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Chiral 2‐azetines and allenes are highly valuable structural units in natural products and useful chemicals. However, enantioselective synthesis of both 2‐azetines and allenes has been extremely challenging. Herein, we present asymmetric construction of chiral 2‐azetines (70–98 % yields and up to 96 % ee) through chiral phosphine‐catalyzed [2+2] annulation of yne‐enones with sulfamate‐derived cyclic imines. These 2‐azetines were easily transformed into chiral allenes upon treatment with Et3SiH, BF3 ⋅ Et2O and water at rt for 2 minutes. Based on the above transformations, a concise one‐pot synthetic procedure combining [2+2] annulation of yne‐enones and sulfamate‐derived cyclic imines under phosphine catalysis and sequential reduction/isomerization/ring‐opening reaction through Et3SiH, BF3 ⋅ Et2O and water was thus set up, providing axially chiral tetrasubstituted allenes in satisfactory yields and enantioselectivities (56–90 % yields and up to 91 % ee). [ABSTRACT FROM AUTHOR]

INTRODUCTION: We examined the burden of Alzheimer's disease and other dementias (ADOD) and attributable factors at the national and provincial levels in China. METHODS: Using the Global Burden of Diseases Study 2021, we estimated incidence, prevalence, mortality rate, disability‐adjusted life years (DALYs), and the ratio of years lived with disability (YLD) to DALYs for ADOD in China. Estimated annual percentage changes (EAPCs) were used to quantify the temporal trends from 1990 to 2021. RESULTS: In 2021, China experienced the highest ADOD burden among Group of 20 member nations. The EAPCs for age‐standardized rates for incidence, age‐standardized rates for prevalence, and age‐standardized mortality rate were 0.41 (uncertainty intervals [UIs] 0.34–0.49); 0.44 (UI: 0.36–0.52); and –0.19 (UI: ‐0.23 to ‐0.15), respectively. Between 1990 and 2021, the number of people with ADOD increased by 322.18% and DALYs associated with ADOD increased by 272.71%; most of these increases were explained by population aging. DISCUSSION: Considering the aging Chinese population, targeted strategies to prevent dementia are urgently needed. Highlights: China experienced the highest dementia burden among Group of 20 member nations.High body mass index, high fasting plasma glucose, and smoking were major risk factors for Alzheimer's disease and other dementias (ADOD) burden.Since 1990, the incidence and prevalence of ADOD increased substantially in China.The mortality rate related to ADOD decreased consistently.Considering the aging Chinese population, targeted strategies are urgently needed. [ABSTRACT FROM AUTHOR]

ABSTRACT The limit equilibrium method has been widely used in the study of searching the slip surface of slopes. However, the method ignores the deformation characteristics of the rock mass and assumes that the shape of the slip surface is circular, which is quite different from the actual situation of the slope. For this reason, this paper proposes a fast search method for noncircular slip surface considering the deformation characteristics of the rock mass. The method is able to calculate the compression and shear deformation energies stored in the slip surface, as well as the virtual displacement generated by the slide mass when the slope is in a critical equilibrium state. The direction of motion of the slide mass is further calculated from the magnitude of the virtual displacement. In addition, this paper improves the generation of new solutions in the simulated annealing (SA) algorithm for the structural characteristics of the slip surface of the slope, thus achieving a fast search of the slip surface. Finally, the method of this paper is compared with the test question of ACADS and the simulation results of the finite difference method (FDM) to verify the effectiveness of the method of this paper. [ABSTRACT FROM AUTHOR]

Background: Periprosthetic bone loss is a well‐known phenomenon following total hip arthroplasty (THA). However, the choice of drugs for prevention remains controversial. Therefore, the aim of this study was to determine the best drug to treat periprosthetic bone loss by comparing changes in bone mineral density (BMD) at different times after THA. Methods: A comprehensive search of five databases and two clinical trial registration platforms was undertaken from their inception through to August 31, 2023 to identify eligible randomized controlled trials. A Bayesian network meta‐analysis (NMA) was carried out for calculating the standardized mean difference (SMD) and the surface under cumulative ranking curve (SUCRA) of the BMD in calcar (Gruen zone 7) at 6 months, 12 months, and 24 months and over. Results: Twenty‐nine trials involving 1427 patients and 10 different interventions were included. The results demonstrated that at 6 months, denosumab had the highest ranking (SUCRA = 0.90), followed by alendronate (SUCRA = 0.76), and zoledronate (SUCRA = 0.73). At 12 months, clodronate ranked highest (SUCRA = 0.96), followed by denosumab (SUCRA = 0.84) and teriparatide (SUCRA = 0.82). For interventions with a duration of 24 months and over, denosumab had the highest SUCRA value (SUCRA = 0.96), followed by raloxifene (SUCRA = 0.90) and zoledronate (SUCRA = 0.75). Conclusion: Investigating the existing body of evidence revealed that denosumab demonstrates potential as an intervention of superior efficacy at the three specifically examined time points. However, it remains crucial to conduct further research to confirm these findings and determine the most effective treatment strategy. [ABSTRACT FROM AUTHOR]

Synaptojanin 2 (SYNJ2) has crucial role in various tumors, but its role in papillary thyroid carcinoma (PTC) remains unexplored. This study first detected SYNJ2 protein expression in PTC using immunohistochemistry method and further assessed SYNJ2 mRNA expression through mRNA chip and RNA sequencing data and its association with clinical characteristics. Additionally, KEGG, GSVA, and GSEA analyses were conducted to investigate potential biological functions, while single‐cell RNA sequencing data were used to explore SYNJ2's underlying mechanisms in PTC. Meanwhile, immune infiltration status in different SYNJ2 expression groups were analyzed. Besides, we investigated the immune checkpoint gene expression and implemented drug sensitivity analysis. Results indicated that SYNJ2 is highly expressed in PTC (SMD = 0.66 [95% CI: 0.17–1.15]) and could distinguish between PTC and non‐PTC tissues (AUC = 0.74 [0.70–0.78]). Furthermore, the study identified 134 intersecting genes of DEGs and CEGs, mainly enriched in the angiogenesis and epithelial‐mesenchymal transition (EMT) pathways. Subsequent analysis showed the above pathways were activated in PTC epithelial cells. PTC patients with high SYNJ2 expression showed higher sensitivity to the six common drugs. Summarily, SYNJ2 may promote PTC progression through angiogenesis and EMT pathways. High SYNJ2 expression is associated with better response to immunotherapy and chemotherapy. [ABSTRACT FROM AUTHOR]

By integrating TiO2 with rare earth upconversion nanocrystals (NaREF4), efficient energy transfer can be achieved between the two subunits under near‐infrared (NIR) excitation, which hold tremendous potential in the fields of photocatalysis, photodynamic therapy (PDT), etc. However, in the previous studies, the combination of TiO2 with NaREF4 is a non‐epitaxial random blending mode, resulting in a diminished energy transfer efficiency between the NaREF4 and TiO2. Herein, we present a fluorine doping‐mediated epitaxial growth strategy for the synthesis of TiO2‐NaREF4 heteronanocrystals (HNCs). Due to the epitaxial growth connection, NaREF4 can transfer energy through phonon‐assisted pathway to TiO2, which is more efficient than the traditional indirect secondary photon excitation. Additionally, F doping brings oxygen vacancies in the TiO2 subunit, which further introduces new impurity energy levels in the intrinsic band gap of TiO2 subunit, and facilitates the energy transfer through phonon‐assisted method from NaREF4 to TiO2. As a proof of concept, TiO2‐NaGdF4 : Yb,Tm@NaYF4@NaGdF4 : Nd@NaYF4 HNCs were rationally constructed. Taking advantage of the dual‐model up‐ and downconversion luminescence of the delicately designed multi‐shell structured NaREF4 subunit, highly efficient photo‐response capability of the F‐doped TiO2 subunit and the efficient phonon‐assisted energy transfer between them, the prepared HNCs provide a distinctive nanoplatform for bioimaging‐guided NIR‐triggered PDT. [ABSTRACT FROM AUTHOR]

This article presents a case report of a 19-year-old female with neuropsychiatric lupus who initially presented with mood disorders and psychiatric symptoms. The patient did not respond well to mood stabilizers, leading to a diagnosis of systemic lupus erythematosus (SLE). The article emphasizes the importance of a multidisciplinary approach in evaluating and managing patients with psychiatric symptoms and highlights the need for vigilance for other systemic manifestations in patients with new psychiatric symptoms. The article also discusses the diagnostic challenges of neuropsychiatric SLE (NPSLE) and potential biomarkers for its detection. The case report demonstrates the improvement of cognitive function after treatment for NPSLE. The article concludes by emphasizing the importance of diagnosing NPSLE when mood disorders are the initial symptoms and the need for collaboration between psychiatrists and internists in the diagnosis and treatment of NPSLE. [Extracted from the article]

Food web robustness is a critical aspect of ecosystem stability and has been extensively studied in ecology. However, the potential of machine learning techniques in predicting food web robustness and the identification of key network structure indicators have not been fully explored. We compared the suitability of different machine learning methods and assessed the relative importance of network structure indicators for predicting the robustness of food webs. We utilized a variety of food web datasets spanning different ecosystems to calculate network structure indicators, which include average distance (AD), betweenness centrality (BC), directional connectivity (C), closeness centrality (CC), diameter (D), degree centrality (DC), edge betweenness centrality (EBC), number of links (L), linkage density (LD), and number of nodes (N). We then compared the performance of machine learning methods, including artificial neural network (ANN), random forest (RF), least absolute shrinkage and selection operator (LASSO), and decision tree (DT), and evaluated the relative importance of network structure indicators on robustness predictions. The results demonstrate that the RF model has the best performance (MAE = 0.0178, RMSE = 0.0263, R2 = 0.9063). Meanwhile, the CC indicator has a significant impact in predicting robustness of food webs. It is suggested that both the RF model and the CC indicator should be considered seriously in predicting food web robustness. This research elucidates the differential outcomes when various machine learning methodologies and indicators are employed to predict the robustness of food webs. It significantly enhances our understanding by demonstrating the precise capability of machine learning models in forecasting the robustness of food webs. [ABSTRACT FROM AUTHOR]

Aim: To investigate the relationship between thyroid function and weight regain in patients with obesity after metabolic surgery. Methods: This retrospective study enrolled 162 patients who underwent metabolic surgery. Correlations between decreases in thyroid hormone levels and changes in weight, waist circumference (WC) and the Chinese visceral adiposity index (CVAI) were assessed. Binary logistic regression and receiver operating characteristic (ROC) curves were used to identify predictors and clinically useful cut‐off values, respectively. Results: The levels of thyroid‐stimulating hormone (TSH) and free triiodothyronine (FT3) decreased markedly at 1 year after surgery, as did weight, body mass index (BMI), triglycerides, total cholesterol, high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, WC and CVAI. Decreases in TSH and FT3 after metabolic surgery were associated with changes in weight, BMI and CVAI. Binary logistic regression and ROC curve analyses confirmed that decreases in TSH can predict good weight loss after metabolic surgery to some extent. Finally, binary logistic regression and ROC curve analyses confirmed that changes in TSH can predict weight regain after metabolic surgery. Conclusions: Changes in TSH and FT3 after metabolic surgery were correlated with changes in weight and CVAI. Changes in thyroid hormones can predict weight regain in patients with obesity who underwent metabolic surgery. [ABSTRACT FROM AUTHOR]

Background: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL‐S) is a rare autosomal dominant systemic microvascular disorder attributed to TREX1 (three‐prime repair exonuclease‐1) gene mutations, often proned to misdiagnosed. Methods: We reported a case of RVCL‐S coexisting with systemic lupus erythematosus due to a mutation in the TREX1 gene. This study provided a summary and discussion of previously documented cases related to TREX1 mutations or RVCL‐S. Results: A 39‐year‐old female patient visited the clinic due to progressive memory loss and speech difficulties. Magnetic resonance imaging results showed corpus callosum atrophy and multiple subcortical calcifications in both brain hemispheres. Genetic testing revealed a TREX1 gene mutation (c.294dupA). Treatment with immunosuppressive therapy for 2 months led to improvements in communication and mobility. We also summarized previously reported cases providing an overview of TREX1 gene mutation or RCVL‐S. Conclusion: Our case establishes a compelling foundation for future RVCL‐S diagnosis and treatment paradigms. Notably, conducting systemic immunity screening in patients with RVCL‐S emerges as a strategic approach to prevent potential diagnostic oversights. [ABSTRACT FROM AUTHOR]

The suddenness and destructive power of earthquake disasters pose significant threats to ecosystems. Understanding the changes in post‐earthquake ecosystem services and the complex relationships of their trade‐offs and synergistic effects is crucial for post‐disaster recovery and achieving a holistic and sustainable balance of human well‐being. However, quantifying post‐disaster ecosystem services and these intricate relationships, as well as probing the mechanisms behind their formation from a spatial perspective, remain challenging. This study presents a comprehensive framework that integrates spatial statistical methods, the InVEST model, geodetectors, and the Multiscale Geographically Weighted Regression model (MGWR) to quantify trade‐offs and synergistic effects among ecosystem services before and after earthquakes, and to investigate the spatial heterogeneity of these relationship effects with various driving factors. Results indicate (1) Typical ecosystem services, that is, water yield, soil conservation, carbon storage, and habitat quality, have more weak trade‐off effects and fewer synergistic effects. These relationship intensities vary considerably spatially, demonstrating some agglomerative distribution, suggesting that the ecosystem has not yet recovered to a good state after the quake; (2) The impact of different factors on the trade‐offs and synergies between ecosystem services varies. Interaction effects of driving factors are stronger than singular effects. Relationships between soil conservation and other ecosystem services are primarily influenced by topography and climate. Relationships involving carbon storage are mainly affected by vegetation and climate, while those concerning habitat quality are attributed mostly to human and climatic factors; (3) In the modeling process, considering the different spatial scales of driving factors, MGWR outperforms the Geographically Weighted Regression in explaining the relationship between ecosystem services and driving factors. Moreover, several spatially feasible and targeted ecological measures are proposed to enhance the synergy among ecosystem services. By focusing on the changes in ecosystem services, this study reveals the intrinsic mechanisms of trade‐offs and synergies between ecosystem services, offering insights for related studies in other regions. [ABSTRACT FROM AUTHOR]

SnO2, with its high theoretical capacity, abundant resources, and environmental friendliness, is widely regarded as a potential anode material for lithium‐ion batteries (LIBs). Nevertheless, the coarsening of the Sn nanoparticles impedes the reconversion back to SnO2, resulting in low coulombic efficiency and rapid capacity decay. In this study, we fabricated a heterostructure by combining SnO2 nanoparticles with MoS2 nanosheets via plasma‐assisted milling. The heterostructure consists of in‐situ exfoliated MoS2 nanosheets predominantly in 1 T phase, which tightly encase the SnO2 nanoparticles through strong bonding. This configuration effectively mitigates the volume change and particle aggregation upon cycling. Moreover, the strong affinity of Mo, which is the lithiation product of MoS2, toward Sn plays a pivotal role in inhibiting the coarsening of Sn nanograins, thus enhancing the reversibility of Sn to SnO2 upon cycling. Consequently, the SnO2/MoS2 heterostructure exhibits superb performance as an anode material for LIBs, demonstrating high capacity, rapid rate capability, and extended lifespan. Specifically, discharged/charged at a rate of 0.2 A g−1 for 300 cycles, it achieves a remarkable reversible capacity of 1173.4 mAh g−1. Even cycled at high rates of 1.0 and 5.0 A g−1 for 800 cycles, it still retains high reversible capacities of 1005.3 and 768.8 mAh g−1, respectively. Moreover, the heterostructure exhibits outstanding electrochemical performance in both full LIBs and sodium‐ion batteries. [ABSTRACT FROM AUTHOR]

Zeolite synthesis under acidic conditions has always presented a challenge. In this study, we successfully prepared series of ZSM‐5 zeolite nanosheets (Z‐5‐SCA‐X) over a broad pH range (4 to 13) without the need for additional supplements. This achievement was realized through aggregation crystallization of ZSM‐5 zeolite subcrystal (Z‐5‐SC) with highly short‐range ordering and ultrasmall size extracted from the synthetic system of ZSM‐5 zeolite. Furthermore, the crystallization behavior of Z‐5‐SC was investigated, revealing its non‐classical crystallization process under mildly alkaline and acidic conditions (pH<10), and the combination of classical and non‐classical processes under strongly alkaline conditions (pH≥10). What's particularly intriguing is that, the silanol nest content in the resultant Z‐5‐SCA‐X samples appears to be dependent on the pH values during the Z‐5‐SC crystallization process rather than its crystallinity. Finally, the results of the furfuryl alcohol etherification reaction demonstrate that reducing the concentration of silanol nests significantly enhances the catalytic performance of the Z‐5‐SCA‐X zeolite. The ability to synthesize zeolite in neutral and acidic environments without the additional mineralizing agents not only broadens the current view of traditional zeolite synthesis but also provides a new approach to control the silanol nest content of zeolite catalysts. [ABSTRACT FROM AUTHOR]

Aims: Previous neuroimaging studies of vascular cognitive impairment, no dementia (VCIND), have reported functional alterations, but far less is known about the effects of cognitive training on functional connectivity (FC) of intrinsic connectivity networks (ICNs) and how they relate to intervention‐related cognitive improvement. This study provides comprehensive research on the changes in intra‐ and inter‐brain functional networks in patients with VCIND who received computerized cognitive training, with a focus on the underlying mechanisms and potential therapeutic strategies. Methods: We prospectively collected 60 patients with VCIND who were randomly divided into the training group (N = 30) receiving computerized cognitive training and the control group (N = 30) receiving fixed cognitive training. Functional MRI scans and cognitive assessments were performed at baseline, at the 7‐week training, and at the 6‐month follow‐up. Utilizing templates for ICNs, the study employed a linear mixed model to compare intra‐ and inter‐network FC changes between the two groups. Pearson correlation was applied to calculate the relationship between FC and cognitive function. Results: We found significantly decreased intra‐network FC within the default mode network (DMN) following computerized cognitive training at Month 6 (p = 0.034), suggesting a potential loss of functional specialization. Computerized training led to increased functional coupling between the DMN and sensorimotor network (SMN) (p = 0.01) and between the language network (LN) and executive control network (ECN) at Month 6 (p < 0.001), indicating compensatory network adaptations in patients with VCIND. Notably, the intra‐LN exhibited enhanced functional specialization after computerized cognitive training (p = 0.049), with significant FC increases among LN regions, which correlated with improvements in neuropsychological measures (p < 0.05), emphasizing the targeted impact of computerized cognitive training on language abilities. Conclusions: This study provides insights into neuroplasticity and adaptive changes resulting from cognitive training in patients with VCIND, with implications for potential therapeutic strategies. [ABSTRACT FROM AUTHOR]

Microplastics, considered emerging contaminants, have been accumulating excessively within soil ecosystems, conferring potentially detrimental effects with respect to soil carbon turnover and pools. As a major participant in soil carbon processes, microplastics affecting microorganisms may be one of the main agents affecting soil carbon dynamics. However, the microbial metabolism processes through which microplastics affect soil carbon dynamics remain unclear. Therefore, this study aimed to assess the impact of variously sized (1300, 800, 100, and 0.1 μm) polystyrene microplastics on soil microbial metabolism. Soil microplastics of all sizes invariably and consistently affected microbial metabolism, though nanomicroplastics (0.1 μm) stressed soil microorganisms more than micron‐microplastics. Furthermore, microplastics inhibited both microbial carbon use efficiency (CUE) and respiration, the exception being the CUE in the 1300 μm microplastics treatment. As microplastic particle size decreased, the suppressive influence of microplastics on microbial respiration was gradually lost, the inhibitory effect on microbial CUE increased steadily, and the impact on microorganisms shifted from extracellular to intracellular, with intracellular microplastics exhibiting higher toxicity than extracellular microplastics. We used stoichiometric models to provide precise projections of microbial metabolism features associated with microplastic contamination, thereby enhancing the understanding of the effects of microplastic contamination on the carbon cycle and soil ecosystem. [ABSTRACT FROM AUTHOR]

In this paper, Pd‐catalyzed [4+2] decarboxylative cycloaddition of 4‐vinylbenzodioxinones with barbiturate‐derived alkenes has been developed, leading to various spirobarbiturate−chromane derivatives in high yields with excellent diastereo‐ and enantioselectivities. The scale‐up reaction and further derivation of the product were demonstrated. A plausible reaction mechanism was also proposed. [ABSTRACT FROM AUTHOR]

Knee osteoarthritis (KOA) is widely recognized as a chronic joint disease characterized by degeneration of knee cartilage and subsequent bone hyperplasia. However, it is important to acknowledge the significant role of muscles in the development and progression of KOA. Muscle function (MF) and muscle quality (MQ) are key factors in understanding the involvement of muscles in KOA. Quantitative indices such as muscle mass, muscle strength, muscle cross‐sectional area, muscle thickness, and muscle fatigue are crucial in assessing MF and MQ. Despite the growing interest in KOA, there is a scarcity of studies investigating the relationship between muscles and this condition. This review aims to examine the commonly used indices and measurement methods for assessing MF and MQ in clinical settings, while also exploring the association between muscles and KOA. Furthermore, this article highlights the importance of restoring MF and MQ to enhance symptom management and improve the quality of life for patients with KOA. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC), a very aggressive tumour, is currently the third leading cause of cancer‐related deaths. Unfortunately, many patients face the issue of inoperability at the diagnostic phase leading to a quite dismal prognosis. The onset of metastatic processes has a crucial role in the elevated mortality rates linked to PDAC. Individuals with metastatic advances receive only palliative therapy and have a grim prognosis. It is essential to carefully analyse the intricacies of the metastatic process to enhance the prognosis for individuals with PDAC. Malignancy development is greatly impacted by the process of macrophage efferocytosis. Our current knowledge about the complete range of macrophage efferocytosis activities in PDAC and their intricate interactions with tumour cells is still restricted. This work aims to resolve communication gaps and pinpoint the essential transcription factor that is vital in the immunological response of macrophage populations. We analysed eight PDAC tissue samples sourced from the gene expression omnibus. We utilized several software packages such as Seurat, DoubletFinder, Harmony, Pi, GSVA, CellChat and Monocle from R software together with pySCENIC from Python, to analyse the single‐cell RNA sequencing (scRNA‐seq) data collected from the PDAC samples. This study involved the analysis of a comprehensive sample of 22,124 cells, which were classified into distinct cell types. These cell types encompassed endothelial and epithelial cells, PDAC cells, as well as various immune cells, including CD4+ T cells, CD8+ T cells, NK cells, B cells, plasma cells, mast cells, monocytes, DC cells and different subtypes of macrophages, namely C0 macrophage TGM2+, C1 macrophage PFN1+, C2 macrophage GAS6+ and C3 macrophage APOC3+. The differentiation between tumour cells and epithelial cells was achieved by the implementation of CopyKat analysis, resulting in the detection and categorization of 1941 PDAC cells. The amplification/deletion patterns observed in PDAC cells on many chromosomes differ significantly from those observed in epithelial cells. The study of Pseudotime Trajectories demonstrated that the C0 macrophage subtype expressing TGM2+ had the lowest level of differentiation. Additionally, the examination of gene set scores related to efferocytosis suggested that this subtype displayed higher activity during the efferocytosis process compared to other subtypes. The most active transcription factors for each macrophage subtype were identified as BACH1, NFE2, TEAD4 and ARID3A. In conclusion, the examination of human PDAC tissue samples using immunofluorescence analysis demonstrated the co‐localization of CD68 and CD11b within regions exhibiting the presence of keratin (KRT) and alpha‐smooth muscle actin (α‐SMA). This observation implies a spatial association between macrophages, fibroblasts, and epithelial cells. There is variation in the expression of efferocytosis‐associated genes between C0 macrophage TGM2+ and other macrophage cell types. This observation implies that the diversity of macrophage cells might potentially influence the metastatic advancement of PDAC. Moreover, the central transcription factor of different macrophage subtypes offers a promising opportunity for targeted immunotherapy in the treatment of PDAC. [ABSTRACT FROM AUTHOR]

Mosquitoes (Anopheles sinensis), widely geographically distributed in Asia including China, are the primary vector of the malaria parasite Plasmodium vivax and other parasitic diseases such as Malayan filariasis. An. sinensis can survive through low winter temperatures. Aquaporin channels are found in all life forms, where they facilitate environmental adaptation by allowing rapid trans‐cellular movement of water (classical aquaporins) or water and solutes such as glycerol (aquaglyceroporins). Here, we identified and characterized 2 aquaporin (AQP) homologs in An. sinensis: AsAQP2 (An. sinensis aquaglyceroporin) and AsAQP4 (An. sinensis aquaporin). When expressed in frog (Xenopus laevis) oocytes, AsAQP2 transported water, glycerol, and urea; AsAQP4 transported only water. Water permeation through AsAQP2 and AsAQP4 was inhibited by mercuric chloride. AsAQP2 expression was slightly higher in adult female mosquitoes than in males, and AsAQP4 expression was significantly higher in adult males. The 2 AsAQPs were highly expressed in Malpighian tubules and midgut. AsAQP2 and AsAQP4 expression was up‐regulated by blood feeding compared with sugar feeding. At freezing point (0 °C), the AsAQP4 expression level increased and An. sinensis survival time reduced compared with those at normal temperature (26 °C). At low temperature (8 °C), the AsAQP2 and AsAQP4 expression levels decreased and survival time was significantly longer compared with those at 26 °C. These results suggest that AsAQP2 and AsAQP4 have roles in water homeostasis during blood digestion and in low temperature adaptation of A. sinensis. Together, our results show that the 2 AQPs are important for mosquito diuresis after blood feeding and when exposed to low temperatures. [ABSTRACT FROM AUTHOR]

Hydrazine (HD) and mono‐methyl hydrazine (MMH), as the compositions of rocket fuels and corrosion inhibitor, have a significant impact on the atmospheric environment. The effects of them on the reaction between NO2 and H2O were investigated theoretically from mechanism and kinetics, and it is expected that they can promote the hydrolysis of NO2 due to their lower free energy barriers. For the subsequent reaction HNO3+HONO+HD/MMH, acid base complex and zwitterionic structure were produced through isomerization. When one or two water molecules were involved in the subsequent reaction, only zwitterionic structure can be found with the lower free energy barrier, and the products were more stable than those without water molecules. To study the atmospheric behavior of HD/MMH, the structures, thermodynamics, interaction forces and temperature dependence of the clusters, which were consisted with HNO3 and HONO with the base molecules including ammonia, amine and amide, were further calculated, and the results show that the hydrogen bond is the main interaction in the clusters. The global minima remained fixed when the temperature increases from 200 K to 325 K. The forming reactions of the clusters were spontaneous, suggesting that ammonia, amine and amide can promote the nucleation of HNO3 and HONO molecules. [ABSTRACT FROM AUTHOR]

Introduction: Patients with hemophilia (PWH) constantly suffer hemarthrosis, which leads to deformity of the hip joint. Therefore, PWH who are going to receive total hip arthroplasty (THA) should be exclusively treated before the surgery with careful measurement of their proximal femur. Hence, we conducted a retrospective study to explore the anatomical parameters of and differences in the proximal femur in hemophilic patients who underwent THA. Methods: The retrospective study comprised data of adult patients who received total hip arthroplasty from 2020 to 2022 in the research center. Patients having a diagnosis of hemophilic arthritis and received THA were included in experimental group, and patients with hip arthritis or femoral head necrosis were taken as control group. Parameters including femoral offset, neck‐shaft angle (NSA), medullary cavity of 20 mm above mid‐lesser trochanter level (T+20), mid‐lesser trochanter level (T), and 20 mm blow it (T−20), and canal flare index (CFI), femoral cortical index (FCI) were measured on X‐ray and CT images with PACS by two independent doctors. Data was analyzed by SPSS 20. Kolmogorov–Smirnov test was used to test data normality. Student's t‐test was performed between PWH and control group. p < 0.05 was considered statistically significant. Results: Among the 94 hips, 39 (41.5%) were included in group hemophilia and 55(58.5%) in control group. The mean age of the patients was 49.36 ± 12.92 years. All cases were male patients. Data demonstrated significantly smaller femoral cortical index (FCI), femoral offset, medullary cavity of 20 mm above mid‐lesser trochanter level, mid‐lesser trochanter level, and 20 mm below it, and neck‐shaft angle (NSA) was obviously larger in PWH than control group (p < 0.05). No significant difference was found in canal flare index (CFI). Conclusion: Hemophilic patients undergoing THA were prone to longer and thinner proximal femur. Preoperative morphological analysis of femur is recommended. [ABSTRACT FROM AUTHOR]

Accurately battery state of health (SOH) estimation in electric vehicles (EVs) is crucial for optimal performance and safety. This article presents an in‐depth investigation into the utilization of an optimized decision tree (DT) model for precise SOH estimation. Two aging features (AFs) are extracted through incremental capacity analysis from the partial charging process, and their efficacy is thoroughly validated on both battery cells and packs. To capture the relationship between AFs and capacity degradation, a robust DT model is established. Furthermore, Bayesian optimization is employed to optimize the model hyperparameters, enhancing the learning and generalization capabilities of the DT model. To validate the optimized DT model, a battery management system (BMS) is developed using a hybrid programming approach with LabVIEW and MATLAB, enabling online SOH estimation. The BMS undergoes rigorous evaluation using publicly available aging datasets of battery cells, as well as private datasets of battery packs. The results demonstrate that the optimized DT model outperforms traditional DT models, back propagation neural networks, and support vector machine approaches in accurately estimating battery SOH across diverse datasets. This research contributes to the advancement of BMS and holds profound implications for the efficient utilization of batteries in EVs. [ABSTRACT FROM AUTHOR]

The construction of effective conductive networks can enhance the electromagnetic interference (EMI) shielding performance of the conductive polymer composites (CPCs). Herein, poly (l‐lactide) (PLLA) micro‐particles were used as a volume‐occupying phase to design and prepare the PLLA/polydimethylsiloxane/multi‐walled carbon nanotubes (PLLA/PDMS/MWCNT) composites with honeycomb‐like conductive networks. The interfacial morphology of the composites was adjusted by changing the surface morphology of the PLLA micro‐particles. The effects of the morphology and particle size of the PLLA phase on the EMI shielding effectiveness (SE) of the composites were investigated in this study. The results indicate that the PLLA micro‐particles with regular shape and rough surface can effectively improve the EMI shielding performance of the PLLA/PDMS/MWCNT composites with the same filler loadings and the particle size of PLLA micro‐particles. Specifically, the EMI SE of the composites with etched 300‐μm spherical micro‐particles with rough surface can achieve 35.1 dB, which is 15% higher than the EMI SE of 30.6 dB for the composites with the 300‐μm irregular micro‐particles. In addition, the R values of the composites with honeycomb‐like conductive networks are below 0.5, indicating absorption dominated shielding mechanism. Highlights: Micro‐particle surface tunes the interfacial structure of the honeycomb‐like samples.Micro‐particles with different sizes endow different EMI SE for the composites.Samples with regular micro‐particles have higher EMI SE than irregular ones.The samples with etched micro‐particles have the highest EMI SE.The honeycomb‐like samples show an absorption‐dominated shielding mechanism. [ABSTRACT FROM AUTHOR]

Traditional mindfulness interventions have been frequently reported to be effective in improving cognitive functions. In recent years, however, traditional programs are being increasingly replaced by technology‐enabled mindfulness training programs. The aim of the present systematic review (PROSPERO ID: CRD42021289480) is to evaluate the research evidence on their effects on cognitive functions. Empirical training studies in the realm of digital mindfulness training that fulfilled the inclusion criteria led to 19 studies and 1654 participants being included in this review from among the papers searched in PubMed, Scopus, and Web of Knowledge. Results support previous assumptions on the potential of digital mindfulness training, with the most robust effect on attention control, followed by executive regulation, memory, cognitive flexibility, and other cognitive functions. However, the number of studies that did not find significant changes at least equaled, if not exceeded, the number of studies that found increases. The heterogeneity of identified studies prompted us to discuss several aspects in order to help the future development of digital applications. [ABSTRACT FROM AUTHOR]

Incorporating conductive and porous components as pillaring materials into the interlayers of two‐dimensional (2D) materials offers a solution to the restacking issue and enables the creation of multifunctional hetero‐superstructures. Here, multilayer MXene superlattices intercalated with monolayer mesoporous carbon frameworks (MMCFs) are synthesized by colloidal co‐assembly of MXene Ti3C2Tx nanosheets and Fe3O4 nanoparticles. The intercalated MMCFs not only increase interlayer spacing and create porous channels for fast mass transport but also act as conductive pillars to facilitate electron transfer along the z‐direction. These unique structural features allow for the full utilization of unilamellar MXene, making the resulting Ti3C2Tx/MMCF superlattices particularly suitable for capacitive energy storage in organic electrolytes containing bulky ions. As a demonstration, supercapacitors made from Ti3C2Tx/MMCFs exhibit a volumetric capacitance of 317 F cm−3 in a tetraethylammonium tetrafluoroborate/propylene carbonate electrolyte. Furthermore, on‐chip micro‐supercapacitors (MSCs) fabricated from Ti3C2Tx/MMCFs, using the ionic liquid 1‐ethyl‐3‐methylimidazolium tetrafluoroborate as an electrolyte, achieve an areal energy density of 0.10 mWh cm−2, surpassing that of most state‐of‐the‐art MXene‐based MSCs developed to date. This study not only highlights the significant potential of Ti3C2Tx/MMCFs for efficient capacitive energy storage in organic electrolytes but also introduces a new method for synthesizing 2D porous hetero‐superstructures for various applications. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer, marked by its heterogeneous nature, showcases various molecular subtypes and clinical trajectories. This research delves into the significance of metabolic and immune‐driven pathways in gastric cancer, constructing a prognostic signature derived from differentially expressed metabolic and immune‐correlated genes (DE‐MIGs). Methods: Metabolic and immune‐associated gene were sourced from the GeneCards database. Differential expression analysis on the TCGA‐STAD dataset was executed using the limma package, unveiling 51 DE‐MIGs that underwent functional enrichment scrutiny. The LASSO Cox regression methodology guided the creation of the prognostic signature, and individual patient risk scores were determined. Assessment tools like CIBERSORT, ESTIMATE and ssGSEA were deployed to study the immune microenvironment, while mutation profiles, genomic stability, resistance to chemotherapy and immunotherapy responsiveness were scrutinized across distinct signature categorizations. Results: Among the identified DE‐MIGs, 26 were significantly tied to the overall survival of gastric cancer patients. The developed prognostic signature proficiently differentiated patients into high‐risk and low‐risk cohorts, with the latter showing markedly better outcomes. The study underscored the centrality of the immune microenvironment in influencing gastric cancer outcomes. Key pathways such as TGF‐Beta, TP53 and NRF2 dominated the high‐risk group, whereas the LRTK−RAS and WNT pathways characterized the low‐risk group. Interestingly, the low‐risk segment also manifested a heightened tumor mutation burden and enhanced susceptibility to immunotherapy. Conclusions: Our findings introduce a pivotal prognostic signature, rooted in DE‐MIGs, that effectively segregates gastric cancer patients into distinct risk‐based segments. Insights into the influential role of the immune microenvironment in gastric cancer progression pave the way for more refined therapeutic interventions. [ABSTRACT FROM AUTHOR]

Lipid metabolism and oxidative stress are key mechanisms in Alzheimer's disease (AD). The link between plasma lipid metabolites and oxidative stress in AD patients is poorly understood. This study was to identify markers that distinguish AD and amnestic mild cognitive impairment (aMCI) from NC, and to reveal potential links between lipid metabolites and oxidative stress. We performed non‐targeted lipid metabolism analysis of plasma from patients with AD, aMCI, and NC using LC–MS/MS. The plasma malondialdehyde (MDA), glutathione peroxidase (GSH‐Px), and superoxide dismutase (SOD) levels were assessed. We found significant differences in lipid metabolism between patients with AD and aMCI compared to those in NC. AD severity is associated with lipid metabolites, especially TG (18:0_16:0_18:0) + NH4, TG (18:0_16:0_16:0) + NH4, LPC(16:1e)‐CH3, and PE (20:0_20:4)‐H. SPH (d16:0) + H, SPH (d18:1) + H, and SPH (d18:0) + H were high‐performance markers to distinguish AD and aMCI from NC. The AUC of three SPHs combined to predict AD was 0.990, with specificity and sensitivity as 0.949 and 1, respectively; the AUC of three SPHs combined to predict aMCI was 0.934, with specificity and sensitivity as 0.900, 0.981, respectively. Plasma MDA concentrations were higher in the AD group than in the NC group (p = 0.003), whereas plasma SOD levels were lower in the AD (p < 0.001) and aMCI (p = 0.045) groups than in NC, and GSH‐Px activity were higher in the AD group than in the aMCI group (p = 0.007). In addition, lipid metabolites and oxidative stress are widely associated. In conclusion, this study distinguished serum lipid metabolism in AD, aMCI, and NC subjects, highlighting that the three SPHs can distinguish AD and aMCI from NC. Additionally, AD patients showed elevated oxidative stress, and there are complex interactions between lipid metabolites and oxidative stress. [ABSTRACT FROM AUTHOR]

Spin‐dependent electron transport is theoretically studied for a system with an interacting quantum dot sandwiched between a pair of ferromagnetic electrodes. By separately applying an electrical bias or a temperature gradient across the junction, a spin‐polarized current can be obtained and controlled by tuning the gate voltage. Interestingly, regardless of whether the electron transport is driven by the bias voltage or temperature difference, the current in the device always exhibits negative magnetoresistance under the control of the gate voltage. Such magnetoresistance anomalies in the current profile originate from the spin‐selective tunneling channels in quantum dots, which have been proven experimentally feasible. This device scheme is compatible with current technologies and has potential applications in spintronics or spin caloritronics. [ABSTRACT FROM AUTHOR]

Electroreduction of CO2 to multi‐carbon (C2+) products is a promising approach for utilization of renewable energy, in which the interfacial water quantity is critical for both the C2+ product selectivity and the stability of Cu‐based electrocatalytic sites. Functionalization of long‐chain alkyl molecules on a catalyst surface can help to increase its stability, while it also tends to block the transport of water, thus inhibiting the C2+ product formation. Herein, we demonstrate the fine tuning of interfacial water by surface assembly of toluene on Cu nanosheets, allowing for sustained and enriched CO2 supply but retarded water transfer to catalytic surface. Compared to bare Cu with fast cathodic corrosion and long‐chain alkyl‐modified Cu with main CO product, the toluene assembly on Cu nanosheet surface enabled a high Faradaic efficiency of 78 % for C2+ and a partial current density of 1.81 A cm−2. The toluene‐modified Cu catalyst further exhibited highly stable CO2‐to‐C2H4 conversion of 400 h in a membrane‐electrode‐assembly electrolyzer, suggesting the attractive feature for both efficient C2+ selectivity and excellent stability. [ABSTRACT FROM AUTHOR]

We uncovered and reconstituted a concise biosynthetic pathway of the strained dipeptide (+)‐azonazine A from marine‐derived Aspergillus insulicola. Formation of the hexacyclic benzofuranoindoline ring system from cyclo‐(l‐Trp‐N‐methyl‐l‐Tyr) is catalyzed by a P450 enzyme through an oxidative cyclization. Supplementing the producing strain with various indole‐substituted tryptophan derivatives resulted in the generation of a series of azonazine A analogs. [ABSTRACT FROM AUTHOR]

The utilization of biomass‐derived sugars as the emerging hydrogen donor in catalytic transfer hydrogenation (CTH) reactions has received great attention in recent years. In this work, we proposed two CTH routes of alditol production in the aqueous solution, i. e. self‐disproportionation of sugar and cross CTH of different sugars. Both could realize the process of sugar towards alditol. Taking advantage of the differences in hydrogenation and dehydrogenation capabilities of different sugars, a high C4 alditol yield of 85.9 % was surprisingly obtained via cross CTH route using glucose as the hydrogen donor, which is much better than that obtained when using traditional hydrogen donor isopropanol. The CTH reactions using sugars as the hydrogen donor can not only reduce the utilization of fossil energy, but also provide a new pathway for the production of alditols. [ABSTRACT FROM AUTHOR]

Bowenoid papulosis (BP) is a benign and possibly carcinogenic disease associated with human papillomavirus (HPV) infection, which has been increasingly recognised and paid attention to in recent years, but the potential mechanisms still remain unclear. In our study, three patients who were diagnosed with BP were enrolled into our research. Skin biopsies were taken and were separated into two parts, one part was for HE staining and the others were for RNA‐sequencing (RNA‐seq). All the three patents were human papillomavirus (HPV) positive and HE staining revealed typical skin histopathological changes in BP, including dyskeratosis, hyperplasia and hypertrophy of the granular and spinous layers, atypical keratinocytes. RNA‐seq analysis demonstrated that a total of 486 differentially expressed genes (DEGs) were detected between the skin tissues from BP and the controls, among which, 320 genes were significantly upregulated and 166 genes were dramatically downregulated. GO enrichment revealed that antigen binding, cell cycle, immune response and keratinisation to be the most notably altered pathways, whereas KEGG analysis indicated that cell cycle cytokine‐cytokine receptor interaction, ECM receptor interaction and p53 signalling pathway to be the most significantly changed signalling pathways in BP. Furthermore, metabolism‐associated enrichment analysis showed that cholesterol metabolism, metabolism of xenobiotics by cytochrome p450 and pyrimidine metabolism to be the most dramatically dysregulated metabolic pathways in BP as compared to normal controls. Our study revealed that inflammation, metabolism and cell proliferation signalling pathways might be the most important pathways for BP disease, targeted inhibiting of these signals might be a potential method for BP treatment. [ABSTRACT FROM AUTHOR]

Background and Objectives: Alcohol use disorder (AUD) is a significant public health concern, with underutilized effective treatments, particularly in special populations. This article summarizes the current evidence and guidelines for treating AUD in special populations. Methods: This article is a literature review that synthesizes the latest research on AUD treatment for special populations. We screened 242 articles and included 57 in our final review. Results: There are four food and Drug Administration‐approved medications for AUD (MAUD): disulfiram, oral naltrexone, extended‐release injectable naltrexone (XR‐NTX), and acamprosate. Naltrexone and disulfiram have the potential to cause liver toxicity, and acamprosate should be avoided in patients with severe kidney disease. Psychosocial treatments should be considered first‐line for pregnant and nursing patients. Naltrexone is contraindicated in patients on opioids, as it may precipitate acute withdrawal. For patients experiencing homelessness, nonabstinent treatment goals may be more practical, and XR‐NTX should be considered to improve adherence. Limited evidence suggests medication can improve AUD treatment outcomes in adolescents and young adults. For patients with poor treatment response despite adequate medication adherence, switching to a different medication and augmentation with psychosocial treatments should be considered. Discussion and Conclusions: Understanding the unique considerations for special populations with AUD is crucial, and addressing their special needs may improve their treatment outcomes. Scientific Significance: Our study significantly contributes to the existing literature by summarizing crucial information for the treatment of AUD in special populations, highlighting distinct challenges, and emphasizing tailored approaches to improve overall health and well‐being. [ABSTRACT FROM AUTHOR]

We report the case of a Chinese male with schizoaffective disorder, an active smoker and a nonresponder to clozapine (600 mg daily). Therapeutic clozapine monitoring was analyzed, revealing a low concentration‐dose ratio. A pharmacogenetic test showed that the patient had the CYP1A2*1F/*1F genotype, indicating an ultra‐rapid clozapine metabolizer. In combination with fluvoxamine, a CYP1A2 enzyme inhibitor, clozapine plasma concentrations approached the reference range and achieved clinical improvement. This case demonstrates how pharmacogenetics can help understand the value of therapeutic drug monitoring to enhance the treatment of refractory schizoaffective disorder. [ABSTRACT FROM AUTHOR]

INTRODUCTION: It is challenging to predict which patients who meet criteria for subcortical ischemic vascular disease (SIVD) will ultimately progress to subcortical vascular cognitive impairment (SVCI). METHODS: We collected clinical information, neuropsychological assessments, T1 imaging, diffusion tensor imaging, and resting‐state functional magnetic resonance imaging from 83 patients with SVCI and 53 age‐matched patients with SIVD without cognitive impairment. We built an unsupervised machine learning model to isolate patients with SVCI. The model was validated using multimodal data from an external cohort comprising 45 patients with SVCI and 32 patients with SIVD without cognitive impairment. RESULTS: The accuracy, sensitivity, and specificity of the unsupervised machine learning model were 86.03%, 79.52%, and 96.23% and 80.52%, 71.11%, and 93.75% for internal and external cohort, respectively. DISCUSSION: We developed an accurate and accessible clinical tool which requires only data from routine imaging to predict patients at risk of progressing from SIVD to SVCI. Highlights: Our unsupervised machine learning model provides an accurate and accessible clinical tool to predict patients at risk of progressing from subcortical ischemic vascular disease (SIVD) to subcortical vascular cognitive impairment (SVCI) and requires only data from imaging routinely used during the diagnosis of suspected SVCI.The model yields good accuracy, sensitivity, and specificity and is portable to other cohorts and to clinical practice to distinguish patients with SIVD at risk for progressing to SVCI.The model combines assessment of diffusion tensor imaging and functional magnetic resonance imaging measures in patients with SVCI to analyze whether the "disconnection hypothesis" contributes to functional and structural changes and to the clinical presentation of SVCI. [ABSTRACT FROM AUTHOR]

Aims: The DELIVER study demonstrates a significant improvement in cardiovascular death or hospitalization for heart failure among heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF).Cost‐utility of the adjunct use of dapagliflozin to standard therapy among patients with HFpEF or HFmrEF remains unclear. Methods and results: A five‐state Markov mode was constructed to project health and clinical outcomes of the adjunct use of dapagliflozin to standard therapy among 65‐year‐old patients with HFpEF or HFmrEF. A cost‐utility analysis was performed based on the DELIVER study and national statistical database. The cost and utility was inflated to 2022 by the usual discount rate of 5%. The primary outcomes were total cost and quality‐adjusted life‐years (QALYs) per patients as well as the incremental cost‐effectiveness ratio. Sensitivity analyses were also applied. Over a 15 year lifetime horizon, the average cost per patient was $7245.77 and $5407.55 in the dapagliflozin group and the standard group, along with an incremental cost of $1838.22. The average QALYs per patient was 6.00 QALYs and 5.84 QALYs in the dapagliflozin group and the standard group, along with an incremental QALYs of 0.15 QALYs, resulting in the incremental cost‐effectiveness ratio of $11 865.33/QALY, which was below the willingness‐to‐pay (WTP) of $12 652.5/QALY. The univariate sensitivity analysis indicated the cardiovascular death in both group was the most sensitive variable. Probability sensitivity analysis revealed that when the WTP thresholds were $12 652.5/QALY and $37 957.5/QALY, the probabilities of being cost‐effective with dapagliflozin as an add‐on were 54.6% and 71.6%, respectively. Conclusions: From a public healthcare system perspective, the adjunct use of dapagliflozin to standard therapy among patients with HFpEF or HFmrEF generated advantages in cost‐effectiveness in China at a WTP of $12 652.5/QALY, which promoted the rational use of dapagliflozin for heart failure. [ABSTRACT FROM AUTHOR]

Objectives: The mechanisms of regional acceleratory phenomenon (RAP) induced by orthognathic osteotomy are unclear. It was not known if locally hypoxic microenvironment changes were involved in this phenomenon. Methods: Hypoxia‐induced factor‐1α knockout mice harboring Cathepsin K (CTSK) Cre were used to investigate the effect of hypoxia‐driven osteoclasts on alveolar bone remodeling. RAW264.7 cells were induced by CoCl2 to observe the effects of dendritic cell‐specific transmembrane protein (DC‐STAMP) on the fusion and differentiation of osteoclasts. Results: We found mandibular osteotomy of C57 mice induced active alveolar osteoclasts and increased hypoxia‐induced factor‐1α (HIF‐1α) positive staining areas. Alveolar bone density of the 10‐week‐old HIF‐1α conditional knockout (CKO) mouse was increased at 10 and 14 days after bilateral mandibular osteotomy. Moreover, decreased numbers of osteoclasts and matrix metalloproteinase 9 (MMP‐9)‐positive cells were observed on the surface of bone resorption lacunae in the CKO group. HIF‐1α could increase the expression level of DC‐STAMP to enhance osteoclastogenesis and cell fusion in active RAW264.7 cells. Conclusion: Our data considered hypoxia‐driven osteoclasts resorption to be an adaptive mechanism to permit alveolar bone loss after bilateral mandibular osteotomy of mice. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Common urinary symptoms may arise from metastases from uncommon sites. In patients with a history of cancer, the focus should be on the currently affected organ and the status of the underlying malignancy. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors have been approved for the treatment of advanced hepatocellular carcinoma (HCC). However, immunotherapy requires the identification of suitable biomarkers to guide treatment. The gene for rhomboid 5 homolog 2 (IRHom2), which encodes the rhombus protease iRhom2, activates the MAP3K7‐dependent pathway and promotes hepatic steatosis. Thus, we hypothesized an involvement of this gene in HCC. We report that RHBDF2 expression is dramatically upregulated in HCC. RHBDF2 upregulation is associated with tumor stage, lymph node metastasis, tumor protein P53 mutation, and worse prognoses in HCC patients. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and gene set enrichment analysis enrichment analysis indicated that RHBDF2 was involved in immune signal pathways. Moreover, RHBDF2 expression was positively related not only to immune infiltration, but also to immune cell markers. Examination of several types of HCC infiltrated by immune cells revealed that the group with high expression of RHBDF2 showed the worst outcomes. Therefore, RHBDF2 may have potential as a novel biomarker for predicting prognosis and is related to immune infiltrates in HCC. [ABSTRACT FROM AUTHOR]

β‐catenin signaling is abnormally activated in cancer. Here, this work screens the mevalonate metabolic pathway enzyme PMVK to stabilize β‐catenin signaling using a human genome‐wide library. On the one hand, PMVK‐produced MVA‐5PP competitively binds to CKIα to prevent β‐catenin Ser45 phosphorylation and degradation. On the other hand, PMVK functions as a protein kinase to directly phosphorylate β‐catenin Ser184 to increase its protein nuclear localization. This synergistic effect of PMVK and MVA‐5PP together promotes β‐catenin signaling. In addition, PMVK deletion impairs mouse embryonic development and causes embryonic lethal. PMVK deficiency in liver tissue alleviates DEN/CCl4‐induced hepatocarcinogenesis. Finally, the small molecule inhibitor of PMVK, PMVKi5, is developed and PMVKi5 inhibits carcinogenesis of liver and colorectal tissues. These findings reveal a non‐canonical function of a key metabolic enzyme PMVK and a novel link between the mevalonate pathway and β‐catenin signaling in carcinogenesis providing a new target for clinical cancer therapy. [ABSTRACT FROM AUTHOR]

Osteoclasts are bone‐resorbing polykaryons responsible for skeletal remodeling during health and disease. Coincident with their differentiation from myeloid precursors, osteoclasts undergo extensive transcriptional and metabolic reprogramming in order to acquire the cellular machinery necessary to demineralize bone and digest its interwoven extracellular matrix. While attempting to identify new regulatory molecules critical to bone resorption, we discovered that murine and human osteoclast differentiation is accompanied by the expression of Zeb1, a zinc‐finger transcriptional repressor whose role in normal development is most frequently linked to the control of epithelial‐mesenchymal programs. However, following targeting, we find that Zeb1 serves as an unexpected regulator of osteoclast energy metabolism. In vivo, Zeb1‐null osteoclasts assume a hyperactivated state, markedly decreasing bone density due to excessive resorptive activity. Mechanistically, Zeb1 acts in a rheostat‐like fashion to modulate murine and human osteoclast activity by transcriptionally repressing an ATP‐buffering enzyme, mitochondrial creatine kinase 1 (MtCK1), thereby controlling the phosphocreatine energy shuttle and mitochondrial respiration. Together, these studies identify a novel Zeb1/MtCK1 axis that exerts metabolic control over bone resorption in vitro and in vivo. Synopsis: Osteoporosis and similar bone‐wasting conditions can be caused by an increase in osteoclast‐mediated bone resorption. Here, we learn that both murine and human osteoclasts are activated by a Zeb1‐dependent regulation of mitochondrial energy metabolism.The transcription factor Zeb1 is a negative regulator of giant multinucleated osteoclast‐mediated skeletal remodeling.Zeb1 regulates mitochondrial energy metabolism in myeloid lineage‐derived osteoclasts.The mitochondrial creatine kinase MtCK1 is a transcriptional target of Zeb1 that enables bone resorption by buffering ATP availability. [ABSTRACT FROM AUTHOR]

Southeast China is one of the core areas of the Sino‐Japanese floristic region and a hotspot of biodiversity in East Asia. This region has been considered as both a museum and a cradle of woody genera in China. Why a region with highly stable topography and climate could be a cradle of species diversity remains unclear. In this study, the phylogeographic pattern and genetic structure of Wikstroemia monnula, an endemic species to southeast China, were analyzed by sequencing four chloroplast DNA fragments (4679 bp in total) of 836 individuals from 39 populations. Extremely high diversity and endemism of chlorotypes were found. Out of 54 chlorotypes, 51 (94.44%) were private, with genetic diversity index (HT) near 1 (HT = 0.992), and 96.51% of the genetic variation occurring among populations, indicating that this species has undergone strong intraspecific differentiation and very limited migration. The correlational analysis showed that the population differentiation of W. monnula was driven not only via isolation by distance (IBD), but more importantly via isolation by environment (IBE). A significant phylogeographic structure was not found (NST = 0.979, GST = 0.833, P > 0.05); however, the spatial pattern of the sublineages of chlorotypes was largely consistent with the biogeographic boundaries on a smaller scale in the region. These results suggest that habitat heterogeneity in southeast China not only promoted speciation on a long time‐scale, but still continues to impact population differentiation in recent times. [ABSTRACT FROM AUTHOR]