Psychotherapeutic and pharmacological agents for post-traumatic stress disorder with sleep disorder: network meta-analysis.

OBJECTIVE: The current guidelines and canonical norms of diagnosis or treatment for Post-traumatic stress disorder (PTSD) with sleep disorder are still conflicting and have not yet reached a consensus. This study aimed to unravel the most effective countermeasures between two categories (psychotherapy and pharmacotherapy) put forward by the National Institute for Health and Clinical Excellence (NICE) and World Federation of Societies of Biological Psychiatry (WFSBP) respectively to treat PTSD individuals co-exist with sleep disorders. METHODS: Four databases, including PubMed, EMBASE, Cochrane Library, and APA PsyNet, were searched from inception to February 02, 2023. RESULTS: Twenty articles with 24 Randomized controlled trials (RCTs) and a total number of 1,647 participants were included. As demonstrated in the network meta-analysis comparison results, CBT-I (standardized mean differences (SMD) = -1.51,95% confidence interval (CI):-2.55 to -0.47), CBT-I plus IRT (SMD = -1.71, 95%CI:-3.39, -0.03), prazosin (SMD = -0.87,95%CI:-1.59 to -0.16) and hydroxyzine (SMD = -1.06, 95%CI: -1.94 to -0.19) significantly reduced PTSD symptoms compared with placebo. In contrast to placebo, CBT-I (SMD = -5.61,95%CI:-8.82 to -2.40) significantly improved sleep quality. For nightmare severity, IRT (SMD =-0.65, 95%CI:-1.00 to -0.31), prazosin (SMD = -1.20,95%CI:-1.72 to -0.67) and hydroxyzine (SMD = -0.98,95%CI:-1.58 to -0.37) significantly reduced nightmare severity in comparison with placebo. CONCLUSIONS: This study suggested that under most circumstances, psychotherapy namely CBT-I had a favorable profile, but pharmacotherapy with prazosin was effective in managing nightmare severity. The sole avail of CBT-I was recommended to improving sleep quality while CBT-I and CBT-I plus IRT showed excellent management of PTSD symptom severity. Exposure to CBT-I isrecommended for depression. The relevant clinical guidelines for the management of individuals with PTSD and sleep disorders may regard this as a reference. PROSPERO: CRD42023415240.

Ultrafast Visual Detection of a Trace Amount of Water by Highly Efficient Hybrid Manganese Halides.

A quantitative water detection method is urgently needed in storage facilities, space exploration, and the chemical industry. Although numerous physical techniques have been widely utilized to determine the water content, they still suffer from many disadvantages such as highly expensive special instruments, complicated analysis processes, etc. Hence, a convenient, rapid, and sensitive water analysis method is highly desirable. Herein, we developed a visual fluorescence sensing technology for water detection based on reversible PL off-on switching of organic-inorganic hybrid zero-dimensional (0D) manganese halides. In this work, a family of hybrid manganese halides were synthesized through a facile solution method, namely, [NH4(18-Crown-6)]2MnBr4, [Ca(18-Crown-6)·3H2O](18-Crown-6)MnBr4, [NH4(dibenzo-18-Crown-6)]2MnBr4, and [Ca(dibenzo-18-Crown-6)·2H2O]MnBr4. Excited by UV light, these highly crystalline manganese halides exhibit strong green light emissions from the d-d electron transition of Mn2+ with near-unity photoluminescence quantum yield and submillisecond lifetime. Benefiting from the dynamic and weak ionic bonding interactions, these 0D manganese halides display reversible water-response on/off luminescence switching but fail in any other aprotic solvents. Therefore, these 0D hybrid manganese halides can be explored as ultrafast visual fluorescence probes to detect the trace amount of water in organic solvents with multiple superiorities of rapid response time (< 2 s), ultralow detection limit (9.71 ppm), excellent repeatability, etc. The reversible water-response luminescent on/off switching also provides a binary optical gate with advanced applications in anticounterfeiting and information security, etc.

The Flavonoid Glycoside from Abrus cantoniensis Hance Alleviates Alcoholic Liver Injury by Inhibiting Ferroptosis in an AMPK-Dependent Manner.

Abrus cantoniensis Hance is a vegetative food and can be used as a folk beverage or soup to clear liver toxins and prevent liver damage. However, the components and effects of A. cantoniensis Hance in alcohol-induced liver injury were unknown. This study aimed to obtain abundant phytochemicals from A. cantoniensis Hance and identify the potency of the isolates in preventing alcohol-induced liver injury. Alcohol-stimulated AML12 cells and Lieber-DeCarli diet-fed mice were used to establish in vitro and in vivo models, respectively. Our findings indicated that flavonoid glycosides, especially AH-15, could significantly alleviate alcohol-induced liver injury by inhibiting oxidative stress. Furthermore, we demonstrated that AH-15 inhibited ferroptosis induced by lipid peroxidation. Mechanically, we found that AH-15 regulated nuclear factor erythroid 2-related factor 2 (NRF2) expression via activation of AMP-activated protein kinase (AMPK) signaling. These results indicate that A. cantoniensis Hance is a great potential functional food for alleviating alcohol-induced liver injury.

Missing data imputation using classification and regression trees.

Background: Missing data are common when analyzing real data. One popular solution is to impute missing data so that one complete dataset can be obtained for subsequent data analysis. In the present study, we focus on missing data imputation using classification and regression trees (CART). Methods: We consider a new perspective on missing data in a CART imputation problem and realize the perspective through some resampling algorithms. Several existing missing data imputation methods using CART are compared through simulation studies, and we aim to investigate the methods with better imputation accuracy under various conditions. Some systematic findings are demonstrated and presented. These imputation methods are further applied to two real datasets: Hepatitis data and Credit approval data for illustration. Results: The method that performs the best strongly depends on the correlation between variables. For imputing missing ordinal categorical variables, the rpart package with surrogate variables is recommended under correlations larger than 0 with missing completely at random (MCAR) and missing at random (MAR) conditions. Under missing not at random (MNAR), chi-squared test methods and the rpart package with surrogate variables are suggested. For imputing missing quantitative variables, the iterative imputation method is most recommended under moderate correlation conditions.

Designed Synthesis of an Aluminum Molecular Ring Based Rotaxane and Polyrotaxane.

Mechanically interlocked molecules, such as rotaxanes, have drawn significant attention within supramolecular chemistry. Although a variety of macrocycles have been thoroughly explored in rotaxane synthesis, metal-organic macrocycles remain relatively under-investigated. Aluminum molecular rings, with their inner cavities and numerous binding sites, present a promising option for constructing rotaxanes. Here, we introduce an innovative "ring-donor···axle-acceptor" motif utilizing Al8 molecular rings, enabling the stepwise assembly of molecules, complexes, and polymers through tailored coordination chemistry. This novel approach can not only be applied to macrocycle-based systems like catenanes but also enhance specific functionalities progressively.

The effect of citral loading and fatty acid distribution on the oleogels: Physicochemical properties and in vitro digestion.

Oleogels containing bioactive substances such as citral (CT) are used as functional food ingredients. However, little information is available on the influence of different oleogel network structure caused by CT addition and fatty acid distribution on its digestion behavior. Coconut oil, palm oil, high oleic peanut oil, safflower seed oil, and perilla seed oil were used in this study. The results showed that perilla seed oil-CT-based oleogels had the highest oil-holding capacity (99.03 ± 0.3), whereas CT addition higher than 10 wt% could lead to the morphology collapse of oleogels. Physical and thermodynamic analyses revealed that CT could reduce oleogel hardness and higher unsaturated fatty acid content is more likely to form oleogel with stable and tight crystalline network. Moreover, the dense structure of oleogels hinders the contact between oleogels and lipase, thus weakening triglyceride digestion. These findings provide valuable insights into the design of oleogels loading with CT.

SRY-positive 45,X/46,XY karyotype in a phenotypically Turner-like Chinese adolescent female with ovarian dysgerminoma and gonadoblastoma.

OBJECTIVES: 45,X/46,XY mosaicism is a rare condition with clinical and genetic heterogeneity and have a greatly increased risk of developing germ cell tumors. We describe a rare 45,X/46,XY Chinese girl with malignant tumors, especially focusing on the molecular genetics of gonadal tumor. CASE PRESENTATION: We report a phenotypically Turner-like Chinese adolescent girl who presented primary amenorrhea and a pelvic mass as the chief complaint, which finally demonstrated dysgerminoma replacing the left gonad and gonadoblastoma arising from right gonad respectively. Her chromosome karyotype was 45,X(4)/46,XY(46); Y-chromosome microdeletions in AZFb regions were found on gonadal DNA rather than peripheral blood lymphocyte (PBL) DNA, while no variants were found in the promoter and coding region of SRY gene in both PBL and gonadal tissues. She underwent bilateral gonadectomy; no recurrence or serious complications were identified after 3 years of follow-up. CONCLUSIONS: This case emphasizes the probable correlation between Y chromosome microdeletions in gonadal tissue and the severity of the phenotype in patients with 45,X/46,XY mosaicism and highlights the importance of clinical genetic testing at the chromosomal and molecular level.

Impact of non-surgical periodontal treatment on dental anxiety: A comparative study on patients with periodontitis.

Background/purpose: Dental anxiety is prevalent and may result in the avoidance of periodontal therapy and maintenance. This study aimed to explore the impact of non-surgical periodontal treatment (NSPT) on dental anxiety among patients with periodontitis. Materials and methods: In this study, 122 patients with periodontitis participated. The Chinese version of the Modified Dental Anxiety Scale (MDAS) gauged baseline dental anxiety during the initial appointment. Patients receiving non-surgical periodontal treatment (NSPT) in subsequent appointments formed the NSPT group, while those with a delayed NSPT of at least two months constituted the delayed group. In the NSPT group, the second termination questionnaire was administered one month post the last NSPT visit, just before the periodontal re-evaluation. In the delayed group, the second questionnaire was completed before the delayed NSPT initiation. Results: Baseline MDAS scores were comparable between the delay and NSPT groups. However, the NSPT group exhibited lower total scores and scores for each of the five MDAS items at termination compared with the delay group. At baseline, MDAS total scores were inversely associated with age and were lower in males. A reduction in MDAS total scores between observation points was correlated with NSPT, sex, and age after adjustment. Regarding MDAS item 4 (teeth scaled/polished), score reduction consistently correlated with NSPT and age. Conclusion: Participation in NSPT may alleviate dental anxiety, and consequently enhance the patients' conceptiveness to undergo periodontal maintenance or surgery.

Zero-Dimensional Copper(I) Halide Microcrystals as Highly Efficient Scintillators for Flexible X-ray Imaging.

Commercially available rare-earth-doped inorganic oxide materials have been widely applied as X-ray scintillators, but the fragile characteristics, high detection limit, and harsh preparation condition seriously restrict their wide applications. Furthermore, it remains a huge challenge to realize X-ray flexible imaging technology for real-time monitoring of the curving interface of complex devices. To address these issues, we herein report two isostructural cuprous halides of zero-dimensional (0D) [AEPipz]CuX3·X·H2O (AEPipz = N-aminoethylpiperazine, X = Br and I) with controllable size to nanosize crystal as highly efficient scintillators toward flexible X-ray imaging. These cuprous halides exhibit highly efficient cyan photoluminescence and radioluminescence emissions with the highest quantum yield of 92.1% and light yield of 62,400 photons MeV-1, respectively, surpassing most of the commercially available inorganic scintillators. Meanwhile, the ultralow detection limit of 95.7 nGyair s-1 was far below the X-ray dose required for diagnosis (5.5 µGyair s-1). More significantly, the flexible film is facilely assembled with excellent foldability and high crack resistance, which further acts as a scintillation screen achieving a high spatial resolution of 17.4 lp mm-1 in X-ray imaging, demonstrating the potential application in wearable radiation radiography. The combined advantages of high light yield, low detection limit, and excellent flexibility promote these 0D cuprous halides as the most promising X-ray scintillators.

Changes in metabolic overweight phenotypes over time and risk of nephrolithiasis: a cohort study.

BACKGROUND: Overweight/obesity is considered an independent risk factor for nephrolithiasis, but little is known about its effect on nephrolithiasis according to metabolic health status. OBJECTIVES: We aimed to investigate the association between various metabolic overweight phenotypes and the occurrence of nephrolithiasis. It also explores whether changes in these phenotypes over time influence the risk of nephrolithiasis. MATERIALS AND METHODS: A total of 10,315 participants free of nephrolithiasis who underwent an annual health checkup from 2017 to 2022 were included in our prospective cohort study. They were categorized into four groups according to the presence of overweight and metabolic abnormalities (MA). The primary endpoint was the occurrence of renal stones. Multivariable Cox analysis was conducted to elucidate the relationship between metabolic overweight phenotypes and incident nephrolithiasis. RESULTS: During a median follow-up duration of 4.02 years, nephrolithiasis occurred in 1,468 (14.23%) participants. In the full cohort, we observed that the 5-year cumulative incidences of nephrolithiasis were highest in the metabolically healthy overweight (MHO) and metabolically abnormal overweight (MAO) groups. The hazard ratios (HRs) for nephrolithiasis, relative to metabolically healthy normal weight (MHNW), ranged from 1.19 (95% CI:1.03-1.37; MHO) to 1.32 (95% CI:1.15-1.51; MAO). Furthermore, individuals with persistent MHO throughout follow-up were at a 1.42-fold increased risk of nephrolithiasis (P < 0.001), and 32.17% of individuals experienced changes in phenotype during follow-up. Among MAO subjects, those who transitioned to MHO and MHNW had a 26% and 45% lower risk of incident nephrolithiasis, respectively, compared to those who persisted in the MAO phenotype. CONCLUSION: Individuals in the MHO and MAO groups exhibit an elevated risk of incident nephrolithiasis in this prospective cohort study. A significant proportion of nephrolithiasis cases may be potentially preventable through the appropriate management of metabolic risk factors for MAO subjects.

A Novel Melanin-Targeted 18F-PFPN Positron Emission Tomography Imaging for Diagnosing Ocular and Orbital Melanoma.

OBJECTIVE: 18F-N-(2-(Diethylamino)ethyl)-5-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy) picolinamide (18F-PFPN) is a novel positron emission tomography (PET) probe designed to specifically targets melanin. This study aimed to evaluate the diagnostic feasibility of 18F-PFPN in patients with ocular or orbital melanoma. MATERIALS AND METHODS: Three patients with pathologically confirmed ocular or orbital melanoma (one male, two females; age 41-59 years) were retrospectively reviewed. Each patient underwent comprehensive 18F-PFPN and 18F-fluorodeoxyglucose (18F-FDG) PET scans. The maximum standardized uptake value (SUVmax) of the lesion and the interference caused by background tissue were compared between 18F-PFPN and 18F-FDG PET imaging. In addition, the effect of intrinsic pigments in the uvea and retina on the interpretation of the results was examined. The contralateral non-tumorous eye of each patient served as a control. RESULTS: All primary tumors (3/3) were detected using 18F-PFPN PET, while only two primary tumors were detected using 18F-FDG PET. Within each lesion, the SUVmax of 18F-PFPN was 2.6 to 8.3 times higher than that of 18F-FDG. Regarding the quality of PET imaging, the physiological uptake of 18F-FDG PET in the brain and periocular tissues limited the imaging of tumors. However, 18F-PFPN PET minimized this interference. Notably, intrinsic pigments in the uvea and retina did not cause abnormal concentrations of 18F-PFPN, as no anomalous uptake of 18F-PFPN was detected in the healthy contralateral eyes. CONCLUSION: Compared to 18F-FDG, 18F-PFPN demonstrated higher detection rates for ocular and orbital melanomas with minimal interference from surrounding tissues. This suggests that 18F-PFPN could be a promising clinical diagnostic tool for distinguishing malignant melanoma from benign pigmentation in ocular and orbital melanomas.

Income gap between male and female psychiatric nurses in China: A national survey.

AIM: To investigate gender differences in the actual and expected income among psychiatric nurses in China. BACKGROUND: Although studies have shown that male nurses earn more than female nurses in other countries, there are no published data regarding gender income differences among psychiatric nurses in China. METHODS: We conducted a cross-sectional study involving 41 representative psychiatric hospitals in China. Demographic, income, and job-related data were analyzed using the inverse probability of treatment weighting (IPTW) based on the propensity score. FINDINGS: The sample included 9256 psychiatric nurses, and nearly four-fifths (79.3%) were female. Males earned slightly higher average monthly incomes than female nurses, while initial analysis showed no significant overall gender income difference (p > 0.05). Notably, most participants (92.5%) desired an income increase of at least 10%, with over half (56.2%) expressing significant dissatisfaction with their current income. After adjustment using propensity score combined with IPTW, females in the junior and mid-level groups had significantly lower income than their male counterparts (all p < 0.01), despite having different night shift patterns. However, there were no significant gender differences in actual or expected income among senior-level psychiatric nurses (p > 0.05). CONCLUSION: A majority of psychiatric nurses in China express dissatisfaction with their current incomes and expect higher incomes. Male nurses earned significantly more than female nurses in the junior and mid-level professional groups, potentially due to their differences in night shifts. IMPLICATIONS FOR NURSING POLICY AND HEALTH POLICY: Policymakers and hospital administrators should optimize the income structures of nurses and develop targeted policies to address the gender income gap. Improving nurse income has the potential to enhance motivation and satisfaction within the profession.

Continuous Optical Zoom Compound Eye Imaging Using Alvarez Lenses Actuated by Dielectric Elastomers.

The compound eye is a natural multi-aperture optical imaging system. In this paper, a continuous optical zoom compound eye imaging system based on Alvarez lenses is proposed. The main optical imaging part of the proposed system consists of a curved Alvarez lens array (CALA) and two Alvarez lenses. The movement of the CALA and two Alvarez lenses perpendicular to the optical axis is realized by the actuation of the dielectric elastomers (DEs). By adjusting the focal length of the CALA and the two Alvarez lenses, the proposed system can realize continuous zoom imaging without any mechanical movement vertically to the optical axis. The experimental results show that the paraxial magnification of the target can range from ∼0.30× to ∼0.9×. The overall dimensions of the optical imaging part are 54 mm × 36 mm ×60 mm (L × W × H). The response time is 180 ms. The imaging resolution can reach up to 50 lp/mm during the optical zoom process. The proposed continuous optical zoom compound eye imaging system has potential applications in various fields, including large field of view imaging, medical diagnostics, machine vision, and distance detection.

MicroRNAs in opisthorchiids and their definitive hosts: Current Status and Perspectives.

Opisthorchis felineus, Opisthorchis viverrini, and Clonorchis sinensis (family Opisthorchiidae) are parasitic flatworms that pose serious threats to humans in certain countries and cause opisthorchiasis/clonorchiasis. Opisthorchiid flukes parasitize the biliary tract of the host, causing cholangitis, cholecystitis, cholelithiasis and cholangiocarcinoma. In this review, we primarily focus on recent microRNAs (miRNAs) studies of opisthorchiid flukes and their definitive hosts. Many miRNAs are conserved and expressed in a developmentally stage specific manner in the three opisthorchiid flukes, which play important roles in the growth and development of Opisthorchiidae spp., as well as host-pathogen interactions. Some miRNAs might be potential biomarkers related to carcinogenesis of cholangiocarcinoma. Therefore, this review provides the basis for further investigating the roles of miRNAs in opisthorchiid flukes and their definitive hosts, as well as promoting the development of novel approaches to prevent and treat opisthorchiasis/clonorchiasis.

Lefamulin Overcomes Acquired Drug Resistance via Regulating Mitochondrial Homeostasis by Targeting ILF3 in Hepatocellular Carcinoma.

Acquired resistance represents a critical clinical challenge to molecular targeted therapies such as tyrosine kinase inhibitors (TKIs) treatment in hepatocellular carcinoma (HCC). Therefore, it is urgent to explore new mechanisms and therapeutics that can overcome or delay resistance. Here, a US Food and Drug Administration (FDA)-approved pleuromutilin antibiotic is identified that overcomes sorafenib resistance in HCC cell lines, cell line-derived xenograft (CDX) and hydrodynamic injection mouse models. It is demonstrated that lefamulin targets interleukin enhancer-binding factor 3 (ILF3) to increase the sorafenib susceptibility of HCC via impairing mitochondrial function. Mechanistically, lefamulin directly binds to the Alanine-99 site of ILF3 protein and interferes with acetyltransferase general control non-depressible 5 (GCN5) and CREB binding protein (CBP) mediated acetylation of Lysine-100 site, which disrupts the ILF3-mediated transcription of mitochondrial ribosomal protein L12 (MRPL12) and subsequent mitochondrial biogenesis. Clinical data further confirm that high ILF3 or MRPL12 expression is associated with poor survival and targeted therapy efficacy in HCC. Conclusively, this findings suggest that ILF3 is a potential therapeutic target for overcoming resistance to TKIs, and lefamulin may be a novel combination therapy strategy for HCC treatment with sorafenib and regorafenib.

Associations of prenatal exposure to phthalates and their mixture with lung function in Mexican children.

Early life phthalates exposure has been associated with adverse respiratory outcomes. However, evidence linking prenatal phthalates exposure and childhood lung function has been inconclusive. Additionally, few studies have examined phthalates exposure as a mixture and explored sexually dimorphic associations. We aimed to investigate sex-specific associations of prenatal phthalates mixtures with childhood lung function using the PROGRESS cohort in Mexico (N = 476). Prenatal phthalate concentrations were measured in maternal urine collected during the 2nd and 3rd trimesters. Children's lung function was evaluated at ages 8-13 years. Individual associations were assessed using multivariable linear regression, and mixture associations were modeled using repeated holdout WQS regression and hierarchical BKMR; data was stratified by sex to explore sex-specific associations. We identified significant interactions between 2nd trimester phthalates mixture and sex on FEV1 and FVC z-scores. Higher 2nd trimester phthalate concentrations were associated with higher FEV1 (ß = 0.054, 95 %CI: 0.005, 0.104) and FVC z-scores (ß = 0.074, 95 % CI: 0.024, 0.124) in females and with lower measures in males (FEV1, ß = -0.017, 95 %CI: -0.066, 0.026; FVC, ß = -0.014, 95 %CI: -0.065, 0.030). This study indicates that prenatal exposure to phthalates is related to childhood lung function in a sex-specific manner.

Inhibition of SARS-CoV-2 Nsp9 ssDNA-Binding Activity and Cytotoxic Effects on H838, H1975, and A549 Human Non-Small Cell Lung Cancer Cells: Exploring the Potential of Nepenthes miranda Leaf Extract for Pulmonary Disease Treatment.

Carnivorous pitcher plants from the genus Nepenthes are renowned for their ethnobotanical uses. This research explores the therapeutic potential of Nepenthes miranda leaf extract against nonstructural protein 9 (Nsp9) of SARS-CoV-2 and in treating human non-small cell lung carcinoma (NSCLC) cell lines. Nsp9, essential for SARS-CoV-2 RNA replication, was expressed and purified, and its interaction with ssDNA was assessed. Initial tests with myricetin and oridonin, known for targeting ssDNA-binding proteins and Nsp9, respectively, did not inhibit the ssDNA-binding activity of Nsp9. Subsequent screenings of various N. miranda extracts identified those using acetone, methanol, and ethanol as particularly effective in disrupting Nsp9's ssDNA-binding activity, as evidenced by electrophoretic mobility shift assays. Molecular docking studies highlighted stigmast-5-en-3-ol and lupenone, major components in the leaf extract of N. miranda, as potential inhibitors. The cytotoxic properties of N. miranda leaf extract were examined across NSCLC lines H1975, A549, and H838, focusing on cell survival, apoptosis, and migration. Results showed a dose-dependent cytotoxic effect in the following order: H1975 > A549 > H838 cells, indicating specificity. Enhanced anticancer effects were observed when the extract was combined with afatinib, suggesting synergistic interactions. Flow cytometry indicated that N. miranda leaf extract could induce G2 cell cycle arrest in H1975 cells, potentially inhibiting cancer cell proliferation. Gas chromatography-mass spectrometry (GC-MS) enabled the tentative identification of the 19 most abundant compounds in the leaf extract of N. miranda. These outcomes underscore the dual utility of N. miranda leaf extract in potentially managing SARS-CoV-2 infection through Nsp9 inhibition and offering anticancer benefits against lung carcinoma. These results significantly broaden the potential medical applications of N. miranda leaf extract, suggesting its use not only in traditional remedies but also as a prospective treatment for pulmonary diseases. Overall, our findings position the leaf extract of N. miranda as a promising source of natural compounds for anticancer therapeutics and antiviral therapies, warranting further investigation into its molecular mechanisms and potential clinical applications.

Downregulation of Setdb2 promotes alternative activation of macrophages via the PI3K/Akt pathway to attenuate NAFLD after sleeve gastrectomy.

Non-alcoholic fatty liver disease (NAFLD) stands as the most prevalent hepatic disorder, with bariatric surgery emerging as the most effective intervention for NAFLD remission. Sleeve gastrectomy (SG) has notably ascended as the predominant procedure due to its comparative simplicity and consistent surgical outcomes. Nonetheless, the underlying mechanisms remain unclear. In this study, we probed the therapeutic potential of SG for NAFLD induced by a high-fat diet (HFD) in mice, with a focus on its impact on liver lipid accumulation, macrophage polarization, and the role of the histone methyltransferase Setdb2. SG prompted significant weight loss, diminished liver size and liver-to-body weight ratio, and enhanced liver function, evidenced by reduced serum levels of triglycerides (TG), total cholesterol (T-CHO), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Histological examination confirmed a reduction in liver lipid accumulation. Additionally, flow cytometry unveiled an increased proportion of M2 macrophages and a decrease in Setdb2 expression was shown in the SG group, suggesting an association between Setdb2 levels and postsurgical macrophage polarization. Furthermore, the conditional knockout of Setdb2 in mice further mitigated HFD-induced steatosis and promoted the M2 macrophage phenotype. Mechanistically, Setdb2 knockout in bone marrow-derived macrophages (BMDMs) favored M2 polarization, with RNA sequencing and western blotting analyses corroborating the upregulation of the PI3K/Akt signaling pathway. The effects of Setdb2 on macrophage activation were nullified by the PI3K inhibitor LY294002, suggesting that Setdb2 facilitates alternative macrophage activation through the PI3K/Akt signaling pathway. These comprehensive findings underscore the potential of SG as a therapeutic intervention for NAFLD by regulating the critical function of Setdb2 in macrophage polarization and activation, thereby offering novel insights into NAFLD pathogenesis and therapeutic targets.

An Adjuvanted Vaccine-Induced Pathogenesis Following Influenza Virus Infection.

An incomplete Freund's adjuvant elicited an overt pathogenesis in vaccinated mice following the intranasal challenge of A/California/07/2009 (H1N1) virus despite the induction of a higher specific antibody titer than other adjuvanted formulations. Aluminum hydroxide adjuvants have not induced any pathogenic signs in a variety of formulations with glycolipids. A glycolipid, α-galactosyl ceramide, improved a stimulatory effect of distinct adjuvanted formulations on an anti-influenza A antibody response. In contrast to α-galactosyl ceramide, its synthetic analogue C34 was antagonistic toward a stimulatory effect of an aluminum hydroxide adjuvant on a specific antibody response. The aluminum hydroxide adjuvant alone could confer complete vaccine-induced protection against mortality as well as morbidity caused by a lethal challenge of the same strain of an influenza A virus. The research results indicated that adjuvants could reshape immune responses either to improve vaccine-induced immunity or to provoke an unexpected pathogenic consequence. On the basis of these observations, this research connotes the prominence to develop a precision adjuvant for innocuous vaccination aimed at generating a protective immunity without aberrant responses.

A nation-wide medical record database study: Value of hepatitis B surface antigen loss in chronic hepatitis B patients in Japan.

AIM: Hepatitis B surface antigen (HBsAg) seroclearance is considered to be one of the best surrogate endpoints of functional cure for hepatitis B virus (HBV) infection. However, evidence regarding the relationship between achieving HBsAg seroclearance or a low baseline HBsAg level, and long-term clinical outcomes in Japanese patients with chronic HBV infection remains to be confirmed in a real-world setting. METHODS: A retrospective observational cohort study was performed with an electronic medical record database, including data from 230 hospitals across Japan. Chronic HBV infection was defined as two consecutive, positive HBsAg laboratory measurements for HBV infection. The date of the second positive was used as a baseline to identify subsequent HBsAg seroclearance and liver disease progression. RESULTS: In the database, 2523 patients with chronic HBV infection were identified as the chronic hepatitis B (CHB) cohort. Among the CHB cohort with an average observational period of 5.19 ± 3.87 years, 202 patients (8%) achieved HBsAg seroclearance after baseline. They had a lower risk of developing hepatocellular carcinoma (HCC) (adjusted hazard ratio [aHR] 0.206, p < 0.01) and cirrhosis (aHR 0.361, p < 0.01). When the CHB cohort was stratified into two groups based on baseline HBsAg levels (<100 IU/mL and ≥100 IU/mL), patients with a lower baseline level of HBsAg (<100 IU/mL) had a lower risk of developing liver disease (HCC aHR 0.600, p < 0.01; cirrhosis aHR 0.618, p < 0.05). CONCLUSIONS: These results confirm the clinical significance of HBsAg seroclearance and low HBsAg level at baseline with respect to long-term outcomes of patients with CHB in the Japanese population.