Interleukin-12 in multimodal tumor therapies for induction of anti-tumor immunity.

Interleukin-12 (IL-12) can be used as an immunomodulator in cancer immunotherapy. And it has demonstrated enormous potential in inhibiting tumor growth and improving the tumor microenvironment (TME) by several preclinical models. However, some disappointing results have showed in the early clinical trials when IL-12 used as a single agent for systemic cancer therapy. Combination therapy is an effective way to significantly fulfill the great potential of IL-12 as an immunomodulator. Here, we discuss the effects of IL-12 combined with traditional methods (chemotherapy, radiotherapy and surgery), targeted therapy or immunotherapy in the preclinical and clinical studies. Moreover, we summarized the potential mechanism underlying the anti-tumor effect of IL-12 in the combination strategies. And we also discussed the delivery methods and tumor-targeted modification of IL-12 and outlines future prospects for IL-12 as an immunomodulator.

Identification and characterization of two P450 enzymes from Citrus sinensis involved in TMTT and DMNT biosyntheses and Asian citrus psyllid defense.

The homoterpenes (3E)-4,8-dimethyl-1,3,7-nonatriene (DMNT) and (E,E)-4,8,12-trimethyl-1,3,7,11-tridecatetraene (TMTT) are the major herbivore-induced plant volatiles that help in defense directly by acting as repellants and indirectly by recruiting insects' natural enemies. In this study, DMNT and TMTT were confirmed to be emitted from citrus (Citrus sinensis) leaves infested with Asian citrus psyllid (Diaphorina citri Kuwayama; ACP), and two cytochrome P450 (CYP) genes (CsCYP82L1 and CsCYP82L2) were newly identified and characterized. Understanding the functions of these genes in citrus defense will help plan strategies to manage huanglongbing caused by Candidatus Liberibacter asiaticus (CLas) and spread by ACP. Quantitative real-time PCR (qPCR) analysis showed that CsCYP82L1 and CsCYP82L2 were significantly upregulated in citrus leaves after ACP infestation. Yeast recombinant expression and enzyme assays indicated that CsCYP82L1 and CsCYP82L2 convert (E)-nerolidol to DMNT and (E,E)-geranyllinalool to TMTT. However, citrus calluses stably overexpressing CsCYP82L1 generated only DMNT, whereas those overexpressing CsCYP82L2 produced DMNT and TMTT. Furthermore, ACPs preferred wild-type lemon (Citrus limon) over the CsCYP82L1-overexpressing line in dual-choice feeding assays and mineral oil over TMTT or DMNT in behavioral bioassays. Finally, yeast one-hybrid, electrophoretic mobility shift, and dual luciferase assays demonstrated that CsERF017, an AP2/ERF transcription factor, directly bound to the CCGAC motif and activated CsCYP82L1. Moreover, the transient overexpression of CsERF017 in lemon leaves upregulated CsCYP82L1 in the absence and presence of ACP infestation. These results provide novel insights into homoterpene biosynthesis in C. sinensis and demonstrate the effect of homoterpenes on ACP behavior, laying a foundation to genetically manipulate homoterpene biosynthesis for application in huanglongbing and ACP control.

Eight-Electron Copper Nanoclusters for Photothermal Conversion.

Owing to distinct physicochemical properties in comparison to gold and silver counterparts, atomically precise copper nanoclusters are attracting embryonic interest in material science. The introduction of copper cluster nanomaterials in more interesting fields is currently urgent and desired. Reported in this work are novel copper nanoclusters of [XCu54Cl12(tBuS)20(NO3)12] (X=S or none, tBuSH=2-methyl-2-propanethiol), which exhibit high performance in photothermal conversion. The clusters have been prepared in one pot and characterized by combinatorial techniques including ultraviolet-visible spectroscopy (UV-vis), electrospray ionization mass spectrometry (ESI-MS), and X-ray photoelectron spectroscopy (XPS). The molecular structure of the clusters, as revealed by single crystal X-ray diffraction analysis (SCXRD), shows the concentric three-shell Russian doll arrangement of X@Cu14@Cl12@Cu40. Interestingly, the [SCu54Cl12(tBuS)20(NO3)12] cluster contains 8 free valence electrons in its structure, making it the first eight-electron copper nanocluster stabilized by thiolates. More impressively, the clusters possess an effective photothermal conversion (temperature increases by 71 °C within ~50 s, λex=445 nm, 0.5 W cm-2) in a wide wavelength range (either blue or near-infrared). The photothermal conversion can be even driven under irradiation of simulated sunlight (3 sun), endowing the clusters with great potency in solar energy utilization.

Associations of MSK1 Methylation and Executive Function With Suicidal Ideation in Adolescents With Major Depressive Disorder: A Prospective Cohort Study.

Objective: Adolescent suicide is a major public health problem, and risk of suicide is higher among those with major depressive disorder (MDD), which may be linked to alterations in mitogen- and stress-activated kinase 1 (MSK1) and to defects in executive function. Here, we aimed to investigate the potential impacts of executive function and MSK1 methylation on suicidal ideation in adolescents with MDD.Methods: The study enrolled 66 drug-naive adolescents who were experiencing their first episode of MDD from February 2019 until October 2020. After 6 weeks of receiving antidepressant treatment, 65 participants remained in the study. Suicidal ideation and depressive severity were assessed using the Hamilton Depression Rating Scale, while executive function was evaluated using the Cambridge Neuropsychological Test Automated Battery. MSK1 methylation was measured using bisulfite DNA analysis.Results: Among the 66 adolescents with MDD, 43 (65.15%) reported suicidal ideation, while 23 (34.85%) did not. Individuals with suicidal ideation had worse executive function and higher MSK1 methylation than those without suicidal ideation. The MSK1 methylation percentage may predict suicidal ideation in adolescents with MDD (odds ratio [OR] 1.227, 95% CI [1.031 to 1.461]). Improvement in executive function was significantly associated with reduced suicidal ideation during antidepressant treatment (ß = -0.200, 95% CI [-0.877 to -0.085]).Conclusions: Our results strengthen the evidence for a link among MSK1 methylation, executive function, and suicidal ideation in adolescent MDD.Trial Registration: Chinese Clinical Trial Registry identifier: ChiCTR2000033402.

The association between neuroendocrine/glucose metabolism and clinical outcomes and disease course in different clinical states of bipolar disorders.

Objective: The treatment of bipolar disorder (BD) remains challenging. The study evaluated the impact of the hypothalamic-pituitary-adrenal (HPA) axis/hypothalamic-pituitary-thyroid (HPT) axis and glucose metabolism on the clinical outcomes in patients with bipolar depression (BD-D) and manic bipolar (BD-M) disorders. Methods: The research design involved a longitudinal prospective study. A total of 500 BD patients aged between 18 and 65 years treated in 15 hospitals located in Western China were enrolled in the study. The Young Mania Rating Scale (YMRS) and Montgomery and Asberg Depression Rating Scale (MADRS) were used to assess the BD symptoms. An effective treatment response was defined as a reduction in the symptom score of more than 25% after 12 weeks of treatment. The score of symptoms was correlated with the homeostatic model assessment of insulin resistance (HOMA-IR) index, the HPA axis hormone levels (adrenocorticotropic hormone (ACTH) and cortisol), and the HPT axis hormone levels (thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), free triiodothyronine (fT3), and free thyroxine (fT4)). Results: In the BD-M group, the YMRS was positively correlated with baseline T4 (r = 0.349, p = 0.010) and fT4 (r = 0.335, p = 0.013) and negatively correlated with fasting insulin (r = -0.289, p = 0.013). The pre-treatment HOMA-IR was significantly correlated with adverse course (p = 0.045, OR = 0.728). In the BD-D group, the baseline MADRS was significantly positively correlated with baseline fT3 (r = 0.223, p = 0.032) and fT4 (r = 0.315, p = 0.002), while baseline T3 (p = 0.032, OR = 5.071) was significantly positively related to treatment response. Conclusion: The HPT axis and glucose metabolism were closely associated with clinical outcomes at 12 weeks in both BD-D and BD-M groups. If confirmed in further longitudinal studies, monitoring T3 in BD-D patients and HOMA-IR for BD-M could be used as potential treatment response biomarkers.

Association between psychological distress and mental help-seeking intentions in international students of national university of Singapore: a mediation analysis of mental health literacy.

BACKGROUND: International students encounter a wide range of challenges that can have a significant impact on their mental health. Seeking help is one of the primary means of managing mental health, and more attention is required. This study aimed to investigate the psychological distress(PD), mental health literacy(MHL), and mental help-seeking intentions(MHSI) in international students of National University of Singapore(NUS), to explore the correlation between the three and to verify the mediating role of MHL in PD and MHSI. METHODS: This cross-sectional study was conducted between May and July 2023 using the Mental Help Seeking Intention Scale(MHSIS), Patient Health Questionnaire-9(PHQ-9), Generalized Anxiety Disorder-7(GAD-7), and Mental Health Literacy Scale(MHLS). 281 international students(177 males, 104 females;) in NUS completed self-report questionnaires. SPSS 25.0 was applied to the data for descriptive analysis, Pearson correlation analysis and stepwise regression analysis. Mediation analysis fully for all potential confounding factors were conducted. RESULTS: Significant correlations were found between PD, MHL and MHSI. MHLS- knowledge of how to seek professional information(MHLS- H) completely mediated the association of anxiety with MHSI[B=-0.271; 95% confidence interval(CI): (-0.067, 0.0037)]; MHLS- attitude that promote recognition or appropriate help-seeking behavior(stigma)(MHLS- H) partially mediated the association of PD with MHSI[B = 0.104, 95% CI: (0.008, 0.179)]; with mediating effects accounting for 100% and 24.847% of the total effect. In addition, demographic variables such as gender, years in Singapore and residence type mediated both the direct and indirect effect of the mediation model. CONCLUSIONS: MHL mediated both the direct and indirect effects on the association between PD and MHSI, especially, the mediator of the MHLS- H and MHL-A. It means that MHSI in this population can be improved by increasing MHL and thus the PD. The findings suggest that, such as providing information about how to access to professional services and promoting disorder recognition to the international students, may help them develop their psychological well-being and good mental health care decisions.

Hydride-doped Ag17Cu10 nanoclusters as high-performance electrocatalysts for CO2 reduction.

The atomically precise metal electrocatalysts for driving CO2 reduction reactions are eagerly pursued as they are model systems to identify the active sites, understand the reaction mechanism, and further guide the exploration of efficient and practical metal nanocatalysts. Reported herein is a nanocluster-based electrocatalyst for CO2 reduction, which features a clear geometric and electronic structure, and more importantly excellent performance. The nanocatalysts with the molecular formula of [Ag17Cu10(dppm)4(PhC≡C)20H4]3+ have been obtained in a facile way. The unique metal framework of the cluster, with silver, copper, and hydride included, and dedicated surface structure, with strong (dppm) and labile (alkynyl) ligands coordinated, endow the cluster with excellent performance in electrochemical CO2 reduction reaction to CO. With the atomically precise electrocatalysts in hand, not only high reactivity and selectivity (Faradaic efficiency for CO up to 91.6%) but also long-term stability (24 h), are achieved.

DppfCuBH4: new reducing agents for the synthesis of ferrocene-functionalized metal nanoclusters.

A facile synthesis of atomically precise metal nanoclusters, especially those decorated with functional groups, is the prerequisite for finding applications in special fields and studying structure-and-property relationships. The exploration of simple and efficient synthetic prototypes for introducing functional ligands (such as ferrocene) into cluster moieties is thus of high interest. In this work, a type of reducing agent of dppfCuBH4 (dppf is 1,1'-bis(diphenyphosphino)ferrocene) is introduced for the first time to prepare ferrocene-functionalized metal nanoclusters. Two new clusters of [Ag25Cu4(dppf)6(3-F-PhCC)12Cl6]3+ (1) and [Ag4(dppf)5Cl2]2+ (2) have been obtained from the simple synthetic method. The two compounds have been fully characterized by advanced techniques of electrospray ionization mass spectroscopy (ESI-MS), nuclear magnetic resonance (NMR), and ultraviolet-visible spectroscopy (UV-Vis). The total structure of the clusters, as determined by X-ray single-crystal diffraction, describes the Ag13@Ag12Cu4(dppf)6(3-F-PhCC)12Cl6 core-shell structure of 1 and [Ag2Cl(dppf)2]+-dppf-[Ag2Cl(dppf)2]+ polymeric structure of 2. This work opens the door to employing dppfCuBH4 as a functional reducing agent to discover many underlying metal nanoclusters and even other nanomaterials which feature ferrocene-groups.

Ag10Cu16 nanoclusters with triple-ligand protection: total structure and electronic structure analysis.

Illustrating the molecular structure of metal nanoclusters with the protection of multiple ligands is a prerequisite to understand structure-property relationships of nano or bulk materials with hybrid interfaces. Reported herein is the synthesis, total structure and electronic structure analysis of a new Ag/Cu alloy nanocluster with triple-ligand protection. The cluster with the formula of Ag10Cu16(C8H9S)16(PPh3)4(CF3CO2)8 has been attained in one-pot in a simple way. X-ray single crystal analysis displays its unique metal framework and more importantly rich interface structures. The ligands of phosphine, thioate and carboxylic acid are coordinated to the surface of the cluster in distinctive modes. The electronic structure of the cluster has been revealed by density functional theory, showing that it is a 2-electron superatom with jellium configurations of 1S2. In good accordance with the closure of the geometric and electronic structures, the cluster exhibits moderate stability, which makes it a candidate for further application in many fields.

Problematic internet gaming and non-suicidal self-injury in Chinese adolescents: Moderating and mediating roles of anxiety.

INTRODUCTION: Despite consistent reports of the association between problematic internet gaming (PIG) and non-suicidal self-injury (NSSI), an increase in PIG does not necessarily lead to increased NSSI. This apparent paradox indicates the presence of other mediators and moderators in the PIG-NSSI association. This study aimed to investigate the role of anxiety as a potential moderating and mediating factor of the PIG-NSSI association in Chinese adolescents. METHODS: A cross-sectional study was conducted among 10,479 Chinese adolescents (50.5% male; age range, 9-18 years). Standardized self-report questionnaires were used to assess the severity of PIG, anxiety, and NSSI. Spearman correlation and multiple linear regression were applied to examine the relationships among PIG, anxiety, and NSSI. Both moderating and mediating effects of anxiety were assessed using Hayes' methods. RESULTS: PIG, anxiety symptoms, and NSSI significantly correlated with one another. Anxiety significantly moderated the relationship between PIG and NSSI [B = 0.002, standard error (SE) = 0.000, p < 0.001], and it partially mediated the PIG-NSSI association [B = 0.017, SE = 0.001, 95% confidence interval (CI) 0.014-0.021]. Social concern and concentration were the two dimensions of anxiety that exerted the strongest mediation effect (B = 0.017, SE = 0.002, 95% CI 0.014-0.020). CONCLUSIONS: Adolescents with PIG and high anxiety are likely to suffer more severe NSSI and may benefit from interventions to reduce anxiety symptoms.

COVID-19-associated impact and post-traumatic stress symptoms 39 days after pandemic in a sample of home-quarantined Chinese college students: the mediating effecting of past stressful events, psychological resilience, and social support.

BACKGROUND: During the COVID-19 outbreak, most Chinese college students were home-quarantined to prevent the spread of the virus. COVID-19-associated impact has been shown to be a risk factor for the development of post-traumatic symptoms disorder (PTSD). However, little is known about the psychological processes that mediate this association. This study investigated the association between COVID-19-associated impact and PTSD and examined whether past stressful events, psychological resilience, and social support have mediating effects on this association. METHODS: The 12,397 valid responses from 31cities in China via an online survey assessed PTSD symptoms, past stressful events, psychological resilience, social support and social-demographic variables. AMOS was used to test the hypotheses of mediating effects. RESULTS: On the 39th day of the declared COVID-19 epidemic in China, 6.75% of the surveyed sample showed PTSD symptoms. A positive mediating effect of past stressful events was found between COVID-19-associated impact and PTSD, whereas psychological resilience and social support had negative mediating effects. The fit indices for the path model were found to be significant (ß = 0.28, p < 0.001), COVID-19-associated impact indirectly affects the risk of PTSD through mediating pathways (past stressful events → psychological resilience → social support) on PTSD. CONCLUSIONS: Attention should be paid to the effects of past stressful events of Chinese college students who were home-quarantined during the COVID-19 epidemic, and strategies should also be implemented to improve social support and develop psychological resilience. TRIAL REGISTRATION: The study was approved by the ethics committee of the Southwest Minzu University.

Chiral copper-hydride nanoclusters: synthesis, structure, and assembly.

An effective strategy is developed to synthesize a novel and stable layered Cu nanocluster using a one-pot reduction method. The cluster, with a molecular formula of [Cu14(tBuS)3(PPh3)7H10]BF4 which has been unambiguously characterized by single crystal X-ray diffraction analysis, exhibits different structures from previously reported analogues with core-shell geometries. In the absence of chiral ligands, the cluster displays intrinsic chirality owing to the non-covalent ligand-ligand interactions (e.g., C-H⋯Cu interactions and C-H⋯π interactions) to lock the central copper core. The interlacing of chiral-cluster enantiomers forms a large cavity, which lays the foundation for a series of potential applications such as drug filling and gas adsorption. Moreover, the C-H⋯H-C interactions of phenyl groups between different cluster moieties promote the formation of a dextral helix and realization of the self-assembly of nanostructures.

A new model for the treatment of type 2 diabetes mellitus based on rhythm regulations under the framework of psychosomatic medicine: a real-world study.

We aimed to explore a new treatment model for type 2 diabetes mellitus (DM) based on rhythm regulation under the framework of psychosomatic medicine. Using psychotropics as rhythm regulators, 178 patients with DM were evaluated and divided into three groups: the antidiabetic treatment group (AT group), psychotropic treatment group (PT group), and combined antidiabetic + psychotropic treatment group (combined group), for a course of 16 weeks. The West China Psychiatry Association (WCPA) Somatic Symptom Classification Scale (SSCS) was used to evaluate each patient. The levels of hormones in the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-thyroid axes and of blood glucose and glycosylated hemoglobin (HbA1c) were evaluated both before and after treatment. After the treatment, the blood glucose and HbA1c levels in all three groups were lower than those at baseline. Furthermore, the incidence of the abnormal HPA axis in the PT group was significantly decreased (P = 0.003), while the incidence of the abnormal HPA axis in the combined group was 0.0%. The five factor scores of the SSCS in the PT and combined groups after treatment were both significantly low (P < 0.01). Both the incidence of abnormal neuroendocrine axes and SSCS scores in the AT group showed no significant difference before and after treatment. "Blood glucose control + rhythm regulation" should be considered as optimised treatment goals for DM. Moreover, some psychotropics could be used as biorhythm regulators, which have good potential value for clinical application.Clinical trial registration number: ChiCTR1800019064. Name of trial registration: Reinterpretation of mechanism and the optimization of treatment for non-infectious chronic diseases under the "stress-dysrhythmia" theory hypothesis. The full trial protocol can be accessed at the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ).

Sex- and age-specific differences in associations of a body shape index with all-cause and cardiovascular death risks among US adults with diabetes.

BACKGROUND AND AIMS: Evidence regarding the effect of body shape index (ABSI) on mortality is scarce among individuals with diabetes mellitus (DM). Herein, we explored the relationships between ABSI and all-cause and cardiovascular death risks among US individuals with DM. METHODS AND RESULTS: A total of 4657 US adults with DM were enrolled from the National Health and Nutrition Examination Survey (NHANES 2003-2014) who had baseline waist circumference, height, and weight data. ABSI was calculated as [Formula: see text] and the survival information of patients was available from recruitment until 2015 utilizing the national death index. We employed Cox proportional hazards models to estimate the association of ABSI with survival. A total of 817 adults with DM died after a median follow-up period of 5.6 years, with an annual all-cause death rate per 1000 person-years of 30.0 [95% CI, 28.0-32.1]. Continuous ABSI z score was positively and significantly associated with all-cause mortality with adjustment for potential confounders (HR = 1.16, 95% CI: 1.06-1.28). ABSI tended to show a higher all-cause and CVD (cardiovascular disease) mortality among men (HR = 1.35, 95% CI: 1.19-1.53 and HR = 1.45, 95% CI: 1.12-1.87, respectively) and patients younger than 60 years (HR = 1.45, 95% CI: 1.16-1.80 and HR = 1.66, 95% CI: 1.09-2.53, respectively). Statistically significant interactions were found between the ABSI and both sex and age for total mortality. CONCLUSIONS: Among US adults with DM from NHANES, ABSI exhibited a linear and positive relationship with total and CVD mortality risk, especially in men and younger patients.

An atomically precise Ag18Cu8 nanocluster with rich alkynyl-metal coordination structures and unique SbF6- assembling modes.

Elucidating the coordination structures and assembling modes of atomically precise metal nanoclusters (NCs) remains a hot topic as it gives answers to the underlying mechanism of nanomaterials and bulk materials in terms of structure-property relationships. Here we report a novel silver-copper alloy NC featuring rich alkynyl-metal coordination modes and unique SbF6- assembling structures. The NC, with the composition of [Ag18Cu8(dppp)4(tBu-C6H4CC)22](SbF6)4 (dppp = 1,3-bis(diphenylphosphino)-propane), was prepared by a stepwise synthetic approach. Single-crystal X-ray diffraction analysis revealed that such a NC featured a staircase-like Ag18Cu8 kernel, which was protected by hybrid alkynyl and dppp ligands in diverse coordination structures and multiple environments. The structural analysis also revealed the unique function of SbF6- in inducing the assembly of cluster moieties, highlighting the importance of counterions in assembling nanomolecules. The diverse coordination structures of the protective ligands with metal ions and the indispensable roles of counterions in assembling the cluster moieties have also been supported by nuclear magnetic resonance (NMR) and electrospray ionization mass spectrometry (ESI-MS) studies, making it a model system to showcase the uniqueness of atomically precise metal NCs in illustrating the coordination chemistry of nanomaterials and bulk materials at the molecular level.

An alkynyl-protected Ag13-xCu6+x nanocluster for catalytic hydrogenation.

A novel alkynyl-stabilized silver-copper alloy nanocluster with the composition of [Ag13-xCu6+x(tBuC6H4CC)14(PPh3)6](SbF6)3 was prepared by the (PPh3)2CuBH4-mediated reduction approach. The nanocluster features a centred disordered-octahedral Ag7Cu6 kernel, which is protected by hybrid alkynyl and triphenylphosphine ligands. Structural comparison of this two-electron nanocluster with other alkynyl-capped Ag/Cu ones suggested that the structure of alkynyl ligands played an important role in dictating the structures of the resulting nanoclusters. The title cluster showed high performance in the catalytic hydrogenation of 4-nitrophenol, indicative of the bright future of cluster-based catalysts.

Functional Characterization of the Ryanodine Receptor Gene in Diaphorina citri.

The Asian citrus psyllid Diaphorina citri (Hemiptera: Liviidae) is a major citrus pest spread around the world. It is also a vector of the bacterium 'Candidatus Liberibacter asiaticus', considered the cause of the fatal citrus disease huanglongbing (HLB). Insect ryanodine receptors (RyRs) are the primary target sites of diamide insecticides. In this study, full-length RyR cDNA from D. citri (named DcRyR) was isolated and identified. The 15,393 bp long open reading frame of DcRyR encoded a 5130 amino acid protein with a calculated molecular weight of 580,830 kDa. This protein had a high sequence identity (76-79%) with other insect homologs and a low sequence identity (43-46%) with mammals. An MIR domain, two RIH domains, three SPRY domains, four RyR repeat domains, an RIH-associated domain at the N-terminus, two consensus calcium-binding EF-hands, and six transmembrane domains were among the characteristics that DcRyR shared with insect and vertebrate RyRs. In expression analysis, the DcRyR gene displayed transcript abundance in all tissues and developmental stages as well as gene-differential and stage-specific patterns. In addition, diagnostic PCR experiments revealed that DcRyR had three potential alternative splice variants and that splicing events might have contributed to the various functions of DcRyR. However, diamide resistance-related amino acid residue mutations I4790M/K and G4946E were not found in DcRyR. These results can serve as the basis for further investigation into the target-based diamide pesticide resistance of D. citri.

[Comparative Energy Consumption Structure and Mode between China and Major Energy-Consuming Countries Under the Background of Carbon Emission Reduction].

The top 23 countries with energy consumption accounting for 80% of the worldwide total in 2020 were selected as the research objects for this study. The energy consumption structure of these countries has been compared and studied from the proportion of clean energy in primary energy, the clean utilization rate of fossil energy, and the proportion of electric energy in terminal energy consumption, and the characteristics of energy consumption intensity were also analyzed based on the energy consumption per unit GDP, capital, and unit land area. The energy consumption patterns of various countries in social-economic operation, production, and life were also discussed, combined with the characteristics of industrial structure and subsector energy consumption. The concept of natural carbon sink load ratio of energy consumption was put forward, and the advantages and challenges of energy consumption mode transformation under carbon peak and carbon neutralization goals in China were identified and analyzed. The results showed that:the proportion of clean energy in primary energy, the proportion of energy consumption for power generation, the clean utilization rate of fossil energy, and the proportion of electric energy in terminal energy consumption in China were 15.90%, 53.48%, 37.51%, and 26.54%,respectively,all of which were in the forefront among the major energy-consuming countries in the world. China has built a favorable structural foundation for energy-intensive and clean utilization and formed a green and low-carbon energy consumption model; the proportion of non-industrial and agricultural energy consumption, especially that of transportation energy consumption, were both the lowest among major energy-consuming countries, and there is still much room for improvement in overall energy productivity based on the optimization of industrial structure. However, the relatively short carbon peak and neutralization target period poses a great challenge to the development speed and scale of clean energy to China, and the international situation under the constraint of carbon emission also increases the difficulty for China to achieve the carbon reduction goal by optimizing and adjusting the industrial structure.

Brain white matter microstructure abnormalities in children with optimal outcome from autism: a four-year follow-up study.

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder, with only a small proportion of people obtaining optimal outcomes. We do not know if children with ASD exhibit abnormalities in the white matter (WM) microstructure or if this pattern would predict ASD prognosis in a longitudinal study. 182 children with ASD were recruited for MRI and clinical assessment; 111 completed a four-year follow-up visit (30 with optimal outcomes, ASD-; 81 with persistent diagnosis, ASD+). Additionally, 72 typically developing controls (TDC) were recruited. The microstructural integrity of WM fiber tracts was revealed using tract-based spatial statistics (TBSS) and probabilistic tractography analyses. We examined the neuroimaging abnormality associated with ASD and its relationship to ASD with optimal outcome. The ASD+ and TDC groups were propensity score matched to the ASD- group in terms of age, gender, and IQ. TBSS indicated that children with ASD exhibited abnormalities in the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), and extending to the anterior thalamic radiation (ATR) and cingulum; whereas the ASD+ group showed more severe abnormalities than the ASD- group. Probabilistic tractography analysis revealed that ASD+ group exhibited lower Fractional Anisotropy (FA) of the left superior thalamic radiation (STR L) than ASD- group, and that FA value of the STR L was a significant predictor of optimal outcome (EX(B), 6.25; 95% CI 2.50-15.63; p < 0.001). Children with ASD showed significant variations in SLF_L and STR_L, and STR_L was a predictor of 'ASD with optimal outcome'. Our findings may aid in comprehension of the mechanisms of 'ASD with optimal outcome'.

Re-interpretation of the mechanism of type 2 diabetes mellitus based on a framework of psychosomatic medicine: a real-world study.

OBJECTIVE: Using bipolar disorder (BD) as a control, we explored the possible developmental process of impaired glucose metabolism rhythm. METHODS: In total, 441 subjects (77, 162, 134, 54, and 14 in the pre-diabetes [pre-DM], DM, BD, BD + pre-DM, and BD + DM groups, respectively) and 160 controls were included. All subjects were assessed using the Neuroticism Extraversion Openness Five-Factor Inventory (NEO-FFI). The hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-thyroid (HPT) axes were measured. RESULTS: Cluster analysis showed that the BD, BD + DM, and DM groups were classified as the 'disease group, the BD + pre-DM group as the 'mixed period group', and the pre-DM group as the 'pre-disease group'. The conscientiousness factor scores of the NEO-FFI in the 'disease group' were higher than the norm but lower than the norm in the 'pre-disease group'. The scores of neurotic factors in the 'pre-disease' and 'mixed period' groups were both significantly higher than that in the 'disease group' (corrected p < 0.001). The incidences of the abnormal HPA axis decreased gradually from the 'pre-disease group' to the 'mixed period group' then to the 'disease group', while those of the HPT axis slightly increased at first and then significantly decreased. The overall prediction rate of the multiple logistic regression model was 92.7%. CONCLUSION: This study suggests that progression of pre-diabetes to DM is a continuous process from local abnormalities to rhythm disorder of glucose metabolism. This understanding can be applied to the whole course management and early intervention of DM and to the future development of optimised treatment based on rhythm regulation. TRIAL REGISTRATION: Clinical trial registration number: ChiCTR1800019064. Name of trial registration: Identify and the optimization of treatment for non-infectious chronic diseases under the "stress-dysrhythmia" theory hypothesis (Registration date: 24/10/2018). The full trial protocol can be accessed at the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ).