Arrestin-3 binds parkin and enhances parkin-dependent mitophagy.

Arrestins were discovered for their role in homologous desensitization of G-protein-coupled receptors (GPCRs). Later non-visual arrestins were shown to regulate several signaling pathways. Some of these pathways require arrestin binding to GPCRs, the regulation of others is receptor independent. Here, we demonstrate that arrestin-3 binds the E3 ubiquitin ligase parkin via multiple sites, preferentially interacting with its RING0 domain. Identification of the parkin domains involved suggests that arrestin-3 likely relieves parkin autoinhibition and/or stabilizes the enzymatically active "open" conformation of parkin. Arrestin-3 binding enhances ubiquitination by parkin of the mitochondrial protein mitofusin-1 and facilitates parkin-mediated mitophagy in HeLa cells. Furthermore, arrestin-3 and its mutant with enhanced parkin binding rescue mitofusin-1 ubiquitination and mitophagy in the presence of the Parkinson's disease-associated R275W parkin mutant, which is defective in both functions. Thus, modulation of parkin activity via arrestin-3 might be a novel strategy of anti-parkinsonian therapy.

Integrating network pharmacology and experimental validation reveals therapeutic effects of D-mannose on NAFLD through mTOR suppression.

Non-alcoholic fatty liver disease (NAFLD), a chronic liver condition and metabolic disorder, has emerged as a significant health issue worldwide. D-mannose, a natural monosaccharide widely existing in plants and animals, has demonstrated metabolic regulatory properties. However, the effect and mechanism by which D-mannose may counteract NAFLD have not been studied. In this study, network pharmacology followed by molecular docking analysis was utilized to identify potential targets of mannose against NAFLD, and the leptin receptor-deficient, genetically obese db/db mice was employed as an animal model of NAFLD to validate the regulation of D-mannose on core targets. As a result, 67 targets of mannose are predicted associated with NAFLD, which are surprisingly centered on the mechanistic target of rapamycin (mTOR). Further analyses suggest that mTOR signaling is functionally enriched in potential targets of mannose treating NAFLD, and that mannose putatively binds to mTOR as a core mechanism. Expectedly, repeated oral gavage of supraphysiological D-mannose ameliorates liver steatosis of db/db mice, which is based on suppression of hepatic mTOR signaling. Moreover, daily D-mannose administration reduced hepatic expression of lipogenic regulatory genes in counteracting NAFLD. Together, these findings reveal D-mannose as an effective and potential NAFLD therapeutic through mTOR suppression, which holds translational promise.

Treatment-related pneumonitis after thoracic radiotherapy/chemoradiotherapy combined with anti-PD-1 monoclonal antibodies in advanced esophageal squamous cell carcinoma.

PURPOSE: This study aims to evaluate the risk factors of treatment-related pneumonitis (TRP) following thoracic radiotherapy/chemoradiotherapy combined with anti-PD­1 monoclonal antibodies (mAbs) in patients with advanced esophageal squamous cell carcinoma (ESCC). METHODS: We retrospectively reviewed 97 patients with advanced ESCC who were treated with thoracic radiotherapy/chemoradiotherapy combined with anti-PD­1 mAbs. Among them, 56 patients received concurrent radiotherapy with anti-PD­1 mAbs and 41 patients received sequential radiotherapy with anti-PD­1 mAbs. The median prescribed planning target volume (PTV) dose was 59.4 Gy (range from 50.4 to 66 Gy, 1.8-2.2 Gy/fraction). Clinical characteristics, the percentage of lung volume receiving more than 5-50 Gy in increments of 5 Gy (V5-V50, respectively) and the mean lung dose (MLD) were analyzed as potential risk factors for TRP. RESULTS: 46.4% (45/97), 20.6% (20/97), 20.6% (20/97), 4.1% (4/97), and 1.0% (1/97) of the patients developed any grade of TRP, grade 1 TRP, grade 2 TRP, grade 3 TRP, and fatal (grade 5) TRP, respectively. Anti-PD­1 mAbs administered concurrently with radiotherapy, V5, V10, V15, V25, V30, V35, V40 and MLD were associated with the occurrence of grade 2 or higher TRP. Concurrent therapy (P = 0.010, OR = 3.990) and V5 (P = 0.001, OR = 1.126) were independent risk factors for grade 2 or higher TRP. According to the receiver operating characteristic (ROC) curve analysis, the optimal V5 threshold for predicting grade 2 or higher TRP was 55.7%. CONCLUSION: The combination of thoracic radiotherapy/chemoradiotherapy with anti-PD­1 mAbs displayed a tolerable pulmonary safety profile. Although the incidence of TRP was high, grade 1-2 TRP accounted for the majority. Anti-PD­1 mAbs administered concurrently with radiotherapy and the lung V5 were significantly associated with the occurrence of grade 2 or higher TRP. Therefore, it seems safer to control V5 below 55% in clinical, especially for the high-risk populations receiving concurrent therapy.

Clinico-pathological study of esophageal mucoepidermoid carcinoma: a 10-year survival from a single center.

BACKGROUND: Mucoepidermoid Carcinoma of the Esophagus (MECE) is a relatively rare tumor type, with most of the current data derived from case reports or small sample studies. This retrospective study reports on the 10-year survival data and detailed clinicopathological characteristics of 48 patients with esophageal MEC. METHODS: Data were collected from 48 patients who underwent curative surgery for esophageal MEC at the Fourth Hospital of Hebei Medical University between January 1, 2004, and December 31, 2020. These were compared with contemporaneous cases of Esophageal Squamous Cell Carcinoma (ESCC) and Esophageal Adenocarcinoma (EAC). Using the Kaplan-Meier method and multivariate Cox regression analysis, we investigated the clinicopathological factors affecting the survival of patients with MEC. RESULTS: The incidence of MECE was predominantly higher in males, with a male-to-female ratio of approximately 7:1. The mid-thoracic segment emerged as the most common site of occurrence. A mere 6.3% of cases were correctly diagnosed preoperatively. The lymph node metastasis rate stood at 35.4%. The overall 1-year, 3-year, 5-year, and 10-year survival rates for all patients were 85.4%, 52.1%, 37.0%, and 31.0%, respectively. Post 1:1 propensity score matching, no significant statistical difference was observed in the Overall Survival (OS) between MEC patients and those with Esophageal Squamous Cell Carcinoma (ESCC) and Esophageal Adenocarcinoma (EAC) (P = 0.119, P = 0.669). Univariate analysis indicated that T staging and N staging were the primary factors influencing the prognosis of esophageal MEC. CONCLUSIONS: MECE occurs more frequently in males than females, with the mid-thoracic segment being the most common site of occurrence. The rate of accurate preoperative endoscopic diagnosis is low. The characteristic of having a short lesion length yet exhibiting significant extramural invasion may be a crucial clinicopathological feature of MECE. The OS of patients with MEC does not appear to significantly differ from those with esophageal squamous carcinoma and adenocarcinoma.

Co-Removal of Perfluorooctanoic Acid and Nitrate from Water by Coupling Pd Catalysis with Enzymatic Biotransformation.

PFAS (poly- and per-fluorinated alkyl substances) represent a large family of recalcitrant organic compounds that are widely used and pose serious threats to human and ecosystem health. Here, palladium (Pd0)-catalyzed defluorination and microbiological mineralization were combined in a denitrifying H2-based membrane biofilm reactor to remove co-occurring perfluorooctanoic acid (PFOA) and nitrate. The combined process, i.e., Pd-biofilm, enabled continuous removal of ∼4 mmol/L nitrate and ∼1 mg/L PFOA, with 81% defluorination of PFOA. Metagenome analysis identified bacteria likely responsible for biodegradation of partially defluorinated PFOA: Dechloromonas sp. CZR5, Kaistella koreensis, Ochrobacterum anthropic, and Azospira sp. I13. High-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and metagenome analyses revealed that the presence of nitrate promoted microbiological oxidation of partially defluorinated PFOA. Taken together, the results point to PFOA-oxidation pathways that began with PFOA adsorption to Pd0, which enabled catalytic generation of partially or fully defluorinated fatty acids and stepwise oxidation and defluorination by the bacteria. This study documents how combining catalysis and microbiological transformation enables the simultaneous removal of PFOA and nitrate.

Reliability and validity of the cancer-related dysfunctional beliefs and attitudes about sleep scale in cancer patients.

BACKGROUND: Insomnia is a common health problem among cancer patients, which is not only a physical problem but also a psychological problem. Sleep plays an important role in the mental and somatic rehabilitation of cancer patients, and the sleep beliefs and attitudes of cancer patients are key factors in improving their sleep situation and quality of life. The aim of this study was to translate the Cancer-Related Dysfunctional Beliefs and Attitudes about Sleep (C-DBAS-14) scale into Chinese and to validate its reliability and validity in cancer patients. METHOD: The C-DBAS-14 scale was translated into Chinese using the backward and forward translation procedure. The reliability of the scale was measured by internal consistency, split-half reliability and retest reliability. The validity of the scale was assessed through the content validity indicators, exploratory factor analysis and validation factor analysis. RESULT: The Cronbach's ɑ coefficient of the Chinese version of the C-DBAS-14 was 0.932 while the McDonald's omega coefficient (ω t) was 0.934. The split-half reliability coefficient was 0.908, and the test-retest reliability was 0.857. The four-factor model was obtained using exploratory factor analysis, explaining 72.7% of the variance, with each item loading greater than 0.4 on the common factor. The results of the confirmatory factor analysis revealed that all indicators of model fit were within an acceptable range, indicating a well-fitting model. CONCLUSION: The Chinese version of the C-DBAS-14 has good reliability and validity among cancer patients. It can be used to measure the sleep beliefs and attitudes of Chinese cancer patients.

Effect of ethanol on the elasticities of double-stranded RNA and DNA revealed by magnetic tweezers and simulations.

The elasticities of double-stranded (ds) DNA and RNA, which are critical to their biological functions and applications in materials science, can be significantly modulated by solution conditions such as ions and temperature. However, there is still a lack of a comprehensive understanding of the role of solvents in the elasticities of dsRNA and dsDNA in a comparative way. In this work, we explored the effect of ethanol solvent on the elasticities of dsRNA and dsDNA by magnetic tweezers and all-atom molecular dynamics simulations. We found that the bending persistence lengths and contour lengths of dsRNA and dsDNA decrease monotonically with the increase in ethanol concentration. Furthermore, the addition of ethanol weakens the positive twist-stretch coupling of dsRNA, while promotes the negative twist-stretch coupling of dsDNA. Counter-intuitively, the lower dielectric environment of ethanol causes a significant re-distribution of counterions and enhanced ion neutralization, which overwhelms the enhanced repulsion along dsRNA/dsDNA, ultimately leading to the softening in bending for dsRNA and dsDNA. Moreover, for dsRNA, ethanol causes slight ion-clamping across the major groove, which weakens the major groove-mediated twist-stretch coupling, while for dsDNA, ethanol promotes the stretch-radius correlation due to enhanced ion binding and consequently enhances the helical radius-mediated twist-stretch coupling.

RotatedStomataNet: a deep rotated object detection network for directional stomata phenotype analysis.

KEY MESSAGE: Innovatively, we consider stomatal detection as rotated object detection and provide an end-to-end, batch, rotated, real-time stomatal density and aperture size intelligent detection and identification system, RotatedeStomataNet. Stomata acts as a pathway for air and water vapor in the course of respiration, transpiration, and other gas metabolism, so the stomata phenotype is important for plant growth and development. Intelligent detection of high-throughput stoma is a key issue. Nevertheless, currently available methods usually suffer from detection errors or cumbersome operations when facing densely and unevenly arranged stomata. The proposed RotatedStomataNet innovatively regards stomata detection as rotated object detection, enabling an end-to-end, real-time, and intelligent phenotype analysis of stomata and apertures. The system is constructed based on the Arabidopsis and maize stomatal data sets acquired destructively, and the maize stomatal data set acquired in a non-destructive way, enabling the one-stop automatic collection of phenotypic, such as the location, density, length, and width of stomata and apertures without step-by-step operations. The accuracy of this system to acquire stomata and apertures has been well demonstrated in monocotyledon and dicotyledon, such as Arabidopsis, soybean, wheat, and maize. The experimental results that the prediction results of the method are consistent with those of manual labeling. The test sets, the system code, and their usage are also given ( https://github.com/AITAhenu/RotatedStomataNet ).

The effect of different high-intensity interval training protocols on cardiometabolic and inflammatory markers in sedentary young women: A randomized controlled trial.

Few studies have reported the cardiovascular health effects of different high-intensity interval training (HIIT) protocols among sedentary young women. We investigated the impact of a traditional HIIT programme and a high-intensity circuit training (HICT) programme on lipid profiles and inflammatory cytokine levels in sedentary young women. Forty-two women were randomly assigned to HICT (body weight-based training), HIIT (cycling-based training), or control groups (n = 14 each). HICT and HIIT participants completed an 8-week training programme of three sessions per week. Total cholesterol (TC), triglyceride, high- and low-density lipoprotein, leptin, resistin, tumour necrosis factor-alpha (TNF-α), interleukin-8, and interferon-gamma levels were measured before and after the intervention. Post-intervention, TC and leptin were decreased in the HICT group. The HICT group also demonstrated increased lean mass, upper and lower limb strength, and balance, while the HIIT group displayed improved lower limb strength. Additionally, the control group showed significant increases in triglyceride levels, weight, body mass index, and fat mass. In conclusion, although both HICT and HIIT interventions showed improvements in cardiovascular health and physical fitness, participants in the HICT group experienced more health benefits.

A novel simplified approach for endodontic retrograde surgery in short single-rooted teeth.

BACKGROUND: High technical thresholds, long operative times, and the need for expensive and specialized equipment impede the widespread adoption of endodontic microsurgery in many developing countries. This study aimed to compare the effects of a simplified, cost-effective, and time-efficient surgical approach involving orthograde obturation using biological ceramic material greater than 6 mm combined with apicoectomy for single-rooted teeth with short lengths with those of the conventional and current standard methods. MATERIALS AND METHODS: Forty-five premolars equally categorized into three groups: conventional surgery group, standard surgery group, and modified surgery group. A µCT scan was used to calculate the volume of voids. A micro-leakage test and scanning electron microscope (SEM) were performed to assess the sealing effect. Additionally, four cases of chronic periapical periodontitis in the anterior region were selected, and the patients received either the modified approach or the standard surgery for endodontic microsurgery. RESULTS: The volumes of voids in the apical 0-3 mm of the modified group and the standard group were comparable. The micro-leakage test and SEM examination demonstrated closely bonded fillings in the dentinal walls in both the modified surgery group and standard surgery group. The outcomes of the preliminary application of this modified procedure on patients were successful at the time of the follow-up cutoff. CONCLUSIONS: The modified surgery group exhibited similar root canal filling and apical sealing abilities with the standard procedure for single-rooted teeth with short lengths (< 20 mm). The preliminary application of this modified surgical procedure achieved favorable results.

Physical exercise-related manifestations of long COVID: A systematic review and meta-analysis.

Objective: This study aims to systematically assess physical exercise-related symptoms of post-acute sequelae of SARS-CoV-2 infection (PASC or long COVID) in coronavirus disease 2019 (COVID-19) survivors. Methods: Eight databases were systematically searched on March 03, 2024. Original studies that compared physical exercise-related parameters measured by exercise testing between COVID-19 survivors who recovered from SARS-CoV-2 infection over 3 months and non-COVID-19 controls were included. A random-effects model was utilized to determine the mean differences (MDs) or standardized MDs in the meta-analysis. Results: A total of 40 studies with 6241 COVID-19 survivors were included. The 6-min walk test, maximal oxygen consumption (VO2max), and anaerobic threshold were impaired in COVID-19 survivors 3 months post-infection compared with non-COVID-19 controls in exercise testing, while VO2 were comparable between the two groups at rest. In contrast, no differences were observed in SpO2, heart rate, blood pressure, fatigue, and dyspnea between COVID-19 survivors and non-COVID-19 controls in exercise testing. Conclusion: The findings suggest an underestimation of the manifestations of PASC. COVID-19 survivors also harbor physical exercise-related symptoms of PASC that can be determined by the exercise testing and are distinct from those observed at rest. Exercise testing should be included while evaluating the symptoms of PASC in COVID-19 survivors.

[FMECA and Failure Data Analysis of Domestic Wheeled Walking-Aid].

The gradual acceleration of the aging population in China has led to an increased demand for mobility aids, and the reliability of domestic wheeled walking-aid is one of their important attributes, but there is little research on the reliability of mobility aids. This paper conducts the failure mode, effects and criticality analysis on domestic wheeled walking-aid. By collecting, collating and analyzing the 26 failure modes, the key modules are the chassis and the lifting system. The key modules are obtained, and the failure data is analyzed to find out that the lifetime distribution model is log-normal and the 0.95 lower confidence limit for reliability life of product t 0.9 is 2489.4 hours. The study aims to provide ideas for the reliability analysis of other active medical devices and calls for the formation of a reliability study review point for the industry that meets the requirements of Chinese medical device regulations.

Putting it Together, Together.

People are not as fast or as strong as many other creatures that evolved around us. What gives us an evolutionary advantage is working together to achieve common aims. Coordinating joint action begins at a tender age with such cooperative activities as alternating babbling and clapping games. Adult joint activities are far more complex and use multiple means of coordination. Joint action has attracted qualitative analyses by sociolinguists, cognitive scientists, and philosophers as well as empirical analyses and theories by cognitive scientists. Here, we analyze how joint action is spontaneously coordinated from start to finish in a novel complex real-life joint activity, assembling a piece of furniture, a task that captures the essentials of joint action, collaborators, things in the world, and communicative devices. Pairs of strangers assembled a TV cart from a stack of parts and a photo of the completed cart. Coordination prior to each assembly action was coded as explicit, using speech or gesture, or implicit, actions that both advanced the task and communicated the next step. Initial planning relied on explicit communication about structure, but not action nor division of labor, which were improvised. That served to establish a joint representation of the goal that informed actions and monitored progress. As assembly progressed, coordination was increasingly implicit, through actions alone. Joint action is a dynamic interplay of explicit and implicit signaling with respect to things in the world to coordinate ongoing progress, guided by a shared representation of the goal.

Psychometric properties of the Chinese version of the health behavior motivation scale: a translation and validation study.

Objective: This study's objectives were to translate the Health Behavior Motivation Scale (HBMS) into Chinese and verify the scale's validity and reliability among Chinese healthy adults. Method: The HBMS scales were translated into Chinese based on Brislin's principles. The Chinese version of HBMS is created through translation, back translation, and cross-cultural adaptation. This investigation implemented the convenience sampling method to conduct a survey on 781 healthy respondents, utilizing the Chinese version of the HBMS and a general demographic questionnaire. We used AMOS (v28.0) and SPSS (v26.0) for statistical analysis. We employed test-retest reliability, split-half reliability, and internal consistency to assess the reliability of the translation questionnaire. Structure validity and content validity were used to assess validity. Results: The Chinese version of the Health Behavior Motivation Scale (HBMS) had a Cronbach's alpha coefficient of 0.885, and the range of Cronbach's alpha values for each dimension was 0.820-0.885. The scale's test-retest reliability was 0.824, and its split-half reliability was 0.906. Five public factors with a cumulative variance contribution of 56.527% were retrieved from the exploratory factor analysis. Moreover, the factor loading value for each item exceeded 0.4.In confirmatory factor analysis, the indicators were reported as follows: χ2/df = 1.567, GFI = 0.900, CFI = 0.952, IFI = 0.952, TLI = 0.946, AGFI = 0.881, PGFI = 0.757, PNFI = 0.789, RMSEA = 0.039, and the results of the model fit metrics were within the reference range. Conclusion: The Chinese version of the HBMS exhibits strong discrimination, validity, and reliability. The tool effectively identifies the motivation of healthy people to engage in healthy behaviors. It can be used by healthcare practitioners to assist in the development of follow-up interventions to reduce the prevalence of chronic disease in older people and the incidence of chronic disease in populations of young and middle-aged people.

Mn Cluster-Embedded N/F Co-Doped Carbon toward Mild Aqueous Supercapacitors.

Aqueous supercapacitors have occupied a significant position among various types of stationary energy storage equipment, while their widespread application is hindered by the relatively low energy density. Herein, N/F co-doped carbon materials activated by manganese clusters (NCM) are constructed by the straightforward experimental routine. Benefiting from the elevated conductivity structure at the microscopic level, the optimized NCM-0.5 electrodes exhibited a remarkable specific capacitance of 653 F g-1 at 0.4 A g-1 and exceptional cycling stability (97.39% capacity retention even after 40,000 cycles at the scanning rate of 100 mV s-1) in a neutral 5 M LiCl electrolyte. Moreover, we assembled an asymmetric device pairing with a VOx anode (NCM-0.5//VOx), which delivered a durable life span of 95% capacity retention over 30,000 cycles and an impressive energy density of 77.9 Wh kg-1. This study provides inspiration for transition metal element doping engineering in high-energy storage equipment.

Comparison between thermal ablation and surgery in low risk papillary thyroid carcinoma: a prospective study.

Objective: To conduct a comparative analysis of the efficacy, safety, and impact on quality of life outcomes between thermal ablation and surgical interventions in patients diagnosed with papillary thyroid carcinoma (PTC). Methods: A prospective study was undertaken, enrolling patients with PTC ≤5mm who underwent radiofrequency ablation (RFA), laser ablation (LA), or surgery, for analysis of efficacy and safety outcomes. The Thyroid Cancer-Specific Quality of Life questionnaire was administered to all patients before treatment and at 3, 6, and 12 months post-treatment. Results: A total of 162 eligible patients were included in the study. Major complications were not observed in the RFA and LA groups, while five cases were reported in the surgery group, although no statistically significant differences were observed. Minor complications were documented in two, three, and 14 patients in the RFA, LA, and surgery groups, respectively, with no significant variances noted. Surgical duration and hospitalization time were notably shorter in the thermal ablation groups. At the final follow-up, complete disappearance of nodules was seen in 71.4% of cases treated with RFA and 71.0% of cases managed with LA, with no significant disparities between the groups. Both RFA and LA exhibited similar effects on quality of life, with thermal ablation techniques showing better functional outcomes in comparison to surgery. Across all groups, adverse effects were most pronounced at the 3-month post-treatment mark but gradually reverted to baseline levels in the thermal ablation group, contrasting with the surgery group. Conclusions: For PTC ≤5mm, both RFA and LA exhibited similar cancer control outcomes and superior quality of life on par with surgery, while minimizing complications. These findings underscore the promise of RFA and LA as potential standard treatments for small PTCs, subject to further confirmation in future studies.

Effects of intermittent dieting with break periods on body composition and metabolic adaptation: a systematic review and meta-analysis.

CONTEXT: Intermittent dieting incorporated with break periods (INT-B) has recently been promoted as an alternative dietary approach for optimal weight management. OBJECTIVE: This study assessed the effectiveness of INT-B compared with that of conventional continuous energy restriction (CER) for improving body composition and attenuating metabolic adaptation. DATA SOURCES: A systematic search was conducted on 6 databases using all available records until July 2023. DATA EXTRACTION: The extracted data included the lead author, year of publication, population characteristics, intervention protocols, duration, and adherence. DATA ANALYSIS: Random-effects meta-analyses were conducted for within-group and between-group comparisons of anthropometric and metabolic outcomes. Subgroup moderator analysis was performed for the types of INT-B, intervention duration, and population characteristics. RESULTS: Of the 1469 records, 12 randomized trials (with 881 participants) were included. Within-group analyses demonstrated significant improvements in body mass, fat mass, body mass index, body fat percentage, and waist circumference following both INT-B and CER, with no significant group differences. However, resting metabolic rate (RMR) was significantly reduced following CER only. The compensatory reduction in RMR was significantly smaller following INT-B compared with CER, suggesting a lesser degree of metabolic adaptation. INT-B had a more significant effect on RMR retention in individuals with overweight/obesity compared with resistance-trained individuals. CONCLUSION: This review provides up-to-date evidence for INT-B as a viable dietary strategy to improve body composition and attenuate metabolic adaptation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42023448959.

One-pot green solid-state synthesis of Cu2O/microcrystalline cellulose composite with high anti-pathogenic activity.

Cuprous oxide (Cu2O) is proven as an excellent anti-harmful microbial material. However, the liquid and vapor pha5se preparation methods reported so far hardly make pure Cu2O-containing composites and suffer environmental issues caused by chemical reducing agents with multiple processing steps. This work develops a facile one-pot solid-state sintering method to synthesize Cu2O/microcrystalline cellulose (MCC) composite via the thermal decomposition and oxidation-reduction reactions where copper formate was reduced by MCC. The Cu2O/MCC composite exhibits superior purity, dispersibility, stability, high yield, and high efficacy of antibacterial and antiviral properties, e.g., against E. coli, S. aureus, and Equine Arteritis Viral. This work utilizes elegantly the strong reducing capability of cellulose to develop an environmentally benign method to prepare high-purity Cu2O-polymer composites with low cytotoxicity and cost, which can be incorporated readily into other substrate materials to form various forms of anti-harmful microbial materials widely used in public health care products. In addition, the preparation of Cu2O-containing composites based on the reducing capability of cellulose is also expected to be applied to other cellulose-based materials for the loading of Cu2O particles.

Dapagliflozin ameliorates hepatic steatosis via suppressing LXRα-mediated synthesis of lipids and bile acids.

Nonalcoholic fatty liver disease (NAFLD) prevalence is rising globally with no pharmacotherapies approved. Hepatic steatosis is closely associated with progression and prognosis of NAFLD. Dapagliflozin, kind of sodium-glucose cotransporter 2 (SGLT2) inhibitor, was found to improve NAFLD in clinical trials, while the underlying mechanism remains poorly elucidated. Here, we reported that dapagliflozin effectively mitigated liver injury and relieved lipid metabolism disorders in vivo. Further investigation showed that dapagliflozin markedly suppressed Liver X Receptor α (LXRα)-mediated synthesis of de novo lipids and bile acids (BAs). In AML12 cells, our results proved dapagliflozin decreased lipid contents via inhibiting the expression of LXRα and downstream liposynthesis genes. Proteosome inhibitor MG132 eliminated the effect of dapagliflozin on LXRα-mediated signaling pathway, which suggested that dapagliflozin downregulated LXRα expression through increasing LXRα degradation. Knockdown of LXRα with siRNA abolished the reduction of lipogenesis from dapagliflozin treatment, indicating that LXRα might be the pivotal target for dapagliflozin to exhibit the aforementioned benefits. Furthermore, the data showed that dapagliflozin reversed gut dysbiosis induced by BAs disruption and altered gut microbiota profile to reduce intestinal lipids absorption. Together, our study deciphered a novel mechanism by which dapagliflozin relieved hepatic steatosis and highlighted the potential benefit of dapagliflozin in treating NAFLD.

Long-term causal effects estimation via latent surrogates representation learning.

Estimating long-term causal effects based on short-term surrogates is a significant but challenging problem in many real-world applications such as marketing and medicine. Most existing methods estimate causal effects in an idealistic and simplistic manner - disregarding unobserved surrogates and treating all short-term outcomes as surrogates. However, such methods are not well-suited to real-world scenarios where the partially observed surrogates are mixed with the proxies of unobserved surrogates among short-term outcomes. To address this issue, we develop our flexible method called LASER to estimate long-term causal effects in a more realistic situation where the surrogates are either observed or have observed proxies. In LASER, we employ an identifiable variational autoencoder to learn the latent surrogate representation by using all the surrogate candidates without the need to distinguish observed surrogates or proxies of unobserved surrogates. With the learned representation, we further devise a theoretically guaranteed and unbiased estimation of long-term causal effects. Extensive experimental results on the real-world and semi-synthetic datasets demonstrate the effectiveness of our proposed method.