Where do high-risk drinking occasions occur more often? A cross-sectional, cross-country study.

INTRODUCTION: The current paper examines the proportion of drinking occasions and total alcohol consumed that takes place at off-premise locations. Comparisons are made between high-income countries: Australia, New Zealand, England and Scotland, and across drinker-types: high-risk and lower-risk. METHODS: Data were taken from the International Alcohol Control study in Australia (N = 1789), New Zealand (N = 1979), England (N = 2844) and Scotland (N = 1864). The cross-national survey measures location and beverage-specific alcohol consumption. The number of drinking occasions and mean consumption across on- and off-premise locations and the proportion of drinking occasions that high- and lower-risk drinkers had at on- and off-premise locations was estimated for each country. RESULTS: The majority of drinking occasions among high-risk drinkers occurred at off-premise locations across all four countries; Australia 80.1%, New Zealand 72.0%, England 61.7% and Scotland 60.7%. High-risk drinkers in Australia had significantly larger proportions of drinking occasions occurring at off-premise locations compared to England and Scotland. Across all countries, high-risk drinkers and lower-risk drinkers consumed significantly larger quantities of alcohol per occasion at off-premise locations compared to on-premises locations. Finally, the majority of total alcohol consumed occurred at off-premise locations across all countries for high- and lower-risk drinkers. DISCUSSION AND CONCLUSIONS: As the accessibility to alcohol outside of licensed premises continues to increase, particularly with the expansion of home delivery services, it is important to be mindful of the high proportion of heavy drinking occasions that occur off-premise.

Construction of Functional Phenolic Resin and Carbon Hollow Spheres by Manipulating Structural Inhomogeneity.

Hollow carbonaceous spheres are extraordinarily attractive for their unique structural features and wide applications in various fields. Herein, a facile and effective synthesis methodology based on the extended Stöber process for construction of phenolic resin hollow spheres has been presented. Combined with a series of characterization techniques, the synthesis process was systematically investigated, and a possible synthesis mechanism was proposed. It is revealed that the structural inhomogeneity of the polymer product achieved by using dodecylamine and alkane is responsible for the formation of hollow architecture, which depends on spontaneous selective dissolution during the synthesis process. Different metal-doped carbonaceous hollow spheres can be obtained by introducing corresponding precursors into the synthetic system and meeting requirements of different application fields. This work presented a novel synthesis strategy of hollow carbonaceous spheres, which is significant for building a new platform of advanced functional carbon-based composites.

Public trust in general practitioners and its association with primary care contracts: a cross-sectional study of community residents in China.

OBJECTIVES: This study aimed to assess the level of public trust in general practitioners (GPs) and its association with primary care contract services (PCCS) in China. STUDY DESIGN: Cross-sectional study. METHODS: Between September and December 2021, 4158 residents across eastern, central, and western China completed a structured self-administered questionnaire. Trust was assessed using the Chinese version of Wake Forest Physician Trust Scale. Multivariable linear regression models were established to identify predictors of trust. The effect size of PCCS on trust was estimated by the average treatment effect for the treated (ATT) through propensity score matching. RESULTS: The study participants had a mean Wake Forest Physician Trust Scale score of 36.82 (standard deviation = 5.45). Enrollment with PCCS (ß = 0.14, P < 0.01), Han ethnicity (ß = 0.03, P < 0.05), lower educational attainment (ß = -0.06, P < 0.01), higher individual monthly income (ß = 0.03, P < 0.05), better self-rated health (ß = 0.04, P < 0.05), chronic conditions (ß = 0.07, P < 0.01), and higher familiarity with primary care services (ß = 0.12, P < 0.01) and PCCS (ß = 0.21, P < 0.01) were associated with higher trust in GPs. The ATT of PCCS exceeded 1 (P < 0.05). CONCLUSIONS: PCCS are associated with higher levels of trust in GPs. PCCS may become an effective tool to attract public trust in GPs, although the relationship between the two may be bi-directional.

JAK/STAT3 signaling in cardiac fibrosis: a promising therapeutic target.

Cardiac fibrosis is a serious health problem because it is a common pathological change in almost all forms of cardiovascular diseases. Cardiac fibrosis is characterized by the transdifferentiation of cardiac fibroblasts (CFs) into cardiac myofibroblasts and the excessive deposition of extracellular matrix (ECM) components produced by activated myofibroblasts, which leads to fibrotic scar formation and subsequent cardiac dysfunction. However, there are currently few effective therapeutic strategies protecting against fibrogenesis. This lack is largely because the molecular mechanisms of cardiac fibrosis remain unclear despite extensive research. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling cascade is an extensively present intracellular signal transduction pathway and can regulate a wide range of biological processes, including cell proliferation, migration, differentiation, apoptosis, and immune response. Various upstream mediators such as cytokines, growth factors and hormones can initiate signal transmission via this pathway and play corresponding regulatory roles. STAT3 is a crucial player of the JAK/STAT pathway and its activation is related to inflammation, malignant tumors and autoimmune illnesses. Recently, the JAK/STAT3 signaling has been in the spotlight for its role in the occurrence and development of cardiac fibrosis and its activation can promote the proliferation and activation of CFs and the production of ECM proteins, thus leading to cardiac fibrosis. In this manuscript, we discuss the structure, transactivation and regulation of the JAK/STAT3 signaling pathway and review recent progress on the role of this pathway in cardiac fibrosis. Moreover, we summarize the current challenges and opportunities of targeting the JAK/STAT3 signaling for the treatment of fibrosis. In summary, the information presented in this article is critical for comprehending the role of the JAK/STAT3 pathway in cardiac fibrosis, and will also contribute to future research aimed at the development of effective anti-fibrotic therapeutic strategies targeting the JAK/STAT3 signaling.

Household Decision-Making Choices: Investment in Children's Education or Self-Consumption.

Analyzing the sustainable decision-making mechanism between household consumption and education investment can theoretically develop education. This study uses the continuous-time utility model to demonstrate the independent characteristics of consumption and education investment, as well as the principle of decision incompatibility in the decision-making process of the utility maximization problem. Then, we establish a three-phase logarithmic utility model to obtain the intertemporal decision-making path of a family. The analysis shows that the investment allocation ratio between the two phases depends on the expected and discounted level of the offsprings' abilities, while the total investment level is related to parental altruism. When parents, with foresight, factor in prospective transfer payments from progeny, the optimal decision is to maximize their children's ultimate human capital within a given total investment. Education investment not only squeezes out consumption but also promotes consumption in various periods due to future transfer payments. The decision-making process of three typical growth stages indicates that as offspring mature and their human capital increases, parents' willingness to invest in education decreases while self-consumption escalates. This study provides a new perspective and theoretical basis for studying household education expenditure, motivation, and related policy formulation.

Association between alcohol intake and bone mineral density: results from the NHANES 2005-2020 and two-sample Mendelian randomization.

We used the data from the NHANES cross-sectional study among 14,113 participants and indicated a positive correlation between alcohol intake frequency and bone mineral density in different body sites. Mendelian randomization was conducted, and no causal relationship is significant between these two variables. The study can provide some suggestions on the daily consumption of alcohol for osteoporosis patients. PURPOSE: The effect of alcohol intake on bone mineral density (BMD) remains unclear. This study explored the association and causality between alcohol intake and BMD. METHODS: Based on the 2005-2020 National Health and Nutrition Examination Survey including 14,113 participants, we conducted co-variate-adjusted multilinear regression analyses to explore the association between alcohol intake levels and spine or femur BMD. To evaluate the causal association between alcohol intake frequency and bone mineral density, the inverse variance weighted approach of two-sample Mendelian randomization (MR) was used with genetic data from the Medical Research Council Integrative Epidemiology Unit (462,346 cases) for alcohol intake frequency and the Genetic Factors for Osteoporosis Consortium (28,496 cases) for lumbar spine and femur neck BMD (32,735 cases). RESULTS: Compared with non-drinkers, total femur BMDs but not total spine BMD increased with daily alcohol intake in males (ß = 3.63*10-2 for mild drinkers, ß = 4.21*10-2 for moderate drinkers, and ß = 4.26*10-2 for heavy drinkers). By contrast, the higher total spine BMD in females was related to higher alcohol intake levels (ß = 2.15*10-2 for mild drinkers, ß = 2.59*10-2 for moderate drinkers, and ß = 3.88*10-2 for heavy drinkers). Regarding the two-sample MR results, no causal relationship was observed between alcohol intake frequency and lumbar spine BMD (odds ratio [OR] = 1.016, P = 0.789) or femur neck BMD (OR = 1.048, P = 0.333). CONCLUSION: This study suggests a positive association between alcohol intake frequency and BMD, although the causal relationship was not significant.

Dual-Parasitic Effect Enables Highly Reversible Zn Metal Anode for Ultralong 25,000 Cycles Aqueous Zinc-Ion Batteries.

The use of electrolyte additives is an efficient approach to mitigating undesirable side reactions and dendrites. However, the existing electrolyte additives do not effectively regulate both the chaotic diffusion of Zn2+ and the decomposition of H2O simultaneously. Herein, a dual-parasitic method is introduced to address the aforementioned issues by incorporating 1-ethyl-3-methylimidazolium trifluoromethanesulfonate ([EMIm]OTf) as cosolvent into the Zn(OTf)2 electrolyte. Specifically, the OTf- anion is parasitic in the solvent sheath of Zn2+ to decrease the number of active H2O. Additionally, the EMIm+ cation can construct an electrostatic shield layer and a hybrid organic/inorganic solid electrolyte interface layer to optimize the deposition behavior of Zn2+. This results in a Zn anode with a reversible cycle life of 3000 h, the longest cycle life of full cells (25,000 cycles), and an extremely high initial capacity (4.5 mA h cm-2), providing a promising electrolyte solution for practical applications of rechargeable aqueous zinc-ion batteries.

Advances in amelioration of plasma electrolytic oxidation coatings on biodegradable magnesium and alloys.

Magnesium and its alloys are considered excellent materials for biodegradable implants because of their good biocompatibility and biodegradability as well as their mechanical properties. However, the rapid degradation rate severely limits their clinical applications. Plasma electrolytic oxidation (PEO), also known as micro-arc oxidation (MAO), is an effective surface modification technique. However, there are many pores and cracks on the coating surface under conventional PEO process. The corrosive products tend to penetrate deeply into the substrate, reducing its corrosion resistance and the biocompatibility, which makes PEO-coated Mg difficult to meet the long-term needs of in vivo implants. Hence, it is necessary to modify the PEO coating. This review discusses the formation mechanism and the influential parameters of PEO coatings on Mg. This is followed by a review of the latest research of the pretreatment and typical amelioration of PEO coating on biodegradable Mg alloys in the past 5 years, including calcium phosphate (Ca-P) coating, layered double hydroxide (LDH)-PEO coating, ZrO2 incorporated-PEO coating, antibacterial ingredients-PEO coating, drug-PEO coating, polymer-PEO composite coating, Plasma electrolytic fluorination (PEF) coating and self-healing coating. Meanwhile, the improvements of morphology, corrosion resistance, wear resistance, biocompatibility, antibacterial abilities, and drug loading abilities and the preparation methods of the modified PEO coatings are deeply discussed as well. Finally, the challenges and prospects of PEO coatings are discussed in detail for the purpose of promoting the clinical application of biodegradable Mg alloys.

The burden of alcohol-related caring for others in Australia in the 2021 pandemic period.

OBJECTIVE: The magnitude of caring for others due to excessive alcohol use is unclear in Australia and internationally. This study explores the prevalence, sociodemographic predictors, and consequences of informal care for others due to alcohol use. METHOD: A survey on harm from others' drinking was conducted among 2,574 Australian adults in November 2021 from national random digit dial and "Life in Australia" panel samples to elicit representative data. Respondents who indicated they had "heavy drinker/s" in their lives (n= 1,585), were asked about their experience of caring for these drinkers and their dependents in the last 12 months. Weighted logistic and linear regressions examined a) sociodemographic factors associated with informal care due to others' drinking, and b) the impact of the caregiving burden on caregiver's financial status, overall health, and quality of life. RESULTS: Overall, 20% of participants reported caregiving responsibilities arising from others' drinking. Older age, unemployment, residing in capital cities and reporting birth in a non-English speaking background country were associated with a reduced likelihood of caregiving, whereas higher education and more frequent risky drinking were associated with an increased likelihood. Caregivers reported significantly higher financial disadvantage, a lower quality of life and poorer overall health. CONCLUSIONS: One in five adults reported caring for drinkers in the previous 12 months, with this associated with negative consequences for those providing care. Service providers, health promotion practitioners and policy makers should focus upon younger age groups, those who live in regional areas, and those born in Australia who are at greater risk of being burdened by caregiving due to others' alcohol use.

Changes in the numbers of hospital-based abortions and outpatient early medical abortions in Victoria, 2012-22: a retrospective cohort study.

OBJECTIVES: To assess changes in the monthly numbers of hospital-based abortions and outpatient early medical abortions in Victoria during January 2012 - March 2022, with a particular interest in the impact of the coronavirus disease 2019 (COVID-19) pandemic. STUDY DESIGN: Population-based retrospective cohort study; time series analysis of Victorian Admitted Episodes Dataset (VAED) and Pharmaceutical Benefits Scheme (PBS) data. SETTING, PARTICIPANTS: All admitted care episodes in Victoria during 1 January 2012 - 31 March 2022 with medical abortion as the principal diagnosis; all PBS claims for mifepristone-misoprostol (MS-2 Step) during 1 January 2015 (date of listing) - 31 March 2022. MAIN OUTCOME MEASURES: Changes in monthly numbers (with 95% confidence intervals [CIs]) of admissions for hospital-based and outpatient early medical abortions during the pre-pandemic period (January 2012 - March 2020), the first full month of the COVID-19 pandemic (April 2020), and the pandemic period (May 2020 - March 2022). RESULTS: The monthly number of hospital-based abortions declined in Victoria during the pre-pandemic period (slope, -2.92 [95% CI, -3.45 to -2.38] per month); the rate of decline was greater during the pandemic period (slope, -5.74 [95% CI, -10.5 to -0.96] per month). The monthly number of outpatient early medical abortions increased during the pre-pandemic period (slope, 5.94 [95% CI, 5.34-6.34] per month); it declined during the first month of the pandemic (slope, -26.4 [95% CI, -70.1 to -17.3] per month), but did not significantly change thereafter. The total monthly number of abortions during the pandemic period did not deviate markedly from the pre-pandemic median value. The pre-pandemic declines in monthly numbers of abortions in major city hospitals, in private hospitals, or at earlier than 14 weeks' gestation intensified during the pandemic period. During January 2015 - March 2020, 14 634 of 103 496 abortions were outpatient medical abortions (14%); during the pandemic period, 11 154 of 33 056 abortions were outpatient medical abortions (33%). CONCLUSIONS: The use of outpatient early medical abortion has steadily increased in Victoria since the PBS listing of mifepristone-misoprostol, which helped ensure access to abortion during the COVID-19 pandemic. Outpatient medical abortions may eventually outnumber surgical early abortions in Victoria, but they are not always appropriate: hospitals will continue to be essential for comprehensive abortion care.

Influence on the fermentation quality, microbial diversity, and metabolomics in the ensiling of sunflower stalks and alfalfa.

With the rapid development of the livestock industry, finding new sources of feed has become a critical issue that needs to be addressed urgently. China is one of the top five sunflower producers in the world and generates a massive amount of sunflower stalks annually, yet this resource has not been effectively utilized. Therefore, in order to tap into the potential of sunflower stalks for animal feed, it is essential to explore and develop efficient methods for their utilization.In this study, various proportions of alfalfa and sunflower straw were co-ensiled with the following mixing ratios: 0:10, 2:8, 4:6, 5:5, 6:4, and 8:2, denoted as A0S10, A2S8, A4S6, A5S5, A6S4, and A8S2, respectively. The nutrient composition, fermentation quality, microbial quantity, microbial diversity, and broad-spectrum metabolomics on the 60th day were assessed. The results showed that the treatment groups with more sunflower straw added (A2S8, A4S6) could start fermentation earlier. On the first day of fermentation, Weissella spp.dominated overwhelmingly in these two groups. At the same time, in the early stage of fermentation, the pH in these two groups dropped rapidly, which could effectively reduce the loss of nutrients in the early stage of fermentation.In the later fermentation period, a declining trend in acetic acid levels was observed in A0S10, A2S8, and A4S6, while no butyric acid production was detected in A0S10 and A2S8 throughout the process. In A4S6, butyric acid production was observed only after 30 days of fermentation. From the perspective of metabolites, compared with sunflower ensiling alone, many bioactive substances such as flavonoids, alkaloids, and terpenes are upregulated in mixed ensiling.

Concentration-Driven Interfacial Amorphization toward Highly Stable and High-Rate Zn Metal Batteries.

The interfacial structure holds great promise in suppressing dendrite growth and parasitic reactions of zinc metal in aqueous media. Current advancements prioritize novel component fabrication, yet the local crystal structure significantly impacts the interfacial properties. In addition, there is still a critical need for scalable synthesis methods for expediting the commercialization of aqueous zinc metal batteries (AZMBs). Herein, we propose a scalable concentration-controlled method for realizing crystalline to amorphous transformation of the Zn metal interface with exceptional scalability (>1 m2) and processing consistency (>30 trials). Theoretical and experimental analyses highlight the advantages of amorphous ZnO, which exhibits moderate adsorption energy, strong desolvation ability, and hydrophilicity. Employing the amorphous ZnO-coated zinc metal anode (AZO-Zn) significantly enhances the cycling performance, impressively maintaining 1000 cycles at 100 mA cm-2. The prototype AZO-Zn||MnO2@CNT pouch cell demonstrates a capacity of 15.7 mAh and maintains 91% of its highest capacity over 100 cycles, presenting promising avenues for the future commercialization of AZMBs.

A nomogram prediction model based on clinicopathological combined radiological features for metachronous liver metastasis of colorectal cancer.

Objective: To establish a nomogram prediction model (based on clinicopathological and radiological features) for the development of metachronous liver metastasis (MLM) in patients with colorectal cancer (CRC). Methods: This retrospective study included patients with CRC who underwent surgery at Changshu No.1 People's Hospital and the Second Affiliated Hospital of Soochow University between January 2016 and December 2018. The clinical, pathological, and radiological features of each patient were investigated. Risk factors for MLM were identified by univariable and multivariable analyses. The predictive nomogram for MLM development was constructed. The predictive performance of the nomogram was estimated by the receiver operating characteristics curve, calibration curve, and decision curve analysis. Results: This study included 161 patients with CRC [median age: 66 (range, 33-87) years]. Fifty-nine developed MLM after a median of 12 (range, 2-52) months after surgery. The multivariable logistic regression analysis showed that age >66 years (OR=3.471, 95% CI: 1.272-9.473, P=0.015), N2 stage (OR=6.534, 95% CI: 1.456-29.317, P=0.014), positive vascular invasion (OR=2.995, 95% CI: 1.132-7.926, P=0.027), positive tumor deposit (OR=4.451, 95% CI: 1.153-17.179, P=0.030), and linear (OR=6.774, 95% CI: 1.306-35.135, P=0.023) and nodal pericolic fat infiltration patterns (OR=8.762, 95% CI: 1.521-50.457, P=0.015) were independently associated with MLM. These five factors were used to create a nomogram. The area under the receiver operating characteristics curve of the nomogram was 0.866 (95% CI: 0.803-0.914), indicating favorable prediction performance. The calibration curve of the nomogram showed a satisfactory agreement between the predicted and actual probabilities. Conclusions: A nomogram prediction model based on five clinicopathological and radiological features might have favorable prediction performance for MLM in patients who underwent surgery for CRC. Hence, the present study proposes a nomogram that can easily be used to predict MLM after CRC surgery based on readily available features.

Diatom-dinoflagellate succession in the Bohai Sea: The role of N/P ratios and dissolved organic nitrogen components.

Dissolved organic nitrogen (DON) is a pivotal component of total dissolved nitrogen pools, serving as a crucial nitrogen source for phytoplankton. This study investigated the impact of nitrogen-to-phosphorus (N/P) ratios and different DON components (hydrophilic vs hydrophobic DON) on diatom-dinoflagellate succession through field culture experiments. Results showed that dinoflagellates have a competitive advantage under high N/P ratios and phosphorus limitation, regardless of DON or DIN treatments. Hydrophilic DON exhibits greater bioavailability than hydrophobic DON (40.6% vs. 21.7 %), resulting in increased algal biomass and diatoms dominance in the community. Additionally, DON was categorized into labile and refractory components (LDON and RDON) based on bioavailability. LDON primarily consists of protein-like components that can be readily consumed by algae, whereas RDON is primarily composed of humic-like components that are less accessible to algae. Diatoms and dinoflagellates exhibited differential responses to LDON and RDON, with diatoms thriving in high LDON environments, while dinoflagellates gained a competitive advantage when RDON was the predominant nitrogen source. Furthermore, a significant negative correlation was observed between bioavailable nitrogen concentration (BAN: DIN + LDON) and the ratio of dinoflagellates to diatoms (p<0.05). In conclusion, our study highlights the role of LDON in promoting diatom dominance, whereas environments dominated by RDON foster dinoflagellate success. These findings enhance our comprehension of diatom-dinoflagellate succession dynamics.

Validation of the Patient-Reported Outcomes Measurement Information System (PROMIS®) physical function questionnaire in late-onset Pompe disease using PROPEL phase 3 data.

BACKGROUND: The construct validity and interpretation of the Patient-Reported Outcome Measurement Information System (PROMIS®) Physical Function short form 20a (PF20a) questionnaire were evaluated for patients with late-onset Pompe disease (LOPD), a rare, autosomal recessive, progressive neuromuscular disorder treatable by enzyme replacement therapy (ERT). METHODS: In the phase 3 PROPEL study, adults with LOPD underwent testing of physical functioning and had PRO measurements at baseline and at weeks 12, 26, 38, and 52 while receiving experimental or standard-of-care ERT. All patients were pooled for analyses, without comparisons between treatment groups. Associations and correlations between PROMIS PF20a scores and the 6-minute walk distance (6MWD), % predicted forced vital capacity (FVC), manual muscle test (MMT) of the lower extremities, Gait, Stairs, Gowers' maneuver, Chair (GSGC) score, and Rasch-built Pompe-specific Activity (R-PAct) scale were evaluated by calculating regression coefficients in linear regression models and Pearson correlation coefficients (R); patients' age, sex, race, ERT prior to study, body mass index, and study treatment were included as covariables. The minimal clinically important difference (MCID) of PROMIS PF20a was determined using distribution- and anchor-based methods. RESULTS: 123 patients received at least 1 dose of ERT. In multivariable analyses, PROMIS PF20a scores had strong correlations with R-PAct scores (R = 0.83 at baseline and R = 0.67 when evaluating changes between baseline and 52 weeks) and moderate correlations with the 6MWD (R = 0.57 at baseline and R = 0.48 when evaluating changes between baseline and 52 weeks). Moderate correlations were also observed between PROMIS PF20a and MMT (R = 0.54), GSGC (R=-0.51), and FVC (R = 0.48) at baseline. In multivariable linear regression models, associations were significant between PROMIS PF20a and 6MWD (P = 0.0006), MMT (P = 0.0034), GSGC (P = 0.0278), and R-PAct (P < 0.0001) at baseline, between PROMIS PF20a and 6MWD (P < 0.0001), FVC (P = 0.0490), and R-PAct (P < 0.0001) when combining all measurements, and between PF20a and 6MWD (P = 0.0016) and R-PAct (P = 0.0001) when evaluating changes in scores between baseline and 52 weeks. The anchor-based and distribution-based MCID for a clinically important improvement for PROMIS PF20a were 2.4 and 4.2, respectively. CONCLUSIONS: PROMIS PF20a has validity as an instrument both to measure and to longitudinally follow physical function in patients with LOPD. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03729362. Registered 2 November 2018, https://www. CLINICALTRIALS: gov/search?term=NCT03729362 .

Lysine demethylase 5C inhibits transcription of prefoldin subunit 5 to activate c-Myc signal transduction and colorectal cancer progression.

BACKGROUND: Lysine demethylase 5C (KDM5C) has been implicated in the development of several human cancers. This study aims to investigate the role of KDM5C in the progression of colorectal cancer (CRC) and explore the associated molecular mechanism. METHODS: Bioinformatics tools were employed to predict the target genes of KDM5C in CRC. The expression levels of KDM5C and prefoldin subunit 5 (PFDN5) in CRC cells were determined by RT-qPCR and western blot assays. The interaction between KDM5C, H3K4me3, and PFDN5 was validated by chromatin immunoprecipitation. Expression and prognostic values of KDM5C and PFDN5 in CRC were analyzed in a cohort of 72 patients. The function of KDM5C/PFDN5 in c-Myc signal transduction was analyzed by luciferase assay. Silencing of KDM5C and PFDN5 was induced in CRC cell lines to analyze the cell malignant phenotype in vitro and tumorigenic activity in nude mice. RESULTS: KDM5C exhibited high expression, while PFDN5 displayed low expression in CRC cells and clinical CRC samples. High KDM5C levels correlated with poor survival and unfavorable clinical presentation, whereas elevated PFDN5 correlated with improved patient outcomes. KDM5C mediated demethylation of H3K4me3 on the PFDN5 promoter, suppressing its transcription and thereby enhancing the transcriptional activity of c-Myc. KDM5C knockdown in CRC cells suppressed cell proliferation, migration and invasion, epithelial-mesenchymal transition, and tumorigenic activity while increasing autophagy and apoptosis rates. However, the malignant behavior of cells was restored by the further silencing of PFDN5. CONCLUSION: This study demonstrates that KDM5C inhibits PFDN5 transcription, thereby activating c-Myc signal transduction and promoting CRC progression.

Interfacial solvation-structure regulation for stable Li metal anode by a desolvation coating technique.

Rechargeable lithium (Li) metal batteries face challenges in achieving stable cycling due to the instability of the solid electrolyte interphase (SEI). The Li-ion solvation structure and its desolvation process are crucial for the formation of a stable SEI on Li metal anodes and improving Li plating/stripping kinetics. This research introduces an interfacial desolvation coating technique to actively modulate the Li-ion solvation structure at the Li metal interface and regulate the participation of the electrolyte solvent in SEI formation. Through experimental investigations conducted using a carbonate electrolyte with limited compatibility to Li metal, the optimized desolvation coating layer, composed of 12-crown-4 ether-modified silica materials, selectively displaces strongly coordinating solvents while simultaneously enriching weakly coordinating fluorinated solvents at the Li metal/electrolyte interface. This selective desolvation and enrichment effect reduce solvent participation to SEI and thus facilitate the formation of a LiF-dominant SEI with greatly reduced organic species on the Li metal surface, as conclusively verified through various characterization techniques including XPS, quantitative NMR, operando NMR, cryo-TEM, EELS, and EDS. The interfacial desolvation coating technique enables excellent rate cycling stability (i.e., 1C) of the Li metal anode and prolonged cycling life of the Li||LiCoO2 pouch cell in the conventional carbonate electrolyte (E/C 2.6 g/Ah), with 80% capacity retention after 333 cycles.

Facial feedback manipulation influences the automatic detection of unexpected emotional body expressions.

Unexpected or changing facial expressions are known to be able to engage more automatic processing than frequently occurring facial expressions, thereby inducing a neural differential wave response known as expression mismatch negativity (EMMN). Recent studies have shown that EMMN can be modulated by the observer's facial feedback (i.e., feedback from their own facial movements). A similar EMMN activity has been discovered for body expressions, but thus far only a few emotion types have been investigated. It is unknown whether the EMMNs evoked by body expressions can be influenced by facial feedback. To explore this question, we recorded EEG activity of 29 participants in the reverse oddball paradigm. Here two unexamined categories of body expressions were presented, happy and sad, placed in two paired stimulus sequences: in one the happy body was presented with a probability of 80% (standards) while the sad body was presented with a probability of 20% (deviants), and in the other the probabilities were reversed. The facial feedback was manipulated by different pen holding conditions (i.e., participants holding the pen with the teeth, lips, or nondominant hand). The nonparametric cluster permutation test revealed significant happy and sad body-related EMMN (bEMMN) activities. The happy-bEMMN were more negative than sad-bEMMN within the range of 100-150 ms. Additionally, the bEMMN amplitude of both emotions is modulated by the facial feedback conditions. These results expand the range of emotional types applicable to bEMMN and provide evidence for the validity of the facial feedback hypothesis across emotional carriers.

The complex role of IL-10 in malignant ascites: a review.

The emergence of malignant ascites (MA) indicates poor prognoses in patients with ovarian, gastrointestinal, breast, and pancreatic cancer. Interleukin-10 (IL-10) is a pleiotropic cytokine with immunoregulatory effects in tumor microenvironment. The level of IL-10 in MA varied across cancer types and patients, influencing cancer progression and outcomes. Originating from various immune and cancer cells, IL-10 contributes to complex signaling pathways in MA. Systemic IL-10 administration, although the evidence of its efficacy on MA is limited, still emerges as a promising therapeutic strategy because it can increase CD8+ T cells cytotoxicity and invigorate exhausted CD8+ tumor infiltration lymphocytes (TILs) directly. IL-10 signaling blockade also demonstrates great potential when combined with other immunotherapies in MA treatment. We reviewed the levels, origins, and functions of IL-10 in malignant ascites and overviewed the current IL-10 signaling targeting therapies, aiming to provide insights for MA treatment.

Truncated FRMD7 proteins in congenital Nystagmus: novel frameshift mutations and proteasomal pathway implications.

Idiopathic congenital nystagmus (ICN) manifests as involuntary and periodic eye movements. To identify the genetic defect associated with X-linked ICN, Whole Exome Sequencing (WES) was conducted in two affected families. We identified two frameshift mutations in FRMD7, c.1492dupT/p.(Y498Lfs*15) and c.1616delG/p.(R539Kfs*2). Plasmids harboring the mutated genes and qPCR analysis revealed mRNA stability, evading degradation via the NMD pathway, and corroborated truncated protein production via Western-blot analysis. Notably, both truncated proteins were degraded through the proteasomal (ubiquitination) pathway, suggesting potential therapeutic avenues targeting this pathway for similar mutations. Moreover, we conducted a comprehensive analysis, summarizing 140 mutations within the FRMD7 gene. Our findings highlight the FERM and FA structural domains as mutation-prone regions. Interestingly, exons 9 and 12 are the most mutated regions, but 90% (28/31) mutations in exon 9 are missense while 84% (21/25) mutations in exon 12 are frameshift. A predominant occurrence of shift code mutations was observed in exons 11 and 12, possibly associated with the localization of premature termination codons (PTCs), leading to the generation of deleterious truncated proteins. Additionally, our conjecture suggests that the loss of FRMD7 protein function might not solely drive pathology; rather, the emergence of aberrant protein function could be pivotal in nystagmus etiology. We propose a dependence of FRMD7 protein normal function primarily on its anterior domain. Future investigations are warranted to validate this hypothesis.