, and kinetic coefficient (k) decreased and then increased. Compared to the control, the pH of the digestive fluid decreased during digestion with decreasing pH, and the α-amylase inhibition of BHBSNs with pH 5.0, 4.5, and 4.0 increased by 56.54 %, 75.18 %, and 107.98 %, respectively. In addition, as the pH of BHBSNs decreased, the free phenolic content and the content of released phenolics during digestion increased. Pearson correlations analysis showed that the increase in α-amylase inhibition and phenolic release during digestion induced by acidic pH was negatively correlated with the eGI and C∞ of BHBSNs. This study indicated that acidic pH condition could modulate starch digestion for preparing low GI BHBSNs.

Insights into the enhancement mechanism of immersion resistance of cooked noodles induced by wheat flour post-ripening: The view from protein cross-linking.

To overcome the problem that takeaway noodles possessed poor immersion resistance, in this study noodles were prepared from post-ripened wheat flour, and changes in textural properties, protein components, and water status of noodles were determined. The firmness and tensile distance of noodles were gradually increased by 7.40%-35.88% when wheat flour was post-ripened for 20-40 d. Afterwards, noodle textural qualities were slightly decreased. Compared with control groups, contents of glutenin macropolymer (GMP) and disulfide bonds were significantly (p<0.05) increased and protein network was also more compact, whereas the Glutenin/Gliadin ratio and free sulfhydryl groups content were significantly (p<0.05) reduced. Contents of sodium dodecyl sulfate extractable protein (SDSEP) were reduced by 3.22%-6.23%. Meanwhile, the decrease in A23 indicated that wheat flour post-ripening limited water-absorbing capacity of noodles during immersion. In conclusion, wheat flour post-ripening promoted the immersion resistance of noodles by inducing protein cross-linking, and the best post-ripening time was 20-40 d.

Annual review of PROTAC degraders as anticancer agents in 2022.

Following nearly two decades of development, significant advancements have been achieved in PROTAC technology. As of the end of 2022, more than 20 drugs have entered clinical trials, with ARV-471 targeting estrogen receptor (ER) showing remarkable progress by entering phase III clinical studies. In 2022, significant progress has been made on multiple targets. The first reversible covalent degrader designed to target the KRASG12C mutant protein, based on cyclopropionamide, has been reported. Additionally, the activity HDCA1 degrader surpassed submicromolar levels during the same year. A novel FEM1B covalent ligand called EN106 was also discovered, expanding the range of available ligands. Furthermore, the first PROTAC drug targeting SOS1 was reported. Additionally, the first-in-class degraders that specifically target BRD4 isoforms (BRD4 L and BRD4 S) have recently been reported, providing a valuable tool for further investigating the biological functions of these isoforms. Lastly, a breakthrough was also achieved with the first degrader targeting both CDK9 and Cyclin T1. In this review, we aimed to update the PROTAC degraders as potential anticancer agents covering articles published in 2022. The design strategies, degradation effects, and anticancer activities were highlighted, which might provide an updated sight to develop novel PROTAC degraders with great potential as anticancer agents as well as favorable drug-like properties.

Palmitoylation of PKCδ by ZDHHC5 in hypothalamic microglia presents as a therapeutic target for fatty liver disease.

The hypothalamus plays a fundamental role in controlling lipid metabolism through neuroendocrine signals. However, there are currently no available drug targets in the hypothalamus that can effectively improve human lipid metabolism. In this study, we found that the antimalarial drug artemether (ART) significantly improved lipid metabolism by specifically inhibiting microglial activation in the hypothalamus of high-fat diet-induced mice. Mechanically, ART protects the thyrotropin-releasing hormone (TRH) neurons surrounding microglial cells from inflammatory damage and promotes the release of TRH into the peripheral circulation. As a result, TRH stimulates the synthesis of thyroid hormone (TH), leading to a significant improvement in hepatic lipid disorders. Subsequently, we employed a biotin-labeled ART chemical probe to identify the direct cellular target in microglial cells as protein kinase Cδ (PKCδ). Importantly, ART directly targeted PKCδ to inhibit its palmitoylation modification by blocking the binding of zinc finger DHHC-type palmitoyltransferase 5 (ZDHHC5), which resulted in the inhibition of downstream neuroinflammation signaling. In vivo, hypothalamic microglia-specific PKCδ knockdown markedly impaired ART-dependent neuroendocrine regulation and lipid metabolism improvement in mice. Furthermore, single-cell transcriptomics analysis in human brain tissues revealed that the level of PKCδ in microglia positively correlated with individuals who had hyperlipemia, thereby highlighting a clinical translational value. Collectively, these data suggest that the palmitoylation of microglial PKCδ in the hypothalamus plays a role in modulating peripheral lipid metabolism through hypothalamus-liver communication, and provides a promising therapeutic target for fatty liver diseases.

Time series analysis-based seasonal autoregressive fractionally integrated moving average to estimate hepatitis B and C epidemics in China.

BACKGROUND: Hepatitis B (HB) and hepatitis C (HC) place the largest burden in China, and a goal of eliminating them as a major public health threat by 2030 has been set. Making more informed and accurate forecasts of their spread is essential for developing effective strategies, heightening the requirement for early warning to deal with such a major public health threat. AIM: To monitor HB and HC epidemics by the design of a paradigmatic seasonal autoregressive fractionally integrated moving average (SARFIMA) for projections into 2030, and to compare the effectiveness with the seasonal autoregressive integrated moving average (SARIMA). METHODS: Monthly HB and HC incidence cases in China were obtained from January 2004 to June 2023. Descriptive analysis and the Hodrick-Prescott method were employed to identify trends and seasonality. Two periods (from January 2004 to June 2022 and from January 2004 to December 2015, respectively) were used as the training sets to develop both models, while the remaining periods served as the test sets to evaluate the forecasting accuracy. RESULTS: There were incidents of 23400874 HB cases and 3590867 HC cases from January 2004 to June 2023. Overall, HB remained steady [average annual percentage change (AAPC) = 0.44, 95% confidence interval (95%CI): -0.94-1.84] while HC was increasing (AAPC = 8.91, 95%CI: 6.98-10.88), and both had a peak in March and a trough in February. In the 12-step-ahead HB forecast, the mean absolute deviation (15211.94), root mean square error (18762.94), mean absolute percentage error (0.17), mean error rate (0.15), and root mean square percentage error (0.25) under the best SARFIMA (3, 0, 0) (0, 0.449, 2)12 were smaller than those under the best SARIMA (3, 0, 0) (0, 1, 2)12 (16867.71, 20775.12, 0.19, 0.17, and 0.27, respectively). Similar results were also observed for the 90-step-ahead HB, 12-step-ahead HC, and 90-step-ahead HC forecasts. The predicted HB incidents totaled 9865400 (95%CI: 7508093-12222709) cases and HC totaled 1659485 (95%CI: 856681-2462290) cases during 2023-2030. CONCLUSION: Under current interventions, China faces enormous challenges to eliminate HB and HC epidemics by 2030, and effective strategies must be reinforced. The integration of SARFIMA into public health for the management of HB and HC epidemics can potentially result in more informed and efficient interventions, surpassing the capabilities of SARIMA.

FLPP: A Federated-Learning-Based Scheme for Privacy Protection in Mobile Edge Computing.

Data sharing and analyzing among different devices in mobile edge computing is valuable for social innovation and development. The limitation to the achievement of this goal is the data privacy risk. Therefore, existing studies mainly focus on enhancing the data privacy-protection capability. On the one hand, direct data leakage is avoided through federated learning by converting raw data into model parameters for transmission. On the other hand, the security of federated learning is further strengthened by privacy-protection techniques to defend against inference attack. However, privacy-protection techniques may reduce the training accuracy of the data while improving the security. Particularly, trading off data security and accuracy is a major challenge in dynamic mobile edge computing scenarios. To address this issue, we propose a federated-learning-based privacy-protection scheme, FLPP. Then, we build a layered adaptive differential privacy model to dynamically adjust the privacy-protection level in different situations. Finally, we design a differential evolutionary algorithm to derive the most suitable privacy-protection policy for achieving the optimal overall performance. The simulation results show that FLPP has an advantage of 8∼34% in overall performance. This demonstrates that our scheme can enable data to be shared securely and accurately.

Surface-immobilized cross-linked cationic polyelectrolyte enables CO2 reduction with metal cation-free acidic electrolyte.

Electrochemical CO2 reduction in acidic electrolytes is a promising strategy to achieve high utilization efficiency of CO2. Although alkali cations in acidic electrolytes play a vital role in suppressing hydrogen evolution and promoting CO2 reduction, they also cause precipitation of bicarbonate on the gas diffusion electrode (GDE), flooding of electrolyte through the GDE, and drift of the electrolyte pH. In this work, we realize the electroreduction of CO2 in a metal cation-free acidic electrolyte by covering the catalyst with cross-linked poly-diallyldimethylammonium chloride. This polyelectrolyte provides a high density of cationic sites immobilized on the surface of the catalyst, which suppresses the mass transport of H+ and modulates the interfacial field strength. By adopting this strategy, the Faradaic efficiency (FE) of CO reaches 95 ± 3% with the Ag catalyst and the FE of formic acid reaches 76 ± 3% with the In catalyst in a 1.0 pH electrolyte in a flow cell. More importantly, with the metal cation-free acidic electrolyte the amount of electrolyte flooding through the GDE is decreased to 2.5 ± 0.6% of that with alkali cation-containing acidic electrolyte, and the FE of CO maintains above 80% over 36 h of operation at -200 mA·cm-2.