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Background: Systemic immune-inflammation index (SII) is a novel comprehensive inflammatory marker. Inflammation is associated with impaired lung function. We aimed to explore the possible relationship between SII and lung function to examine the potential of SII in predicting lung function decline. Methods: A cross-sectional survey was conducted using the data of the NHANES from 2007 to 2012. Multiple linear regression models were used to analyze the linear relationship between SII and pulmonary functions. Sensitivity analyses, subgroup analyses, and interaction tests were used to examine the robustness of this relationship across populations. Fitted smooth curves and threshold effect analysis were used to describe the nonlinear relationships. Results: A total of 10,125 patients were included in this study. After adjusting for all covariates, multiple linear regression model analysis showed that high Log2-SII level was significantly associated with decreased FVC(ß, -23.4061; 95% CI, -42.2805- -4.5317), FEV1(ß, -46.7730; 95% CI, -63.3371- -30.2089), FEV1%(ß, -0.7923; 95% CI, -1.1635- -0.4211), FEV1/FVC(ß, -0.6366; 95% CI, -0.8328- -0.4404) and PEF(ß, -121.4468; 95% CI,-164.1939- -78.6998). The negative correlation between Log2-SII and pulmonary function indexes remained stable in trend test and stratified analysis. Inverted U-shaped relationships between Log2-SII and FVC, FEV1, FEV1%, and PEF were observed, while a negative linear correlation existed between FEV1/FVC and Log2-SII. The cutoff values of the nonlinear relationship between Log2-SII and FVC, FEV1, FEV1%, PEF were 8.3736, 8.0688, 8.3745, and 8.5255, respectively. When SII exceeded the critical value, the lung function decreased significantly. Conclusion: This study found a close correlation between SII and pulmonary function indicators. This study investigated the SII threshold when lung functions began to decline in the overall population. SII may become a promising serological indicator for predicting lung function decline. However, prospective studies were needed further to establish the causal relationship between these two factors.

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Common variants in the MicroRNA 137 host gene MIR137HG and its adjacent gene DPYD have been associated with schizophrenia risk and the latest Psychiatric Genomics Consortium (PGC). Genome-Wide Association Study on schizophrenia has confirmed and extended these findings. To elucidate the association of schizophrenia risk-associated SNPs in this genomic region, we examined the expression of both mature and immature transcripts of the miR-137 host gene (MIR137HG) in the dorsolateral prefrontal cortex (DLPFC) and subgenual anterior cingulate cortex (sgACC) of postmortem brain samples of donors with schizophrenia and psychiatrically-unaffected controls using qPCR and RNA-Seq approaches. No differential expression of miR-137, MIR137HG, or its transcripts was observed. Two schizophrenia risk-associated SNPs identified in the PGC study, rs11165917 (DLPFC: P = 2.0e-16; sgACC: P = 6.4e-10) and rs4274102 (DLPFC: P = 0.036; sgACC: P = 0.002), were associated with expression of the MIR137HG long non-coding RNA transcript MIR137HG-203 (ENST00000602672.2) in individuals of European ancestry. Carriers of the minor (risk) allele of rs11165917 had significantly lower expression of MIR137HG-203 compared with those carrying the major allele. However, we were unable to validate this result by short-read sequencing of RNA extracted from DLPFC or sgACC tissue. This finding suggests that immature transcripts of MIR137HG may contribute to genetic risk for schizophrenia.

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The mediodorsal thalamus (MD) and adjacent midline nuclei are important for cognition and mental illness, but their cellular composition is not well defined. Using single-nucleus and spatial transcriptomics, we identified a conserved excitatory neuron gradient, with distinct spatial mapping of individual clusters. One end of the gradient was expanded in human MD compared to mice, which may be related to the expansion of granular prefrontal cortex in hominids. Moreover, neurons preferentially mapping onto the parvocellular division MD were associated with genetic risk for schizophrenia and bipolar disorder. Midbrain-derived inhibitory interneurons were enriched in human MD and implicated in genetic risk for major depressive disorder.

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Objective: The purpose of this study is to develop and assess a nomogram risk prediction model for central precocious puberty (CPP) in obese girls. Methods: We selected 154 cases of obese girls and 765 cases of non-obese girls with precocious puberty (PP) who underwent the gonadotropin-releasing hormone stimulation test at the Jiangxi Provincial Children's Hospital. Univariate analysis and multivariate analysis were conducted to identify predictors of progression to CPP in girls with PP. A predictive model was developed and its predictive ability was preliminarily evaluated. The nomogram was used to represent the risk prediction model for CPP in girls with obesity. The model was validated internally using the Bootstrap method, and its efficacy was assessed using calibration curves and clinical decision analysis curves. Results: In obese girls with PP, basal luteinizing hormone (LH) and follicular stimulating hormone (FSH) levels, as well as uterine volume, were identified as independent risk factors for progression to CPP. In non-obese girls, the basal LH level, bone age, and uterine volume were identified as independent risk factors for progression to CPP. With an AUC of 0.896, the risk prediction model for obese girls, was found to be superior to that for non-obese girls, which had an AUC of 0.810. The model displayed strong predictive accuracy. Additionally, a nomogram was used to illustrate the CPP risk prediction model for obese girls. This model performs well in internal validation and is well calibrated, providing a substantial net benefit for clinical use. Conclusion: A medical nomogram model of CPP risk in obese girls comprised of basal LH value, basal FSH value, and uterine volume, which can be used to identify those at high risk for progression of CPP in obese girls and develop individualized prevention programs.

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Metabolic dysfunction-associated steatohepatitis (MASH) is considered the progressive form of metabolic dysfunction-associated steatotic liver disease, which is the leading cause of chronic liver disease in children. However, the pathogenesis of pediatric MASH remains poorly understood because of the lack of animal models. In this study, we developed a mouse model of pediatric MASH and characterized the hepatic transcriptomic profile using spatial transcriptomics technology. C57BL/6J mice were fed a Western diet (WD) along with weekly injections of carbon tetrachloride (CCl4) from the age of 3 to 8 weeks. After 5 weeks of feeding, WD + CCl4-treated mice showed significant liver injury without the development of insulin resistance. Histologically, WD + CCl4 induced key features of type 2 MASH, the most common type observed in children, characterized by liver steatosis, portal inflammation, and portal fibrosis. Through spatial transcriptomics analysis of liver tissues, we identified that cluster 0 in the mouse from the WD + CCl4 group was enriched in pathways associated with lipid metabolism. Further investigation revealed that cytochrome p450 2E1 was the top marker gene of cluster 0, and its expression was increased in the periportal area of mice from the WD + CCl4 group. These findings suggest that our mouse model of pediatric MASH mirrors the histologic features of human MASH, and the up-regulation of cytochrome p450 2E1 may be linked to the disease pathogenesis.

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Although emerging evidence on the association between per- and polyfluoroalkyl substances (PFASs) and neurodevelopment have been investigated, there is no consensus on the effect of maternal PFASs on neurodevelopment in offspring. Here, we assessed the risk of maternal PFASs exposure on the neurodevelopment of offspring using a novel Targeted Risk Assessment of Environmental Chemicals (TRAEC) strategy based on multiple evidence. The evidence from five online databases were analyzed the effect of PFASs on neurodevelopment. The potential neurodevelopment risk of PFASs was evaluated by the TRAEC strategy, which was conducted on a comprehensive scoring system with reliability, correlation, outcome fitness and integrity. The studies from five databases and additional researchers' experiments were included the present study to proceed following risk assessment. Based on the framework with TRAEC strategy, the comprehensive evaluation of health risks was classified as low (absolute value 0-4), medium (absolute value 4-8), high (absolute value 8-10). In the present study, the effect of PFASs exposure on neurodevelopment was a medium-risk level with 5.61 overall risk-score. The population-attributable risk (PAR) was 8.26 % for maternal PFASs exposure. The study identified a low-risk effect of prenatal PFASs exposure on ASD and behavioral disabilities. The chain length, type of PFASs and neurodevelopmental trajectories contributed to the risk of maternal PFASs on the neurodevelopment of offspring. Consistent with results of four criteria-based tools (ToxRTool, SciRAP, OHAT and IRIS), health risk assessment based on the TRAEC strategy demonstrated robustness and reliability in the present study. These results illustrated a medium-risk effect of maternal PFASs exposure on neurodevelopmental disorders of offspring. In addition, the TRAEC strategy provided a scientific and structured method for effect evaluation between prenatal PFASs and neurodevelopmental disorders, promoting the consistency and validation in risk assessment.

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Chilo suppressalis, a critical rice stem borer pest, poses significant challenges to rice production due to its overlapping generations and irregular developmental duration. These characteristics complicate pest management strategies. According to the dynamic analysis of the overwintering adults of C. suppressalis in fields, it indicates that the phenomenon of irregular development of C. suppressalis exists widely and continuously. This study delves into the potential role of the Broad-Complex (Br-C) gene in the developmental duration of C. suppressalis. Four isoforms of Br-C, named CsBr-C Z1, CsBr-C Z2, CsBr-C Z4, and CsBr-C Z7, were identified. After CsBr-Cs RNAi, the duration of larva development spans extended obviously. And, the average developmental duration of dsCsBr-Cs feeding individuals increased obviously. Meanwhile, the average developmental duration of the dsCsBr-C Z2 feeding group was the longest among all the RNAi groups. After dsCsBr-Cs feeding continuously, individuals pupated at different instars changed obviously: the proportion of individuals pupated at the 5th instar decreased and pupated at the 7th instar or higher increased significantly. Moreover, the pupation rate of dsCsBr-Cs (except dsCsBr-C Z7) were significantly lower than that of dsGFP. The same results were obtained from the mutagenesis in CsBr-C genes mediated by CRISPR/Cas9. The average developmental duration of CsBr-Cs knockout individuals was significantly prolonged. And, the instar of pupation in knockout individuals was also delayed significantly. In conclusion, this work showed that CsBr-Cs played a crucial role in pupal commitment and affected the developmental duration of C. suppressalis significantly.

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As a novel type of macrocycles with attractive planar chirality, pillar[5]arenes have gained increasing research interest over the past decades, enabling their widespread applications in diverse fields such as porous materials, molecular machines, and chiral luminescence materials. However, the catalytic methodology towards the enantioselective synthesis of planar chiral pillar[5]arenes remains elusive. Here we report a novel method for the enantioselective synthesis of planar chiral pillar[5]arenes via asymmetric Sonogashira coupling, giving access to a wide range of highly functionalized planar chiral pillar[5]arenes, including both homo- and hetero-rimmed ones, with excellent enantioselectivities. Attractively, the resultant planar chiral pillar[5]arenes show great potential for widespread use in many areas such as chiral luminescent materials. This work not only enables the successful synthesis of planar chiral pillar[5]arenes with abundant structural and functional diversity as key building blocks for practical applications but also enriches the asymmetric cross-coupling methodologies in organic synthetic chemistry.

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Acute promyelocytic leukemia (APL) is marked by a block at the promyelocyte stage. Treatments like ATRA and ATO face resistance and relapse issues. Plastrum testudinis, a traditional Chinese medicine, may offer therapeutic potential. This study investigated xtr-miR-22-3p from P. testudinis for treating APL. High expression of xtr-miR-22-3p was confirmed, with target prediction indicating interactions with key genes, including PML. xtr-miR-22-3p reduced HL-60 leukemia cell growth, altered the cell cycle, and selectively inhibited HL-60 proliferation while promoting BMSC growth, suggesting its potential as a targeted APL therapy.

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Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death among patients with epilepsy, causing a global public health burden. The underlying mechanisms of SUDEP remain elusive, and effective prevention or treatment strategies require further investigation. A major challenge in current SUDEP research is the lack of an ideal model that maximally mimics the human condition. Animal models are important for revealing the potential pathogenesis of SUDEP and preventing its occurrence; however, they have potential limitations due to species differences that prevent them from precisely replicating the intricate physiological and pathological processes of human disease. This Review provides a comprehensive overview of several available SUDEP animal models, highlighting their pros and cons. More importantly, we further propose the establishment of an ideal model based on brain-computer interfaces and artificial intelligence, hoping to offer new insights into potential advancements in SUDEP research. In doing so, we hope to provide valuable information for SUDEP researchers, offer new insights into the pathogenesis of SUDEP and open new avenues for the development of strategies to prevent SUDEP.

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The phytoplankton Phaeocystis globosa plays an important role in sulfur cycling and climate control, and can develop harmful algal blooms (HABs). Here we report a chromosome-scale reference genome assembly of P. globosa, which enable in-depth analysis of molecular underpinnings of important ecological characteristics. Comparative genomic analyses detected two-rounds of genome duplications that may have fueled evolutionary innovations. The genome duplication may have resulted in the formation of dual HiDP and LoDP dimethylsulphoniopropionate (DMSP) biosynthesis pathways in P. globosa. Selective gene family expansions may have strengthened biological pathways critical for colonial formation that is often associated with the development of algal blooms. The copy numbers of rhodopsin genes are variable in different strains, suggesting that rhodopsin genes may play a role in strain-specific adaptation to ecological factors. The successful reconstruction of the P. globosa genome sets up an excellent platform that facilitates in-depth research on bloom development and DMSP metabolism.

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BACKGROUND: To investigate the effect of different working periods on missed diagnoses in patients with colorectal polyps in colonoscopy. METHODS: We conducted a retrospective analysis of patients who were diagnosed with colorectal polyps during colonoscopy in an outpatient department between July and December 2022. These patients were subsequently hospitalized for resection during this period. Patients with missed diagnoses were those who had newly discovered polyps in a second colonoscopy. The working periods were categorized as work, near the end of work, and delayed work, respectively, in the morning and afternoon. RESULTS: A total of 482 patients were included, and the miss rate of diagnosis was 48.1% (232/482), mainly in the transverse colon (25%), and the ascending colon (23%). Patient age was a risk factor for the miss rate of diagnosis (OR = 1.025, 95%CI: 1.009-1.042, P = 0.003) and was also associated with the number of polyps detected for the first colonoscopy (χ2 = 18.196, P = 0.001). The different working periods had no statistical effect on the missed rate of diagnosis (χ2 = 1.998, P = 0.849). However, there was an increasing trend in miss rates towards the end of work and delayed work periods, both in the morning and afternoon. The highest miss rate (60.0%) was observed during delayed work in the afternoon. Additionally, poor bowel preparation was significantly more common during delayed work in the afternoon. CONCLUSIONS: The increasing trend in miss rates towards the end of work and delayed work periods deserves clinical attention. Endoscopists cannot always stay in good condition under heavy workloads.

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Deep-sea hydrothermal vents are characterized by high hydrostatic pressure, hypoxia, darkness and toxic substances. However, how organisms adapt to such extreme marine ecosystems remain poorly understood. We hypothesize that adaptive evolution plays an essential role in generating novelty for evolutionary adaptation to the deep-sea environment because adaptive evolution has been found to be critical for species origin and evolution. In this project, the chromosome-level genome of the deep-sea hydrothermal vent gastropod T. jamsteci was constructed for the first time to examine molecular mechanisms of its adaptation to the deep-sea environment. The genome size was large (2.54 Gb), ranking at the top of all species in the Vetigastropoda subclass, driven primarily by the bursts of transposable elements (TEs). The transposition of TEs may also trigger chromosomal changes including both inter-chromosomal fusions and intra-chromosomal activities involving chromosome inversions, rearrangements and fusions, as revealed by comparing the genomes of T. jamsteci and its closely related shallow-sea species Gibbula magus. Innovative changes including the expansion of the ABC transporter gene family that may facilitate detoxification, duplication of genes related to endocytosis, immunity, apoptosis, and anti-apoptotic domains that may help T. jamsteci fight against microbial pathogens, were identified. Furthermore, comparative analysis identified positive selection signals in a large number of genes including the hypoxia up-regulated protein 1, which is a chaperone that may promote adaptation of the T. jamsteci to hypoxic deepsea environments, hox2, Rx2, Pax6 and cilia-related genes BBS1, BBS2, BBS9 and RFX4. Notably, because of the critical importance of cilia and IFT in development, positive selection in cilia-related genes may play a critical role in facilitating T. jamsteci to adapt to the high-pressure deep-sea ecosystem. Results from this study thus revealed important molecular clues that may facilitate further research on the adaptation of molluscs to deep-sea hydrothermal vents.

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In recent years, we and others have identified a number of enhancers that, when incorporated into rAAV vectors, can restrict the transgene expression to particular neuronal populations. Yet, viral tools to access and manipulate fine neuronal subtypes are still limited. Here, we performed systematic analysis of single cell genomic data to identify enhancer candidates for each of the cortical interneuron subtypes. We established a set of enhancer-AAV tools that are highly specific for distinct cortical interneuron populations and striatal cholinergic neurons. These enhancers, when used in the context of different effectors, can target (fluorescent proteins), observe activity (GCaMP) and manipulate (opto- or chemo-genetics) specific neuronal subtypes. We also validated our enhancer-AAV tools across species. Thus, we provide the field with a powerful set of tools to study neural circuits and functions and to develop precise and targeted therapy.

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Major depressive disorder (MDD) with childhood trauma represents a heterogeneous clinical subtype of depression. Previous research has observed alterations in the reward circuitry centered around the nucleus accumbens (NAc) in MDD patients. However, limited investigations have focused on aberrant functional connectivity (FC) within NAc subregions among MDD with childhood trauma. Thus, this study adopts analyses of both static FC (sFC) and dynamic FC (dFC) to examine neurobiological changes in MDD with childhood trauma. The bilateral nucleus accumbens shell (NAc-shell) and nucleus accumbens core (NAc-core) were selected as the seeds. Four participant groups were included: MDD with childhood trauma (n = 48), MDD without childhood trauma (n = 30), healthy controls (HCs) with childhood trauma (n = 57), and HCs without childhood trauma (n = 46). Our findings revealed both abnormal sFC and dFC between NAc-shell and NAc-core and regions including the middle occipital gyrus (MOG), anterior cingulate cortex, and inferior frontal gyrus in MDD with childhood trauma. Furthermore, a significant correlation was identified between the dFC of the left NAc-shell and the right MOG in relation to childhood trauma. Additionally, abnormal dFC moderated the link between childhood abuse and depression severity. These outcomes shed light on the neurobiological underpinnings of MDD with childhood trauma.

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Efficiently mining and identification of new compounds from the extensive MS/MS datasets of plant extracts poses a significant challenge due to the structural diversity and compositional complexity inherent in natural products (NPs). Various data post-processing techniques have been developed to simplify the interpretation of MS/MS data; however, they often suffer from limited specificity and precision. Meanwhile, structure annotation following data post-processing is particularly time-consuming. In this study, we introduced an innovative strategy named MS-SMART, which integrates three intelligent algorithms: automatic mining of diagnostic ions, rapid filtration of alkaloids from untargeted MS/MS data, and structural recommendations for filtered components. The feasibility of this approach for rapidly discovering novel compounds was demonstrated using berberine-type alkaloids as an example. Firstly, diagnostic ions were automatically extracted and validated using available reference data. Subsequently, berberine-type compounds were filtered from raw MS/MS data. Finally, the structures of the target components were recommended using building blocks derived from berberines reported in various plants. A total of 103, 198, 60, 80 and 51 berberines were efficiently identified in diverse families and genera, including Stephaniae Epigaeae Radix, Coptidis Rhizoma, Phellodendri Chinensis Cortex, Phellodendri Amurensis Cortex and Corydalis Decumbentis Rhizoma, with 99, 169, 50, 64 and 40 new compounds identified, respectively. Among these, 8, 14, 8, 7 and 12 berberines were confirmed by reference compounds. This strategy provides a new research paradigm for the rapid discovery and identification of different types of new compounds in complex samples.

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In recent years, low-dimensional organic-inorganic hybrid metal halides have garnered significant attention for optoelectronic applications due to their exceptional photophysical properties, despite their persistent challenge of low stability. Addressing this challenge, our study introduces 1-[5-(trifluoromethyl)pyridin-2-yl]piperazinium (TFPP) as a cation, harvesting a novel one-dimensional hybrid cadmium-based halide semiconductor (TFPP)CdCl4, which exhibits intense blue-light emission upon UV excitation. Additionally, (TFPP)CdCl4 demonstrates a high scintillation performance under X-ray excitation, producing 16600 ± 500 photons MeV-1 and achieving a low detection limit of 0.891 µGyair s-1. Notably, (TFPP)CdCl4 showcases remarkable stability against water, intense light sources, heating, and corrosive environments, positioning it as a promising candidate for optoelectronic applications. Through a blend of experimental techniques and theoretical analyses, including density functional theory calculations, we elucidate the unique photophysical properties and structural stability of (TFPP)CdCl4. These findings significantly contribute to the understanding of low-dimensional hybrid halide semiconductors, offering valuable insights into their potential application in advanced optoelectronic devices and paving the way for further research in this field.

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Accurate and early diagnosis of monkeypox virus (MPXV) is crucial for controlling epidemics and treating affected individuals promptly. This study aimed to assess the analytical and clinical performance of the MolecisionTM Monkeypox Virus qPCR Assay, Biorain Monkeypox Virus ddPCR Assay, and MAGLUMI® Monkeypox Virus Ag (chemiluminescence immunoassay, CLIA) Assay. Additionally, it aimed to compare the clinical application of antigen and nucleic acid assays to offer insights into using commercial monkeypox assay kits. Specimens from 117 clinical patients, serial diluted virus cell culture supernatant, and artificially created positive samples were tested to evaluate the performance of these assay kits for MPXV diagnostics. The Biorain Monkeypox Virus ddPCR Assay had a limit of detection (LoD) of 3.89 CCID50/mL, while the MolecisionTM Monkeypox Virus qPCR Assay had an LoD of 15.55 CCID50/mL. The MAGLUMI® Monkeypox Virus Ag (CLIA) Assay had an LoD of 0.500 pg/mL. The accuracy of the MolecisionTM Monkeypox Virus qPCR Assay was comparable to the Biorain Monkeypox Virus ddPCR Assay, and the MAGLUMI® Monkeypox Virus Ag (CLIA) Assay demonstrated high sensitivity. The specificity of all three MPXV diagnostic assays for clinical specimens with potential cross-reacting substances was 100%. In conclusion, this study provides valuable insights into the clinical application of monkeypox assays, supporting efforts to mitigate and control the spread of monkeypox.

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Aiming at the further extension of the application scope of traditional molecular muscles, a novel bispyrene-functionalized chiral molecular [c2]daisy chain was designed and synthesized. Taking advantage of the unique dimeric interlocked structure of molecular [c2]daisy chain, the resultant chiral molecular muscle emits strong circularly polarized luminescence (CPL) attributed to the pyrene excimer with a high dissymmetry factor (glum) value of 0.010. More importantly, along with the solvent- or anion- induced motions of the chiral molecular muscle, the precise regulation of the pyrene stacking within its skeleton results in the switching towards either "inversed" state with sign inversion and larger glum values or "down" state with maintained handedness and smaller glum values, making it a novel multistate CPL switch. As the first example of chiral molecular muscle-based CPL switch, this proof-of-concept study not only successfully widens the application scopes of molecular muscles, but also provides a promising platform for the construction of novel smart chiral luminescent materials for practical applications.