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Abstract Myeloid cells are pivotal in the inflammatory and remodeling phases of fracture repair. Here, we investigate the effect of periostin expressed by myeloid cells on bone regeneration in a monocortical tibial defect (MTD) model. In this study, we show that periostin is expressed by periosteal myeloid cells, primarily the M2 macrophages during bone regeneration. Knockout of periostin in myeloid cells reduces cortical bone thickness, disrupts trabecular bone connectivity, impairs repair impairment, and hinders M2 macrophage polarization. Mechanical stimulation is a regulator of periostin in macrophages. By activating transforming growth factor-β (TGF-β), it increases periostin expression in macrophages and induces M2 polarization. This mechanosensitive effect also reverses the delayed bone repair induced by periostin deficiency in myeloid cells by strengthening the angiogenesis-osteogenesis coupling. In addition, transplantation of mechanically conditioned macrophages into the periosteum over a bone defect results in substantially enhanced repair, confirming the critical role of macrophage-secreted periostin in bone repair. In summary, our findings suggest that mechanical stimulation regulates periostin expression and promotes M2 macrophage polarization, highlighting the potential of mechanically conditioned macrophages as a therapeutic strategy for enhancing bone repair.

Abstract This study investigated how resting-state functional connectivity (rsFC) of the subgenual anterior cingulate cortex (sgACC) predicts antidepressant response in patients with major depressive disorder (MDD). Eighty-seven medication-free MDD patients underwent baseline resting-state functional MRI scans. After 12 weeks of escitalopram treatment, patients were classified into remission depression (RD, n = 42) and nonremission depression (NRD, n = 45) groups. We conducted two analyses: a voxel-wise rsFC analysis using sgACC as a seed to identify group differences, and a prediction model based on the sgACC rsFC map to predict treatment efficacy. Haufe transformation was used to interpret the predictive rsFC features. The RD group showed significantly higher rsFC between the sgACC and regions in the fronto-parietal network (FPN), including the bilateral dorsolateral prefrontal cortex (DLPFC) and bilateral inferior parietal lobule (IPL), compared to the NRD group. These sgACC rsFC measures correlated positively with symptom improvement. Baseline sgACC rsFC also significantly predicted treatment response after 12 weeks, with a mean accuracy of 72.64% (p

Taking Dongmen Fishing Village in Xiangshan, Zhejiang Province as an example, based on the theory of cultural landscape genes, this paper constructs a cultural landscape gene information chain for Dongmen Fishing Village, and proposes the composition and construction method of the information chain, ultimately forming information points including 4 major categories, 14 subcategories, and 29 points, including 4 information elements of fishery industry culture, folk beliefs culture, maritime defense culture, and island settlement culture, as well as an information corridor formed by overlapping village spaces. The study further conducts quantitative evaluation of cultural landscape genes through questionnaire surveys, including the importance of different information points and their correlation with information elements. Through IPA analysis of importance and correlation, the types of cultural landscape genes are clarified, and their type and spatial characteristics are further analyzed. Based on this, the study analyzes the current problems of the cultural landscape in Dongmen Fishing Village and conducts planning and design research on it. The research results provide scientific basis for the protection and utilization of cultural landscapes in Dongmen Fishing Village in the future.

Background: Hyperbaric oxygen (HBO) therapy is widely used to treat bone defects, but the correlation of high oxygen concentration and pressure to osteogenesis is unclear. Methods: Bilateral monocortical tibial defect surgeries were performed on 12-week-old Prrx1-Cre; Rosa26-tdTomato and Prrx1-Cre; Piezo1fl/+ mice. Daily HBO treatment was applied on post-surgery day (PSD) 1–9; and daily mechanical loading on tibia was from PSD 5 to 8. The mice were euthanized on PSD 10, and bone defect repair in their tibias was evaluated using μCT, biomechanical testing, and immunofluorescence deep-tissue imaging. The degree of angiogenesis–osteogenesis coupling was determined through spatial correlation analysis. Bone marrow stromal cells from knockout mice were cultured in vitro, and their osteogenic capacities of the cells were assessed. The activation of genes in the Piezo1–YAP pathway was evaluated using RNA sequencing and quantitative real-time polymerase chain reaction. Results: Lineage tracing showed HBO therapy considerably altered the number of Prrx1+ cells and their progeny in a healing bone defect. Using conditional knockdown mice, we found that HBO stimulation activates the Piezo1–YAP axis in Prrx1+ cells and promotes osteogenesis–angiogenesis coupling during bone repair. The beneficial effect of HBO was similar to that of anabolic mechanical stimulation, which also acts through the Piezo1–YAP axis. Subsequent transcriptome sequencing results revealed that similar mechanosensitive pathways are activated by HBO therapy in a bone defect. Conclusion: HBO therapy promotes bone tissue regeneration through the mechanosensitive Piezo1–YAP pathway in a population of Prrx1+ osteogenic progenitors. Our results contribute to the understanding of the mechanism by which HBO therapy treats bone defects. The Translational Potential of this Article: Hyperbaric oxygen therapy is widely used in clinical settings. Our results show that osteogenesis was induced by the activation of the Piezo1–YAP pathway in osteoprogenitors after HBO stimulation, and the underlying mechanism was elucidated. These results may help improve current HBO methods and lead to the formulation of alternative treatments that achieve the same functional outcomes.

Abstract Background The different symptoms of major depressive disorder (MDD) in adolescents compared to adults suggested there may be differences in the pathophysiology between adolescents and adults with MDD. However, despite the amygdala being considered critical in the pathophysiology, there was limited knowledge about the commonalities and differences in the resting-state functional connectivity (rsFC) of amygdala subregions in MDD patients of different age groups. Methods In the current study, 65 adolescents (46 with MDD and 19 controls) and 91 adults (35 with MDD and 56 controls) were included. A seed-based functional connectivity analysis was performed for each of the amygdala subregions. A 2 × 2 ANOVA was used to analyze the main effect of age, diagnosis, and their interaction on the rsFC of each subregion. Results A significant main effect of age was revealed in the rsFC of bilateral centromedial (CM) subregions and right laterobasal (LB) subregion with several brain regions in the limbic system and frontoparietal network. The significant main effect of diagnosis showed MDD patients of different ages showed higher connectivity than controls between the right LB and left middle frontal gyrus (MFG). Conclusions The rsFC of specific amygdala subregions with brain regions in the limbic system and frontoparietal network is affected by age, indicating a distinct amygdala connectivity profile in adolescents. The decreased rsFC between the right LB and the left MFG in adolescents and adults with MDD could serve as a diagnostic biomarker and a target of nonpharmacological treatment for MDD.

Abstract Purpose Diet plays a fundamental role in promoting resilience against stress-related disorders. We aimed to examine the overall and sex-specific association between food groups and perceived stress in adults. Methods We analyzed the prospective data of 7,434 adults who completed both the 2011 and 2015 surveys of the China Health and Nutrition Survey (CHNS). The Diet Quality Questionnaire (DQQ) was used to code all the food items of 2011 dietary intake into 29 food groups, and perceived stress in 2015 was measured using a 14-item perceived stress scale (PSS-14). Univariate analysis and logistic regression models were used to examine the relationship between food groups and perceived stress. Results People who perceived a higher level of stress (PSS-14 total score > 25) made up 41.5% and 45.1% of the male and female groups, respectively (χ2 = 9.605, p = 0.002). Individuals with increased intake of food groups such as legumes, other vegetables, other fruits, yogurt, poultry, fish & seafood, fluid milk, and fruit juice were less likely to experience a higher level of psychological stress (OR range: 0.544–0.892, p

Background: The effect of transcranial alternating current stimulation (tACS) on major depressive disorder (MDD) was not confirmed. Objective: To evaluate the feasibility, safety, and efficacy of tACS as an add-on treatment for the symptoms of depression and to understand how tACS affects brain activity. Methods: The 4-week, double-blind, randomized, sham-controlled trial was performed from January 29, 2023 to December 22, 2023. Sixty-six participants were recruited and randomly assigned to receive 20 40-min sessions of either active (77.5Hz, 15 mA) or sham stimulation, with one electrode on the forehead and two on the mastoid, each day (n = 33 for each group) for four weeks (till Week 4). The participants were followed for 4 more weeks (till Week 8) without stimulation for efficacy/safety assessment. During the 4-week trial, all participants were required to take 10–20 mg of escitalopram daily. The primary efficacy endpoint was the change in HAMD-17 scores from baseline to Week 4 (with 20 treatment sessions completed). Resting-state electroencephalography (EEG) was collected with a 64-channel EEG system (Brain Products, Germany) at baseline and the Week 4 follow-up. The chi-square test, Fisher's exact test, independent-sample t-test, or Wilcoxon rank-sum test were used, as appropriate, to compare the differences in variables between groups. The effect of the intervention on the HAMD-17 score was also evaluated with linear mixed modeling (LMM) as sensitivity analysis. The correlation between the mean reduction in EEG and the mean reduction in the HAMD-17 total score was evaluated using Spearman correlation analysis. Results: A total of 66 patients (mean [SD] age, 28.4 [8.18] years; 52 [78.8 %] female) were randomized, and 57 patients completed the study. Significant differences were found in the reductions in the HAMD-17 scores at Week 4 (t = 3.44, P = 0.001). Response rates at Week 4 were significantly higher in the active tACS group than in the sham tACS group (22 out of 33 patients [66.7 %] versus 11 out of 33 [33.3 %], P = 0.007). In the active tACS group, a correlation between the mean change in alpha power and HAMD-17 scores at Week 4 was found (r = 2.38, P = 0.024), and the mean change in alpha power was significantly bigger for responders (Z = 2.46, P = 0.014). No serious adverse events were observed in this trial. Conclusion: The additional antidepressant effect of tACS is significant, and the combination of tACS with antidepressants is a feasible and effective approach for the treatment of MDD. The antidepressant mechanism of tACS may be the reduction in alpha power in the left frontal lobe. Future research directions may include exploring more appropriate treatment parameters of tACS.

Abstract Differences in clinical manifestations and biological underpinnings between Major Depressive Disorder (MDD) onset during adolescence and adulthood have been posited in previous studies, implying an influential role of age of onset (AOO) in the clinical subtyping and therapeutic approaches to MDD. However, direct comparisons between the two cohorts and their age-matched controls have been lacking in extant investigations. In this investigation, 156 volunteers participated, comprising 46 adolescents with MDD (adolescent-onset group), 35 adults with MDD (adult-onset group), 19 healthy adolescents, and 56 healthy adults. Resting-state functional MRI scans were undergone by all participants. Large-scale network analyses were applied. Subsequently, a 2 × 2 ANOVA was employed to analyze the main effects of diagnosis, age, and their interaction effect on functional connectivity (FC). Furthermore, regression analysis was employed to scrutinize the association between anomalous FC and HAMD sub-scores. Increased FC in visual network (VN), limbic network (LN), VN-dorsal attention network (DAN), VN-LN, and LN-Default Mode (DMN) was found in both adolescent-onset and adult-onset MDD; however, the increased FC in DAN and LN were only found in adult-onset MDD and the decreased FC in DAN was only found in adolescent-onset MDD. Additionally, the relationship between HAMD factor 1 anxiety somatization and altered FC of DAN, VN, and VN-DAN was moderated by AOO. In conclusion, shared and distinctive large-scale network alterations in adolescent-onset and adult-onset MDD patients were suggested by our findings, providing valuable contributions towards refining clinical subtyping and treatment approaches for MDD.

Background: Secondary myelofibrosis (SMF) is characterized by the excessive deposition of fibrous tissue on top of the primary disease, often causing clinical manifestations to be overshadowed by the primary disease. Unfortunately, current staging systems do not incorporate myelofibrosis, leading to potential treatment delays for SMF. Objectives: To evaluate the prognosis of patients with multiple myeloma (MM) complicated with myelofibrosis Design: The study included the clinical data and treatment results of 208 newly diagnosed multiple myeloma (NDMM) patients who were treated in the Affiliated Hospital of Qingdao University from January 2014 to August 2020, and performed a retrospective analysis. Methods: All patients underwent bone marrow biopsy, and MF severity was classified into grades 0–3 according to the 2016 WHO criteria. Treatment efficacy was evaluated based on the International Myeloma Working Group (IMWG) standard and SPSS was used for analysis. Results: The MM patients without SMF exhibited better treatment response ( p 2.39, monocyte–lymphocyte ratio ⩽0.18, and platelet–lymphocyte ratio ⩽61.6 were associated with significantly reduced median PFS and OS ( p

Abstract As promising energy-storage devices, zinc–air batteries (ZABs) exhibit slow reaction kinetics for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) occurring at their electrodes. High-performance bifunctional catalysts must thus be synthesized to accelerate the reversible conversion of oxygen and improve the rate and overall performance of ZABs. Herein, we reported the promising prospects of self-supported composite electrodes composed of wood-derived carbon (WDC) and bimetallic cobalt-iron alloys/oxides (CoFe-CoFe2O4@WDC) as efficient electrocatalysts for alkaline ORR/OER. WDC provided a favorable three-phase interface for heterogeneous reactions owing to its layered porous structure and genetic stability, thereby enabling mass diffusion and improving reaction kinetics. The CoFe2O4 spinel surface was reduced to bimetallic CoFe alloy to form abundant heterostructure interfaces that promote electron transfer. Under alkaline conditions, the optimized composite electrode exhibited a remarkable high half-wave potential of 0.85 V and an exceptionally low overpotential of 1.49 V. It also exhibited stable performance over an impressive 2340 cycles in a ZAB. Theoretical calculations also confirmed that the heterointerface addresses the issue of proton scarcity throughout the reaction and actively facilitates the creation of O–O bonds during the reversible transformation of oxygen. This study introduces a new concept for developing bifunctional and efficient electrocatalysts based on charcoal and encourages the sustainable and high-value use of forest biomass resources. Graphical Abstract

Sensory evaluation, biochemical analysis, ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry (UPLC-QqQ-MS) and headspace solid-phase microextraction combined with gas chromatography-time-of-flight mass spectrometry (HS-SPME-GC-TOF-MS) were used to detect and analyze different baking degrees of ‘Chungui’ Minbei oolong tea. Partial least squares discriminant analysis model and trend model were established to explore the differences in sensory quality, conventional biochemical components, catechin components, amino acid components and volatile substances. The results showed that the total score of sensory evaluation of light baking degree of ‘Chungui’ (91.3~93.65) was slightly lower than that of medium baking degree (93.6~94.15). Among the biochemical components, the amino acid content of light baking degree was significantly higher than that of medium baking degree (P

Abstract Major depressive disorder (MDD) is a serious mental illness, characterized by disturbances of gut microbiome, it is required to further explore how the carbohydrate-active enzymes (CAZymes) were changed in MDD. Here, using the metagenomic data from patients with MDD (n = 118) and heath controls (HC, n = 118), we found that the whole CAZymes signatures of MDD were significantly discriminated from that in HC. α-diversity indexes of the two groups were also significantly different. The patients with MDD were characterized by enriched Glycoside Hydrolases (GHs) and Polysaccharide Lyases (PLs) relative to HC. A panel of makers composed of 9 CAZymes mainly belonging to GHs enabled to discriminate the patients with MDD and HC with AUC of 0.824. In addition, this marker panel could classify blinded test samples from the two groups with an AUC of 0.736. Moreover, we found that baseline 4 CAZymes levels also could predict the antidepressant efficacy after adjusted confounding factors and times of depressive episode. Our findings showed that MDD was associated with disturbances of gut CAZymes, which may help to develop diagnostic and predictive tools for depression.

Abstract The mechanism involved in major depressive disorder (MDD) is well‐studied but the mechanistic origin of the heterogeneous antidepressant effect remains largely unknown. Single‐cell RNA‐sequencing (scRNA‐seq) and assay for transposase‐accessible chromatin using sequencing (ATAC‐seq) on peripheral blood mononuclear cells from 8 healthy individuals and 8 MDD patients before or after 12 weeks of antidepressant treatment is performed. scRNA‐seq analysis reveals a lower proportion of naive T cells, particularly CD4+ naive T cells, in MDD patients compared to controls, and in nonresponders versus responders at the baseline. Flow cytometry data analysis of an independent cohort of 35 patients and 40 healthy individuals confirms the findings. Enrichment analysis of differentially expressed genes indicated obvious immune activation in responders. A specific activated CD4+ naive T population in responders characterized by enhanced mitogen‐activated protein kinases (MAPK) pathway is identified. E‐twenty six (ETS) is proposed as an upstream regulator of the MAPK pathway and heterogeneous differentiation in activated CD4+ naive T population is associated with the response to antidepressant treatment in MDD patients. A distinct immune feature manifested by CD4+ naive T cells during antidepressant treatment in MDD is identified. Collectively, this proposes the molecular mechanism that underlies the heterogeneous antidepressant outcomes for MDD.

The development of reliable and longevous infrastructures and structural components is the key for the implementation of a hydrogen economy that is currently enjoying unprecedented political and research momentum due to the globally strong demand for clean energy. This is, however, strongly impeded by the risk and concerns of hydrogen embrittlement (or hydrogen-induced degradation in mechanical properties) that generally exists in almost all metallic materials. Structural components and materials operated in the hydrogen production-transport-storage-usage chain can be subjected to a very wide range of temperature, environmental and loading scenarios, which will essentially trigger different hydrogen embrittlement responses and even different embrittling mechanisms. It is thus important to have a systematic assessment and discussion of hydrogen embrittlement behavior of different materials at different testing conditions, which is the focus of the presented review. Here we cover the typical materials (mainly metallic materials) that have been used or planned to be used in the fields of hydrogen energy. We first briefly summarize the current understanding of fundamental hydrogen embrittlement mechanisms in metallic materials and the research progress in recent years. Then we analyze and discuss the hydrogen -induced damage phenomenon in typical materials used in the field of high-pressure hydrogen transport and storage. In addition to room-temperature hydrogen embrittlement behavior, the hydrogen embrittlement phenomenon of some alloys at elevated and cryogenic temperatures is also reviewed, with the aim to provide some guidelines of material selection and design in developing fields such as hydrogen gas turbines and long-flight-duration hydrogen powered aircraft. Finally, the current challenges in the study of hydrogen embrittlement are identified and discussed to guide future research efforts.

Abstract The shortage and unevenness of fossil energy sources are affecting the development and progress of human civilization. The technology of efficiently converting material resources into energy for utilization and storage is attracting the attention of researchers. Environmentally friendly biomass materials are a treasure to drive the development of new‐generation energy sources. Electrochemical theory is used to efficiently convert the chemical energy of chemical substances into electrical energy. In recent years, significant progress has been made in the development of green and economical electrocatalysts for oxygen reduction reaction (ORR). Although many reviews have been reported around the application of biomass‐derived catalytically active carbon (CAC) catalysts in ORR, these reviews have only selected a single/partial topic (including synthesis and preparation of catalysts from different sources, structural optimization, or performance enhancement methods based on CAC catalysts, and application of biomass‐derived CACs) for discussion. There is no review that systematically addresses the latest progress in the synthesis, performance enhancement, and applications related to biomass‐derived CAC‐based oxygen reduction electrocatalysts synchronously. This review fills the gap by providing a timely and comprehensive review and summary from the following sections: the exposition of the basic catalytic principles of ORR, the summary of the chemical composition and structural properties of various types of biomass, the analysis of traditional and the latest popular biomass‐derived CAC synthesis methods and optimization strategies, and the summary of the practical applications of biomass‐derived CAC‐based oxidative reduction electrocatalysts. This review provides a comprehensive summary of the latest advances to provide research directions and design ideas for the development of catalyst synthesis/optimization and contributes to the industrialization of biomass‐derived CAC electrocatalysis and electric energy storage.

Phosphorus (P), a critical macronutrient for plant growth and reproduction, is primarily acquired and translocated in the form of inorganic phosphate (Pi) by roots. Pi deficiency is widespread in many natural ecosystems, including forest plantations, due to its slow movement and easy fixation in soils. Plants have evolved complex and delicate regulation mechanisms on molecular and physiological levels to cope with Pi deficiency. Over the past two decades, extensive research has been performed to decipher the underlying molecular mechanisms that regulate the Pi starvation responses (PSR) in plants. This review highlights the prospects of Pi uptake, transport, and signaling in woody plants based on the backbone of model and crop plants. In addition, this review also highlights the interactions between phosphorus and other mineral nutrients such as Nitrogen (N) and Iron (Fe). Finally, this review discusses the challenges and potential future directions of Pi research in woody plants, including characterizing the woody-specific regulatory mechanisms of Pi signaling and evaluating the regulatory roles of Pi on woody-specific traits such as wood formation and ultimately generating high Phosphorus Use Efficiency (PUE) woody plants.

Understanding canopy nitrogen (N) and phosphorus (P) differences is crucial for optimizing plant nutrient distribution and management. This study evaluated leaf N and P content in citrus trees across three cultivation modes: traditional mode (TM), wide-row and narrow-plant mode (WRNPM), and fenced mode (FM). We used hyperspectral data for non-destructive quantification and compared 1080 leaf samples from upper, middle, and lower canopy layers. Four models—Random Forest (RF), Backpropagation Neural Network (BPNN), Partial Least Squares (PLS), and Support Vector Machine (SVM)—were employed for leaf N and P estimation. Results showed that the TM had significantly lower N content compared to the WRNPM and FM, while the WRNPM exhibited higher P content. The canopy layer had minimal impact on N and P in the FM, and leaves in the upper layer had higher nutrient content in the WRNPM and TM. RF provided the best estimation accuracy, with R2 values of 0.66 for N and 0.72 for P. The cultivation mode and canopy layer significantly influenced the estimation accuracy, with the TM yielding the highest R2, followed by the WRNPM and FM obtaining the lowest accuracy. The labor-saving cultivation mode had different nutrient utilization efficiency compared to the TM. The cultivation mode and canopy layer should be considered when hyperspectral data were used for estimating the leaf N and P content. The study can offer new insights for precise fertilization strategies in fruit trees.

An urban cultural park is a symbol of regional urban culture, and it also reflects the accumulation of human culture. It can become an important way to inherit regional historical and cultural heritage and promote the excellent traditional Chinese cultural spirit. The cultural role, played by the cultural parks, is, however, rather unsatisfactory and remains to be improved. It is extremely important to solve these problems and promote the design of urban cultural parks to better showcase their cultural ideas and meet the needs of cultural dissemination and development. Therefore, this article introduced mountain factors and analyzed the symbolic significance of mountain factors in the design of urban cultural parks. This research attempted to interpret the ideas, contained in modern urban cultural parks, from the perspectives of urban cultural parks and mountain factors, and elaborated on the design strategies, expression methods, expression techniques and exchange of ideas of urban cultural parks. Research has found that introducing mountain factors into the design of cultural parks can make them more aesthetically pleasing, with more complex shapes, and better highlight the theme ideas for regional cultural interpretation and expression. This research provides more design schemes and elements for the design of urban cultural parks by studying mountain factors, enriching the ideological meaning and expression of urban cultural parks, helping to promote the inheritance and development of culture, and providing more theoretical basis for landscape design.

Porcine epidemic diarrhea virus (PEDV) is considered the cause for porcine epidemic diarrhea (PED) outbreaks and hefty losses in pig farming. However, no effective commercial vaccines against PEDV mutant strains are available nowadays. Here, we constructed three native-like trimeric candidate nanovaccines, i.e., spike 1 trimer (S1-Trimer), collagenase equivalent domain trimer (COE-Trimer), and receptor-binding domain trimer (RBD-Trimer) for PEDV based on Trimer-Tag technology. And evaluated its physical properties and immune efficacy. The result showed that the candidate nanovaccines were safe for mice and pregnant sows, and no animal death or miscarriage occurred in our study. S1-Trimer showed stable physical properties, high cell uptake rate and receptor affinity. In the mouse, sow and piglet models, immunization of S1-Trimer induced high-level of humoral immunity containing PEDV-specific IgG and IgA. S1-Trimer-driven mucosal IgA responses and systemic IgG responses exhibited high titers of virus neutralizing antibodies (NAbs) in vitro. S1-Trimer induced Th1-biased cellular immune responses in mice. Moreover, the piglets from the S1-Trimer and inactivated vaccine groups displayed significantly fewer microscopic lesions in the intestinal tissue, with only one and two piglets showing mild diarrhea. The viral load in feces and intestines from the S1-Trimer and inactivated vaccine groups were significantly lower than those of the PBS group. For the first time, our data demonstrated the protective efficacy of Trimer-Tag-based nanovaccines used for PEDV. The S1-Trimer developed in this study was a competitive vaccine candidate, and Trimer-Tag may be an important platform for the rapid production of safe and effective subunit vaccines in the future.

The pile-up processing has a great impact on the flavor of white tea. To investigate the effects of the volatile accumulation of white tea with different piling thickness treatments, tea leaves from different thickness treatments were subjected to sensory quantitative description analysis and ATD-GC–MS detection in this study. As a result, 122 volatile components were identified from white tea with different treatments. A total of 8 key compounds, including isovaleraldehyde, isobutyraldehyde, 2-methyl-butanal, 1-octene-3-ol, linalool, pentanoic acid, hexanal and 1-hexanol were screened out using multivariate statistical analysis, which were characteristic components of grassy, floral-fruity, pekoe aroma and sweet flavors. The results of the selected key characteristic volatile compounds were consistent with the sensory quantitative description. The aroma of mid-pile dried tea (MD) was exhibited a harmonious and pleasant overall flavor. This study provides a novel insight into the accumulation of volatile during the withering step of white tea production.

Abstract Expanding the application scenarios of wood-derived biochar guided by the conversion of traditional energy to new energy shows great promise as a field. As thrilling energy conversion apparatus, zinc-air batteries (ZABs) require cathode catalysts with high oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) activities and stability. Herein, two-dimensional nickel-iron hydroxide nanosheets were creatively assembled in N-doped wood-derived biochar (NiFe-LDH@NC) by an in-situ growth method. The categorized porous organization in wood-derived biochar facilitates the rapid seepage of electrolytes and rapid diffusion of reaction gases. The unique interfacial structure of biochar and NiFe-LDH accelerates electron transfer during oxygen electrocatalysis, and endows NiFe-LDH@NC with first-class catalytic activity and durability for ORR and OER. The ZAB derived from NiFe-LDH@NC showed elevated discharge productivity and cycle endurance, making it promising for viable applications. This work provided a convenient way for the conversion of wood-derived biochar to high-value added electrocatalysts. Graphical Abstract

Abstract Background There is a growing body of evidence suggesting that disturbance of the gut-brain axis may be one of the potential causes of major depressive disorder (MDD). However, the effects of antidepressants on the gut microbiota, and the role of gut microbiota in influencing antidepressant efficacy are still not fully understood. Results To address this knowledge gap, a multi-omics study was undertaken involving 110 MDD patients treated with escitalopram (ESC) for a period of 12 weeks. This study was conducted within a cohort and compared to a reference group of 166 healthy individuals. It was found that ESC ameliorated abnormal blood metabolism by upregulating MDD-depleted amino acids and downregulating MDD-enriched fatty acids. On the other hand, the use of ESC showed a relatively weak inhibitory effect on the gut microbiota, leading to a reduction in microbial richness and functions. Machine learning-based multi-omics integrative analysis revealed that gut microbiota contributed to the changes in plasma metabolites and was associated with several amino acids such as tryptophan and its gut microbiota-derived metabolite, indole-3-propionic acid (I3PA). Notably, a significant correlation was observed between the baseline microbial richness and clinical remission at week 12. Compared to non-remitters, individuals who achieved remission had a higher baseline microbial richness, a lower dysbiosis score, and a more complex and well-organized community structure and bacterial networks within their microbiota. These findings indicate a more resilient microbiota community in remitters. Furthermore, we also demonstrated that it was not the composition of the gut microbiota itself, but rather the presence of sporulation genes at baseline that could predict the likelihood of clinical remission following ESC treatment. The predictive model based on these genes revealed an area under the curve (AUC) performance metric of 0.71. Conclusion This study provides valuable insights into the role of the gut microbiota in the mechanism of ESC treatment efficacy for patients with MDD. The findings represent a significant advancement in understanding the intricate relationship among antidepressants, gut microbiota, and the blood metabolome. Additionally, this study offers a microbiota-centered perspective that can potentially improve antidepressant efficacy in clinical practice. By shedding light on the interplay between these factors, this research contributes to our broader understanding of the complex mechanisms underlying the treatment of MDD and opens new avenues for optimizing therapeutic approaches. Video Abstract

Ovarian cancer is a complex polygenic disease in which genetic factors play a significant role in disease etiology. A genome-wide association study (GWAS) identified a novel variant on chromosome 9q22.33 as a susceptibility locus for epithelial ovarian cancer (EOC) in the Han Chinese population. However, the underlying mechanism of this genomic region remained unknown. In this study, we conducted a fine-mapping analysis of 130 kb regions, including 1,039 variants in 200 healthy women. Ten variants were selected to evaluate the association with EOC risk in 1,099 EOC cases and 1,591 controls. We identified two variants that were significantly associated with ovarian cancer risk (rs7027650, P = 1.91 × 10−7; rs1889268, P = 3.71 × 10−2). Expression quantitative trait locus (eQTL) analysis found that rs7027650 was significantly correlated with COL15A1 gene expression (P = 0.009). The Luciferase reporter gene assay confirmed that rs7027650 could interact with the promoter region of COL15A1, reducing its activity. An electrophoretic mobility shift assay (EMSA) showed the allele-specific binding capacity of rs7027650. These findings revealed that rs7027650 could be a potential causal variant at 9q22.33 region and may regulate the expression level of COL15A1. This study offered insight into the molecular mechanism behind a potential causal variant that affects the risk of ovarian cancer.

Due to the important role of forests in carbon neutrality, it is a big task in accurately calculating and predicting forest carbon storage and carbon sink capacity in recent years. However, considering the factors on the capacity of forest carbon sequestration, ecologists and foresters consider different models to evaluate the forest carbon sink ability at different scales, with foresters focusing more on forest growth models, while ecologists adding more climate and environmental factors, which may result in inconsistent results in carbon storage. Therefore, constructing an integrated model by combining the forestry and ecology models is essential for accurately quantifying and characterizing the forest carbon sink potential at the regional scale. Here, we proposed a new forest carbon sink potential index (FCSPI), which is defined as fractional deficiency of the current forest carbon to its maximum level, based on forest permanent plots, climate, and edaphic data to evaluate the forest sink potential ability from stand level to zonal scale across the northern subtropical zone in Hubei province, China, which coupled the stand growth model and climate-productivity model. The results at stand level showed that the R2 and RMSE of FCSPI were 0.78 and 0.072 respectively, which indicated that the FCSPI is an intuitive, highly practical, straightforward, easy, and rapid to implement methodology for forest carbon sequestration assessment. Moreover, FCSPI can conveniently extended from stand scale to zonal scale based on the site quality index for carbon sink (SIC) and stand age variables, which were derived from the opened climate, edaphic, and topographic data. The results of wall-to-wall FCSPI across the subtropical forest in Hubei province reveal the current and future carbon potential sequestration, which can help managers to focus on forest management for climate-smart actions and planning in forest ecosystem services framework.

Background Veno‐arterial extracorporeal membrane oxygenation serves as a crucial mechanical circulatory support for pediatric patients with severe heart diseases, but the mortality rate remains high. The objective of this study was to assess the short‐term mortality in these patients. Methods and Results We systematically searched PubMed, Embase, and Cochrane Library for observational studies that evaluated the short‐term mortality of pediatric patients undergoing veno‐arterial extracorporeal membrane oxygenation. To estimate short‐term mortality, we used random‐effects meta‐analysis. Furthermore, we conducted meta‐regression and binomial regression analyses to investigate the risk factors associated with the outcome of interest. We systematically reviewed 28 eligible references encompassing a total of 1736 patients. The pooled analysis demonstrated a short‐term mortality (defined as in‐hospital or 30‐day mortality) of 45.6% (95% CI, 38.7%–52.4%). We found a significant difference (P

Abstract Disturbed gut microbiota is a potential factor in the pathogenesis of major depressive disorder (MDD), yet whether gut microbiota dysbiosis is associated with the severity of MDD remains unclear. Here, we performed shotgun metagenomic profiling of cross-sectional stool samples from MDD (n = 138) and healthy controls (n = 155). The patients with MDD were divided into three groups according to Hamilton Depression Rating Scale 17 (HAMD-17), including mild (n = 24), moderate (n = 72) and severe (n = 42) individuals, respectively. We found that microbial diversity was closely related to the severity of MDD. Compared to HCs, the abundance of Bacteroides was significantly increased in both moderate and severe MDD, while Ruminococcus and Eubacterium depleted mainly in severe group. In addition, we identified 99 bacteria species specific to severity of depression. Furthermore, a panel of microbiota marker comprising of 37 bacteria species enabled to effectively distinguish MDD patients with different severity. Together, we identified different perturbation patterns of gut microbiota in mild-to-severe depression, and identified potential diagnostic and therapeutic targets.

Abstract Background From a developmental perspective, this study explored the interplays between subjective social status (SSS), social trust (ST), and health status measured by self-rated health (SRH) among older adults in the context of China. It also tested the longitudinal mediation of ST between SSS and SRH. Methods After excluding samples with missing values, we analyzed 4,877 individual responses from those aged 60 years or older, extracted from the China Family Panel Studies (CFPS) data in 2014, 2016, and 2018. We used latent growth modeling to test the hypothesized relationships among their SSS, ST, and SRH. Results Latent growth modeling based on bootstrapping showed that the SSS, ST, and SRH of older adults all increased linearly and that the mechanism of SSS acted on the SRH as follows: the initial level of SSS indirectly influenced the initial level and the growth rate of the SRH, respectively, through the initial level of ST, and the initial level and growth rate of SSS played an indirect role in the growth rate of the SRH through the growth rate of ST. Conclusion The findings have practical implications for promoting health for older adults and realizing active aging in China. Therefore, we recommend establishing a family-centered and community-supported social support system for those with lower social status among older adults and a friendly community environment with various social, cultural, and recreational activities to improve the ST among older adults, thereby improving their health.

Abstract Thiolation of uridine 34 in the anticodon loop of several tRNAs is conserved in the three domains of life and guarantees fidelity of protein translation. U34-tRNA thiolation is catalyzed by a complex of two proteins in the eukaryotic cytosol (named Ctu1/Ctu2 in humans), but by a single NcsA enzyme in archaea. We report here spectroscopic and biochemical experiments showing that NcsA from Methanococcus maripaludis (MmNcsA) is a dimer that binds a [4Fe-4S] cluster, which is required for catalysis. Moreover, the crystal structure of MmNcsA at 2.8 Å resolution shows that the [4Fe-4S] cluster is coordinated by three conserved cysteines only, in each monomer. Extra electron density on the fourth nonprotein-bonded iron most likely locates the binding site for a hydrogenosulfide ligand, in agreement with the [4Fe-4S] cluster being used to bind and activate the sulfur atom of the sulfur donor. Comparison of the crystal structure of MmNcsA with the AlphaFold model of the human Ctu1/Ctu2 complex shows a very close superposition of the catalytic site residues, including the cysteines that coordinate the [4Fe-4S] cluster in MmNcsA. We thus propose that the same mechanism for U34-tRNA thiolation, mediated by a [4Fe-4S]-dependent enzyme, operates in archaea and eukaryotes.

Abstract Background ABO blood groups has been associated with risk of several cancers; however, the results for an association with ovarian cancer are inconsistent and little is known about the expression of histo‐blood group (ABH) antigens and ABO gene in ovarian tumor tissues. Methods To assess the impact of genotype‐derived ABO blood types on the risk of EOC, we conducted a case–control study in 1,870 EOC and 4,829 controls. Expression of A and B antigen in 70 pairs of ovarian tumor tissues and adjacent normal tissues were detected by immunohistochemistry. Gene expression and DNA methylation profiling was conducted in ovarian tumor tissues. Results We identified that blood group A was associated with increased risk for EOC compared to blood group O (OR = 1.18, 95% CI = 1.03–1.36, p = 0.019). Increased frequency of aberrant expression of histo‐blood group antigens was observed in patients with blood group A (76.5%) compared to patients with blood group O (21.1%) and B (5.0%) by immunohistochemistry (p

Abstract Key message The production of adventitious roots partially counteracts the negative effects of waterlogging on the growth of Syzygium nervosum A. Cunn. ex DC. and Syzygium cumini (L.) Skeels. S. cumini was more responsive and suffered from larger negative effects than S. nervosum after the removal of adventitious roots. Context Adventitious roots contain gas channels and functionally replace or compensate for the loss of primary roots that usually decay during waterlogging. However, the importance of adventitious roots on growth in waterlogged woody plants varies with species. Therefore, there has been some controversy about whether adventitious roots have beneficial effects on the growth of waterlogged plants. Aims We assessed whether S. nervosum and S. cumini differentially responded to the ablation of adventitious roots during waterlogging and whether compensatory responses occurred in the primary roots in both species. Methods S. nervosum and S. cumini saplings were subjected to waterlogging and adventitious root removal for 120 days, and morphological, physiological, biochemical parameters, and biomass were recorded. Results All plants survived waterlogging, and produced adventitious roots at the shoot base. Waterlogging had negative effects on the growth of both species, but the effect was more severe in S. cumini than in S. nervosum as seen from the values of comprehensive evaluation and total biomass. However, S. nervosum compensated for the ablation of adventitious roots with increased primary root dry mass, primary root activity, total root length, root tip number, and peroxidase activity. Conclusions S. nervosum with a high proportion of adventitious roots would be at an advantage during waterlogging. The removal of adventitious roots was detrimental to the growth of both species, but S. nervosum exhibited less damage than S. cumini due to its compensatory physiological responses and its primary roots.

The increasing use of molybdate has raised concerns about its potential toxicity in humans. However, the potential toxicity of molybdate under the current level of human exposure remains largely unknown. Endogenous metabolic alterations that are caused in humans by environmental exposure to pollutants are associated with the occurrence and progression of many diseases. This study exposed eight-week-old male C57 mice to sodium molybdate at doses relevant to humans (0.01 and 1 mg/kg/day) for eight weeks. Inductively coupled plasma mass spectrometry (ICP-MS) and ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS) were utilized to assess changes in urine element levels and serum metabolites in mice, respectively. A total of 838 subjects from the NHANES 2017–2018 population database were also included in our study to verify the associations between molybdenum and cadmium found in mice. Analysis of the metabolome in mice revealed that four metabolites in blood serum exhibited significant changes, including 5-aminolevulinic acid, glycolic acid, l-acetylcarnitine, and 2,3-dihydroxypropyl octanoate. Analysis of the elementome revealed a significant increase in urine levels of cadmium after molybdate exposure in mice. Notably, molybdenum also showed a positive correlation with cadmium in humans from the NHANES database. Further analysis identified a positive correlation between cadmium and 2,3-dihydroxypropyl octanoate in mice. In conclusion, these findings suggest that molybdate exposure disrupted amino acid and lipid metabolism, which may be partially mediated by molybdate-altered cadmium levels. The integration of elementome and metabolome data provides sensitive information on molybdate-induced metabolic disorders and associated toxicities at levels relevant to human exposure.

At present, establishing planted forests, typically composed of not more than two tree species, to avoid forest losses has received increasing attention. In addition, investigating the impact of environmental stress such as waterlogging on different planting patterns is essential for improving wetland ecosystem resilience. Knowledge about the impact of waterlogging on planted forests is crucial for developing strategies to mitigate its adverse effects. Here, we conducted experimentally a simulated pure and mixed planting system composed of two contrasting WL-tolerant species (Cleistocalyx operculatus and Syzygium cumini) to determine their ecophysiological responses based on the type of interaction. Results showed that the aboveground growth performance of S. cumini was better than that of C. operculatus under well-watered conditions regardless of the planting model, which is contrary to the belowground accumulation that was significantly improved in C. operculatus. Intra- and interspecific interactions in different planting models facilitated the growth performance of C. operculatus while provoking a significant competition in S. cumini under waterlogging. Such phenomenon was explained through the remarkable ability of C. operculatus to naturally increase its root network under stress on non-stress conditions compared with S. cumini. In this study, two main factors are proposed to play key roles in the remarkable performance of C. operculatus compared with S. cumini following the planting model under waterlogging. The high level of nitrogen and phosphor absorption through C. operculatus primary roots and the significant starch biosynthesis constituted the key element that characterized the facilitation or competition within the intra- or interspecific interactions shown in C. operculatus compared with S. cumini. Furthermore, the intraspecific competition is more pronounced in S. cumini than in C. operculatus when grown in a pure planting pattern, particularly when subjected to waterlogging. However, when the two species are planted together, this competition is alleviated, resulting in enhanced waterlogging tolerance.

Abstract Using the phase change characteristics of fixed points to trace the temperature of a spaceborne calibration blackbody is an important technical means to carry out the high-precision on-orbit calibration of thermal infrared remote sensors. In contrast to an experimental environment on the ground, a fixed point will produce radiation damage in the high-energy cosmic rays environment and may affect the phase change characteristics. This study investigates the effect of radiation damage caused by cosmic rays irradiation on the phase change characteristics of fixed points in a spaceborne calibration blackbody. In this research, the simulation method of molecular dynamics was used to simulate the irradiation damage effect of a strong cosmic rays environment on fixed-point indium (In). The experimental system was established to measure the phase change curves of samples with different irradiation doses, and then, the influence of irradiation on the phase change characteristics of the samples was analyzed. The results showed that most of the energy of irradiation was deposited on the In fixed point, resulting in the migration of 0.3% of the displacement atoms inside the In to the gap position to form the Frenkel pairs (FPs). The overcooling of the irradiated In fixed point was reduced by 0.3 $$^\circ \hbox {C}$$ ∘ C , the phase change temperature was increased by 30 mK, and the phase change plateau was more stable.

For the problem that the end-to-end delay of the service function chain (SFC) cannot meet the demand of delay-sensitive applications in 5G environment, a variable granularity service function chain mapping (VG-SFCM) algorithm based on microservice architecture was proposed by splitting the traditional virtualized network function (VNF) into mapping units of varying granularity.Firstly, the traditional coarse-grained VNF was decoupled into fine-grained microservice units, and then the instantiation of microservice units was reduced through the consolidation of redundant microservice units within SFC and the reuse of microservice units between SFC, thus reducing the processing time of SFC.The simulation results show that the algorithm reduces the end-to-end delay of SFC by 14.81% compared to the traditional mapping algorithm while reducing the average deployment network cost.

Abstract Gonad somatic cells acquire sex-specific fates during sex determination. In XX gonad, a subset of somatic cells expresses Foxl2 after sex determination which is considered the progenitor of granulosa cells. However, whether these cells also contribute to other cell types at later developmental stages is unknown. In the present study, the cell fate of Foxl2-expressing cells in fetal ovaries was analyzed by lineage tracing and single-cell transcriptomics. We found that Foxl2-expressing cells gave rise to three cell types at later developmental stages, including granulosa cells, theca-interstitial cells, and stromal cells. Series single-cell RNA sequencing revealed FOXL2-positive cells were divided into two clusters at P0. One group further differentiated into granulosa cells and Theca-G (Theca-interstitial cells derived from granulosa) at P14. Another group was classified as stromal cell lineage, then a small portion of them further differentiated into 3β-HSD-positive Theca-S (Theca-interstitial cells derived from stroma). Cyp17a1 was expressed in Theca-S, but not in Theca-G. This study demonstrated that Folx2-expressing cells in XX gonad after sex determination are multipotent and theca-interstitial cells are derived from different progenitors. Our data provided an important resource, at single-cell resolution, for a better understanding of somatic cell differentiation in ovary development.

With the rise of new Internet applications such as the industrial Internet, the Internet of vehicles, and the metaverse, the network’s requirements for low latency, reliability, security, and certainty are facing severe challenges.In the process of virtual network deployment, when using network function virtualization technology, there were problems such as low service function chain mapping efficiency and high deployment resource overhead.The node activation cost and instantiation cost was jointly considered, an integer linear programming model with the optimization goal of minimizing the average deployment network cost was established, and an improved grey wolf optimization service function chain mapping (IMGWO-SFCM) algorithm was proposed.Three strategies: mapping scheme search based on acyclic KSP algorithm, mapping scheme coding and improvement based on reverse learning and nonlinear convergence were added to the standard grey wolf optimization algorithm to form this algorithm.The global search and local search capabilities were well balanced and the service function chain mapping scheme was quickly determined by IMGWO-SFCM.Compared with the comparison algorithm, IMGWO-SFCM reduces the average deployment network cost by 11.86% while ensuring a higher service function chain request acceptance rate.

Abstract Aims Although considerable progress has been made in the diagnosis and treatment of congenital heart disease‐associated pulmonary heart hypertension (CHD‐PAH), the clinical prognosis and overall survival of patients with CHD‐PAH remain poor. Therefore, the molecular pathogenesis of CHD‐PAH requires further investigation. The intermediate filament protein synemin (SYN) is reported to modulate phenotypic alterations and varicose vein development, but there is little understanding of its exact functions in CHD‐PAH. Methods and results SYN expression in the pulmonary arterioles of CHD‐PAH patients and shunt‐induced PAH rat models was evaluated using immunohistochemistry and western blot. Cell counts and Transwell migration assays were used to assess the effect of SYN on the proliferation and migration capability of human pulmonary smooth muscle cells (hPASMCs). Adeno‐associated viruses (AAVs) have been used to suppress SYN expression in the pulmonary arterioles of rats. Such rats were further used to construct a shunt‐induced PAH animal model to investigate the function of SYN in PAH and pulmonary vascular remodelling. Compared with the normal control group, SYN expression was found to be clearly up‐regulated in the remodelled pulmonary arterioles of CHD‐PAH and shunt‐induced PAH rat models. In addition, SYN suppression increased the expression of hPASMC contractile‐phenotype markers and decreased the expression of synthetic phenotype markers, in contrast to the control group. SYN suppression also dramatically attenuated the proliferation and migration capability of hPASMCs. Conversely, SYN overexpression promoted phenotypic switch, proliferation, and migration of hPASMCs, whereas these effects were notably alleviated by the protein kinase B (AKT) inhibitor MK‐2206. Furthermore, we confirmed that SYN suppression mitigated PAH and pulmonary vascular remodelling induced by high blood flow in vivo. Conclusions Our findings indicated that SYN may represent a promising therapeutic target in the treatment of CHD‐PAH.

Abstract The prediction of antidepressant response is critical for psychiatrists to select the initial antidepressant drug for patients with major depressive disorders (MDD). The implicated brain networks supporting emotion regulation (ER) are critical in the pathophysiology of MDD and the prediction of antidepressant response. Therefore, the primary aim of the current study was to identify the neuroimaging biomarkers for the prediction of remission in patients with MDD based on the resting-state functional connectivity (rsFC) of the ER networks. A total of 81 unmedicated adult MDD patients were investigated and they underwent resting-state functional magnetic resonance imagining (fMRI) scans. The patients were treated with escitalopram for 12 weeks. The 17-item Hamilton depression rating scale was used for assessing remission. The 36 seed regions from predefined ER networks were selected and the rsFC matrix was caculated for each participant. The support vector machine algorithm was employed to construct prediction model, which separated the patients with remission from those with non-remission. And leave-one-out cross-validation and the area under the curve (AUC) of the receiver operating characteristic were used for evaluating the performance of the model. The accuracy of the prediction model was 82.08% (sensitivity = 71.43%, specificity = 89.74%, AUC = 0.86). The rsFC between the left medial superior frontal gyrus and the right inferior frontal gyrus as well as the precuneus were the features with the highest discrimination ability in predicting remission from escitalopram among the MDD patients. Results from our study demonstrated that rsFC of the ER brain networks are potential predictors for the response of antidepressant drugs. The trial name: appropriate technology study of MDD diagnosis and treatment based on objective indicators and measurement. URL: http://www.chictr.org.cn/showproj.aspx?proj=21377 . Registration number: ChiCTR-OOC-17012566.

Abstract Ammonia borane (AB), a liquid hydrogen storage material, has attracted increasing attention for hydrogen utilization because of its high hydrogen content. However, the slow kinetics of AB hydrolysis and the indefinite catalytic mechanism remain significant problems for its large‐scale practical application. Thus, the development of efficient AB hydrolysis catalysts and the determination of their catalytic mechanisms are significant and urgent. A summary of the preparation process and structural characteristics of various supported catalysts is presented in this paper, including graphite, metal‐organic frameworks (MOFs), metal oxides, carbon nitride (CN), molybdenum carbide (MoC), carbon nanotubes (CNTs), boron nitride (h‐BN), zeolites, carbon dots (CDs), and metal carbide and nitride (MXene). In addition, the relationship between the electronic structure and catalytic performance is discussed to ascertain the actual active sites in the catalytic process. The mechanism of AB hydrolysis catalysis is systematically discussed, and possible catalytic paths are summarized to provide theoretical considerations for the designing of efficient AB hydrolysis catalysts. Furthermore, three methods for stimulating AB from dehydrogenation by‐products and the design of possible hydrogen product‐regeneration systems are summarized. Finally, the remaining challenges and future research directions for the effective development of AB catalysts are discussed.

Rivers in arid regions serve as crucial freshwater resources for local communities and play an essential role in global hydrological and biogeochemical cycles. The Aral Sea Basin (ASB) in Central Asia is characterized by an arid climate and river dynamics that are sensitive to climate change and human activities. Monitoring the spatiotemporal variations in river water extent in the ASB is essential to maintain an ecological balance and ensure water security. In this study, we extracted data regarding monthly river water bodies in the ASB from 2017 to 2022 by synthesizing monthly Sentinel-2 images. The water extents on the Sentinel images were automatically mapped using the Otsu method, and the river widths for all river channels were calculated using the RivWidth algorithm. We investigated the relationships between the river dynamics and the geomorphology, climatic change, human activities, and the annual and interannual variations in the river width in different reaches of the basin. The results show a seasonal variability in the river width, with most rivers reaching the largest width in the warm season and a few rivers in the middle and lower areas reaching the valley value in the warm season. Compared to their tributaries, the mainstem in the middle/lower regions showed less seasonal variability. According to interannual analysis, most of the rivers in the ASB significantly narrowed between 2017 and 2022, a phenomenon which is generally impacted by temperature and evapotranspiration variations. Comparisons show that our results provide improved information about the narrow river reaches and denser river networks compared to the previous global dataset, demonstrating the advantageous properties of high spatial resolution in Sentinel-2 imagery.

Cellular protein–protein interactions are largely dependent on the activities of signaling proteins. Here, we present a technique to tune gene expression at translation level based on G418-inducible readthrough premature termination codon (PTC-on). To demonstrate how this PTC-on can control the expression level of a cellular signaling protein to regulate signal transduction, we settled a p53 PTC-on system in p53-null H1299 cells. After treating with G418, the cells expressed full-length p53 protein in a dose-dependent manner. We further demonstrated to use this PTC-on approach to dissect p53-dependent and p53-independent apoptosis in response to the DNA double strand breaks in H1299 cells. In principle, the PTC-on can be used as a general approach for exploring the functions of any other signaling proteins.

Abstract Background Pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH) is recognized as a cancer-like disease with a proliferative and pro-migratory phenotype in pulmonary artery smooth muscle cells (PASMCs). Calcyclin-binding protein/Siah-1-interacting protein (CacyBP/SIP) has been implicated in the progression of various cancers; however, it has not been previously studied in the context of CHD-PAH. Here, we aimed to examine the function of CacyBP/SIP in CHD-PAH and explore its potential as a novel regulatory target for the disease. Methods The expression of CacyBP/SIP in PASMCs was evaluated both in the pulmonary arterioles of patients with CHD-PAH and in high-flow-induced PAH rats. The effects of CacyBP/SIP on pulmonary vascular remodeling and PASMC phenotypic switch, proliferation, and migration were investigated. LY294002 (MedChemExpress, NJ, USA) was used to block the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway to explore changes in PASMC dysfunction induced by low CacyBP/SIP levels. Hemodynamics and pulmonary arterial remodeling were further explored in rats after short-interfering RNA-mediated decrease of CacyBP/SIP expression. Results CacyBP/SIP expression was markedly reduced both in the remodeled pulmonary arterioles of patients with CHD-PAH and in high-flow-induced PAH rats. Low CacyBP/SIP expression promoted hPASMC phenotypic switch, proliferation, and migration via PI3K/AKT pathway activation. Our results indicated that CacyBP/SIP protected against pulmonary vascular remodeling through amelioration of hPASMC dysfunction in CHD-PAH. Moreover, after inhibition of CacyBP/SIP expression in vivo, we observed increased right ventricular hypertrophy index, poor hemodynamics, and severe vascular remodeling. Conclusions CacyBP/SIP regulates hPASMC dysfunction, and its increased expression may ameliorate progression of CHD-PAH.

Glioblastoma (GBM) is among the most fatal and recurring malignant solid tumors. It arises from the GBM stem cell population. Conventional neurosurgical resection, temozolomide (TMZ)-dependent chemotherapy and radiotherapy have rendered the prognosis of patients unsatisfactory. Radiotherapy and chemotherapy can frequently induce non-specific damage to healthy brain and other tissues, which can be extremely hazardous. There is therefore a pressing need for a more effective treatment strategy for GBM to complement or replace existing treatment options. Cell-based and cell-free immunotherapies are currently being investigated to develop new treatment modalities against cancer. These treatments have the potential to be both selective and successful in minimizing off-target collateral harm in the normal brain. In this review, several aspects of cell-based and cell-free immunotherapies related to GBM will be discussed.

The rising prevalence of obesity has become a worldwide health concern. Obesity usually occurs when there is an imbalance between energy intake and energy expenditure. However, energy expenditure consists of several components, including metabolism, physical activity, and thermogenesis. Toll-like receptor 4 (TLR4) is a transmembrane pattern recognition receptor, and it is abundantly expressed in the brain. Here, we showed that pro-opiomelanocortin (POMC)-specific deficiency of TLR4 directly modulates brown adipose tissue thermogenesis and lipid homeostasis in a sex-dependent manner. Deleting TLR4 in POMC neurons is sufficient to increase energy expenditure and thermogenesis resulting in reduced body weight in male mice. POMC neuron is a subpopulation of tyrosine hydroxylase neurons and projects into brown adipose tissue, which regulates the activity of sympathetic nervous system and contributes to thermogenesis in POMC-TLR4-KO male mice. By contrast, deleting TLR4 in POMC neurons decreases energy expenditure and increases body weight in female mice, which affects lipolysis of white adipose tissue (WAT). Mechanistically, TLR4 KO decreases the expression of the adipose triglyceride lipase and lipolytic enzyme hormone-sensitive lipase in WAT in female mice. Furthermore, the function of immune-related signaling pathway in WAT is inhibited because of obesity, which exacerbates the development of obesity reversely. Together, these results demonstrate that TLR4 in POMC neurons regulates thermogenesis and lipid balance in a sex-dependent manner.

Objective: This study aimed to investigate the clinical and molecular biology of a patient with a type of diabetes mellitus caused by a mutation in the POC1A (OMIM number: 614783) gene and explore its pathogenesis and related characteristics.Methods: The patient was interviewed about his medical history and subjected to relevant examinations. Blood DNA samples were collected from the patient and his family members (parents) for trio whole-exome sequencing. Whole-exome sequencing was performed using the IDT xGen Exome Research Panel v1.0 whole-exome capture chip and sequenced using an Illumina NovaSeq 6,000 series sequencer (PE150); the sequencing coverage of the target sequence was not less than 99%. After systematic analysis and screening of the cloud platform for accurate diagnosis of genetic diseases, which integrated molecular biology annotation, biology, genetics, and clinical feature analysis, combined with a pathogenic mutation database, normal human genome database, and clinical feature database of 4,000 known genetic diseases, hundreds of thousands of gene variants were graded using the gene data analysis algorithm, a three-element grading system, and the American Society of Medical Genetics gene variant grading system. After polymerase chain reaction testing, the target sequence was verified by Sanger sequencing using an ABI3730 sequencer, and the verification result was obtained using sequence analysis software.Results: The patient had a peculiar face, a thin body, and a body mass index of 16.0 kg/m2. His fasting connecting peptide was 10.2 ug/L, his fasting insulin was 44 mIU/L, his fasting blood glucose was 10.5 mmol/L, and his glycosylated haemoglobin was 12.5%. After hospitalisation, the patient was given 0.75 g/d metformin tablets and 15 mg/d pioglitazone dispersible tablets, and his fasting blood glucose reduced to 9.2 mmol/L. After 48 U/L insulin treatment, the patient’s fasting blood glucose was reduced to 8.5 mmol/L. Genetic screening revealed that there was a pathogenic variant at the POC1A gene locus and a cytosine-to-thymine mutation at the G81 locus, turning the Arg to a termination codon and shortening the POC1A protein from 359 amino acids (aa) to 80 aa. No mutation was detected in the patient’s parents’ POC1A gene loci.Conclusion: The patient’s diabetes was caused by a POC1A gene mutation at the G81 locus, which is rarely reported in the clinic. The specific manifestations of this mutation need to be further investigated.

Abstract Background Despite the recent findings presenting the benefits of measurement-based care (MBC) compared to treatment as usual (TAU), MBC is still not the standard of care used in clinical settings. The aim of the present study was to achieve the optimization of MBC (OMBC) for major depressive disorder (MDD) by establishing a comprehensive MBC framework based on all-round, continuous assessment for depression. Methods The target recruitment size is 900 patients, and the study is conducted at 8 centers in China. The patients are randomly assigned to the MBC and TAU groups at a 2:1 ratio. The subjects are scheduled to remain for 12 weeks in the acute phase and for 12 months in the maintenance phase. The primary outcomes are the complete remission rate and the proportion of patients with a 16-item Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR 16) total score ≤ 5 of the MBC and TAU groups at the acute phase, and the recurrence rate/time between the two groups is measured at the maintenance phase. Secondary outcomes included the changes in the parameters QIDS-SR 16, Patient Health Questionnaire-9 (PHQ-9), and 17-item Hamilton Rating Scale for Depression (HAMD-17) from baseline and the response rate between the two groups at the acute phase as well as the comparison of recurrence rate between the two groups at the end of the study. Trial registration Chinese Clinical Trial Registry, ChiCTR-OOC-17012566 . The registration was performed retrospectively on 4 September 2017.

The development of premature coronary artery disease (PCAD) is dependent on both genetic predisposition and traditional risk factors. Strategies for unraveling the genetic basis of PCAD have evolved with the advent of modern technologies. Genome-wide association studies (GWASs) have identified a considerable number of common genetic variants that are associated with PCAD. Most of these genetic variants are attributable to lipid and blood pressure-related single-nucleotide polymorphisms (SNPs). The genetic variants that predispose individuals to developing PCAD may depend on race and ethnicity. Some characteristic genetic variants have been identified in Chinese populations. Although translating this genetic knowledge into clinical applications is still challenging, these genetic variants can be used for CAD phenotype identification, genetic prediction and therapy. In this article we will provide a comprehensive review of genetic variants detected by GWASs that are predicted to contribute to the development of PCAD. We will highlight recent findings regarding CAD-related genetic variants in Chinese populations and discuss the potential clinical utility of genetic variants for preventing and managing PCAD.

The survival of Escherichia coli (E. coli) bacteria, the most common faecal indicator bacteria (FIB), may be significantly affected by cyanobacteria present during a harmful algal bloom (HAB). Therefore, the effect of Microcystis on the survival of FIB E.coli and coliforms was investigated. Microcosms containing two species of Microcystis (M. aeruginosa and M. smithii) were established and then inoculated with four reference strains of E. coli (ATCC 25922, 8739, 51813, and 11775) to explore the cyanobacteria-bacteria dynamics at a laboratory setting. Monitoring over several days showed normal growth of Microcystis, with or without the presence of E. coli. However, Microcystis was shown to dramatically decrease the survival of E. coli over time. Analysis of microcystin production by Microcystis was found to correlate with loss of E. coli, suggesting a toxic effect of microcystins on E. coli bacteria. This phenomenon was also demonstrated for a natural consortium of E. coli and coliform bacteria by inoculating with contaminated lake water. The results indicate that the use of E. coli as FIB may be greatly compromised in the presence of Microcystis spp. such as during a HAB when associated toxins are produced.

To address the demands of precision agriculture and the measurement of plant photosynthetic response and nitrogen status, it is necessary to employ advanced methods for estimating chlorophyll content quickly and non-destructively at a large scale. Therefore, we explored the utilization of both linear regression and machine learning methodology to improve the prediction of leaf chlorophyll content (LCC) in citrus trees through the analysis of hyperspectral reflectance data in a field experiment. And the relationship between phenology and LCC estimation was also tested in this study. The LCC of citrus tree leaves at five growth seasons (May, June, August, October, and December) were measured alongside measurements of leaf hyperspectral reflectance. The measured LCC data and spectral parameters were used for evaluating LCC using univariate linear regression (ULR), multivariate linear regression (MLR), random forest regression (RFR), K-nearest neighbor regression (KNNR), and support vector regression (SVR). The results revealed the following: the MLR and machine learning models (RFR, KNNR, SVR), in both October and December, performed well in LCC estimation with a coefficient of determination (R2) greater than 0.70. In August, the ULR model performed the best, achieving an R2 of 0.69 and root mean square error (RMSE) of 8.92. However, the RFR model demonstrated the highest predictive power for estimating LCC in May, June, October, and December. Furthermore, the prediction accuracy was the best with the RFR model with parameters VOG2 and Carte4 in October, achieving an R2 of 0.83 and RMSE of 6.67. Our findings revealed that using just a few spectral parameters can efficiently estimate LCC in citrus trees, showing substantial promise for implementation in large-scale orchards.