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Abstract Micro RNAs (miRs) have been implicated in various tumorigenic processes. Osteosarcoma (OS) is a primary bone malignancy seen in adolescents. However, the mechanism of miRs in OS has not been fully demonstrated yet. Here, miR-134-5p was found to inhibit OS progression and was also expressed at significantly lower levels in OS tissues and cells relative to normal controls. miR-134-5p was found to reduce vasculogenic mimicry, proliferation, invasion, and migration of OS cells, with miR-134-5p knockdown having the opposite effects. Mechanistically, miR-134-5p inhibited expression of the ITGB1/MMP2/PI3K/Akt axis, thus reducing the malignant features of OS cells. In summary, miR-134-5p reduced OS tumorigenesis by modulation of the ITGB1/MMP2/PI3K/Akt axis, suggesting the potential for using miR-134-5p as a target for treating OS.

Abstract The thermal Hall effect has emerged as a potential probe of exotic excitations in spin liquids. In the Kitaev magnet $${{\alpha }}$$ α -RuCl3, the thermal Hall conductivity $${{{\kappa }}}_{{{xy}}}$$ κ x y has been attributed to Majorana fermions, chiral magnons, or phonons. Theoretically, the former two types of heat carriers can generate a “planar” $${{{\kappa }}}_{{{xy}}}$$ κ x y , whereby the magnetic field is parallel to the heat current, but it is unknown whether phonons also could. Here we show that a planar $${{{\kappa }}}_{{{xy}}}$$ κ x y is present in another Kitaev candidate material, Na2Co2TeO6. Based on the striking similarity between $${{{\kappa }}}_{{{xy}}}$$ κ x y and the phonon-dominated thermal conductivity $${{{\kappa }}}_{{{xx}}}$$ κ x x , we attribute the effect to phonons. We observe a large difference in $${{{\kappa }}}_{{{xy}}}$$ κ x y between different configurations of heat current and magnetic field, which reveals that the direction of heat current matters in determining the planar $${{{\kappa }}}_{{{xy}}}$$ κ x y . Our observation calls for a re-evaluation of the planar $${{{\kappa }}}_{{{xy}}}$$ κ x y observed in $$\,{{\alpha }}$$ α -RuCl3.

Abstract Bloch oscillations (BOs), an important transport phenomenon, have been studied extensively in static systems but remain mysterious in Floquet systems. Here, by harnessing notions from photonic analogy, we propose a generalization of the existing BOs in photonic Floquet lattices, namely the “photonic Floquet–Bloch oscillations”, which refer to rescaled photonic Bloch oscillations with a period of extended least common multiple of the modulation period and the Bloch oscillation period. Next, we report the first visual observation of such photonic Floquet–Bloch oscillations (FBOs) by employing waveguide fluorescence microscopy. Most significantly, the FBOs surpass the existing BOs in Floquet systems and exhibit exotic properties on their own, including fractal spectrum and fractional Floquet tunneling. This new transport mechanism offers an intriguing method of wave manipulation that may contribute to rapidly developing fields in photonics, condensed matter physics, and quantum physics.

Abstract Background Neoadjuvant therapy followed by surgery has become the standard of care for locally advanced esophageal squamous cell carcinoma (ESCC) and accurate pathological response assessment is critical to assess the therapeutic efficacy. However, it can be laborious and inconsistency between different observers may occur. Hence, we aim to develop an interpretable deep-learning model for efficient pathological response assessment following neoadjuvant therapy in ESCC. Methods This retrospective study analyzed 337 ESCC resection specimens from 2020–2021 at the Pudong-Branch (Cohort 1) and 114 from 2021–2022 at the Puxi-Branch (External Cohort 2) of Fudan University Shanghai Cancer Center. Whole slide images (WSIs) from these two cohorts were generated using different scanning machines to test the ability of the model in handling color variations. Four pathologists independently assessed the pathological response. The senior pathologists annotated tumor beds and residual tumor percentages on WSIs to determine consensus labels. Furthermore, 1850 image patches were randomly extracted from Cohort 1 WSIs and binarily classified for tumor viability. A deep-learning model employing knowledge distillation was developed to automatically classify positive patches for each WSI and estimate the viable residual tumor percentages. Spatial heatmaps were output for model explanations and visualizations. Results The approach achieved high concordance with pathologist consensus, with an R^2 of 0.8437, a RAcc_0.1 of 0.7586, a RAcc_0.3 of 0.9885, which were comparable to two senior pathologists (R^2 of 0.9202/0.9619, RAcc_0.1 of 8506/0.9425, RAcc_0.3 of 1.000/1.000) and surpassing two junior pathologists (R^2 of 0.5592/0.5474, RAcc_0.1 of 0.5287/0.5287, RAcc_0.3 of 0.9080/0.9310). Visualizations enabled the localization of residual viable tumor to augment microscopic assessment. Conclusion This work illustrates deep learning's potential for assisting pathological response assessment. Spatial heatmaps and patch examples provide intuitive explanations of model predictions, engendering clinical trust and adoption (Code and data will be available at https://github.com/WinnieLaugh/ESCC_Percentage once the paper has been conditionally accepted). Integrating interpretable computational pathology could help enhance the efficiency and consistency of tumor response assessment and empower precise oncology treatment decisions.

Abstract Mounting data hints that the gut microbiota's role may be pivotal in understanding the emergence of psoriasis. However, discerning a direct causal link is yet elusive. In this exploration, we adopted a Mendelian randomization (MR) strategy to probe the prospective causal interplay between the gut's microbial landscape and the predisposition to psoriasis. Genetic markers acting as instrumental variables for gut microbiota were extrapolated from a genome-wide association study (GWAS) encompassing 18,340 individuals. A separate GWAS yielded summary data for psoriasis, which covered 337,159 patients and 433,201 control subjects. The primary analysis hinged on inverse variance weighting (IVW). Additional methods like the weighted median approach and MR-Egger regression were employed to validate the integrity of our findings. Intriguing correlations emerged between psoriasis risk and eight specific bacterial traits. To illustrate: Mollicutes presented an odds ratio (OR) of 1.003 with a 95% confidence interval (CI) spanning 1.001–1.005 (p = 0.016), while the family. Victivallaceae revealed an OR of 0.998 with CI values between 0.997 and 0.999 (p = 0.023). Eubacterium (coprostanoligenes group) revealed an OR of 0.997 with CI values between 0.994 and 0.999 (p = 0.027). Eubacterium (fissicatena group) revealed an OR of 0.997 with CI values between 0.996 and 0.999 (p = 0.005). Holdemania revealed an OR of 1.001 with CI values 1–1.003 (p = 0.034). Lachnospiraceae (NK4A136 group) revealed an OR of 0.997 with CI values between 0.995 and 0.999 (p = 0.046). Lactococcus revealed an OR of 0.998 with CI values between 0.996 and 0.999 (p = 0.008). Tenericutes revealed an OR of 1.003 with CI values between 1.001 and 1.006 (p = 0.016). Sensitivity analysis for these bacterial features yielded congruent outcomes, reinforcing statistically significant ties between the eight bacterial entities and psoriasis. This comprehensive probe underscores emerging evidence pointing towards a plausible causal nexus between diverse gut microbiota and the onset of psoriasis. It beckons further research to unravel the intricacies of how the gut's microbial constituents might sway psoriasis's pathogenesis.

Abstract The stress measurements determined by both the overcoring (OC) and hydraulic fracturing (HF) methods in the Shuichang iron mine and Sanshandao gold mine were compared and evaluated, respectively. The results indicate that the independent OC and HF data in the two mines reveal the same dominant faulting stress regime. The σ H orientations derived from the OC and HF methods in the Shuichang iron mine are dominantly oriented in the N81.1°W–N89.4°W and N77.0°E–N88.0°E, respectively, and the σ H orientations yielded from the OC and HF techniques in the Sanshandao gold mine are predominantly in the N30°W–N90°W and N55.5°W–N60.4°W, respectively; hence, the σ H orientations obtained by the two different methods in the two mines are comparatively similar. In addition, the shapes of the probability density diagrams using an improved Bayesian regression approach of the three principal stresses measured by the OC and HF methods in the same mine are quite similar, and all the obtained Kolmogorov–Smirnov test p-values are larger than the selected significance level of 0.01, indicating that the stress data interpreted by the two methods approximately follow the same distribution law. Thus, the performance of the two techniques and the reliability of the measured data are satisfactory.

Abstract Background Predicting patient mortality risk facilitates early intervention in intensive care unit (ICU) patients at greater risk of disease progression. This study applies machine learning methods to multidimensional clinical data to dynamically predict mortality risk in ICU patients. Methods A total of 33,798 patients in the MIMIC-III database were collected. An integrated model NIMRF (Network Integrating Memory Module and Random Forest) based on multidimensional variables such as vital sign variables and laboratory variables was developed to predict the risk of death for ICU patients in four non overlapping time windows of 0–1 h, 1–3 h, 3–6 h, and 6–12 h. Mortality risk in four nonoverlapping time windows of 12 h was externally validated on data from 889 patients in the respiratory critical care unit of the Chinese PLA General Hospital and compared with LSTM, random forest and time-dependent cox regression model (survival analysis) methods. We also interpret the developed model to obtain important factors for predicting mortality risk across time windows. The code can be found in https://github.com/wyuexiao/NIMRF . Results The NIMRF model developed in this study could predict the risk of death in four nonoverlapping time windows (0–1 h, 1–3 h, 3–6 h, 6–12 h) after any time point in ICU patients, and in internal data validation, it is suggested that the model is more accurate than LSTM, random forest prediction and time-dependent cox regression model (area under receiver operating characteristic curve, or AUC, 0–1 h: 0.8015 [95% CI 0.7725–0.8304] vs. 0.7144 [95%] CI 0.6824–0.7464] vs. 0.7606 [95% CI 0.7300–0.7913] vs 0.3867 [95% CI 0.3573–0.4161]; 1–3 h: 0.7100 [95% CI 0.6777–0.7423] vs. 0.6389 [95% CI 0.6055–0.6723] vs. 0.6992 [95% CI 0.6667–0.7318] vs 0.3854 [95% CI 0.3559–0.4150]; 3–6 h: 0.6760 [95% CI 0.6425–0.7097] vs. 0.5964 [95% CI 0.5622–0.6306] vs. 0.6760 [95% CI 0.6427–0.7099] vs 0.3967 [95% CI 0.3662–0.4271]; 6–12 h: 0.6380 [0.6031–0.6729] vs. 0.6032 [0.5705–0.6406] vs. 0.6055 [0.5682–0.6383] vs 0.4023 [95% CI 0.3709–0.4337]). External validation was performed on the data of patients in the respiratory critical care unit of the Chinese PLA General Hospital. Compared with LSTM, random forest and time-dependent cox regression model, the NIMRF model was still the best, with an AUC of 0.9366 [95% CI 0.9157–0.9575 for predicting death risk in 0–1 h]. The corresponding AUCs of LSTM, random forest and time-dependent cox regression model were 0.9263 [95% CI 0.9039–0.9486], 0.7437 [95% CI 0.7083–0.7791] and 0.2447 [95% CI 0.2202–0.2692], respectively. Interpretation of the model revealed that vital signs (systolic blood pressure, heart rate, diastolic blood pressure, respiratory rate, and body temperature) were highly correlated with events of death. Conclusion Using the NIMRF model can integrate ICU multidimensional variable data, especially vital sign variable data, to accurately predict the death events of ICU patients. These predictions can assist clinicians in choosing more timely and precise treatment methods and interventions and, more importantly, can reduce invasive procedures and save medical costs.

Abstract Background High-grade serous ovarian carcinoma (HGSOC) is the most aggressive and prevalent subtype of ovarian cancer and accounts for a significant portion of ovarian cancer-related deaths worldwide. Despite advancements in cancer treatment, the overall survival rate for HGSOC patients remains low, thus highlighting the urgent need for a deeper understanding of the molecular mechanisms driving tumorigenesis and for identifying potential therapeutic targets. Whole-exome sequencing (WES) has emerged as a powerful tool for identifying somatic mutations and alterations across the entire exome, thus providing valuable insights into the genetic drivers and molecular pathways underlying cancer development and progression. Methods Via the analysis of whole-exome sequencing results of tumor samples from 90 ovarian cancer patients, we compared the mutational landscape of ovarian cancer patients with that of TCGA patients to identify similarities and differences. The sequencing data were subjected to bioinformatics analysis to explore tumor driver genes and their functional roles. Furthermore, we conducted basic medical experiments to validate the results obtained from the bioinformatics analysis. Results Whole-exome sequencing revealed the mutational profile of HGSOC, including BRCA1, BRCA2 and TP53 mutations. AP3S1 emerged as the most weighted tumor driver gene. Further analysis of AP3S1 mutations and expression demonstrated their associations with patient survival and the tumor immune response. AP3S1 knockdown experiments in ovarian cancer cells demonstrated its regulatory role in tumor cell migration and invasion through the TGF-β/SMAD pathway. Conclusion This comprehensive analysis of somatic mutations in HGSOC provides insight into potential therapeutic targets and molecular pathways for targeted interventions. AP3S1 was identified as being a key player in tumor immunity and prognosis, thus providing new perspectives for personalized treatment strategies. The findings of this study contribute to the understanding of HGSOC pathogenesis and provide a foundation for improved outcomes in patients with this aggressive disease.

Abstract Parity detection is essential in quantum error correction. Error syndromes coded in parity are detected routinely by sequential CNOT gates. Here, different from the standard CNOT-gate based scheme, we propose a reliable joint parity measurement (JPM) scheme inspired by stimulated emission. By controlling the collective behavior between data qubits and syndrome qubit, we realize the parity detection and experimentally implement the weight-2 and weight-4 JPM scheme in a tunable coupling superconducting circuit, which shows comparable performance to the CNOT scheme. Moreover, with the aid of the coupling tunability in quantum system, this scheme can be further utilized for specific joint entangling state preparation (JEP) with high fidelity, such as multiqubit entangled state preparation for non-adjacent qubits. This strategy, combined with the superconducting qubit system with tunable couplers, reveals tremendous potential and applications in the surface code architecture without adding extra circuit elements. Besides, the method we develop here can readily be applied in large-scale quantum computation and quantum simulation.

Abstract The partitioning behavior of platinum group elements in magmas is critical for their use as tracers of planetary accretion and in understanding magmatic sulfide deposits. Here we use laboratory experiments to determine sulfide liquid–silicate melt partition coefficients for platinum and palladium at 1.5 GPa, 1400 °C, and oxygen fugacity 1.5–2 log units above the fayalite–magnetite–quartz buffer. We find that the partitioning coefficients of these elements are 2.3 × 105 to 1.1 × 106 and are independent of the platinum and palladium concentration in the system. Combined with previous data obtained at oxygen fugacity below the fayalite–magnetite–quartz buffer, this indicates redox-controlled partitioning behavior whereby at oxidizing conditions platinum- and palladium-enrichments are achieved through their dissolution in sulfide liquids, while at reducing conditions the entrapment of platinum- and palladium-rich clusters in sulfide liquids is more critical. This redox-controlled partitioning behavior should be considered when studying crust–mantle differentiation and the formation of magmatic sulfide deposits.

Euryodendron excelsum H. T. Chang, a rare and endangered evergreen tree that is endemic to China. The micropropagation system of this species has been established, but some challenges associated with in vitro rooting remained to be improved. In this study, the in vitro rooting of E. excelsum plantlets were optimized by dark exposure, and the network of gene expression and endogenous hormones levels during dark-induced adventitious root (AR) formation were revealed. AR formation of E. excelsum plantlets were significantly promoted by dark exposure, especially by dark exposure for 15 d. In the stems of E. excelsum plantlets under the treatment of dark exposure for 15 d, lower level of abscisic acid (ABA), gibberellic acid 1 (GA1), isopentenyladenine (IP), isopentenyladenosine (IPA) and zeatin (ZT), as well as higher level of GA7, jasmonic acid (JA) and salicylic acid (SA), promoted the whole course of AR formation. The higher level of trans-zeatin riboside (TZR) and T-zeatin (TZT) promoted the elongation of dark-induced AR, while higher level of indole-3-acetic acid (IAA) stimulated the process of AR primordia formation. Differentially expressed genes (DEGs) involved in hormone biosynthesis, plant hormone signal transduction and phenylpropanoid biosynthesis participated in the regulation of dark-induced AR development. The weighted gene co-expression network (WGCNA) analysis identified five modules that had highly correlation with phytohormone contents, and numerous hub genes associated with carotenoid biosynthesis, tryptophan metabolism, zeatin biosynthesis, alpha-Linolenic acid metabolism, phenylalanine metabolism, plant hormone signal transduction and phenylpropanoid biosynthesis were revealed. Those result will provide technical reference for in vitro rooting of woody species, and promote biological conservation and genetic engineering of rare and endangered species.

BackgroundHerpes zoster is more prevalent among the older adult due to the age-related immune decline, leading to significant pain and complications. Although vaccination effectively prevents viral infections, vaccine hesitancy remains a major barrier to achieving high vaccination rates.To address this, we conducted a qualitative survey using Vaccine Hesitancy Determinants Matrix and 5C model to understand and improve vaccination rates in this group.MethodsDescriptive qualitative research design based on the philosophical underpinnings of naturalistic inquiry and purposive sampling methodology was conducted on adults aged 50 and above, as well as community health workers. Data were collected through semi-structured, in-depth personal interviews. The interview outline was constructed following a comprehensive review of the literature and consideration of the theoretical framework.ResultsSeventeen adults over 50 years and four community healthcare workers were included in this study. The study found that information asymmetry in immunization planning was evident at all stages of vaccine supply, dissemination and demand. The main manifestations included limited access to authoritative information, insufficient community awareness of herpes zoster as a route of vaccination, insufficient vocational training, significant gaps in vaccine knowledge, and high levels of complacency among individual residents.ConclusionHerpes zoster vaccine hesitancy is prevalent among middle-aged and older adults in China due to information asymmetry, vaccine complacency, inadequate community services, and other multiple layers of factors. Public health strategies should aim to reduce cognitive biases and information gaps by disseminating diverse and credible vaccine information through social media, medical institutions, and offline channels to promote higher vaccination rates.

Soil salinity, a major environmental stress, restricts agricultural production worldwide. Gynura divaricata (L.) DC. is widely cultivated on tropical islands in China and has both edible and medicinal value. NaCl stress and growth indicators, antioxidant enzyme activity, as well as MDA, proline, and soluble sugar content, were determined. Based on the transcriptomic data of tissue-cultured G. divaricata plantlets grown in control (0 mM NaCl) and salt stress (50 and 200 mM NaCl) conditions, gene expression patterns were examined. KEGG enrichment analysis of differentially expressed genes indicated significant enrichment of plant hormone signaling, MAPK signaling, and starch and sucrose metabolism pathways. These findings allowed key biological pathways and salt stress-responsive genes to be identified, thus providing a molecular basis for breeding salt-tolerant G. divaricata varieties. This transcriptomic analysis revealed a complex tolerance mechanism of G. divaricata in response to NaCl, laying a foundation for screening and cloning key genes related to NaCl tolerance and studying their interactions. These findings would allow the molecular basis of NaCl tolerance to be explored, with the aim of breeding NaCl-tolerant varieties.

Da Chuanxiong Formula (DCXF) is a traditional herbal prescription used for pain management. It consists of Chuanxiong Rhizoma (CR) and Gastrodiae Rhizoma (GR). Despite its long history of use, the underlying therapeutic mechanism of DCXF remains insufficiently understood. Therefore, in this study, key target genes were obtained through network pharmacology research methods and molecular docking techniques, including transient receptor potential vanilloid 1 (TRPV1), adenosine A2a receptor (ADORA2A), nuclear receptor subfamily 3 group C member 1 (NR3C1), and protein kinase C beta (PRKCB). Molecular dynamics simulations demonstrated the favorable binding between all four key genes and their corresponding compounds. Notably, chronic constriction injury (CCI) treatment resulted in a significant decrease in mechanical threshold and thermal latency period for rat foot contraction, which was ameliorated upon administration of DCXF. Furthermore, real-time quantitative reverse transcription PCR (RT-qPCR) and western blot (WB) analyses indicated an upregulation of TRPV1, ADORA2A, NR3C1, and PRKCB expression in the rat dorsal root ganglion following CCI, which was attenuated by treatment with DCXF. The expressions of inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6), in the rat dorsal root ganglion were assessed using ELISA, confirming consistent trends with the aforementioned findings. The results of this study offer a promising theoretical foundation for the utilization of DCXF in the treatment of neuropathic pain (NP).

Radiation therapy for cancer treatment brings about a series of radiation injuries to normal tissues. In recent years, the discovery of copper-regulated cell death, cuproptosis, a novel form of programmed cell death, has attracted widespread attention and exploration in various biological functions and pathological mechanisms of copper metabolism and cuproptosis. Understanding its role in the process of radiation injury may open up new avenues and directions for exploration in radiation biology and radiation oncology, thereby improving tumor response and mitigating adverse reactions to radiotherapy. This review provides an overview of copper metabolism, the characteristics of cuproptosis, and their potential regulatory mechanisms in radiation injury.

IntroductionOsimertinib, a third-generation EGFR-TKI, is known for its high efficacy against brain metastases (BM) in non-small cell lung cancer (NSCLC) due to its ability to penetrate the blood–brain barrier. This study aims to evaluate the use of brain MRI radiomics in predicting the intracranial efficacy to osimertinib in NSCLC patients with BM.Materials and methodsThis study analyzed 115 brain metastases from NSCLC patients with the EGFR-T790M mutation treated with second-line osimertinib. The primary endpoint was intracranial response, and the secondary endpoint was intracranial progression-free survival (iPFS). We performed tumor delineation, image preprocessing, and radiomics feature extraction. Using a 5-fold cross-validation strategy, we built radiomic models with eight feature selectors and eight machine learning classifiers. The models’ performance was evaluated by the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis.ResultsThe dataset of 115 brain metastases was divided into training and validation sets in a 7:3 ratio. The radiomic model utilizing the mRMR feature selector and stepwise logistic regression classifier showed the highest predictive accuracy, with AUCs of 0.879 for the training cohort and 0.786 for the validation cohort. This model outperformed a clinical-MRI morphological model, which included age, ring enhancement, and peritumoral edema (AUC: 0.794 for the training cohort and 0.697 for the validation cohort). The radiomic model also showed strong performance in calibration and decision curve analyses. Using a radiomic-score threshold of 199, patients were classified into two groups with significantly different median iPFS (3.0 months vs. 15.4 months, p

BackgroundAlpha-synuclein oligomers (o-α-syn) are pivotal in the pathogenesis of α-synucleinopathy. Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) serves as an early indicator of the disease, offering insights into disease mechanisms and early intervention. Nevertheless, the diagnostic and predictive potential of o-α-syn in iRBD remains largely unexplored. This study aimed to evaluate the plasma levels of o-α-syn in patients and investigate their utility as biomarkers for diagnosis of and predicting phenoconversion in iRBD.MethodsA total of 143 participants, including 77 polysomnography-confirmed iRBD patients and 66 normal controls (NC), were recruited for this longitudinal observational study. Baseline clinical assessments and plasma collection were conducted for all iRBD patients, with 72 of them undergoing regularly prospective follow-up assessments for parkinsonism or dementia. Plasma levels of o-α-syn were quantified using enzyme-linked immunosorbent assay, and were compared between groups using a general linear model adjusted for age and sex. The diagnostic performance of plasma o-α-syn in iRBD was evaluated by area under the receiver operating characteristic curve (AUC) with 95% CI. Cox regression analysis and Kaplan–Meier survival curves were employed to assess the predictive value of plasma o-α-syn for phenoconversion in iRBD.ResultsPlasma o-α-syn levels did not exhibit statistically significant differences among iRBD converter patients, iRBD nonconverter patients, and NC. The AUC for distinguishing NC from iRBD was 0.52 (95% CI: 0.42–0.62, p = 0.682). Spearman correlation analysis revealed a significant positive correlation between plasma o-α-syn levels and MOCA scores in the iRBD group (p

Abstract SH2B1 mutations are associated with obesity, type 2 diabetes, and metabolic dysfunction‐associated steatotic liver disease (MASLD) in humans. Global deletion of Sh2b1 results in severe obesity, type 2 diabetes, and MASLD in mice. Neuron‐specific restoration of SH2B1 rescues the obesity phenotype of Sh2b1‐null mice, indicating that the brain is a main SH2B1 target. However, SH2B1 neurocircuits remain elusive. SH2B1‐expressing neurons in the paraventricular hypothalamus (PVHSH2B1) and a PVHSH2B1→dorsal raphe nucleus (DRN) neurocircuit are identified here. PVHSH2B1 axons monosynaptically innervate DRN neurons. Optogenetic stimulation of PVHSH2B1 axonal fibers in the DRN suppresses food intake. Chronic inhibition of PVHSH2B1 neurons causes obesity. In male and female mice, either embryonic‐onset or adult‐onset deletion of Sh2b1 in PVH neurons causes energy imbalance, obesity, insulin resistance, glucose intolerance, and MASLD. Ablation of Sh2b1 in the DRN‐projecting PVHSH2B1 subpopulation also causes energy imbalance, obesity, and metabolic disorders. Conversely, SH2B1 overexpression in either total or DRN‐projecting PVHSH2B1 neurons protects against diet‐induced obesity. SH2B1 binds to TrkB and enhances brain‐derived neurotrophic factor (BDNF) signaling. Ablation of Sh2b1 in PVHSH2B1 neurons induces BDNF resistance in the PVH, contributing to obesity. In conclusion, these results unveil a previously unrecognized PVHSH2B1→DRN neurocircuit through which SH2B1 defends against obesity by enhancing BDNF/TrkB signaling.

BackgroundInflammatory Bowel Diseases (IBDs), encompassing Ulcerative Colitis (UC) and Crohn’s Disease (CD), are chronic, recurrent inflammatory conditions of the gastrointestinal tract. The microRNA (miRNA) -mRNA regulatory network is pivotal in the initiation and progression of IBDs. Although individual studies provide valuable insights into miRNA mechanisms in IBDs, they often have limited scope due to constraints in population diversity, sample size, sequencing platform variability, batch effects, and potential researcher bias. Our study aimed to construct comprehensive miRNA-mRNA regulatory networks and determine the cellular sources and functions of key miRNAs in IBD pathogenesis.MethodsTo minimize potential bias from individual studies, we utilized a text mining-based approach on published scientific literature from PubMed and PMC databases to identify miRNAs and mRNAs associated with IBDs and their subtypes. We constructed miRNA-mRNA regulatory networks by integrating both predicted and experimentally validated results from DIANA, Targetscan, PicTar, Miranda, miRDB, and miRTarBase (all of which are databases for miRNA target annotation). The functions of miRNAs were determined through gene enrichment analysis of their target mRNAs. Additionally, we used two large-scale single-cell RNA sequencing datasets to identify the cellular sources of miRNAs and the association of their expression levels with clinical status, molecular and functional alternation in CD and UC.ResultsOur analysis systematically summarized IBD-related genes using text-mining methodologies. We constructed three comprehensive miRNA-mRNA regulatory networks specific to IBD, CD, and UC. Through cross-analysis with two large-scale scRNA-seq datasets, we determined the cellular sources of the identified miRNAs. Despite originating from different cell types, hsa-miR-142, hsa-miR-145, and hsa-miR-146a were common to both CD and UC. Notably, hsa-miR-145 was identified as myofibroblast-specific in both CD and UC. Furthermore, we found that higher tissue repair and enhanced glucose and lipid metabolism were associated with hsa-miR-145 in myofibroblasts in both CD and UC contexts.ConclusionThis comprehensive approach revealed common and distinct miRNA-mRNA regulatory networks in CD and UC, identified cell-specific miRNA expressions (notably hsa-miR-145 in myofibroblasts), and linked miRNA expression to functional alterations in IBD. These findings not only enhance our understanding of IBD pathogenesis but also offer promising diagnostic biomarkers and therapeutic targets for clinical practice in managing IBDs.

Optically spatial displacement and material modification hold great potential for the appealing applications in nanofabrication and reconfiguration of functional optical devices. Here, we propose and demonstrate a scheme to achieve simultaneous deformation and phase change in vanadium dioxide (VO2)/Si3N4/Au hybrid nanostructures by laser stimuli. Low triggering threshold and significant deformation characteristics of VO2, based on controllable phase transition, are demonstrated in microscale cantilevers. The plasmonic properties of the nanostructure array are further utilized to achieve a polarization-selective dynamic response. The persistence of deformation and dynamical optical modulation are further demonstrated. Such high-precision fabrication methods and non-contact reconfiguration methods are useful for future applications in dynamic optical manipulation.

To investigate the association between heart rate (HR) at diagnosis and long-term pulmonary embolism (PE) recurrence among elderly (≥ 50 year-old) female patients after acute PE (APE). Hospitalized patients with APE were grouped separately according to whether they experienced recurrent PE and whether the HR was

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder that affects the central nervous system (CNS). Neuroinflammation is a crucial factor in the pathological advancement of PD. PD is characterized by the presence of activated microglia and increased levels of proinflammatory factors, which play a crucial role in its pathology. During the immune response of PD, microglia regulation is significantly influenced by microRNA (miRNA). The excessive activation of microglia, persistent neuroinflammation, and abnormal polarization of macrophages in the brain can be attributed to the dysregulation of certain miRNAs. Additionally, there are miRNAs that possess the ability to inhibit neuroinflammation. miRNAs, which are small non-coding epigenetic regulators, have the ability to modulate microglial activity in both normal and abnormal conditions. They also have a significant impact on promoting communication between neurons and microglia.

Abstract Unlike bulky and rigid traditional power systems, 1D fiber batteries possess appealing features such as flexibility and adaptability, which are promising for use in wearable electronic devices. However, the performance and energy density fiber batteries are limited by the contradiction between ionic transfer and robust structure of fiber electrodes. Herein, these problems are addressed via polymer engineering to regulate the microenvironment in electrodes, realizing high‐linear‐capacity thick fiber electrodes with excellent cycling performance. The porosity of the electrodes is regulated using polymer crosslink networks designed with various components, and lithium‐ion transfer is optimized through ether‐abundant polymer chains. Furthermore, reinforced covalent bonding with carbon nanotube networks is established based on the modified functional groups of polymer networks. The multiscale optimizations of the porous structure, ionic transportation, and covalent bonding network enhance the lithium‐ion dynamics property and structural stability. Therefore, ultrahigh linear‐capacity fiber electrodes (17.8 mAh m−1) can be fabricated on a large scale and exhibit excellent stability (92.8% after 800 cycles), demonstrating obvious superiority among the reported fiber electrodes. Moreover, this study highlights the high effectiveness of polymer regulation in fiber electrodes and offers new avenues for designing next‐generation wearable energy‐storage systems.

ABSTRACT Platinum-based chemotherapy failure represents a significant challenge in the management of ovarian cancer (OC) and contributes to disease recurrence and poor prognosis. Recent studies have shed light on the involvement of the gut microbiota in modulating anticancer treatments. However, the precise underlying mechanisms, by which gut microbiota regulates the response to platinum-based therapy, remain unclear. Here, we investigated the role of gut microbiota on the anticancer response of cisplatin and its underlying mechanisms. Our results demonstrate a substantial improvement in the anticancer efficacy of cisplatin following antibiotic-induced perturbation of the gut microbiota in OC-bearing mice. 16S rRNA sequencing showed a pronounced alteration in the composition of the gut microbiome in the cecum contents following exposure to cisplatin. Through metabolomic analysis, we identified distinct metabolic profiles in the antibiotic-treated group, with a notable enrichment of the gut-derived metabolite 3-methylxanthine in antibiotic-treated mice. Next, we employed a strategy combining transcriptome analysis and chemical–protein interaction network databases. We identified metabolites that shared structural similarity with 3-methylxanthine, which interacted with genes enriched in cancer-related pathways. It is identified that 3-methylxanthinesignificantly enhances the effectiveness of cisplatin by promoting apoptosis both in vivo and in vitro. Importantly, through integrative multiomics analyses, we elucidated the mechanistic basis of this enhanced apoptosis, revealing a dopamine receptor D1-dependent pathway mediated by 3-methylxanthine. This study elucidated the mechanism by which gut-derived metabolite 3-methylxanthine mediated cisplatin-induced apoptosis. Our findings highlight the potential translational significance of 3-methylxanthine as a promising adjuvant in conjunction with cisplatin, aiming to improve treatment outcomes for OC patients.IMPORTANCEThe precise correlation between the gut microbiota and the anticancer effect of cisplatin in OC remains inadequately understood. Our investigation has revealed that manipulation of the gut microbiota via the administration of antibiotics amplifies the efficacy of cisplatin through the facilitation of apoptosis in OC-bearing mice. Metabolomic analysis has demonstrated that the cecum content from antibiotic-treated mice exhibits an increase in the levels of 3-methylxanthine, which has been shown to potentially enhance the therapeutic effectiveness of cisplatin by an integrated multiomic analysis. This enhancement appears to be attributable to the promotion of cisplatin-induced apoptosis, with 3-methylxanthine potentially exerting its influence via the dopamine receptor D1-dependent pathway. These findings significantly contribute to our comprehension of the impact of the gut microbiota on the anticancer therapy in OC. Notably, the involvement of 3-methylxanthine suggests its prospective utility as a supplementary component for augmenting treatment outcomes in patients afflicted with ovarian cancer.

Abstract High‐energy blue light is highly detrimental to health as it can penetrate the lens into the retina, potentially causing atrophy or even death of retinal pigment epithelial cells. To prevent the harmful effects of high‐energy blue light on our health, here the preparation of a photoconversion film specifically designed to block high‐energy blue light is reported, which is composed of green‐emissive carbon dots (G‐CDs) with a high photoluminescence quantum yield (PLQY = 95%) dispersed in polyvinyl alcohol (PVA) matrix. Notably, such a film (named as G‐CDs@PVA) not only converts an incident laser light with a short wavelength into a fluorescence with a longer wavelength, but also exhibits concentration‐dependent (0, 10, 20, and 30 wt.%) blue light barrier rate and green‐emissive intensity. With the increase of the concentration of G‐CDs in the film, the blue light barrier rate of the film as well as the maximum intensity of the green emission are also increased. When the concentration of G‐CDs reaches 30 wt.%, the blue light barrier rate of G‐CDs@PVA achieves up to 97%. Furthermore, G‐CDs@PVA film is attached to a blue light‐emitting diode (LED) chip to explore its practical application in the field of blocking blue light damage.

The adult mammalian cardiomyocyte has a limited capacity for self-renewal, which leads to the irreversible heart dysfunction and poses a significant threat to myocardial infarction patients. In the past decades, research efforts have been predominantly concentrated on the cardiomyocyte proliferation and heart regeneration. However, the heart is a complex organ that comprises not only cardiomyocytes but also numerous noncardiomyocyte cells, all playing integral roles in maintaining cardiac function. In addition, cardiomyocytes are exposed to a dynamically changing physical environment that includes oxygen saturation and mechanical forces. Recently, a growing number of studies on myocardial microenvironment in cardiomyocyte proliferation and heart regeneration is ongoing. In this review, we provide an overview of recent advances in myocardial microenvironment, which plays an important role in cardiomyocyte proliferation and heart regeneration.

IntroductionLucerne (Medicago sativa), is a cornerstone of China’s livestock industry, however, due to the backward agronomic strategies and technology, lucerne in China faces cultivation challenges that result in lower productivity and quality than global standards. Therefore, we undertook a meta-analysis to evaluate the impact of five distinct fertilization types on lucerne yield and nutritional quality in various locations in China. The fertilizer practices included manure application, combined mineral fertilizer and manure application (FM), biological fertilizer application, unbalanced application of two or more mineral fertilizer types, and balanced mineral fertilizer application. Furthermore, we investigate influential factors of yield and quality of lucerne under fertilization, including climatic variables (mean annual precipitation, mean annual temperature), initial soil properties (soil organic carbon; total nitrogen, pH), and agronomic factors (seeding rate, harvest frequency, and lucerne stand age).MethodsOur study analyzed 53 published papers to discern the most beneficial fertilizer for enhancing lucerne yield and nutritional quality.Results and discussionThe results showed that the fertilizer practices, on average, significantly improved yield by 31.72% and crude protein content by 11.29%, with FM emerging as the most effective, this is because mineral fertilizers provide available nutrients for lucerne, manure provides essential organic matter for microorganisms and improve soil properties. In addition, the fertilizer practices significantly reduced neutral and acid detergent fiber contents by 6.28% and 8.50%, respectively, while increasing ash content and relative feeding value. Furthermore, climatic variables, soil properties, and planting system factors such as sowing date and harvest frequency significantly affected yield and nutritional quality. The practical implications of our results emphasize the need for balanced and strategic fertilizer application to optimize lucerne production and highlight the potential to adjust cultivation practices according to environmental conditions. Balanced and strategic fertilizer application can simultaneously improve soil properties, enhance soil carbon sequestration, and reduce the emission of greenhouse gases from the soil, which is a vital measure for realizing sustainable agricultural development.

IntroductionImmunotherapy is critical for treating many cancers, and its therapeutic success is linked to the tumor microenvironment. Although anti-angiogenic drugs are used to treat gastric cancer (GC), their efficacy remains limited. Cancer-associated fibroblast (CAF)-targeted therapies complement immunotherapy; however, the lack of CAF-specific markers poses a challenge. Therefore, we developed a CAF angiogenesis prognostic score (CAPS) system to evaluate prognosis and immunotherapy response in patients with GC, aiming to improve patient stratification and treatment efficacy.MethodsWe assessed patient-derived GC CAFs for promoting angiogenesis using EdU, cell cycle, apoptosis, wound healing, and angiogenesis analysis.ResultsWe then identified CAF-angiogenesis-associated differentially-expressed genes, leading to the development of CAPS, which included THBS1, SPARC, EDNRA, and VCAN. We used RT-qPCR to conduct gene-level validation, and eight GEO datasets and the HPA database to validate the CAPS system at the gene and protein levels. Six independent GEO datasets were utilized for validation. Overall survival time was shorter in the high- than the low-CAPS group. Immune microenvironment and immunotherapy response analysis showed that the high-CAPS group had a greater tendency toward immune escape and reduced immunotherapy efficacy than the low-CAPS group.DiscussionCAPS is closely associated with GC prognosis and immunotherapy outcomes. It is therefore an independent predictor of GC prognosis and immunotherapy efficacy.

General anesthesia, as a commonly used medical intervention, has been widely applied during surgical procedures to ensure rapid loss of consciousness and pain relief for patients. However, recent research suggests that general anesthesia may be associated with the occurrence of perioperative neurocognitive disorder (PND). PND is characterized by a decline in cognitive function after surgery, including impairments in attention, memory, learning, and executive functions. With the increasing trend of population aging, the burden of PND on patients and society’s health and economy is becoming more evident. Currently, the clinical consensus tends to believe that peripheral inflammation is involved in the pathogenesis of PND, providing strong support for further investigating the mechanisms and prevention of PND.

BackgroundAccumulating evidence reveals mitochondrial dysfunction exacerbates intestinal barrier dysfunction and inflammation. Despite the growing knowledge of mitochondrial dysfunction and ulcerative colitis (UC), the mechanism of mitochondrial dysfunction in UC remains to be fully explored.MethodsWe integrated 1137 UC colon mucosal samples from 12 multicenter cohorts worldwide to create a normalized compendium. Differentially expressed mitochondria-related genes (DE-MiRGs) in individuals with UC were identified using the “Limma” R package. Unsupervised consensus clustering was utilized to determine the intrinsic subtypes of UC driven by DE-MiRGs. Weighted gene co-expression network analysis was employed to investigate module genes related to UC. Four machine learning algorithms were utilized for screening DE-MiRGs in UC and construct MiRGs diagnostic models. The models were developed utilizing the over-sampled training cohort, followed by validation in both the internal test cohort and the external validation cohort. Immune cell infiltration was assessed using the Xcell and CIBERSORT algorithms, while potential biological mechanisms were explored through GSVA and GSEA algorithms. Hub genes were selected using the PPI network.ResultsThe study identified 108 DE-MiRGs in the colonic mucosa of patients with UC compared to healthy controls, showing significant enrichment in pathways associated with mitochondrial metabolism and inflammation. The MiRGs diagnostic models for UC were constructed based on 17 signature genes identified through various machine learning algorithms, demonstrated excellent predictive capabilities. Utilizing the identified DE-MiRGs from the normalized compendium, 941 patients with UC were stratified into three subtypes characterized by distinct cellular and molecular profiles. Specifically, the metabolic subtype demonstrated enrichment in epithelial cells, the immune-inflamed subtype displayed high enrichment in antigen-presenting cells and pathways related to pro-inflammatory activation, and the transitional subtype exhibited moderate activation across all signaling pathways. Importantly, the immune-inflamed subtype exhibited a stronger correlation with superior response to four biologics: infliximab, ustekinumab, vedolizumab, and golimumab compared to the metabolic subtype.ConclusionThis analysis unveils the interplay between mitochondrial dysfunction and the immune microenvironment in UC, thereby offering novel perspectives on the potential pathogenesis of UC and precision treatment of UC patients, and identifying new therapeutic targets.

Background: Fecal microbiota transplantation (FMT) is recommended for treating patients with recurrent Clostridioides difficile infection (CDI). However, the therapeutic efficacy of FMT in elderly patients with complex medical conditions remains uncertain. The new method of FMT, washed microbiota transplantation (WMT) has been widely used in China to improve the safety of transplantation. Case report: A 94-year-old man with chronic lymphocytic leukemia (CLL) was admitted to our hospital due to recurrent diarrhea persisting for eight months. The patient had experienced multiple relapses of CDI despite receiving standard therapies. He underwent colonic transendoscopic enteral tubing (TET) and subsequently received WMT during the procedure. Following the treatment, no episodes of diarrhea or adverse events were observed, and the patient remained stable over a three-month follow-up period. Conclusion: This case demonstrates the efficacy and safety of WMT in treating elderly patients with CLL. The successful management of this case offers valuable clinical insights into the use of WMT for elderly CDI patients with complex medical conditions. Moreover, this report contributes practical experience regarding the administration of WMT through the colonic TET.

Bladder cancer (BC) is the most common malignancy of the urinary system and often recurs after tumor removal and/or is resistant to chemotherapy. In cancer cells, the activity of the signaling pathway changes significantly, affecting a wide range of cell activities from growth and proliferation to apoptosis, invasion and metastasis. Nrf2 is a transcription factor that plays an important role in cellular defense responses to a variety of cellular stresses. There is increasing evidence that Nrf2 acts as a tumor driver and that it is involved in the maintenance of malignant cell phenotypes. Abnormal expression of Nrf2 has been found to be common in a variety of tumors, including bladder cancer. Over-activation of Nrf2 can lead to DNA damage and the development of bladder cancer, and is also associated with various pathological phenomena of bladder cancer, such as metastasis, angiogenesis, and reduced toxicity and efficacy of therapeutic anticancer drugs to provide cell protection for cancer cells. However, the above process can be effectively inhibited or reversed by inhibiting Nrf2. Therefore, Nrf2 signaling may be a potential targeting pathway for bladder cancer. In this review, we will characterize this signaling pathway and summarize the effects of Nrf2 and crosstalk with other signaling pathways on bladder cancer progression. The focus will be on the impact of Nrf2 activation on bladder cancer progression and current therapeutic strategies aimed at blocking the effects of Nrf2. To better determine how to promote new chemotherapy agents, develop new therapeutic agents, and potential therapeutic targets.

In this study, we investigate the enhancement of effective transconductance and gain linearity in submicrometer gate AlGaN-barrier-based transistors utilizing ScAlN/GaN coupling-channel structures. A novel asymmetric gate design, incorporating an AlGaN cap on ScAlN/GaN HEMT, is proposed. This configuration demonstrates a flat transconductance profile and significantly reduced transconductance derivative, thereby improving the linearity of GaN-based transistors. For transistors with a gate length of 0.5 μm, both the current gain cut-off frequency and power gain cut-off frequency are measured at 53.52 GHz and 72.98 GHz, respectively. These values represent a more than threefold increase from the corresponding frequencies of conventional devices. Moreover, the theoretical Output Third-Order Intercept value of the proposed structure has increased by 7.5 dBm compared to conventional HEMTs. This superior linear performance can be attributed to the combined effect of AlGaN cap layer and air cavity. Furthermore, the introduction of the ScAlN layer results in a substantial impact, including a decrease in electron concentration from 4.96 × 1019/cm3 to 1.98 × 1019/cm3 and an increase in electron velocity from 4.5 × 107 to 7.6 × 108 cm/s. These findings underscore the potential of the proposed device for high-frequency applications requiring superior linearity.

Background and objective As a new technique developed in recent years, bronchoscopic intervention therapy has the advantages of minimal invasion, high safety and repeatability. The aim of this study is to investigate the clinical characteristics of bronchopleural fistula (BPF) induced by surgeries for lung malignancies or benign diseases and the effect of bronchoscopic intervention therapy for BPF, so as to provide support for prevention and treatment of BPF. Methods Data 64 patients with BPF who were treated by bronchoscopic intervention in Respiratory Disease Center of Dongzhimen Hospital, Beijing University of Chinese Medicine from June 2020 to September 2023 were collected. Patients with fistula diameter ≤5 mm were underwent submucous injection of macrogol, combined with blocking therapy with N-butyl cyanoacrylate, medical bioprotein glue or silicone prosthesis. Patients with fistula diameter >5 mm were implanted with different stents and cardiac occluders. Locations and characteristics of fistulas were summarized, meanwhile, data including Karnofsky performance status (KPS), shortbreath scale (SS), body temperature, pleural drainage volume and white blood cell count before and after operation were observed. Results For all 64 patients, 96 anatomic lung resections including pneumonectomy, lobectomy and segmentectomy were executed and 74 fistulas occurred in 65 fistula locations. The proportion of fistula in the right lung (63.5%) was significantly higher than that in the left (36.5%). Besides, the right inferior lobar bronchial fistula was the most common (40.5%). After operation, KPS was significantly increased, while SS, body temperature, pleural drainage volume and white blood cell count were significantly decreased compared to the preoperative values (P

Abstract Objective This study aimed to explore the association between slow‐wave sleep and the progression of motor and nonmotor symptoms in patients with PD. Methods Data were collected from the Parkinson's Progression Markers Initiative study. Slow‐wave sleep, also known as deep non‐rapid eye movement (DNREM) sleep, was objectively assessed using the Verily Study Watch. Motor function was assessed using the Movement Disorder Society‐Unified Parkinson's Disease Rating Scale Part III score, Hoehn and Yahr stage, freezing of gait, motor fluctuations, and dyskinesia severity. Comprehensive assessments were conducted on nonmotor symptoms, including depression, anxiety, global cognitive function, and autonomic dysfunction. Statistical analyses involved repeated‐measures analysis of variance and linear regression. Results A total of 102 patients with PD were included in the study, with a median follow‐up duration of 3.4 years. In the long DNREM sleep duration group (n = 55), better motor function (DNREM × time interaction: F(1,100) = 4.866, p = 0.030), less severe sexual dysfunction (p = 0.026), and improved activities of daily living (p = 0.033) were observed at the last follow‐up visit compared with the short DNREM sleep duration group (n = 47). Reduced DNREM sleep duration is a risk factor for motor progression (β = −0.251, p = 0.021; 95% confidence interval = −0.465 to −0.038). Interpretation The findings suggest an association between longer DNREM sleep duration and slower motor and nonmotor progression in patients with PD.

Abstract Background To explore whether SARS-CoV-2 infection affects the pregnancy outcomes of assisted reproductive techniques (ART). Methods A prospective cohort study recruited patients for embryo transfer from December 01, 2022, to December 31, 2022. All patients were closely followed up for SARS-CoV-2 infection after embryo transfer. The SARS-CoV-2 “diagnosed group” was defined as RNA or antigen-positive. The SARS-CoV-2 “suspected infection group” was defined as having apparent SARS-CoV-2 symptoms without an RNA or antigen test, while the “uninfected group” was defined as having a negative SARS-CoV-2 RNA or antigen test and no SARS-CoV-2 symptoms. Results A total of 1330 patients participated in the study, 687 of whom were in the SARS-CoV-2 diagnosed group, 219 in the suspected infection group, and 424 in the uninfected group. There was no significant difference in basic characteristics among the three groups. The clinical pregnancy rate was 68% in the SARS-CoV-2 diagnosed group, 63% in the uninfected group, and 51% in the suspected infection group (P

Abstract Observational studies have previously reported an association between depression and certain female reproductive disorders. However, the causal relationships between depression and different types of female reproductive disorders remain unclear in terms of direction and magnitude. We conducted a comprehensive investigation using a two-sample bi-directional Mendelian randomization analysis, incorporating publicly available GWAS summary statistics. Our aim was to establish a causal relationship between genetically predicted depression and the risk of various female reproductive pathological conditions, such as ovarian dysfunction, polycystic ovary syndrome(PCOS), ovarian cysts, abnormal uterine and vaginal bleeding(AUB), endometriosis, leiomyoma of the uterus, female infertility, spontaneous abortion, eclampsia, pregnancy hypertension, gestational diabetes, excessive vomiting in pregnancy, cervical cancer, and uterine/endometrial cancer. We analyzed a substantial sample size, ranging from 111,831 to 210,870 individuals, and employed robust statistical methods, including inverse variance weighted, MR-Egger, weighted median, and MR-PRESSO, to estimate causal effects. Sensitivity analyses, such as Cochran's Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and funnel plots, were also conducted to ensure the validity of our results. Furthermore, risk factor analyses were performed to investigate potential mediators associated with these observed relationships. Our results demonstrated that genetic predisposition to depression or dysthymia was associated with an increased risk of developing PCOS (OR = 1.43, 95% CI 1.28–1.59; P = 6.66 × 10–11), ovarian cysts (OR = 1.36, 95% CI 1.20–1.55; P = 1.57 × 10–6), AUB (OR = 1.41, 95% CI 1.20–1.66; P = 3.01 × 10–5), and endometriosis (OR = 1.43, 95% CI 1.27–1.70; P = 2.21 × 10–7) after Bonferroni correction, but no evidence for reverse causality. Our study did not find any evidence supporting a causal or reverse causal relationship between depression/dysthymia and other types of female reproductive disorders. In summary, our study provides evidence for a causal relationship between genetically predicted depression and specific types of female reproductive disorders. Our findings emphasize the importance of depression management in the prevention and treatment of female reproductive disorders, notably including PCOS, ovarian cysts, AUB, and endometriosis.

Canopy temperature strongly influences crop yield formation and is closely related to plant physiological traits. However, the effects of nitrogen treatment on canopy temperature and rice growth have yet to be comprehensively examined. We conducted a two-year field experiment with three rice varieties (HD-5, NJ-9108, and YJ-805) and three nitrogen treatments (zero-N control (CK), 200 kg ha−1 (MN), and 300 kg ha−1 (HN)). We measured canopy temperature using a drone equipped with a high-precision camera at the six stages of the growth period. Generally, canopy temperature was significantly higher for CK than for MN and HN during the tillering, jointing, booting, and heading stages. The temperature was not significantly different among the nitrogen treatments between the milky and waxy stages. The canopy temperature of different rice varieties was found to follow the order: HD-5>NJ-9108>YJ-805, but the difference was not significant. The canopy temperature of rice was mainly related to plant traits, such as shoot fresh weight (correlation coefficient r=–0.895), plant water content (–0.912), net photosynthesis (–0.84), stomatal conductance (–0.91), transpiration rate (–0.90), and leaf stomatal area (–0.83). A structural equation model (SEM) showed that nitrogen fertilizer was an important factor affecting the rice canopy temperature. Our study revealed: (1) A suite of plant traits was associated with the nitrogen effects on canopy temperature, (2) the heading stage was the best time to observe rice canopy temperature, and (3) at that stage, canopy temperature was negatively correlated with rice yield, panicle number, and grain number per panicle. This study suggests that canopy temperature can be a convenient and accurate indicator of rice growth and yield prediction.

Background: To investigate the diagnostic value of computed tomography (CT)-guided aspiration biopsy combined with rapid field evaluation for pulmonary lesions. Methods: The PubMed and EMBASE databases were searched systematically for studies related to the diagnosis of lung lesions by CT-guided puncture biopsy combined with a rapid on-site indexed through October 2022. The updated Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool was applied as the main method to assess the risk of bias and applicability of the studies. Meta-analysis software was used to perform heterogeneity tests on the data. Based on the heterogeneity results, the appropriate effect model was selected to calculate the overall sensitivity, specificity, and diagnostic odds ratio (DOR), and to plot the summary receiver operating characteristic (SROC) curve, forest plot, and funnel plot. The results of the analysis of six studies (n=951) using a random-effects model showed pooled sensitivity, specificity, and diagnostic odds ratio with 95% confidence intervals of 94%, 95%, and 159.05, respectively, with an SROC AUC of 0.98. Further analysis of the four studies that established control groups showed that the sampling adequacy and diagnostic accuracy in the ROSE group were 12% and 13% higher than those in the non-ROSE group. In conclusion, CT-guided puncture biopsy combined with rapid on-site evaluation is a practical and feasible method for diagnosing pulmonary lesions and can be used as an important clinical diagnostic method.

Pulmonary sarcomatoid carcinoma (PSC) is a rare and highly malignant tumor, which includes the following five pathologic types: pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma and pulmonary blastoma. The onset of PSC is occult with non-specific clinical symptoms and signs. The clinical manifestations include irritating cough, bloody sputum, dyspnea, chest pain and so on, which are closely related to the growth and invasion site of the tumor. PSC tends to metastasize early, so most patients are already in local advanced stage or advanced stage with a median survival of 9 months at the time of hospital visit. A patient with primary PSC which led to 90% stenosis in central airway was treated by combined method of vascular and tracheoscopic intervention in our respiratory center. This treatment prolonged the patient’s survival time and got a satisfactory effect at 19-month follow-up after surgery. Herein we report the case for clinical reference.

Abstract The report of a half-quantized thermal Hall effect and oscillatory structures in the magnetothermal conductivity in the Kitaev material α-RuCl3 have sparked a strong debate on whether it is generated by Majorana fermion edge currents, spinon Fermi surface, or whether other more conventional mechanisms are at its origin. Here, we report low temperature thermal conductivity (κ) of another candidate Kitaev material, Na2Co2TeO6. The application of a magnetic field (B) along different principal axes of the crystal reveals a strong directional-dependent B impact on κ, while no evidence for mobile quasiparticles except phonons can be concluded at any field. Instead, severely scattered phonon transport prevails across the B−T phase diagram, revealing cascades of phase transitions for all B directions. Our results thus cast doubt on recent proposals for significant itinerant magnetic excitations in Na2Co2TeO6, and emphasize the importance of discriminating true spin liquid transport properties from scattered phonons in candidate materials.

Abstract In the dense and cold atmosphere of Titan, the presence of C2H4 haze has been confirmed by the observations of spacecraft. In the present study, original cryogenic experimental equipment was developed to simulate the low-temperature solid formation of C2H4 in combination with in-situ infrared spectroscopic measurements. As a result, out-of-plane bending vibration ν7 of solid-phase C2H4 located at ~ 10.5 μm was successfully detected with high sensitivity, and two-dimensional spectrographs of C2H4 at low temperatures were obtained. The obtained spectra of C2H4 can be fitted to the double Lorentzian function with various heights, central wavelengths, and full widths at half the maximum (FWHM) of the two-component Lorentzian functions. They were classified into three types using the fitting parameters. However, their spectral shapes are different from the amorphous, metastable, and crystalline forms obtained by the previous laboratory experiment in terms of the distance of two peak wavelengths and FWHM. The results may link to understanding the spectral band properties of C2H4 condensation in the haze component of Titan. Graphical Abstract

Abstract To evaluate whether single acetabular column can be reserved and the effect of reconstruction with femoral head plus total hip replacement (THR) for primary malignant peri-acetabulum tumors. From 2007 to 2015, nineteen patients with primary malignant peri-acetabulum tumors were enrolled. All cases underwent single column resection with clear surgical margins. Ten of the 19 tumor’s resections were assisted by computer navigation. Femoral heads were applied to reconstruct anterior or posterior column defects; THR was used for joint reconstruction. The surgical safety, oncologic outcome and prosthesis survivorship and function were evaluated by regular follow-up. The average follow-up period was 65.9 months. Surgical margins contained wide resection in 12 cases and marginal resection in 7 cases. One patient with Ewing's sarcoma died 14 months postoperative due to lung metastasis. One case with chondrosarcoma had recurrence. One prosthesis was removed due to infection. The average MusculoSkeletal Tumor Society (MSTS) function score was 83.7%. Due to the relative small number of cases, there was no significant difference in the recurrence rate and prosthesis failure rate between the navigation group and non-navigation group. Single column resection and reconstruction with femoral head autograft plus THR is an effective, safe method with less complication rate and better functional outcome for patients with peri-acetabular tumors.

Abstract Chinese sturgeon Dmrt gene family was identified and characterized for the first time. A total of 5 putative Dmrt genes were identified. The gene structure, conserved protein domain and the phylogenetic relationship of Dmrt gene family were systematically analyzed. The expressed profile of Chinese sturgeon Dmrt genes in gonad, pituitary and hypothalamus in the male and female were investigated. The results indicated that the accumulation of Dmrt genes was involved in different tissues, and the expression profile also differed among each Dmrt genes. ASDmrt1A, ASDmrt2, ASDmrt3, and ASDmrtA1 were highly expressed in the testis in comparison with other tissue. This result showed that ASDmrt1A, ASDmrt2, ASDmrt3, and ASDmrtA1 played an important role in the development of testicle, and may be useful tool in distinguishing between male and female of Chinese sturgeon. Our study will provide a basis for additional analyses of Chinese sturgeon Dmrt genes. This systematic analysis provided a foundation for further functional characterization of Dmrt genes with an aim of study of Chinese sturgeon Dmrt gene family.

Abstract Background For high-risk stageIImismatch repair deficient (dMMR) colon cancers, the benefit of adjuvant chemotherapy remains debatable. The principal aim of this study was to evaluate the prognostic value of high-risk factors and the effect of oxaliplatin-based adjuvant chemotherapy among dMMR stageIIcolon cancers. Methods Patients with stage II dMMR colon cancers diagnosed between June 2011 and May 2018 were enrolled in the study. Clinicopathological characteristics, treatment, and follow-up data were retrospectively collected. The high-risk group was defined as having one of the following factors: pT4 disease, fewer than twelve lymph nodes harvested (

Abstract Background In our previous investigation, we revealed a significant increase in the expression of microRNA-6881-3p (miR-6881-3p) in follicular fluid granulosa cells (GCs) from women with diminished ovarian reserve (DOR) compared to those with normal ovarian reserve (NOR). However, the role of miR-6881-3p in the development of DOR remains poorly understood. Objective This study aimed to elucidate the involvement of miR-6881-3p in the regulation of granulosa cells (GCs) function and the pathogenesis of DOR. Materials and methods Initially, we assessed the expression levels of miR-6881-3p in GCs obtained from human follicular fluid in both NOR and DOR cases and explored the correlation between miR-6881-3p expression and clinical outcomes in assisted reproduction technology (ART). Bioinformatic predictions and dual-luciferase reporter assays were employed to identify the target gene of miR-6881-3p. Manipulation of miR-6881-3p expression was achieved through the transfection of KGN cells with miR-6881-3p mimics, inhibitor, and miRNA negative control (NC). Following transfection, we assessed granulosa cell apoptosis and cell cycle progression via flow cytometry and quantified target gene expression through quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) analysis. Finally, we examined the correlation between target gene expression levels in GCs from NOR and DOR patients and their association with ART outcomes. Results Our findings revealed elevated miR-6881-3p levels in GCs from DOR patients, which negatively correlated with ovarian reserve function and ART outcomes. We identified a direct binding interaction between miR-6881-3p and the 3’-untranslated region of the SMAD4. Transfection with miR-6881-3p mimics induced apoptosis in KGN cell. Furthermore, miR-6881-3p expression negatively correlated with both mRNA and protein levels of the SMAD4. The mRNA and protein levels of SMAD4 were notably reduced in GCs from DOR patients, and SMAD4 mRNA expression positively correlated with ART outcomes. In addition, the mRNA levels of FSHR, CYP11A1 were notably reduced after transfection with miR-6881-3p mimics in KGN cell, while LHCGR notably increased. The mRNA and protein levels of FSHR, CYP11A1 were notably reduced in GCs from DOR patients, while LHCGR notably increased. Conclusion This study underscores the role of miR-6881-3p in directly targeting SMAD4 mRNA, subsequently diminishing granulosa cell viability and promoting apoptosis, and may affect steroid hormone regulation and gonadotropin signal reception in GCs. These findings contribute to our understanding of the pathogenesis of DOR.