Comparative efficacy, safety, and tolerability of pharmacotherapies for acute mania in adults: a systematic review and network meta-analysis of randomized controlled trials.

The aim of this study was to provide evidence-based recommendations regarding the efficacy, safety, and tolerability of currently used pharmacological treatments for adults with acute bipolar mania. To achieve this, we conducted a systematic review and network meta-analysis (NMA) using R software and related packages. We searched primary clinical databases until February 2023 for reports of randomized controlled trials of drug treatments and adjunctive therapies for adults with acute bipolar mania, with outcomes including efficacy (mean change from baseline to endpoint in mania rating scores), safety (clinically significant adverse events from baseline to end of treatment), and tolerability (the proportion of patients who completed the whole trial to the planned endpoint). A total of 113 studies were included in our analysis, in which 23,491 participants (50.38% males; mean age = 38.6 years; mean study duration = 3.39 weeks; mean manic baseline score = 29.37) were randomly allocated to one of 51 monotherapies, adjunctive treatments, or placebo. Our results showed that tamoxifen (mean difference, -22.31 [-25.97, -18.63], N = 2, n1 = 43, n2 = 39) and tamoxifen+ lithium or valproate (LIT/VAL) (-16.37 [-22.55, -10.25], N = 1, n1 = 20, n2 = 20) had the best and second-best clinical efficacy in adults with acute bipolar mania over the placebo. Furthermore, olanzapine, paliperidone, quetiapine, ziprasidone, risperidone, divalproex, and haloperidol were significantly better tolerated than placebo. Combination therapies of antipsychotics and LIT/VAL appeared to be more effective than their corresponding monotherapies. While pharmacotherapies were associated with specific common adverse events, we found no evidence of increased incidence of headache or depression events compared to the placebo. Overall, our NMAs provided important insights into the effectiveness, safety, and tolerability of pharmacological treatments for acute bipolar mania and can help guide treatment decisions for clinicians.

Tunable green syngas generation from CO2 and H2O with sunlight as the only energy input.

The carbon-neutral synthesis of syngas from CO2 and H2O powered by solar energy holds grand promise for solving critical issues such as global warming and the energy crisis. Here we report photochemical reduction of CO2 with H2O into syngas using core/shell Au@Cr2O3 dual cocatalyst-decorated multistacked InGaN/GaN nanowires (NWs) with sunlight as the only energy input. First-principle density functional theory calculations revealed that Au and Cr2O3 are synergetic in deforming the linear CO2 molecule to a bent state with an O-C-O angle of 116.5°, thus significantly reducing the energy barrier of CO2RR compared with that over a single component of Au or Cr2O3. Hydrogen evolution reaction was promoted by the same cocatalyst simultaneously. By combining the cooperative catalytic properties of Au@Cr2O3 with the distinguished optoelectronic virtues of the multistacked InGaN NW semiconductor, the developed photocatalyst demonstrated high syngas activity of 1.08 mol/gcat/h with widely tunable H2/CO ratios between 1.6 and 9.2 under concentrated solar light illumination. Nearly stoichiometric oxygen was evolved from water splitting at a rate of 0.57 mol/gcat/h, and isotopic testing confirmed that syngas originated from CO2RR. The solar-to-syngas energy efficiency approached 0.89% during overall CO2 reduction coupled with water splitting. The work paves a way for carbon-neutral synthesis of syngas with the sole inputs of CO2, H2O, and solar light.

Posttranslational regulation of liver kinase B1 in human cancer.

Liver kinase B1 (LKB1) is a serine-threonine kinase that participates in multiple cellular and biological processes, including energy metabolism, cell polarity, cell proliferation, cell migration, and many others. LKB1 is initially identified as a germline-mutated causative gene in Peutz-Jeghers syndrome and is commonly regarded as a tumor suppressor due to frequent inactivation in a variety of cancers. LKB1 directly binds and activates its downstream kinases including the AMP-activated protein kinase (AMPK) and AMPK-related kinases by phosphorylation, which has been intensively investigated for the past decades. An increasing number of studies have uncovered the posttranslational modifications (PTMs) of LKB1 and consequent changes in its localization, activity, and interaction with substrates. The alteration in LKB1 function as a consequence of genetic mutations and aberrant upstream signaling regulation leads to tumor development and progression. Here, we review current knowledge about the mechanism of LKB1 in cancer and the contributions of PTMs, such as phosphorylation, ubiquitination, SUMOylation, acetylation, prenylation, and others, to the regulation of LKB1 function, offering new insights into the therapeutic strategies in cancer.

Deep learning models for disease-associated circRNA prediction: a review.

Emerging evidence indicates that circular RNAs (circRNAs) can provide new insights and potential therapeutic targets for disease diagnosis and treatment. However, traditional biological experiments are expensive and time-consuming. Recently, deep learning with a more powerful ability for representation learning enables it to be a promising technology for predicting disease-associated circRNAs. In this review, we mainly introduce the most popular databases related to circRNA, and summarize three types of deep learning-based circRNA-disease associations prediction methods: feature-generation-based, type-discrimination and hybrid-based methods. We further evaluate seven representative models on benchmark with ground truth for both balance and imbalance classification tasks. In addition, we discuss the advantages and limitations of each type of method and highlight suggested applications for future research.

Light-Driven Photocatalyst-Free Synthesis of ß, δ-Functionalized Ketones from Aldehydes.

The synthesis of ketones has been a long focus of chemistry research, on account of its unique reactivity. Herein, we report a simple light-driven photocatalyst-free synthesis of ß, δ-functionalized ketones from aldehydes, using inexpensive and commercially abundant feedstock chemicals. This reaction is enabled by the direct acyl radical generation via hydrogen atom transfer and the subsequent radical addition process, avoiding the need for prefunctionalized substrates and organometallic reagent.

Performance of ChatGPT Across Different Versions in Medical Licensing Examinations Worldwide: Systematic Review and Meta-Analysis.

BACKGROUND: Over the past 2 years, researchers have used various medical licensing examinations to test whether ChatGPT (OpenAI) possesses accurate medical knowledge. The performance of each version of ChatGPT on the medical licensing examination in multiple environments showed remarkable differences. At this stage, there is still a lack of a comprehensive understanding of the variability in ChatGPT's performance on different medical licensing examinations. OBJECTIVE: In this study, we reviewed all studies on ChatGPT performance in medical licensing examinations up to March 2024. This review aims to contribute to the evolving discourse on artificial intelligence (AI) in medical education by providing a comprehensive analysis of the performance of ChatGPT in various environments. The insights gained from this systematic review will guide educators, policymakers, and technical experts to effectively and judiciously use AI in medical education. METHODS: We searched the literature published between January 1, 2022, and March 29, 2024, by searching query strings in Web of Science, PubMed, and Scopus. Two authors screened the literature according to the inclusion and exclusion criteria, extracted data, and independently assessed the quality of the literature concerning Quality Assessment of Diagnostic Accuracy Studies-2. We conducted both qualitative and quantitative analyses. RESULTS: A total of 45 studies on the performance of different versions of ChatGPT in medical licensing examinations were included in this study. GPT-4 achieved an overall accuracy rate of 81% (95% CI 78-84; P<.01), significantly surpassing the 58% (95% CI 53-63; P<.01) accuracy rate of GPT-3.5. GPT-4 passed the medical examinations in 26 of 29 cases, outperforming the average scores of medical students in 13 of 17 cases. Translating the examination questions into English improved GPT-3.5's performance but did not affect GPT-4. GPT-3.5 showed no difference in performance between examinations from English-speaking and non-English-speaking countries (P=.72), but GPT-4 performed better on examinations from English-speaking countries significantly (P=.02). Any type of prompt could significantly improve GPT-3.5's (P=.03) and GPT-4's (P<.01) performance. GPT-3.5 performed better on short-text questions than on long-text questions. The difficulty of the questions affected the performance of GPT-3.5 and GPT-4. In image-based multiple-choice questions (MCQs), ChatGPT's accuracy rate ranges from 13.1% to 100%. ChatGPT performed significantly worse on open-ended questions than on MCQs. CONCLUSIONS: GPT-4 demonstrates considerable potential for future use in medical education. However, due to its insufficient accuracy, inconsistent performance, and the challenges posed by differing medical policies and knowledge across countries, GPT-4 is not yet suitable for use in medical education. TRIAL REGISTRATION: PROSPERO CRD42024506687; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=506687.

SD-YOLOv8: An Accurate Seriola dumerili Detection Model Based on Improved YOLOv8.

Accurate identification of Seriola dumerili (SD) offers crucial technical support for aquaculture practices and behavioral research of this species. However, the task of discerning S. dumerili from complex underwater settings, fluctuating light conditions, and schools of fish presents a challenge. This paper proposes an intelligent recognition model based on the YOLOv8 network called SD-YOLOv8. By adding a small object detection layer and head, our model has a positive impact on the recognition capabilities for both close and distant instances of S. dumerili, significantly improving them. We construct a convenient S. dumerili dataset and introduce the deformable convolution network v2 (DCNv2) to enhance the information extraction process. Additionally, we employ the bottleneck attention module (BAM) and redesign the spatial pyramid pooling fusion (SPPF) for multidimensional feature extraction and fusion. The Inner-MPDIoU bounding box regression function adjusts the scale factor and evaluates geometric ratios to improve box positioning accuracy. The experimental results show that our SD-YOLOv8 model achieves higher accuracy and average precision, increasing from 89.2% to 93.2% and from 92.2% to 95.7%, respectively. Overall, our model enhances detection accuracy, providing a reliable foundation for the accurate detection of fishes.

Redox Approaches to Carbene Generation in Catalytic Cyclopropanation Reactions.

Transition metal-catalyzed carbene transfer reactions have a century-old history in organic chemistry and are a primary method for the synthesis of cyclopropanes. Much of the work in this field has focused on the use of diazo compounds and related precursors, which can transfer a carbene fragment to a catalyst with concomitant loss of a stable byproduct. Despite the utility of this approach, there are persistent limitations in the scope of viable carbenes, most notably those lacking stabilizing substituents. By coupling carbene transfer chemistry with two-electron redox cycles, it is possible to expand the available starting materials that can be used as carbene precursors. In this Minireview, we discuss emerging catalytic reductive cyclopropanation reactions using either gem-dihaloalkanes or carbonyl compounds. This strategy is inspired by classic stoichiometric transformations, such as the Simmons-Smith cyclopropanation and the Clemmensen reduction, but instead entails the formation of a catalytically generated transition metal carbene or carbenoid. We also present recent efforts to generate carbenes directly from methylene (CR2H2) groups via a formal 1,1-dehydrogenation. These reactions are currently restricted to substrates containing electron-withdrawing substituents, which serve to facilitate deprotonation and subsequent oxidation of the anion.

Targeting cancer stem cell pathways for lung cancer therapy.

PURPOSE OF REVIEW: The unique properties of cancer stem cells (CSCs) make lung cancer untargetable for quite an extended period. The functional mechanism of this cell type has been illustrated step by step. However, the outcomes of lung cancer patients are still lower than expected clinically. The attempts made by scientists to make challenge history against stemness maintenance of lung cancer cells and their druggable targets are worth elucidating. RECENT FINDINGS: Many agents, including the Bispecific T-cell engager (BiTE) and AMG 119 targeting DLL3-positive cells, are a tremendous breakthrough in the preclinical and clinical treatment of SCLC. More studies focus on targeting CSCs to overcome TKI resistance in NSCLC. The combo targeting of CSC and the immune microenvironment can favor the treatment of lung cancer patients. SUMMARY: The current review elucidates the characteristics and related regulating pathways of lung CSCs from essential to preclinical research. We retrospectively introduce an update on the clinical development of therapeutics targeting CSC-associated developmental signaling pathways and discuss the opportunities to target CSC-immune interactions in lung cancer.

Reduced-Cost Production of Sophorolipids by Starmerella bombicola CGMCC1576 Grown on Cottonseed Molasses and Cottonseed Oil-Based Medium.

A large-scale application of sophorolipids (SLs) was blocked by their high production cost. One feasible way to reduce the cost of SL production is to develop cheap feedstocks as the substrates for SL fermentation. In the present work, cottonseed molasses (CM), a waste from raffinose production, was used as the hydrophilic substrate;, and cottonseed oil (CO) was used as a hydrophobic substrate for SL production by Starmerella bombicola CGMCC 1576. The primary optimization of carbon sources, nitrogen source and inorganic salts, produced 57.6 ± 2.3 g/L of total SLs and 24.0 ± 1.2 g/L of lactonic SLs on CM and CO, almost equal to the titer of SLs produced from glucose and oleic. A response surface method was applied to optimize the fermentation medium for growth and SL production of S. bombicola. The production of total SLs reached 58.4 ± 3.4 g/L, and lactonic SLs were elevated to more than 25.0 ± 1.9 g/L. HPLC-MS analysis showed that the compositions of SLs produced by S. bombicola on CM and CO were very similar to those on glucose and oleic acid. These results suggested that cottonseed molasses and cottonseed oil can be used as renewable cheap substrates for the reduced-cost production of SLs.

[A glass micropipette vacuum technique of cerebrospinal fluid sampling in C57BL/6 mice].

The purpose of this study was to establish a suitable method for extracting cerebrospinal fluid (CSF) from C57BL/6 mice. A patch clamp electrode puller was used to draw a glass micropipette, and a brain stereotaxic device was used to fix the mouse's head at an angle of 135° from the body. Under a stereoscopic microscope, the skin and muscle tissue on the back of the mouse's head were separated, and the dura mater at the cerebellomedullary cistern was exposed. The glass micropipette (with an angle of 20° to 30° from the dura mater) was used to puncture at a point 1 mm inboard of Y-shaped dorsal vertebral artery for CSF sampling. After the first extraction, the glass micropipette was connected with a 1 mL sterile syringe to form a negative pressure device for the second extraction. The results showed that the successful rate of CSF extraction was 83.33% (30/36). Average CSF extraction amount was (7.16 ± 0.43) µL per mouse. In addition, C57BL/6 mice were given intranasally ferric ammonium citrate (FAC) to establish a model of brain iron accumulation, and the CSF extraction technique established in the present study was used for sampling. The results showed that iron content in the CSF from the normal saline control group was not detected, while the iron content in the CSF from FAC-treated group was (76.24 ± 38.53) µmol/L, and the difference was significant. These results suggest that glass micropipette vacuum technique of CSF sampling established in the present study has the advantages of simplicity, high success rate, large extraction volume, and low bleeding rate, and is suitable for the research on C57BL/6 mouse neurological disease models.

Nucleophilic Carbenes Derived from Dichloromethane.

Nickel PyBox catalysts promote nucleophilic cyclopropanation reactions using CH2 Cl2 as a methylene source and Mn as a stoichiometric reductant. The substrate scope includes a broad range of alkenes bearing electron-withdrawing substituents, including esters, amides, ketones, nitriles, sulfones, phosphonate esters, trifluoromethyl groups, and electron-deficient arenes. Enantioselective cyclopropanations of α,ß-unsaturated esters have been developed using chiral PyBox ligands. Mechanistic studies suggest the intermediacy of a (PyBox)Ni=CH2 species, which adds to the alkene by a stepwise [2+2]-cycloaddition/C-C reductive elimination mechanism. DFT models provide a rationale for the nucleophilic character of the nickel carbene and the sense of enantioinduction.

Assembly-level topology optimization and additive manufacturing of aluminum alloy primary mirrors.

Additive manufacturing can realize complex structures that cannot be achieved by conventional manufacturing methods. At the same time, topology optimization provides more excellent solutions for structural design. In the field of guidance and navigation optics, ultra-lightweight, high rigidity, and high integration are important requirements. Metal mirrors are widely used in this field due to their good processing performance. In this paper, we describe the integrated design and manufacturing of aluminum alloy primary mirror assembly (mirrors and mirror backplane) through the combination of additive manufacturing technology and topology optimization. Compared with the conventional design, it shows better performance.

MFAP4 deletion attenuates the progression of angiotensin II-induced atrial fibrosis and atrial fibrillation.

AIMS: Microfibrillar-associated protein 4 (MFAP4) is associated with atrial fibrillation (AF). Nevertheless, the specific role and underlying mechanism of MFAP4 in atrial fibrosis, the hallmark of AF, remain undefined. This study aims to elucidate the role of MFAP4 in the regulation of atrial fibrosis and to explore the underlying mechanism. METHODS AND RESULTS: This study used MFAP4 knockout (MFAP4-KO) mice and their wild-type (WT) littermates to investigate the effect of angiotensin II (Ang II) (2000 ng/kg/min for 3 weeks) on atrial fibrosis and susceptibility to AF in terms of morphology, histology, electrophysiology, and molecular biology. MFAP4 deletion in mice did not alter cardiac structure and function at baseline. After treatment with Ang II, the MFAP4-KO mice showed a decreased left atrial enlargement and fibrosis, slowed atrial conduction, and reduced susceptibility to AF compared with the WT mice. Regarding the mechanism, we found that MFAP4 deletion markedly inhibited activated focal adhesion kinase (FAK)-mediated PI3K-AKT signalling and MEK1/2-ERK1/2 signalling after Ang II treatment. CONCLUSIONS: Overall, our study showed that loss of MFAP4 attenuates Ang II-mediated left atrial fibrosis and dilation and decreases susceptibility to AF by decreasing the phosphorylation of FAK and inhibiting the activation of the PI3K-AKT and MEK1/2-ERK1/2 signalling pathways. These findings further indicate that targeting MFAP4 may be a potential upstream therapeutic option for atrial fibrosis and AF.

Gab1 Overexpression Attenuates Susceptibility to Ventricular Arrhythmias in Pressure Overloaded Heart Failure Mouse Hearts.

PURPOSE: Grb2 associated binding protein 1 (Gab1) is an adaptor protein that is important for intracellular signal transduction which involved in several pathological process. However, the role of Gab1 in pressure overload-induced ventricular arrhythmias (VAs) remain poorly understood. In the current study, we aimed to test the role of Gab1 in VA susceptibility induced by pressure overload. METHODS: We overexpressed Gab1 in the hearts using an adeno-associated virus 9 (AAV9) system through tail vein injection. Aortic banding (AB) surgery was performed in C57BL6/J mice to induce heart failure (HF). Four weeks following AB, histology, echocardiography, and biochemical analysis were conducted to investigate cardiac structural remodeling and electrophysiological studies were performed to check the electrical remodeling. Western blot analysis was used to explore the underlying mechanisms. RESULTS: The mRNA and protein expression were downregulated in AB hearts compared to sham hearts. Gab1 overexpression significantly reversed AB-induced cardiac structural remodeling including ameliorated AB-induced cardiac dysfunction, cardiac fibrosis, and inflammatory response. Moreover, Gab1 overexpression also markedly alleviated AB-induced electrical remodeling including ion channel alterations and VA susceptibility. Mechanistically, we found that TLR4/MyD88/NF-κB contributes to the cardio protective effect of Gab1 overexpression on AB-induced VAs. CONCLUSIONS: Our study manifested that Gab1 may serve as a promising anti-arrhythmic target via inhibiting TLR4/MyD88/NF-κB signaling pathway induced by AB.

Silencing of IGF2BP1 restrains ox-LDL-induced lipid accumulation and inflammation by reducing RUNX1 expression and promoting autophagy in macrophages.

Atherosclerosis (AS) is a chronic inflammatory disease with the formation and accumulation of macrophage-derived foam cells in the subendothelial space of blood vessels as one major characteristic. Insulin-like growth factor 2 messenger RNA (mRNA) binding protein 1 (IGF2BP1) is an RNA-binding factor and its elevation has been reported to be associated with macrophage infiltration into the atherosclerotic vascular wall. This study aims to investigate the roles of IGF2BP1 in AS-associated foam cell formation. Herein, ApoE-/- mice fed with high-fat diet developed atherosclerotic lesions in the aorta, where IGF2BP1 expression was upregulated and autophagy was impaired. IGF2BP1 expressed in F4/80+ macrophages and coexisted with p62. In vitro, IGF2BP1 expression was upregulated in RAW264.7 macrophages exposed to oxidized low-density lipoprotein (ox-LDL) (100 µg/ml). Interestingly, silencing of IGF2BP1 ameliorated ox-LDL-induced lipid accumulation and inflammation, and enhanced autophagic flux in macrophages. Furthermore, the expression of RUNX family transcription factor 1 (RUNX1), a gene that is able to inhibit autophagy in multiple cell types, was elevated in atherosclerotic aortas and in ox-LDL-treated macrophages. In addition, RNA immunoprecipitation results revealed that IGF2BP1 is bound to RUNX1 mRNA. Alterations induced by IGF2BP1 knockdown in ox-LDL-treated macrophages were abolished by RUNX1 overexpression. Furthermore, after autophagy inhibitor 3-methyladenine administration, silencing of IGF2BP1-reduced lipid accumulation and inflammation were recovered in RAW264.7 cells. In summary, our study demonstrated that silencing of IGF2BP1 restrained ox-LDL-induced lipid accumulation and inflammation by reducing RUNX1 expression and facilitating autophagy in macrophages. IGF2BP1/RUNX1 axis may be considered as a potential therapeutic target in AS.

The altering in sensory sensitivity: a current issue of female breast surgery.

Breast surgery is an important treatment for women with malignant breast diseases. In addition to breast appearance, the integrity of breast function is increasing in patients with breast diseases. As the basis of breast physiological function, breast skin sensitivity is important to the quality of life of patients after surgery. Breast skin sensitivity gives the patient a "real" breast feeling. The sensory recovery after breast surgery has also become one of the important goals of breast surgery. In this review, we aim to discuss the research progress on recovery of breast skin sensitivity after different treatment modalities for breast disease.

Corrigendum to "Evaluation of different air distribution systems in a commercial airliner cabin in terms of comfort and COVID-19 infection risk" Build. Environ., Volume 208, January 2022, 108590.

[This corrects the article DOI: 10.1016/j.buildenv.2021.108590.].

Evaluation of different air distribution systems in a commercial airliner cabin in terms of comfort and COVID-19 infection risk.

The air distribution system in an airliner plays a key role in maintaining a comfortable and healthy environment in the aircraft cabin. To evaluate the performance of a novel displacement ventilation (DV) system and a traditional mixing ventilation (MV) system in an airliner cabin, this study conducted experiments and simulations in a seven-row cabin mockup. This investigation used ultrasonic anemometers and T-thermocouples to measure the air velocity, temperature and distribution of 1 µm and 5 µm particles. Simulation verifications were performed for these operating conditions, and additional scenarios with different occurrence source locations were also simulated. This study combined the Wells-Riley equation with a real case based on a COVID-19 outbreak among passengers on a long-distance bus to obtain the COVID-19 quanta value. Through an evaluation of the airflow organization, thermal comfort, and risk of COVID-19 infection, the two ventilation systems were compared. This investigation found that polydisperse particles should be used to calculate the risk of infection in airliner cabins. In addition, at the beginning of the pandemic, the infection risk with DV was lower than that with MV. In the middle and late stages of the epidemic, the infection risk with MV can be reduced when passengers wear masks, leading to an infection risk approximately equal to that of DV.

Influencing factors in the simulation of airflow and particle transportation in aircraft cabins by CFD.

To control the transport of particles such as the SARS-CoV-2 virus in airliner cabins, which is a significant concern for the flying public, effective ventilation systems are essential. Validated computational fluid dynamics (CFD) models are frequently and effectively used to investigate air distribution and contaminant transportation. The complex geometry and airflow characteristics in airliner cabins pose a challenge to numerical CFD validation. The objective of this investigation was to identify accurate and affordable validation processes for studying the airflow field and particulate contaminant distribution in airliner cabins during the design process for different ventilation systems. This study quantitatively evaluated the effects of ventilation system, turbulence model, particle simulation method, geometry simplification, and boundary condition assignment on airflow and particulate distributions in airliner cabins with either a mixing ventilation (MV) system or a displacement ventilation (DV) system calculated by CFD. The results showed that among four turbulence models, the standard k-ε, RNG k-ε, realizable k-ε and SST k-ω models, the prediction by the realizable k-ε model agreed most closely with the experimental data. Meanwhile, the steady Eulerian method provided a reasonable prediction of the particle concentration field with low computing cost. The computational domain should be simplified differently for the DV system and the MV system with consideration of the simulation accuracy and computing cost. For more accurate modeling results, the boundary conditions should be assigned in greater detail, taking into account the uniformity on the boundary.