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Abstract Glucocorticoids (GCs) are key inducers of osteonecrosis, yet not all patients treated with GCs develop glucocorticoid-associated osteonecrosis (GAON). The factors mediating this relationship are unclear. Studies have shown that gut microbiota and their metabolites influence bone metabolism, but their role in GAON is unclear. This study aimed to explore the connection between GAON and gut microbiota. Through bidirectional Mendelian randomization analysis, we identified 14 gut microbial taxa, including Lachnospiraceae (IVW, P = 0.011), associated with GAON. RNA-seq analysis revealed that GAON differentially expressed genes (DEGs) were enriched for intestinal inflammatory response mechanisms. We then compared patients who developed GAON (17 cases), those who did not (GAnON, 15 cases), and those untreated with GCs (Blank, 15 cases) for gut microbiota composition, short-chain fatty acids (SCFAs), and serum inflammatory factors. Our findings indicated a decrease in Lachnospiraceae abundance (GAON 17.13%, GAnON 12.51%, Blank 24.52%) in GC-treated patients. Serum inflammatory factors (IL-17 A, IL-33, and TNF-α) associated with GAON (59.603 ± 12.147, 89.337 ± 20.714, 42.584 ± 9.185) showed significant differences between Blank (1.446 ± 0.683, 11.534 ± 4.705, 4.682 ± 1.48) and GAnON (25.353 ± 8.181, 32.527 ± 7.352, 12.49 ± 3.217) groups, with a negative correlation between these factors and Lachnospiraceae levels. Butyric acid levels in SCFAs varied among groups (P

Abstract Background Despite the global standardization of hemoglobin (Hb) testing in early pregnancy, the impact of first trimester Hb concentrations on pregnancy outcomes remains inadequately understood. Also, the early pregnancy Hb concentrations have not been well documented in Western China. Therefore, this study aimed to assess the Hb concentrations during early pregnancy and their associations with adverse pregnancy outcomes in Western China. Methods This cross-sectional study used data from the Chengdu Maternal and Child Health Information System for pregnant women who delivered between January 1, 2019, and December 31, 2023. A total of 454,815 Chinese females aged 15 to 49 years with available first trimester Hb data, including those with singleton or multiple gestations, were included in the analysis. Multivariable logistic regression models were performed to estimate the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for associations between Hb categories and adverse pregnancy outcomes. Results The average first trimester Hb concentration was 126.0 (SD 10.5) g/L, with 5.8% of pregnant women experiencing anemia during early pregnancy. Multivariable logistic regression analyses revealed significantly increased odds of developing gestational diabetes mellitus (GDM) and gestational hypertensive disorders (GHD) across increasing Hb concentration categories. Compared to Hb concentrations of 110–119 g/L, Hb ≥ 140 g/L was associated with elevated risk of GDM (aOR: 1.57, 95% CI: 1.52, 1.62) and GHD (aOR: 1.87, 95% CI: 1.79, 1.96). Moreover, both Hb ≤ 99 g/L (aOR: 1.15, 95% CI: 1.03, 1.29) and Hb ≥ 140 g/L (aOR: 1.20, 95% CI: 1.13, 1.26) were associated with higher odds of preterm birth compared to Hb concentrations of 110–119 g/L. In addition, the restricted cubic spline demonstrated a U-shaped relationship for cesarean delivery, low birthweight and small for gestational age (p 0.05). Conclusions Our research findings suggest associations between first trimester Hb concentrations and various adverse pregnancy outcomes. We recommend interventions for early pregnancy anemia, particularly moderate to severe cases, and emphasize monitoring females with high Hb concentrations to reduce adverse outcomes.

Background: Kidney disease has become a growing public health problem worldwide, and there is an urgent need to develop reliable models for investigating novel and effective treatment strategies. In recent years, kidney organoids, as novel models different from traditional two-dimensional cells and model animals, have attracted more and more attention. Current advances have allowed the generation of kidney organoids from the directed differentiation of induced pluripotent stem cells (iPSCs), which possess similar characteristics to embryonic stem cells (ESCs), but bypass ethical constraints and have a wide range of sources. Summary: Herein, the methods of generating renal organoids from iPSCs, the applications of iPSC-derived renal organoids in disease modeling, drug effectiveness detection, and regenerative medicine as well as the challenges were reviewed. Key messages: iPSC-derived renal organoids can be used to model kidney diseases, and are great models for studying kidney injury and toxicity. Many efforts are needed to finally apply organoids into clinical application.

Abstract Epileptogenesis is the process whereby the previously normally functioning brain begins to generate spontaneous, unprovoked seizures. Status epilepticus (SE), which entails a massive release of neuronal glutamate and other neuroactive substances, is one of the best-known triggers of epileptogenesis. We here asked whether pharmacologically promoting glymphatic clearance during or after SE is beneficial and able to attenuate the subsequent epileptogenesis. We induced SE in adult male mice by intrahippocampal kainic acid (KA) infusion. Acute administration of a cocktail of adrenergic receptor antagonists (propranolol, prazosin, and atipamezole: PPA), enhanced glymphatic flow and effectively reduced the severity of spontaneous seizures in the chronic phase. The PPA treatment also reduced reactive gliosis and inhibited the loss of polarized expression of AQP4 water channels in the vascular endfeet of astrocytes. Administration of PPA after cessation of SE (30 hours post KA) also effectively suppressed epileptogenesis and improved outcome. Conversely, mice with constitutively low glymphatic transport due to genetic deletion of the aquaporin 4 (AQP4) water channel showed exacerbation of KA-induced epileptogenesis. We conclude that the pharmacological modulation of glymphatic fluid transport may represent a potential strategy to dampen epileptogenesis and the occurrence of spontaneous seizures following KA-induced SE.

The community stability of coral reefs and fish is the focus of ecological monitoring of coral reefs. Among them, the realization of effective metrics of variations in reef fish communities (i.e., the combined communities of coral reefs and fish) is important for analyzing the stability of communities as well as maintaining the ecological balance of coral reefs. Based on coral reef and fish data collected at St. John's Island from 2004 to 2010, this study proposes a symbiotic graph modeling method to express the biological relationships of reef fish communities, and a Pyramid Match graph kernel method for fusing Attributes (PMA) to quantify community fluctuations to measure interannual variability of communities. The results showed that the community similarity was low in 2006, 2007, and 2008. The total coral cover rate in the study area decreased by 32.04% from 2006 to 2007 and increased by 24% in 2008. The total number of fish fell from 3780 in 2006 to 2596 in 2007 and rose to 6249 in 2008. Among them, the proportion of herbivorous fish decreased to 30.84% in 2007. Furthermore, we have combined the Louvain algorithm with the proposed PMA method to effectively identify the regions that should be prioritized for protection. Experiments were conducted on real datasets with good results, demonstrating the potential of the proposed method to assist in the analysis of community stability and identification of priority conservation areas.

Abstract Several clinical trials have been conducted to evaluate the use of flavopiridol (FP) to treat a variety of cancers, and almost all cancer drugs were found to be associated with toxicity and side effects. It is not clear whether the use of FP will affect the female reproductive system. Granulosa cells, as the important cells that constitute the follicle, play a crucial role in determining the reproductive ability of females. In this study, we investigated whether different concentrations of FP have a toxic effect on the growth of immortalized human ovarian granulosa cells. The results showed that FP had an inhibitory effect on cell proliferation at a level of nanomole concentration. FP reduced cell proliferation and induced apoptosis by inducing mitochondrial dysfunction and oxidative stress, as well as increasing BAX/BCL2 and pCDK1 levels. These results suggest that toxicity to the reproductive system should be considered when FP is used in clinical applications.

Abstract The toxicity of lunar dust (LD) to astronauts' health has been confirmed in the Apollo missions and subsequent biological experiments. Therefore, it is crucial to understand the biological toxicity of lunar dust for future human missions to the Moon. In this study, we exposed human lung epithelial cells (BEAS-2B) and peripheral blood B lymphocytes (AHH-1) to varying concentrations (0, 500, 1000, and 1500 μg/ml) of a lunar dust simulant (LDS) called CLDS-i for 24 and 48 h. The results provided the following key findings: (1) LDS induction of cell damage occurred through oxidative stress, with the levels of reactive oxygen species (ROS) in BEAS-2B cells being dependent on the duration of exposure. (2) Necrosis and early apoptosis were observed in BEAS-2B cells and AHH-1 cells, respectively. In addition, both cells showed lysosomal damage. (3) Genes CXCL1, SPP1, CSF2, MMP1, and POSTN are implicated in immune response and cytoskeletal arrangement regulation in BEAS-2B cells. Considering the similarities in composition and properties between CLDS-i and real lunar dust, our findings not only enhance the understanding of LDS toxicity, but also contribute to a better comprehension of the genomic alterations and molecular mechanisms underlying cellular toxicity induced by LD. These insights will contribute to the development of a biotoxicology framework aimed at safeguarding the health of astronauts and, consequently, facilitating future human missions to the Moon.

Through the analysis of natural gas composition, carbon and hydrogen isotopes of alkane gases, reservoir bitumen, source rock conditions, and source–reservoir combinations, this study clarifies the differences in gas sources and the origins of natural gas in the Permian Changxing Formation–Triassic Feixianguan Formation on both sides of the Kaijiang–Liangping Trough. Additionally, it identifies favorable exploration directions for coal-formed gas generated by the Longtan Formation in the Sichuan Basin. The following understanding was obtained: (1) The natural gas in the Changxing–Feixianguan formations mainly composed of alkane gas, typical of dry gas. (2) The carbon isotope values of methane and ethane in the Changxing–Feixianguan formations on the east side of the trough are lower than those on the west side. Specifically, the ethane carbon isotope value in the Longgang Gas Field on the west side is higher than that in the Yuanba Gas Field, while the methane hydrogen isotope value is lower in the Longgang Gas Field compared to the Yuanba Gas Field. (3) The natural gas in the Dongyuezhai, Puguang, and Yuanba gas fields predominantly originates from sapropelic organic matter of the Wujiaping Formation, with kerogen types II1–I; in contrast, the Longgang Gas Field contains a mixture of coal-formed gas and oil-type gas, with a slightly higher content of coal-formed gas, originating from mixed organic matter of the Wujiaping Formation, with kerogen type II1–II2. (4) Multiple types of gas, such as coal rock gas, tight sandstone gas, and shale gas, can be formed within the Longtan Formation. The Suining–Luzhou and Langzhong–Guang'an–Fuling areas are identified as favorable zones for the exploration of coal rock gas and marine–continental transitional shale gas, respectively. Additionally, the reef and shoal development areas of the Changxing Formation in the Suining–Hechuan and Guang'an–Nanchong regions are also favorable exploration areas for coal-formed gas.

Abstract Background Clear cell renal cell carcinoma (ccRCC) arises from the renal parenchymal epithelium and is the predominant malignant entity of renal cancer, exhibiting increasing incidence and mortality rates over time. SEC14-like 3 (SEC14L3) has emerged as a compelling target for cancer intervention; nevertheless, the precise clinical implications and molecular underpinnings of SEC14L3 in ccRCC remain elusive. Methods By leveraging clinical data and data from the TCGA-ccRCC and GEO datasets, we investigated the association between SEC14L3 expression levels and overall survival rates in ccRCC patients. The biological role and mechanism of SEC14L3 in ccRCC were investigated via in vivo and in vitro experiments. Moreover, siRNA-SEC14L3@PDA@MUC12 nanoparticles (SSPM-NPs) were synthesized and assessed for their therapeutic potential against SEC14L3 through in vivo and in vitro assays. Results Our investigation revealed upregulated SEC14L3 expression in ccRCC tissues, and exogenous downregulation of SEC14L3 robustly suppressed the malignant traits of ccRCC cells. Mechanistically, knocking down SEC14L3 facilitated the ubiquitination-mediated degradation of ribosomal protein S3 (RPS3) and augmented IκBα accumulation in ccRCC. This concerted action thwarted the nuclear translocation of P65, thereby abrogating the activation of the nuclear factor kappa B (NFκB) signaling pathway and impeding ccRCC cell proliferation and metastasis. Furthermore, diminished SEC14L3 levels exerted a suppressive effect on NFKB1 expression within the NFκB signaling cascade. NFKB1 functions as a transcriptional regulator capable of binding to the SEC14L3 enhancer and promoter, thereby promoting SEC14L3 expression. Consequently, the inhibition of SEC14L3 expression was further potentiated, thus forming a positive feedback loop. Additionally, we observed that downregulation of SEC14L3 significantly increased the sensitivity of ccRCC cells to sunitinib. The evaluation of SSPM-NPs nanotherapy highlighted its effectiveness in combination with sunitinib for inhibiting ccRCC growth. Conclusion Our findings not only underscore the promise of SEC14L3 as a therapeutic target but also unveil an SEC14L3/RPS3/NFκB positive feedback loop that curtails ccRCC progression. Modulating SEC14L3 expression to engage this positive feedback loop might herald novel avenues for ccRCC treatment.

Abstract Objective Our aim was to comprehensively investigate the relationship between blood volatile organic compounds (VOCs) and kidney stone prevalence for U.S. adults. Methods In this cross-sectional study, 10,052 participants from the 2007–2020 National Health and Nutrition Examination Survey (NHANES) were included. Multivariate logistic regression model was employed to investigate the association between 9 blood VOCs and kidney stones. We explored the dose–response relationship between blood VOCs and kidney stones using restricted cubic spline (RCS) analysis. Additionally, weighted quantile sum (WQS) regression model was performed to assess the overall association of 9 blood VOCs with kidney stones. Finally, subgroup analyses were conducted to identify the findings in different populations at high prevalence. Results Logistic regression analysis and dose–response risk curves revealed that blood benzene (aOR = 1.308, 95% CI: 1.118–1.530, P = 0.001), blood ethylbenzene (aOR = 1.280, 95% CI: 1.054–1.554, P = 0.013), blood m-/p-xylene (aOR = 1.187, 95% CI: 1.008–1.398, P = 0.040), blood 2,5-dimethylfuran (aOR = 1.319, 95% CI: 1.135–1.533, P

Abstract To prevent the early breakage of anchor cables under shear loads in support engineering, a combined structure of Anchor Cable with C-shaped Tube (ACC) has been proposed. The shear resistance enhancement mechanism of this structure and the mechanisms of various influencing factors have yet to be fully revealed. A refined nonlinear finite element model of ACC was original established using ABAQUS software, taking into account the actual structure of the steel strands and the interactions, such as contact and failure between the various components. Various anchor cable pretension forces and block strengths were set to investigate their effects on the shear mechanical response of ACC. The results successfully demonstrated a high correlation between peak shear load and pretension force. The results demonstrate that an increase in pretension force reduces the ACC’s peak shear load and break displacement. Additionally, the structure exhibited higher flexural stiffness, the block strength was mobilized earlier, and the block failed locally more quickly. Under high pretension forces, the system exhibited higher shear stiffness in the early stages of shearing due to the influence of the axial force component. With low pretension forces, the ACC exhibited a larger break displacement due to the minor tensile deformation at the shear plane position for the same shear displacement. At low pretension forces, the structure’s bending angle increased more rapidly during the middle and later stages of shearing, accompanied by a larger break displacement. Both of these factors led to a greater bending angle at the shear plane position at the point of failure. The results reveal the characteristic of the peak shear load initially increasing and then decreasing with the increase in test block strength, along with its underlying mechanism. As the block strength increased, the bending angle of the structure at the shear plane position increased more rapidly, resulting in higher shear stiffness. With high block strength, the combination of smaller break displacement and greater shear stiffness led to an initial increase followed by a decrease in peak shear load. A comprehensive RSSB (Relative Stiffness between Structure and Test Block) that considers both structural and test block stiffness was proposed. The deformation pattern of the structure was controlled by the RSSB. The higher the RSSB, the wider the plastic hinge extension range for the same shear displacement, the smaller the bending angle at the shear plane position, and the smaller the maximum curvature of the structure. The contact force of the C-shaped tube generally exhibited a “single peak” distribution. As the shear displacement increased, the peak position of the contact force moved away from the shear plane, and the maximum contact force increased rapidly and remained relatively stable. At the end of the shearing process, the contact force of the C-shaped tube exhibited a “double peak” distribution.

Background: Hyperbaric oxygen therapy (HBOT), which is widely used in clinical practice, is aimed at improving nerve function impairment after brain injury. Meanwhile, the effects of music therapy on brain function are unclear. This retrospective study was conducted to explore the application effect of HBOT combined with music therapy on patients suffering from aneurysmal subarachnoid hemorrhage (aSAH). Methods: For this retrospective study, 130 patients with aSAH after HBOT were selected from our hospital from June 2021 to June 2022. The patients were divided into the observation (n = 70) and control (n = 60) groups based on whether they received music therapy. Comparisons were made on general demographic data, blood flow rate in median cerebral artery (MCA), cerebral vasospasm (CVS), National Institutes of Health Stroke Scale (NIHSS), activities of daily living (ADL) score, Self-Rating Depressive Scale (SDS), and Self-Rating Anxiety Scale (SAS) of patients. Results: Baseline data between the two groups showed no statistically significant difference (P > 0.05). After management, patients in the observation group presented significantly lower SAS and SDS scores (P < 0.05), lower blood flow rate in MCA, CVS and NIHSS scores (P < 0.05), and higher ADL scores than the control group (P < 0.05). Conclusions: The combination of HBOT and music therapy can considerably improve cerebral neurological deficits, slow down cerebral arterial blood flow, promote the recovery of postoperative cerebral function in aSAH patients, and improve anxiety and depression and the patients’ ADL.

Abstract Liver metastasis remains the primary cause of mortality in patients with colon cancer. Identifying specific driver gene mutations that contribute to metastasis may offer viable therapeutic targets. To explore clonal evolution and genetic heterogeneity within the metastasis, we conducted single-cell exome sequencing on 150 single cells isolated from the primary tumor, liver metastasis, and lymphatic metastasis from a stage IV colon cancer patient. The genetic landscape of the tumor samples revealed that both lymphatic and liver metastases originated from the same region of the primary tumor. Notably, the liver metastasis was derived directly from the primary tumor, bypassing the lymph nodes. Comparative analysis of the sequencing data for individual cell pairs within different tumors demonstrated that the genetic heterogeneity of both liver and lymphatic metastases was also greater than that of the primary tumor. This finding indicates that liver and lymphatic metastases arose from clusters of circulating tumor cell (CTC) of a polyclonal origin, rather than from a single cell from the primary tumor. Single-cell transcriptome analysis suggested that higher EMT score and CNV scores were associated with more polyclonal metastasis. Additionally, a mutation in the TRPS1 (Transcriptional repressor GATA binding 1) gene, TRPS1 R544Q, was enriched in the single cells from the liver metastasis. The mutation significantly increased CRC invasion and migration both in vitro and in vivo through the TRPS1R544Q/ZEB1 axis. Further TRPS1 mutations were detected in additional colon cancer cases, correlating with advanced-stage disease and inferior prognosis. These results reveal polyclonal seeding and TRPS1 mutation as potential mechanisms driving the development of liver metastases in colon cancer.

Background: Distantly supervised relation extraction (DSRE) aims to identify semantic relations in large-scale texts automatically labeled via knowledge base alignment. It has garnered significant attention due to its high efficiency, but existing methods are plagued by noise at both the word and sentence level and fail to address these issues adequately. The former level of noise arises from the large proportion of irrelevant words within sentences, while noise at the latter level is caused by inaccurate relation labels for various sentences. Method: We propose a novel multi-level noise reduction neural network (MLNRNN) to tackle both issues by mitigating the impact of multi-level noise. We first build an iterative keyword semantic aggregator (IKSA) to remove noisy words, and capture distinctive features of sentences by aggregating the information of keywords. Next, we implement multi-objective multi-instance learning (MOMIL) to reduce the impact of incorrect labels in sentences by identifying the cluster of correctly labeled instances. Meanwhile, we leverage mislabeled sentences with cross-level contrastive learning (CCL) to further enhance the classification capability of the extractor. Results: Comprehensive experimental results on two DSRE benchmark datasets demonstrated that the MLNRNN outperformed state-of-the-art methods for distantly supervised relation extraction in almost all cases. Conclusions: The proposed MLNRNN effectively addresses both word- and sentence-level noise, providing a significant improvement in relation extraction performance under distant supervision.

The gear friction pairs in RV reducer always withstand a broad range of temperature, sliding velocity and heavy load. In the research, three types of heat treatment methods (carburizing + quenching, nitrocarburizing and high concentration nitrocarburizing) are applied on the 20CrMo (cycloidal gear material) disc to study the tribological behavior and wear mechanism. The friction coefficient, wear depth and wear rate of the three types of friction pairs under various temperature (−20 °C, 25 °C, 50 °C, 100 °C) are measured and the microstructure characteristics are analyzed by SEM and EDS. The results reveal that high temperature can dramatically decrease the wear scar dimensions and wear rate due to the more active lubricant. Although the lubricant lost its activity at −20 °C, the friction coefficient and maximum wear depth for GCr15/20CrMo (carburizing + quenching) and GCr15/20CrMo (high concentration nitrocarburizing) are relatively less than 0.1 and 4 μm. The wear rate of GCr15/20CrMo (carburizing + quenching) and GCr15/20CrMo (high concentration nitrocarburizing) are 14.49 μm3/N·m and 17.20 μm3/N·m, which are only 28.7% and 34.1% of GCr15/20CrMo (nitrocarburizing). With the temperature increases to 25 °C, tribofilm is more likely to form on the 20CrMo specimen after nitrocarburizing, leading to better wear resistance. At high temperature (50 °C and 100 °C), GCr15/20CrMo (high concentration nitrocarburizing) system presents excellent tribological behavior by the combination of good lubricant activity, formation of tribofilm and refined nitrides. The wear rate even reaches 0.45 μm3/N·m and 0.43 μm3/N·m at the sliding velocity of 300 mm/s and 562 mm/s under 100 °C. Overall, specimen with high concentration nitrocarburizing process exhibits exceptional wear performance under full operating conditions of RV reducer.

Abstract The combination of ASC22, an anti-PD-L1 antibody potentially enhancing HIV-specific immunity and chidamide, a HIV latency reversal agent, may serve as a strategy for antiretroviral therapy-free virological control for HIV. People living with HIV, having achieved virological suppression, were enrolled to receive ASC22 and chidamide treatment in addition to their antiretroviral therapy. Participants were monitored over 24 weeks to measure changes in viral dynamics and the function of HIV-specific CD8+ T cells (NCT05129189). 15 participants completed the study. At week 8, CA HIV RNA levels showed a significant increase from baseline, and the values returned to baseline after discontinuing ASC22 and chidamide. The total HIV DNA was only transiently increased at week 4 (P = 0.014). In contrast, integrated HIV DNA did not significantly differ from baseline. Increases in the proportions of effector memory CD4+ and CD8+ T cells (TEM) were observed from baseline to week 24 (P = 0.034 and P = 0.002, respectively). The combination treatment did not succeed in enhancing the function of HIV Gag/Pol- specific CD8+ T cells. Nevertheless, at week 8, a negative correlation was identified between the proportions of HIV Gag-specific TEM cells and alterations in integrated DNA in the T cell function improved group (P = 0.042 and P = 0.034, respectively). Nine adverse events were solicited, all of which were graded 1 and resolved spontaneously. The combined treatment of ASC22 and chidamide was demonstrated to be well-tolerated and effective in activating latent HIV reservoirs. Further investigations are warranted in the context of analytic treatment interruption.

Abstract In IIB string theory on AdS3 background with NS-NS fluxes, we show that Brown-Henneaux asymptotic Killing vectors can be derived by requiring both the worldsheet equations of motion and Virasoro constraints are preserved near the asymptotic boundary of the target spacetime. The charges on the worldsheet that generate the corresponding transformations can be written down in both the Lagrangian formalism and Hamiltonian formalism. This provides a method of studying asymptotic symmetry of the target spacetime directly from worldsheet string theories, without using results from the supergravity limit. As an example, we apply this method to flat spacetime in three dimensions and obtain the BMS3 generators on the worldsheet theory.

Abstract Accurate cannulation of the adrenal vein is challenging during adrenal venous sampling (AVS) because of the variations in adrenal vein anatomy. This study aimed to investigate the adrenal venous morphology in Chinese and improve the success rate of AVS. A total of 221 participants with primary aldosteronism (PA) who underwent AVS were enrolled. Compare the morphology among subgroups divided according to sex, body mass index (BMI), and with or without adenoma. The success rate of right, left, and bilateral AVS was 98.60%, 97.20%, and 96.85%, respectively. The triangular pattern was the most common (39.37%) on the right side, while the glandlike pattern (70.14%) on the left. The proportion of adrenal venous morphology varies among patients with different sexes (χ2 = 21.335, P

Abstract It remained debates on metabolic‐related disorders in patients with primary aldosteronism (PA) and essential hypertension (EH). A systematic review and meta‐analysis was conducted to explore the prevalence of metabolic syndrome (MS) and the related indicators in PA and EH. PubMed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials from their commencement to December 2023 were searched for eligible studies. The meta‐analysis was performed by Review Manager 5.3 and STATA 15.1 software. A total of 12 studies were included, revealing that there was no significant difference between PA and EH in the prevalence of MS (1.27[0.92, 1.76], p = 0.14) with higher heterogeneity (I2 = 68%, p = 0.0002), while it became significant different (1.45[1.17, 1.81], p = 0.0008) and lower heterogeneity (I2 = 26%, p = 0.19) in patients who were overweight or obese by subgroup analysis. Higher systolic blood pressure (2.99[0.67, 5.31], p = 0.01; I2 = 43%, p = 0.06) and diastolic blood pressure (2.10[0.82, 3.38], p = 0.001; I2 = 36%, p = 0.11) with lower heterogeneity, and lower triglyceride in PA group with higher heterogeneity (‐0.23[‐0.37, ‐0.09], p = 0.001; I2 = 76%, p

Abstract Objectives Pulmonary neuroendocrine neoplasms (NENs) are the most frequent cause of ectopic adrenocorticotropic hormone syndrome (EAS); lung infection is common in EAS. An imaging finding of infection in EAS patients can mimic NENs. This retrospective study investigated EAS-associated pulmonary imaging indicators. Methods Forty-five pulmonary NENs and 27 tumor-like infections from 59 EAS patients (45 NEN and 14 infection patients) were included. Clinical manifestations, CT features, 18F-FDG, or 68Ga-DOTATATE-PET/CT images and pathological results were collected. Results High-sensitivity C-reactive protein (p

ObjectiveTo analyze the epidemiological characteristics of hepatitis C incidence and incidence trend from 2012 to 2023 and predict the incidence for 2024 – 2025 in Gansu province for the development of hepatitis C prevention and control strategies among local residents. MethodsData on hepatitis C incidence reported in Gansu province from 2012 to 2023 were collected from the Infectious Disease Reporting Information Management System of the Chinese Center for Disease Control and Prevention. A descriptive analysis of the epidemiological characteristics of hepatitis C incidence in Gansu province was conducted, and both the GM(1,1) model, linear and nonlinear curve regression analysis were performed to fit the annual incidence of hepatitis C. The optimal model was selected to predict the incidence of hepatitis C incidence for 2024–2025 among residents of Gansu province. ResultsDuring the 12-year period, a total of 83 306 hepatitis C cases were reported in Gansu province, with an average annual incidence rate (1/100 000) of 26.53 and annual specific incidence rates of 34.93, 29.10, 25.87, 30.21, 24.28, 29.71, 29.47, 28.04, 23.40, 22.49, 19.62, and 21.29 for the years from 2012 to 2023, respectively. There was an overall downward trend in the hepatitis C incidence rate during this period (χ2trend = 458.167, P = 0.006), with an average annual decrease of 1.13%. The average annual incidence rate of hepatitis C varied significantly among different regions of the province (χ2trend = 431.086, P = 0.007), with the top three average annual incidence rates of 96.78, 63.62, and 34.13 for Wuwei, Zhangye, and Lanzhou municipalities. The average annual incidence rate of hepatitis C for the male population (31.27) was significantly higher than that for the female population (19.36) (χ2 = 307.512, P = 0.008) and the rate differed significantly among the populations of different age groups (χ2trend = 53.104, P = 0.007), with the highest rate (46.13) for the population aged 45 – 54 years. The majority of the hepatitis C cases reported during the period (51 928, 64.48% of the total) were among farmers. Comparison of two models to fit the incidence data showed that the GM(1,1) model, with a mean absolute error (MAE) of 525.3 and a mean absolute percentage error (MAPE) of 0.06%, outperformed the quadratic curve regression model, which had an MAE of 551.0 and a MAPE of 0.07%, indicating a better fit of the GM(1,1) model. Based on the GM(1,1) model analysis, the predicted number of hepatitis C cases in Gansu province would be 5 958 in 2024 and 5 801 in 2025, with a declining trend. ConclusionThe incidence of hepatitis C in Gansu province from 2012 to 2023 showed a decreasing trend, with a higher incidence rate among males, people aged 45 – 54 years, and farmers. The GM(1,1) model performs well in predicting the incidence trend of hepatitis C. The results suggest that comprehensive preventive measures against hepatitis C should be taken.

Abstract Soil extractable nitrate, ammonium, and organic nitrogen (N) are essential N sources supporting primary productivity and regulating species composition of terrestrial plants. However, it remains unclear how plants utilize these N sources and how surface-earth environments regulate plant N utilization. Here, we establish a framework to analyze observational data of natural N isotopes in plants and soils globally, we quantify fractional contributions of soil nitrate (f NO3-), ammonium (f NH4+), and organic N (f EON) to plant-used N in soils. We find that mean annual temperature (MAT), not mean annual precipitation or atmospheric N deposition, regulates global variations of f NO3-, f NH4+, and f EON. The f NO3- increases with MAT, reaching 46% at 28.5 °C. The f NH4+ also increases with MAT, achieving a maximum of 46% at 14.4 °C, showing a decline as temperatures further increase. Meanwhile, the f EON gradually decreases with MAT, stabilizing at about 20% when the MAT exceeds 15 °C. These results clarify global plant N-use patterns and reveal temperature rather than human N loading as a key regulator, which should be considered in evaluating influences of global changes on terrestrial ecosystems.

Abstract Background The purpose of this study was to improve the deep learning (DL) model performance in predicting and classifying IMRT gamma passing rate (GPR) by using input features related to machine parameters and a class balancing technique. Methods A total of 2348 fields from 204 IMRT plans for patients with nasopharyngeal carcinoma were retrospectively collected to form a dataset. Input feature maps, including fluence, leaf gap, leaf speed of both banks, and corresponding errors, were constructed from the dynamic log files. The SHAP framework was employed to compute the impact of each feature on the model output for recursive feature elimination. A series of UNet++ based models were trained on the obtained eight feature sets with three fine-tuning methods including the standard mean squared error (MSE) loss, a re-sampling technique, and a proposed weighted MSE loss (WMSE). Differences in mean absolute error, area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were compared between the different models. Results The models trained with feature sets including leaf speed and leaf gap features predicted GPR for failed fields more accurately than the other models (F(7, 147) = 5.378, p

Abstract Prenatal exposure to Benzo[a]pyrene (BaP) has been suggested to increase the risk of adverse pregnancy outcomes. However, the role of placental apoptosis on BaP reproductive toxicity is poorly understood. We conducted a maternal animal model of C57BL/6 wild-type (WT) and transformation-related protein 53 (Trp53) heterozygous knockout (p53KO) mice, as well as a nested case–control study involving 83 women with PB and 82 term birth from a birth cohort on prenatal exposure to BaP and preterm birth (PB). Pregnant WT and p53KO mice were randomly allocated to BaP treatment and control groups, intraperitoneally injected of low (7.8 mg/kg), medium (35 mg/kg), and high (78 mg/kg) doses of 3,4-BaP per day and equal volume of vegetable oil, from gestational day 10.5 until delivery. Results show that high-dose BaP treatment increased the incidence of preterm birth in WT mice. The number of fetal deaths and resorptions increased with increasing doses of BaP exposure in mice. Notably, significant reductions in maternal and birth weights, increases in placental weights, and decrease in the number of livebirths were observed in higher-dose BaP groups in dose-dependent manner. We additionally observed elevated p53-mediated placental apoptosis in higher BaP exposure groups, with altered expression levels of p53 and Bax/Bcl-2. In case–control study, the expression level of MMP2 was increased among women with high BaP exposure and associated with the increased risk of all PB and moderate PB. Our study provides the first evidence of BaP-induced reproductive toxicity and its adverse effects on maternal–fetal outcomes in both animal and population studies.

Baicalin (BA), a flavonoid extracted from the roots of Scutellaria baicalensis, has significant neuroprotective, anti-inflammatory, antioxidant, and anti-apoptotic properties, with a notable safety profile and low negative effects. BA has been acknowledged for its capacity to prevent and cure cognitive deficits and learning impairments linked to illnesses of the central nervous system. Simultaneously, sleep disorders (SD), which often occur along with cognitive dysfunctions, have shown improvement with BA therapy, but the exact reasons behind this improvement are not yet completely understood. This study presents a comprehensive overview of the existing pharmacological knowledge on BA and examines its recent progress in treating cognitive deficits. The goal is to provide fresh insights on how to effectively use BA and traditional Chinese medicine for addressing cognitive dysfunctions.

Abstract Patulin (PAT) is a common mycotoxin in moldy fruits that causes gastrointestinal injury if accidentally ingested. Some studies have reported the symptoms of intestinal injury caused by PAT. However, the effects of PAT on the gut microbiota and gut metabolism remain to be investigated, which is important for clarifying the toxicological mechanisms. Thus, C57/BL6J mice were gavaged once with 0, 1, 4, and 16 mg/kg body weight PAT, and the small intestinal and colonic contents were collected. The 16S rRNA sequencing and targeted and untargeted metabolomics were applied to assess the alterations in microbiota and metabolism, respectively. The results showed that Mycoplasma, Dubosiella, and Enterorhabdus were jointly affected by acute PAT exposure in the small intestinal and colonic contents. Some inflammation‐related bacteria, such as Mycoplasma in the small intestine and Mycoplasma, Alistipes, Eubacterium_coprostanoligenes_group, and Candidatus_saccharimona in the colon, increased with increasing doses of PAT. In metabolic results, amino acids decreased and bile acids elevated in both intestinal contents; lipids increased in the small intestinal contents but decreased in the colonic contents. PAT mainly affected host amino acid and lipid metabolism; it also downregulated microbial tryptophan metabolism and short‐chain fatty acid levels (mainly in the colon), which could be explained by the decrease of Bacteroides and Lactobacillus. These influences in microbial abundances and metabolic levels persisted after PAT and its products were cleared. These results fill a gap in the effects of PAT on the gut microbiota and provide a theoretical basis for elucidating the toxic mechanism of mycotoxins.

Abstract Exploring the promiscuity of native enzymes presents a promising strategy for expanding their synthetic applications, particularly for catalyzing challenging reactions in non-native contexts. In this study, we explore the promiscuous potential of old yellow enzymes (OYEs) to facilitate the Morita-Baylis-Hillman reaction (MBH reaction), leveraging substrate similarities between MBH reaction and reduction reaction. Using mass spectrometry and spectroscopic techniques, we confirm promiscuity of GkOYE in both MBH and reduction reactions. By blocking H- and H+ transfer pathways, we engineer GkOYE.8, which loses its reduction ability but enhances its MBH activity. The structural basis of MBH reaction catalyzed by GkOYE.8 is obtained through mutation studies and kinetic simulations. Furthermore, enantiocomplementary mutants GkOYE.11 and GkOYE.13 are obtained by directed evolution, exhibiting the ability to accept various aromatic aldehydes and alkenes as substrates. This study demonstrates the potential of leveraging substrate similarities to unlock enzyme functionalities, enabling the catalysis of new-to-nature reactions.

Abstract The leaf beetle Ophraella communa LeSage (Coleoptera: Chrysomelidae) is an effective biological control agent of the common ragweed. Here, we assembled a chromosome-level genome of the O. communa by combining Illumina, Nanopore, and Hi-C sequencing technologies. The genome size of the final genome assembly is 733.1 Mb, encompassing 17 chromosomes, with an improved contig N50 of 7.05 Mb compared to the original version. Genome annotation reveals 25,873 protein-coding genes, with functional annotations available for 22,084 genes (85.35%). Non-coding sequence annotation identified 204 rRNAs, 626 tRNAs, and 1791 small RNAs. Repetitive elements occupy 414.41 Mb, constituting 57.76% of the genome. This high-quality genome is fundamental for advancing biological control strategies employing O. communa.

Abstract Purpose To examine whether there is a significant difference in image quality between the deep learning reconstruction (DLR [AiCE, Advanced Intelligent Clear-IQ Engine]) and hybrid iterative reconstruction (HIR [AIDR 3D, adaptive iterative dose reduction three dimensional]) algorithms on the conventional enhanced and CE-boost (contrast-enhancement-boost) images of indirect computed tomography venography (CTV) of lower extremities. Materials and methods In this retrospective study, seventy patients who underwent CTV from June 2021 to October 2022 to assess deep vein thrombosis and varicose veins were included. Unenhanced and enhanced images were reconstructed for AIDR 3D and AiCE, AIDR 3D-boost and AiCE-boost images were obtained using subtraction software. Objective and subjective image qualities were assessed, and radiation doses were recorded. Results The CT values of the inferior vena cava (IVC), femoral vein ( FV), and popliteal vein (PV) in the CE-boost images were approximately 1.3 (1.31–1.36) times higher than in those of the enhanced images. There were no significant differences in mean CT values of IVC, FV, and PV between AIDR 3D and AiCE, AIDR 3D-boost and AiCE-boost images. Noise in AiCE, AiCE-boost images was significantly lower than in AIDR 3D and AIDR 3D-boost images ( P

Abstract Background Anthracnose, mainly caused by Colletotrichum fructicola, leads to severe losses in pear production. However, there is limited information available regarding the molecular response to anthracnose in pears. Results In this study, the anthracnose-resistant variety ‘Seli’ and susceptible pear cultivar ‘Cuiguan’ were subjected to transcriptome analysis following C. fructicola inoculation at 6 and 24 h using RNA sequencing. A total of 3186 differentially expressed genes were detected in ‘Seli’ and ‘Cuiguan’ using Illumina sequencing technology. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses indicated that the transcriptional response of pears to C. fructicola infection included responses to reactive oxygen species, phytohormone signaling, phenylpropanoid biosynthesis, and secondary metabolite biosynthetic processes. Moreover, the mitogen-activated protein kinase (MAPK) signaling pathway and phenylpropanoid biosynthesis were involved in the defense of ‘Seli’. Furthermore, the gene coexpression network data showed that genes related to plant–pathogen interactions were associated with C. fructicola resistance in ‘Seli’ at the early stage. Conclusion Our results showed that the activation of specific genes in MAPK, calcium signaling pathways and phenylpropanoid biosynthesis was highly related to C. fructicola resistance in ‘Seli’ and providing several potential candidate genes for breeding anthracnose-resistant pear varieties.

Abstract Background Tendon stem/progenitor cell (TSPC) senescence contributes to tendon degeneration and impaired tendon repair, resulting in age-related tendon disorders. Ferroptosis, a unique iron-dependent form of programmed cell death, might participate in the process of senescence. However, whether ferroptosis plays a role in TSPC senescence and tendon regeneration remains unclear. Recent studies reported that Platelet-derived exosomes (PL-Exos) might provide significant advantages in musculoskeletal regeneration and inflammation regulation. The effects and mechanism of PL-Exos on TSPC senescence and tendon regeneration are worthy of further study. Methods Herein, we examined the role of ferroptosis in the pathogenesis of TSPC senescence. PL-Exos were isolated and determined by TEM, particle size analysis, western blot and mass spectrometry identification. We investigated the function and underlying mechanisms of PL-Exos in TSPC senescence and ferroptosis via western blot, real-time quantitative polymerase chain reaction, and immunofluorescence analysis in vitro. Tendon regeneration was evaluated by HE staining, Safranin-O staining, and biomechanical tests in a rotator cuff tear model in rats. Results We discovered that ferroptosis was involved in senescent TSPCs. Furthermore, PL-Exos mitigated the aging phenotypes and ferroptosis of TSPCs induced by t-BHP and preserved their proliferation and tenogenic capacity. The in vivo animal results indicated that PL-Exos improved tendon-bone healing properties and mechanical strength. Mechanistically, PL-Exos activated AMPK phosphorylation and the downstream nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling pathway, leading to the suppression of lipid peroxidation. AMPK inhibition or GPX4 inhibition blocked the protective effect of PL-Exos against t-BHP-induced ferroptosis and senescence. Conclusion In conclusion, ferroptosis might play a crucial role in TSPC aging. AMPK/Nrf2/GPX4 activation by PL-Exos was found to inhibit ferroptosis, consequently leading to the suppression of senescence in TSPCs. Our results provided new theoretical evidence for the potential application of PL-Exos to restrain tendon degeneration and promote tendon regeneration.

To understand the evolution characteristics of radar echo, microphysical parameters, and thermal dynamics of the convective systems during different stages of hailstorms, observations from Doppler weather radar, laser raindrop spectrometer, microwave radiometer, and automatic meteorological stations were used to investigate the radar echo characteristics, raindrop spectrum difference, temperature, humidity and water vapor variation characteristics of a hailstorm occurred in Tianjin on July 9, 2017. The results are as follows. (1) The warm and wet air on the east side of the shear line at 850 hPa is superimposed with the cold air at 500 hPa, which is conducive to the accumulation of unstable energy and triggering of convective weather. With hail approaching, the instability of the ambient atmosphere increased significantly. (2) During the evolution stage of the hail cloud, two hailfall events were observed, both of which occurred during the strengthening and merging processes of the convective cells. (3) During the hailfall stage, the maximum diameter, mass-weighted mean diameter, and median volume diameter of the precipitation particles reached their peak values. The contribution rate of medium and large droplets to precipitation intensity reached 94.56%, and the average spectral width during the hailfall stage was the largest. While after hailfall, the contribution rate of particles with a diameter less than 1.0 mm increased. The mean spectrum of particles within the range of less than 1.0 mm showed a bimodal pattern, with the first peak and the second peak occurring near 0.3 mm and 0.6 mm, respectively. (4) Before the hailfall, the water vapor accumulated slowly but continuously. The integrated water vapor and liquid water content showed an obvious increase in 1 h before hailfall. Due to the existence of temperature inversion, the upper layers were dryer and colder, while the lower layers were warmer and wetter. Note that the water vapor content in the whole atmosphere started to decrease after the hailfall.

Abstract The western flower thrips Frankliniella occidentalis (Thysanoptera: Thripidae) is a global invasive species that causes increasing damage by direct feeding on crops and transmission of plant viruses. Here, we assemble a previously published scaffold-level genome into a chromosomal level using Hi-C sequencing technology. The assembled genome has a size of 302.58 Mb, with a contig N50 of 1533 bp, scaffold N50 of 19.071 Mb, and BUSCO completeness of 97.8%. All contigs are anchored on 15 chromosomes. A total of 16,312 protein-coding genes are annotated in the genome with a BUSCO completeness of 95.2%. The genome contains 492 non-coding RNA, and 0.41% of interspersed repeats. In conclusion, this high-quality genome provides a convenient and high-quality resource for understanding the ecology, genetics, and evolution of thrips.

Abstract Climate changes are known to have been a key regulator of the biodiversity in Earth's history. However, the dry‐humid degrees and alternating patterns throughout the Phanerozoic remain largely unconstrained. In this study, we report high contents (2.4 ± 3.8 mg N kg−1) and 17O anomalies (11.0 ± 7.4‰) of nitrate (NO3−) in the early Cambrian black shale from South China, likely caused by atmospheric NO3− intrusion under dry climates that followed tectonic uplift. By developing new methods to quantify aridity indices (AI, 0.06 ± 0.08) in combination with observational data with paleoclimate models, we reconstructed the historical AI variations. Our analyses revealed three significant dry‐to‐humid transitions which include Cambrian‐Ordovician to Silurian‐Permian, Permian‐Triassic boundary to middle Triassic‐early Jurassic, and Jurassic‐Paleogene to Neogene. This study quantitatively unlocked the Phanerozoic climate changes in South China, offering important evidence for understanding the co‐evolution of ecological and climatic systems in Earth's history.

Abstract During the past few decades, pyroelectric sensors have attracted extensive attention due to their prominent features. However, their effectiveness is hindered by low electric output. In this study, the laser processed lithium niobate (LPLN) wafers are fabricated to improve the temperature–voltage response. These processed wafers are utilized to construct pyroelectric sensors as well as human–machine interfaces. The laser induces escape of oxygen and the formation of oxygen vacancies, which enhance the charge transport capability on the surface of lithium niobate (LN). Therefore, the electrodes gather an increased quantity of charges, increasing the pyroelectric voltage on the LPLN wafers to a 1.3 times higher voltage than that of LN wafers. For the human–machine interfaces, tactile information in various modes can be recognized by a sensor array and the temperature warning system operates well. Therefore, the laser modification approach is promising to enhance the performance of pyroelectric devices for applications in human–machine interfaces.

Patients diagnosed with papillary renal cell carcinoma (pRCC) exhibit a high rate of clinical metastasis; however, the underlying molecular mechanism is unclear. In this study, KH-type splicing regulatory protein (KHSRP) participated in pRCC progression and was associated with metastasis. It was positively correlated with the hallmark of epithelial-mesenchymal transition. KHSRP inhibition effectively alleviated the cellular function of migration and invasion. Additionally, KHSRP knockdown inhibited the proliferative ability of pRCC cells. A pharmaceutical screening was based on the KHSRP protein structure. Gemcitabine (Gem) decreased KHSRP expression. UIO-66@Gem@si-KHSRP (UGS) nanoparticles (NPs) were prepared for targeted delivery and applied in both in vitro and in vivo experiments to explore the clinical transition of KHSRP. UGS NPs exhibited better performance in inhibiting cellular proliferation, migration, and invasion than Gem. Additionally, the in vivo experiment results confirmed their therapeutic effects in inhibiting tumor metastasis with excellent biosafety. The silico analysis indicated that KHSRP knockdown increased cytotoxic cell infiltration in the tumor microenvironment to potentiate anti-tumor effects. Thus, KHSRP can promote pRCC progression as an oncogene and serve as a target in clinical transition through UGS NP-based therapy.

ObjectiveTo investigate the relationship between the gut microbiome and the response to anti-PD-1-based combination therapy in unresectable hepatocellular carcinoma (HCC). We aimed to identify potential non-invasive biomarkers and new strategies to modulate immunotherapy in HCC.MethodsIn this study, fresh stool samples and clinical data were collected from unresectable HCC patients treated with anti-PD-1-based combination therapy at the Cancer Hospital of the Chinese Academy of Medical Sciences between January 2020 and December 2021. The patients were divided into two groups based on their response to treatment: the treatment responder group (R group) and the treatment non-responder group (NR group). The composition and diversity of the gut microbiome were bioinformatically analyzed by using the Whole Genome Shotgun strategy, including taxonomic composition analysis, Alpha diversity analysis, Beta diversity analysis, and differentially enriched bacterial taxa analysis. Differentially enriched bacterial taxa between R and NR groups were identified based on the magnitude of the linear discriminant analysis effect size (LEfSe) and analyzed for their impact on the survival of the patient.ResultsA total of 45 eligible patients with unresectable HCC treated with anti-PD-1-based combination therapy participated in this study. The gut microbiological composition and Alpha diversity of patients were not statistically different, but there was a statistically significant difference in Beta diversity between the R and NR groups. (PERMANOVA tests, P = 0.006). We further identified 56 enriched bacterial taxa in the R group and 44 enriched bacterial taxa in the NR group based on the LEfSe analysis (LDA >2.66, P< 0.05). Patients with a high abundance of Collinsella genus, Ruminococcus_AM4211, and Ruminococcus_AF25_28AC had a longer median PFS and median OS compared to those with low abundance (P < 0.05). On the contrary, the median PFS and OS of patients with a high abundance of Bacteroides_AF20_13LB and Veillonella_atypica were significantly shorter than those of patients with low abundance (P < 0.05). The multivariate analysis showed that the abundance of Bacteroides_AF20_13LB and Ruminococcus_ AF25_28AC was independent related factors for PFS, and the abundance of Bacteroides_AF20_13LB was an independent related factor of OS.ConclusionThe enrichment of specific gut microbiota affected clinical efficacy and survival benefits in HCC treated with anti-PD-1 therapy and may be a promising non-invasive gut microbial biomarker and a new strategy for modulating immunotherapy in HCC.

BackgroundGiven the high prevalence of fibrotic interstitial lung abnormalities (ILAs) post-COVID-19, this study aims to evaluate the effectiveness of quantitative CT features in predicting fibrotic ILAs at 3-month follow-up.MethodsThis retrospective study utilized cohorts from distinct clinical settings: the training dataset comprised individuals presenting at the fever clinic and emergency department, while the validation dataset included patients hospitalized with COVID-19 pneumonia. They were classified into fibrotic group and nonfibrotic group based on whether the fibrotic ILAs were present at follow-up. A U-Net-based AI tool was used for quantification of both pneumonia lesions and pulmonary blood volumes. Receiver operating characteristic (ROC) curve analysis and multivariate analysis were used to assess their predictive abilities for fibrotic ILAs.ResultsAmong the training dataset, 122 patients (mean age of 68 years ±16 [standard deviation], 73 men), 55.74% showed fibrotic ILAs at 3-month follow-up. The multivariate analysis identified the pneumonia volume [PV, odd ratio (OR) 3.28, 95% confidence interval (CI): 1.20–9.31, p = 0.02], consolidation volume (CV, OR 3.77, 95% CI: 1.37–10.75, p = 0.01), ground-glass opacity volume (GV, OR 3.38, 95% CI: 1.26–9.38, p = 0.02), pneumonia mass (PM, OR 3.58, 95% CI: 1.28–10.46, p = 0.02), and the CT score (OR 12.06, 95% CI: 3.15–58.89, p 0.05). And the area under the curve (AUC) values were PV (0.79), GV (0.78), PM (0.79), CV (0.80), and the CT score (0.77). The validation dataset, comprising 45 patients (mean age 67.29 ± 14.29 years, 25 males) with 57.78% showing fibrotic ILAs at follow-up, confirmed the predictive validity of these parameters with AUC values for PV (0.86), CV (0.90), GV (0.83), PM (0.88), and the CT score (0.85). Additionally, the percentage of blood volume in vessels

PurposeThe aim of the study was to synthesize previous evidence and clarify the prevalence of developmental coordination disorder (DCD) in children by meta-analysis.MethodsA comprehensive computerized search of databases, including PubMed, Embase, Web of Science, The Cochrane Library, CINAHL, and PsycINFO databases, was conducted to identify relevant national and international articles published before 18 December 2023 on DCD prevalence in children. The meta-analysis of prevalence was conducted using Stata 18.0.ResultsA total of 18 papers involving 31,203 patients were included. The prevalence of children with DCD was found to be 5%. A subgroup analysis showed that prevalence was 7% [95% confidence interval (CI) 4%–10%] and 4% (95% CI 3%–7%) for boys and girls, respectively; 4% (95% CI 2%–8%), 2% (95% CI 2%–2%), and 6% (95% CI 3%–10%) in Asia, Europe, and North America, respectively; and 18% (95% CI 8%–31%) and 6% (95% CI 4%–7%) for preterm (

This study aimed to evaluate the safety and efficacy of pharmacomechanical catheter-directed thrombolysis (PCDT) and stenting for treating acute iliofemoral deep venous thrombosis (DVT) combined with iliac vein compression syndrome (IVCS), and to identify the predictors of stent restenosis. Patients with acute proximal DVT combined with IVCS underwent PCDT and stenting from January 2017 to December 2022 were enrolled. Primary and secondary patency were assessed by duplex ultrasound (DUS). The morbidity of postthrombotic syndrome (PTS) was assessed by the Villalta score. Risk factors for stent restenosis were assessed using univariate and multivariate Cox regression models. Total of 254 patients were included. The mean follow-up time was 36.06 ± 17.66 months. The primary patency rates at 1 year, 3 years, and 5 years were 92.5%±1.7%, 85.4%±2.4%, and 82.4%±2.9%, respectively. The incidence of stent restenosis was 14.2%. Discontinuation of anticoagulants within one year [hazard ratio (HR) = 5.03; P = .048] was the factor associated with acute in-stent thrombosis. Previous DVT history (HR =2.29; P = .037) and stent placement across the inguinal ligament (HR =6.70; P

Background: The association between playing Ma-jong, chess and cards (PMCC) and shoulder pain among elderly adults in China remains unclear. The present study aimed to examine the association based on a nationally representative large-scale survey. Methods: The study used two waves of data from China Health and Retirement Longitudinal Study (CHARLS) in 2015 and 2018. All subjects met the inclusion criteria were classified based on the results of the CHARLS wave questionnaire. Logistic regression models were conducted to analyze the cross-sectional and longitudinal association between PMCC and shoulder pain. Odds ratios (OR) were reported to indicate the strength of the association. Results: In total, 8125 participants aged over 60 years (48.3 % male; mean age 67.9 ± 6.4 years) were enrolled in a cross-sectional association study in 2015, and further 6861 elderly adults were followed up in 2018. The overall prevalence of shoulder pain in the cross-sectional population was 15.6 %. In the non-PMCC and PMCC groups, the incidence of shoulder pain was 16.6 % and 10.7 %, respectively (P

Previous studies have mainly focused on the impact of social media self-presentation on individuals’ happiness and mental health, whereas few have attended to its potential influence on consumer behavior. A mixed-method empirical study with an online survey (N = 408) and an experimental study (N = 160) investigated the effects of social media self-presentation on individuals’ conspicuous consumption in China. We found that consumers’ self-presentation behavior on social media promoted tendencies for social comparison, thereby enhancing their conspicuous consumption. However, compared with individuals using social media less often, self-presentation had a more significant impact on the social comparison tendencies of users who used social media more often. Our study explains why individuals’ self-presentation on social media increases their conspicuous consumption tendencies. The study results contribute to the existing knowledge of how consumers’ behavior on social media affects their product preferences.

Abstract Background The basic helix-loop-helix family member e41 (BHLHE41) is frequently dysregulated in tumors and plays a crucial role in malignant progression of various cancers. Nevertheless, its specific function and underlying mechanism in bladder cancer (BCa) remain largely unexplored. Methods The expression levels of BHLHE41 in BCa tissues and cells were examined by qRT-PCR and western blot assays. BCa cells stably knocking down or overexpressing BHLHE41 were constructed through lentivirus infection. The changes of cell proliferation, cell cycle distribution, migration, and invasion were detected by CCK-8, flow cytometry, wound healing, transwell invasion assays, respectively. The expression levels of related proteins were detected by western blot assay. The interaction between BHLHE41 and PYCR1 was explored by co-immunoprecipitation analysis. Results In this study, we found that BHLHE41 was lowly expressed in bladder cancer tissues and cell lines, and lower expression of BHLHE41 was associated with poor overall survival in bladder cancer patients. Functionally, by manipulating the expression of BHLHE41, we demonstrated that overexpression of BHLHE41 significantly retarded cell proliferation, migration, invasion, and induced cell cycle arrest in bladder cancer through various in vitro and in vivo experiments, while silence of BHLHE41 caused the opposite effect. Mechanistically, we showed that BHLHE41 directly interacted with PYCR1, decreased its stability and resulted in the ubiquitination and degradation of PYCR1, thus inactivating PI3K/AKT signaling pathway. Rescue experiments showed that the effects induced by BHLHE41 overexpression could be attenuated by further upregulating PYCR1. Conclusion BHLHE41 might be a useful prognostic biomarker and a tumor suppressor in bladder cancer. The BHLHE41/PYCR1/PI3K/AKT axis might be a potential therapeutic target for bladder cancer intervention.

Abstract Biodiversity often helps communities resist invasion. However, it is unclear whether this diversity–invasion relationship holds true under environmental changes. Here, we conduct a meta-analysis of 1010 observations from 25 grassland studies in which plant species richness is manipulated together with one or more environmental change factors to test invasibility (measured by biomass or cover of invaders). We find that biodiversity increases resistance to invaders across various environmental conditions. However, the positive biodiversity effect on invasion resistance is strengthened under experimental warming, whereas it is weakened under experimentally imposed drought. When multiple factors are imposed simultaneously, the positive biodiversity effect is strengthened. Overall, we show that biodiversity helps grassland communities resist plant invasions under multiple environmental changes. Therefore, investment in the protection and restoration of native biodiversity is not only important for prevention of invasions under current conditions but also under continued global environmental change.

Abstract Tortricidae is one of the largest families in Lepidoptera, including subfamilies of Tortricinae, Olethreutinae, and Chlidanotinae. Here, we assembled the gap-free genome for the subfamily Chlidanotinae using Illumina, Nanopore, and Hi-C sequencing from Polylopha cassiicola, a pest of camphor trees in southern China. The nuclear genome is 302.03 Mb in size, with 36.82% of repeats and 98.4% of BUCSO completeness. The karyotype is 2n = 44 for males. We identified 15412 protein-coding genes, 1052 tRNAs, and 67 rRNAs. We also determined the mitochondrial genome of this species and annotated 13 protein-coding genes, 22 tRNAs, and one rRNA. These high-quality genomes provide valuable information for studying phylogeny, karyotypic evolution, and adaptive evolution of tortricid moths.

Abstract Signalling through TNFR1 modulates proinflammatory gene transcription and programmed cell death, and its impairment causes autoimmune diseases and cancer. NEDD4-binding protein 1 (N4BP1) is a critical suppressor of proinflammatory cytokine production that acts as a regulator of innate immune signalling and inflammation. However, our current understanding about the molecular properties that enable N4BP1 to exert its suppressive potential remain limited. Here, we show that N4BP1 is a novel linear ubiquitin reader that negatively regulates NFκB signalling by its unique dimerization-dependent ubiquitin-binding module that we named LUBIN. Dimeric N4BP1 strategically positions two non-selective ubiquitin-binding domains to ensure preferential recognition of linear ubiquitin. Under proinflammatory conditions, N4BP1 is recruited to the nascent TNFR1 signalling complex, where it regulates duration of proinflammatory signalling in LUBIN-dependent manner. N4BP1 deficiency accelerates TNFα-induced cell death by increasing complex II assembly. Under proapoptotic conditions, caspase-8 mediates proteolytic processing of N4BP1, resulting in rapid degradation of N4BP1 by the 26 S proteasome, and acceleration of apoptosis. In summary, our findings demonstrate that N4BP1 dimerization creates a novel type of ubiquitin reader that selectively recognises linear ubiquitin which enables the timely and coordinated regulation of TNFR1-mediated inflammation and cell death.

Abstract Background The initial phase II stuty (NCT03215693) demonstrated that ensartinib has shown clinical activity in patients with advanced crizotinib‐refractory, anaplastic lymphoma kinase (ALK)‐positive non‐small cell lung cancer (NSCLC). Herein, we reported the updated data on overall survival (OS) and molecular profiling from the initial phase II study. Methods In this study, 180 patients received 225 mg of ensartinib orally once daily until disease progression, death or withdrawal. OS was estimated by Kaplan‒Meier methods with two‐sided 95% confidence intervals (CIs). Next‐generation sequencing was employed to explore prognostic biomarkers based on plasma samples collected at baseline and after initiating ensartinib. Circulating tumor DNA (ctDNA) was detected to dynamically monitor the genomic alternations during treatment and indicate the existence of molecular residual disease, facilitating improvement of clinical management. Results At the data cut‐off date (August 31, 2022), with a median follow‐up time of 53.2 months, 97 of 180 (53.9%) patients had died. The median OS was 42.8 months (95% CI: 29.3‐53.2 months). A total of 333 plasma samples from 168 patients were included for ctDNA analysis. An inferior OS correlated significantly with baseline ALK or tumor protein 53 (TP53) mutation. In addition, patients with concurrent TP53 mutations had shorter OS than those without concurrent TP53 mutations. High ctDNA levels evaluated by variant allele frequency (VAF) and haploid genome equivalents per milliliter of plasma (hGE/mL) at baseline were associated with poor OS. Additionally, patients with ctDNA clearance at 6 weeks and slow ascent growth had dramatically longer OS than those with ctDNA residual and fast ascent growth, respectively. Furthermore, patients who had a lower tumor burden, as evaluated by the diameter of target lesions, had a longer OS. Multivariate Cox regression analysis further uncovered the independent prognostic values of bone metastases, higher hGE, and elevated ALK mutation abundance at 6 weeks. Conclusion Ensartinib led to a favorable OS in patients with advanced, crizotinib‐resistant, and ALK‐positive NSCLC. Quantification of ctDNA levels also provided valuable prognostic information for risk stratification.

Abstract We investigate the proposed holographic duality between the TsT transformation of IIB string theory on AdS3 × $$\mathcal{N}$$ with NS-NS flux and a single-trace $$T\overline{T }$$ deformation of the symmetric orbifold CFT. We present a non-perturbative calculation of two-point correlation functions using string theory and demonstrate their consistency with those of the $$T\overline{T }$$ deformation. The two-point correlation function of the deformed theory on the plane, written in momentum space, is obtained from that of the undeformed theory by replacing h with $$h+2\frac{\widetilde{\lambda }}{w}p\overline{p }$$ , where h is the spacetime conformal weight, $$\widetilde{\lambda }$$ is a deformation parameter, p and $$\overline{p }$$ are the momenta, and w labels the twisted sectors in the deformed symmetric product. At w = 1, the non-perturbative result satisfies the Callan-Symanzik equation for double-trace $$T\overline{T }$$ deformed CFT derived in [1]. We also perform conformal perturbations on both the worldsheet CFT and the symmetric orbifold CFT as a sanity check. The perturbative and non-perturbative matching between results on the two sides provides further evidence of the conjectured $${\text{TsT}}/T\overline{T }$$ correspondence.

Abstract Objective The diagnosis of hidden hearing loss (HHL) in calm state has not yet been determined, while the nutritional status is not involved in its pathogenic risk factors. In utero iron deficiency (ID) may delay auditory neural maturation in infants. We evaluated the association between ID and HHL as well as the modification effect of socioeconomic status (SES) on this association in newborns. Study design We included 859 mother-newborns from the baseline of this observational northeast cohort. Data on exposure assessment included iron status [maternal hemoglobin (Hb) and neonatal heel prick serum ferritin (SF)] and SES (occupation, education and income). Auditory neural maturation was reflected by auditory brainstem response (ABR) testing and electrocochleography (ECochG). Results Iron status and SES were independently and jointly associated with the prediction of neonatal HHL by logistic and linear regression model. The mediation effects were performed by Process. ID increased absolute latency wave V, interpeak latency (IPL) III-V, and summting potentials (SP) /action potentials (AP), which were combined as HHL. Low SES showed the highest risk of HHL and the highest levels of related parameters in ID newborns. Moreover, after Corona Virus Disease 2019 (COVID-19) were positive, preschool children who experience ID in neonatal period were more likely to suffer from otitis media with effusion (OME). High SES also showed similar risk effects. Conclusion Both low and high SES may strengthen the risk of ID on neonatal HHL in Northeast China.

The Argentine shortfin squid Illex argentinus is a pelagic neritic cephalopod species found in the southwest Atlantic Ocean. The squid is characterized by a short lifespan, fast growth, and semelparous reproduction. The squid is one of most important targeted species in global cephalopod fisheries and plays a key role as transient "biological pumps" in the southwest Atlantic ecosystem. The squid is a highly migratory species and can migrate hundreds or even thousands of miles between its spawning and feeding ground to complete its life cycle. The squid adopts a mixed income-capital breeding strategy, where the reproduction is mainly supported by energy acquired and mobilized rapidly during the breeding season, coupled with using energy reserves when energy demands for reproduction are robust. The squid shows spatial differences in feeding habits and also shift diets as they grow, leading to different trophic niches. In general, the squid diet shifts from crustaceans to fish and cephalopods as they mature. Given the fact that species in a higher trophic position have greater energy content, a diet shift to fish and cephalopods is expected to meet the energy demands for reproduction. In the present review, we summarized the characteristics of energy accumulated in soma and reproductive systems for I. argentinus, which shows a dramatic increase in energy in the reproductive tissues when the squid reaches maturation. In addition, we compiled previous studies that focused on diet composition and trophic roles in the southwest Atlantic ecosystem, where the squid feeds voraciously on many prey species and plays a key role as prey item for many top predators, including marine mammals. Notably, squid changes diets in relation to energy demands and resource availability. However, future research is still needed to address the functional mechanisms of the shifting dietary habits with growth. To justify the mechanism, we suggest the following priorities in the near future studies: (1) evaluate the relationships between energy acquisition and migratory habits; (2) clarify feeding strategies that potentially maximize the energy gain; and (3) address the potential effect of the ongoing global climate change and fishery activity on the role of energy transfer in the southwest Atlantic ecosystem. Such research would advance our understanding of the species and support the sustainability of resource exploitation.