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In a targeted double-scoring procedure for performance assessments that are used for licensure and certification purposes, a subset of responses receives an independent second rating if the first rating falls into a preidentified critical score range (CSR) where an additional rating would lead to considerably more reliable pass-fail decisions. This study evaluates the CSRs using two approaches--one based on imputation of missing scores and the other based on statistical decision theory--using data from the Performance Assessment for School Leaders (PASL). Results from the evaluation indicate that the currently used CSRs are effective.

Sensitivity analysis, a statistical method crucial for validating inferences across disciplines, quantifies the conditions that could alter conclusions (Razavi et al., 2021). One line of work is rooted in linear models and foregrounds the sensitivity of inferences to the strength of omitted variables (Cinelli & Hazlett, 2019; Frank, 2000). A more recent approach is rooted in the potential outcomes framework for causal inference and foregrounds how hypothetical changes in a sample would alter an inference if such cases were otherwise observed (Frank et al., 2008, 2013; Frank & Min, 2007; Xu et al., 2019). One sensitivity measure is the "Impact Threshold of a Confounding Variable," or ITCV, which generates statements about the correlation of an omitted, confounding variable with both a predictor of interest and the outcome (Frank, 2000). The ITCV index can be calculated for any linear model. The "Robustness of an Inference to Replacement," RIR, assesses how replacing a certain percentage of cases with counterfactuals of zero treatment effect could nullify an inference (Frank et al., 2013). The RIR index is more general than the ITCV index.

Abstract Background Drought stress markedly constrains plant growth and diminishes crop productivity. Strigolactones (SLs) exert a beneficial influence on plant resilience to drought conditions. Nevertheless, the specific function of SLs in modulating cotton’s response to drought stress remains to be elucidated. Results In this study, we assess the impact of exogenous SL (rac-GR24) administration at various concentrations (0, 1, 5, 10, 20 µM) on cotton growth during drought stress. The findings reveal that cotton seedlings treated with 5 µM exogenous SL exhibit optimal mitigation of growth suppression induced by drought stress. Treatment with 5 µM exogenous SL under drought stress conditions enhances drought tolerance in cotton seedlings by augmenting photosynthetic efficiency, facilitating stomatal closure, diminishing reactive oxygen species (ROS) generation, alleviating membrane lipid peroxidation, enhancing the activity of antioxidant enzymes, elevating the levels of osmoregulatory compounds, and upregulating the expression of drought-responsive genes. The suppression of cotton SL biosynthesis genes, MORE AXILLARY GROWTH 3 (GhMAX3) and GhMAX4b, impairs the drought tolerance of cotton. Conversely, overexpression of GhMAX3 and GhMAX4b in respective Arabidopsis mutants ameliorates the drought-sensitive phenotype in these mutants. Conclusion These observations underscore that SLs significantly bolster cotton’s resistance to drought stress.

Abstract This paper aims to examine the potential link between maternal COVID-19 infection during pregnancy and the increased risk of congenital heart disease (CHD) in newborns. A comparative analysis was conducted involving two groups: mothers infected with COVID-19 during pregnancy and a control group. Data on maternal characteristics, pregnancy-related complications, and newborn outcomes were collected and analyzed. Additionally, the annual incidence rates of CHD from 2020 to 2023 were evaluated to assess trends over time. No significant differences were found between the COVID-19 cases and the control group in terms of maternal age, BMI, gravidity, parity, use of assisted reproductive technology, adverse obstetric history, or complications during pregnancy, including diabetes mellitus, preeclampsia, and thyroid abnormalities. For newborn outcomes, there were no significant differences in sex distribution, rate of cesarean delivery, Apgar scores, or birth weight. However, a significantly higher prevalence of cardiac ultrasound abnormalities was observed in the COVID-19 group (10.08%) compared to the control group (4.13%, p = 0.012). Further analysis revealed that the majority of cardiac abnormalities in the COVID-19 group occurred in mothers infected before 8 weeks of pregnancy. The annual incidence rates of CHD showed a significant increase during the COVID-19 pandemic, with the highest rate in 2023 (5.46%) compared to previous years. Maternal COVID-19 infection during pregnancy may adversely affect the development of the newborn’s heart. This could be due to the inflammatory response caused by the viral infection or other pathological processes. The findings underscore the importance of vigilant prenatal care and early detection of cardiac abnormalities during the pandemic and suggest the need for further research to explore potential mechanisms and intervention strategies.

Abstract Although some studies have explored the role of meteorological factors in the development of tuberculosis (TB), the majority have been confined to single regions, leading to inconsistent findings. Consequently, we conducted a multi-city study not only to determine whether meteorological factors significantly influence the risk of developing TB but also to assess the magnitude of these effects and explore potential modifying factors. Data on daily reported TB cases and meteorological factors were collected from January 1, 2013, to December 31, 2022, across 11 cities in Zhejiang Province. A distributed lag non-linear model using a quasi-Poisson distribution was employed. Multivariate meta-regression was used to obtain overall pooled estimates and assess heterogeneity. From 2013 to 2022, 267,932 TB cases were reported in Zhejiang Province. Notably, a nonlinear relationship was observed between temperature and TB, with the relative risk (RR) peaking at 1.0 °C (RR = 1.882, 95% CI 1.173–3.020). The effect of low temperature was immediate and significant for a 13-day lag period, with the maximum effect at lag0 (RR = 1.014, 95% CI 1.008–1.021). The exposure-response curve between relative humidity (RH) and TB exhibited an M-shape, with the RR peaking at 47.7% (RR = 1.642, 95% CI 1.044–2.582). The lag effect of low RH was significant at lag 25–59, with the highest RR observed at lag 32 (RR = 1.011, 95% CI 1.001–1.022). Gross domestic product (GDP) per person, population density, and latitude demonstrated significant modification effects. Our study showed that low temperature and RH were associated with an increased risk of TB. Additionally, GDP per person, population density, and latitude may play important roles in explaining the association between RH and TB. These findings provide scientific evidence for the development of geographically specific public health policies.

Abstract Near-neutral HCO3 – aqueous solution plays an essential role in respiratory, mineralization and catalysis, yet the interconversion between hydrated CO2, HCO3 – and CO3 2– and the associated proton transfer under such proton-deficient conditions remain uncovered. Here we reveal that cation enables HCO3 – to self-dissociate into OH– and CO2 through a pH-independent process, where CO2 hydration and subsequent proton transfer in acid-base reactions lead to the overall exchange of oxygen isotopes between HCO3 – and H2O tracked by oxygen isotope-labeled Raman spectroscopy. Isolating HCO3 – from cations with crown ether impedes HCO3 – dissociation and the following reactions. Further molecular dynamics simulations demonstrate that the interplay between HCO3 – and hydrated cations drives HCO3 – dissociation. This study suggests a natural proton channel upon coupling HCO3 – with cations.

Abstract Compared to H2-assisted activation mode, the direct dissociation of CO2 into carbonyl (*CO) with a simplified reaction route is advantageous for CO2-related synthetic processes and catalyst upgrading, while the stable C = O double bond makes it very challenging. Herein, we construct a subnano MoO3 layer on the surface of Mo2N, which provides a dynamically changing surface of MoO3↔MoO x (x < 3) for catalyzing CO2 hydrogenation. Rich oxygen vacancies on the subnano MoO x surface with a high electron donating capacity served as a scissor to directly shear the C = O double bond of CO2 to form CO at a high rate. The O atoms leached in CO2 dissociation are removed timely by H2 to regenerate active oxygen vacancies. Owing to the greatly enhanced dissociative activation of CO2, this MoO x /Mo2N catalyst without any supported active metals shows excellent performance for catalyzing CO2 hydrogenation to CO. The construction of highly disordered defective surface on heterostructures paves a new pathway for molecule activation.

Abstract Background The maternal gut microbiome is the direct and important source of early colonization and development of the neonatal gut microbiome. However, differences in unique and shared features between mothers with different physiological phenotypes and their newborns still lack exhaustive investigation. Here, using a cow-to-calf model, a comprehensive investigation was conducted to elucidate the pattern and characterization of microbial transfer from the maternal source to the offspring. Results The microbiota in the rumen and feces of dairy cows were divided into two clusters via enterotype analysis. The cows from the enterotype distinguished by Prevotella in the rumen had better production performance, whereas no difference was observed in the cows classified by feces enterotype. Furthermore, through a pairwise combination of fecal and ruminal enterotypes, we screened a group of dairy cows with excellent phenotypes. The gastrointestinal microbiomes of cows with different phenotypes and their offspring differed significantly. The rumen was a more important microbial source for meconium than feces. Transmission of beneficial bacteria from mother to offspring was observed. Additionally, the meconium inherits advantageous metabolic functions of the rumen. The resistome features of the rumen, feces, and meconium were consistent, and resistome abundance from cows to calves showed an expanding trend. The interaction between antibiotic-resistance genes and mobile genetic elements from the rumen to meconium was the most remarkable. The diversity of core metabolites from cows to calves was stable and not affected by differences in phenotypes. However, the abundance of specific metabolites varied greatly. Conclusions Our study demonstrates the microbial taxa, metabolic function, and resistome characteristics of maternal and neonatal microbiomes, and reveals the potential vertical transmission of the microbiome from a cow-to-calf model. These findings provide new insights into the transgenerational transmission pattern of the microbiome. Video Abstract

Abstract Background Accurate and up-to-date estimates of the global cancer burden in adolescents and young adults (AYA) are scarce. This study aims to assess the global burden and trends of AYA cancer, with a focus on socioeconomic disparities, to inform global cancer control strategies. Methods AYA cancer, defined as cancer occurring in individuals aged 15–39, was analyzed using data from the Global Burden of Disease (GBD) 2021 study and the Global Cancer Observatory (GLOBOCAN) 2022 project. We examined the global burden by age, sex, geographic location, and Human Development Index (HDI), as well as its temporal trends. Primary outcomes included age-standardized incidence and mortality rates (ASIR, ASMR) and the average annual percent change (AAPC). Results In 2022, an estimated 1,300,196 incidental cases and 377,621 cancer-related deaths occurred among AYAs worldwide, with an ASIR of 40.3 per 100,000 and an ASMR of 11.8 per 100,000. The most common cancers were breast, thyroid, and cervical, while the leading causes of death were breast, cervical, and leukemia. The incidence and mortality were disproportionately higher among females (ASIR: 52.9 for females vs. 28.3 for males; ASMR: 13.1 for females vs. 10.6 for males). Countries with higher HDI experienced a higher incidence of AYA cancers (ASIR: 32.0 [low HDI] vs. 54.8 [very high HDI]), while countries with lower HDI faced a disproportionately higher mortality burden (ASMR: 17.2 [low HDI] vs. 8.4 [very high HDI]) despite their relatively low incidence. Disproportionality and regression measures highlighted significant HDI-related inequalities. AYA cancer incidence was stable from 2000 to 2011 (AAPC: − 0.04) but increased from 2012 to 2021 (AAPC: 0.53), driven by growing gonadal and colorectal cancers. Mortality decreased substantially from 2000 to 2011 (AAPC: − 1.64), but the decline slowed from 2012 (AAPC: − 0.32) probably due to increased deaths from gonadal cancers. These trends varied by sex, cancer type, geography, and HDI. Conclusion AYA cancers present a significant and growing global burden, with marked disparities across sex, geographic locations, and HDI levels. Policymakers should prioritize equitable resource allocation and implement targeted interventions to reduce these inequalities, particularly in low-HDI regions and with regard to gonadal cancers.

Abstract Periprosthetic joint infection (PJI) is a severe complication after joint replacement surgery that demands precise diagnosis for effective treatment. We enhanced PJI diagnostic accuracy through three steps: (1) developing a self-supervised PJI model with DINO v2 to create a large dataset; (2) comparing multiple intelligent models to identify the best one; and (3) using the optimal model for visual analysis to refine diagnostic practices. The self-supervised model generated 27,724 training samples and achieved a perfect AUC of 1, indicating flawless case differentiation. EfficientNet v2-S outperformed CAMEL2 at the image level, while CAMEL2 was superior at the patient level. By using the weakly supervised PJI model to adjust diagnostic criteria, we reduced the required high-power field diagnoses per slide from five to three. These findings demonstrate AI’s potential to improve the accuracy and standardization of PJI pathology and have significant implications for infectious disease diagnostics.

Abstract Background To evaluate the feasibility and safety of the superficial circumflex iliac perforator flap (SCIP) for maxillary reconstruction with intraoral anastomosis, pedicle elongation, and super-microsurgery techniques to overcome its anatomical shortcomings due to the attractive merits of the flap. Methods Patients who underwent reconstruction of maxillary defects with SCIPs from July 2020 to December 2022 were included. Intraoral anastomosis, pedicle elongation, and super-microsurgery were performed during surgery with or without a neck incision. The sizes, pedicle lengths, inner calibres of vessels, complications and flap survival statuses were recorded. Results A total of 12 patients were included, with 3 males and 9 females, and the median age was 45 years, ranging from 14 to 74 years. There were 5 class IIa and 7 class IIb defects, 6 cases underwent maxillary defect reconstruction via SCIPs with intraoral anastomosis, and the other 6 cases with distally design and/or de-epidermis pedicle elongation. Super-microsurgery interventions were needed in 5 patients. The size ranged from 3 cm×4 cm to 6 cm×8 cm. The pedicle length ranged from 4 cm to 12 cm, with a median of 6 cm. The inner caliber of the arteries ranged from 0.7 mm to 2 mm, with a median of 1 mm, and the veins ranged from 1.5 mm to 4 mm, with a median of 2.5 mm. All the flaps survived, and no donor site complications occurred. Conclusion Superficial circumflex iliac perforator flaps can be regarded as feasible and safe choices for maxillary defects with the support of intraoral anastomosis, pedicle elongation and super-microsurgery.

The lipid nanoparticle (LNP) has been so far proven as a strongly effective delivery system for mRNA and siRNA. However, the mechanisms of LNP's distribution, metabolism, and elimination are complicated, while the transportation and pharmacokinetics (PK) of LNP are just sparsely investigated and simply described. This study aimed to build a model for the transportation of RNA-LNP in Hela cells, rats, mice, and humans by physiologically based pharmacokinetic (PBPK) and quantum mechanics (QM) models with integrated multi-source data. LNPs with different ionizable lipids, particle sizes, and doses were modeled and compared by recognizing their critical parameters dominating PK. Some interesting results were found by the models. For example, the metabolism of ionizable lipids was first limited by the LNP disassembly rate instead of the hydrolyzation of ionizable lipids; the ability of RNA release from endosomes for three ionizable lipids was quantitively derived and can predict the probability of RNA release. Moreover, the biodegradability of three ionizable lipids was estimated by the QM method and the is generally consistent with the result of PBPK result. In summary, the transportation model of RNA LNP among various species for the first time was successfully constructed. Various in vitro and in vivo pieces of evidence were integrated through QM/PBPK multi-level modeling. The resulting new understandings are related to biodegradability, safety, and RNA release ability which are highly concerned issues of the formulation. This would benefit the design and research of RNA-LNP in the future.

Objective: To investigate the oxidation mechanism of walnut kernels. Methods: Walnut kernels were subjected to vacuum or non-vacuum packaging before accelerated oxidation at 60 ℃. Samples were taken periodically for ultrastructural and morphological observation by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) and for the measurement of oxidation indicators such as peroxide value, carbonyl value, and cell membrane permeability. Changes in cellular ultrastructure during the oxidation process of walnut kernels were analyzed and compared under vacuum and non-vacuum packaging conditions. The oxidation process was assessed from a multi-dimensional perspective and the oxidation mechanism was explored as well. Results: Under non-vacuum conditions, walnut kernel oil began to become sticky on the 14th day of accelerated oxidation and then gradually became stickier. With oxidation time, intracellular protein bodies (PB) exhibited sequential changes including an increase in surface roughness, aggregation, movement toward the cell periphery, decomposition and reassembly. The oil body membrane (OBM) was ruptured and the intracellular reticulum was disrupted, thus causing oil leakage into the intercellular space and resulting in a reduction in the cell volume. Cellular structural changes were much smaller under vacuum conditions than under non-vacuum conditions, the oil started to become sticky on the 28th day, and the oxidation indicators were significantly lower than those under non-vacuum conditions (P < 0.01). The trend of changes in three oxidation indicators was consistent with that of cell ultrastructure. Conclusion: TEM and SEM combined with oxidation indicators can provide clearer insights into cellular ultrastructural changes in walnut kernels after oxidation. The oxidation mechanisms of vacuum and non-vacuum packaged walnut kernels are the same, but their oxidation degrees are different. Notably, vacuum packaging can significantly reduce the oxidation of walnut kernels.

Abstract Background Uric acid as a prominent causal factor in the pathogenesis of hypertension is well recognized. Nevertheless, the influence of uric acid on the transition from prehypertension to hypertension within the Chinese population remains understudied. Methods A cohort of 1,516 prehypertensive individuals, aged 35 to 84 years, underwent recruitment following a comprehensive health assessment in 2017 and subsequent re-evaluation in 2022. Baseline characteristics and relevant clinical data were collected. The analytical approach encompassed multiple logistic regression and propensity score matching. Results Over 5 years, the cumulative incidence of hypertension amounted to 35.1%, with 33.9% in males and 37.3% in females, respectively. Notably, prehypertensive subjects concomitant with hyperuricemia exhibited a higher cumulative incidence of hypertension in comparison to the non-hyperuricemic counterparts (40.7% vs. 34.0%, p = 0.041). Multiple logistic regression unveiled a significant association between hyperuricemia and heightened hypertension risk (adjusted odds ratio [OR] = 1.44; 95% confidence interval [CI], 1.05–1.98; p = 0.022). Nonetheless, this association did not reach statistical significance when examining female subjects (adjusted OR = 1.10; 95% CI, 0.58–2.09; p = 0.781) or participants aged ≥ 60 years (adjusted OR = 1.07; 95% CI, 0.61–1.88; p = 0.814). Further validation through propensity score matching affirmed that subjects afflicted by hyperuricemia experienced a substantially elevated risk of transitioning from prehypertension to hypertension over the course of five years compared with the non-hyperuricemic counterparts (41.3% vs. 32.3%, p = 0.045), after adjusting for 12 covariates including age and gender. Hyperuricemia emerged as an independent risk factor predisposing individuals to the development of hypertension from a prehypertensive state. Conclusion This observation prompted the formulation of a hypothesis suggesting that ameliorating elevated uric acid levels may potentially mitigate the progression from prehypertension to hypertension.

Abstract The prevalence of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) and carbapenem-resistant Enterobacterales (CRE) has become a global public health problem. ESBL-E/CRE colonization can increase the risk of infection in patients and lead to poor disease prognosis. We conducted a systematic review and meta-analysis to evaluate current decolonization strategies regarding ESBL-E/CRE and their efficacy. A literature search was conducted until August 2023 on the five databases to review decolonization strategies associated with ESBL-E/CRE. A meta-analysis was conducted using RevMan 5.4 to compare differences in the decolonization strategy with placebo controls. The primary outcome was decolonization rates, with secondary outcomes of attributable death and adverse events. Quality of identified studies was determined using the Newcastle–Ottawa scale and cochrane risk assessment tool. Random and fixed effects meta-analyses were performed to calculate pooled value. A total of 25 studies were included. In five randomized controlled trial (RCT) studies, the decolonization effect of selective digestive decontamination(SDD) on ESBL-E/CRE at the end of treatment was significantly better in the experimental group than the controls [risk radio (RR): 3.30; 95% CI 1.78–6.14]. In three n-RCT studies, the decolonization effect in the experimental group was still better than the controls one month after SDD therapy [odds ratio (OR): 4.01; 95% CI 1.88–8.56]. The combined decolonization rates reported by six single-arm trial studies of SDD therapy ranged from 53.8 to 68.0%. Additionally, TSA analysis confirmed the effectiveness of SDD therapy. In studies on Faecal microbiota transplantation (FMT) therapy, the decolonization effect of the experimental group was significantly better than the controls 1 month after treatment (OR: 2.57; 95% CI 1.07–6.16). In studies without a control group and with varying follow-up times, the decolonization rates varied widely but indicated the effectiveness trend of FMT therapy (61.3–81.2%). Currently, research on the decolonization effect of probiotic therapy on ESBL-E/CRE is insufficient, and only a systematic review was conducted. SDD and FMT strategies have short-term benefits for ESBL-E/CRE decolonization, but long-term effects are unclear. The effect of probiotic therapy on ESBL-E/CRE decolonization is an interesting topic that still requires further investigation.

Abstract Probe-based nucleic acid enrichment represents an effective route to enhance the detection capacity of next-generation sequencing (NGS) in a set of clinically diverse and relevant microbial species. In this study, we assessed the effect of the enrichment-based sequencing on identifying respiratory infections using tiling RNA probes targeting 76 respiratory pathogens and sequenced using both Illumina and Oxford Nanopore platforms. Forty respiratory swab samples pre-tested for a panel of respiratory pathogens by qPCR were used to benchmark the sequencing data. We observed a general improvement in sensitivity after enrichment. The overall detection rate increased from 73 to 85% after probe capture detected by Illumina. Moreover, enrichment with probe sets boosted the frequency of unique pathogen reads by 34.6 and 37.8-fold for Illumina DNA and cDNA sequencing, respectively. This also resulted in significant improvements on genome coverage especially in viruses. Despite these advantages, we found that library pooling may cause reads mis-assignment, probably due to crosstalk issues arise from post-capture PCR and from pooled sequencing, thus increasing the risk of bleed-through signal. Taken together, an overall improvement in the breadth and depth of pathogen coverage is achieved using enrichment-based sequencing method. For future applications, automated library processing and pooling-free sequencing could enhance the precision and timeliness of probe enrichment-based clinical metagenomics.

Abstract Antibody-dependent enhancement (ADE) is a potential concern for the development of Zika virus (ZIKV) vaccines. Cross-reactive but poorly neutralizing antibodies, usually targeting viral pre-membrane or envelope (E) proteins, can potentially enhance dengue virus (DENV) infection. Although E domain III (EDIII) contains ZIKV-specific epitopes, its immunogenicity is poor. Here, we show that dimeric EDIII, fused to human IgG1 Fc fragment (EDIII-Fc) and encoded by circular RNA (circRNA), induces better germinal center reactions and higher neutralizing antibodies compared to circRNAs encoding monomeric or trimeric EDIII. Two doses of circRNAs encoding EDIII-Fc and ZIKV nonstructural protein NS1, another protective antigen, prevent lethal ZIKV infection in neonates born to immunized C57BL/6 mice and in interferon-α/β receptor knockout adult C57BL/6 mice. Importantly, a single-dose optimized circRNA vaccine with improved antigen expression confers potent and durable protection without inducing obvious DENV ADE in mice, laying the groundwork for developing flavivirus vaccines based on circRNAs encoding EDIII-Fc and NS1.

Abstract The RAB interacting factor (RABIF) is a putative guanine nucleotide exchange factor that also functions as a RAB-stabilizing holdase chaperone. It has been implicated in pathogenesis of several cancers. However, the functional role and molecular mechanism of RABIF in hepatocellular carcinoma (HCC) are not entirely known. Here, we demonstrate an upregulation of RABIF in patients with HCC, correlating with a poor prognosis. RABIF inhibition results in decreased HCC cell growth both in vitro and in vivo. Our study reveals that depleting RABIF attenuates the STOML2-PARL-PGAM5 axis-mediated mitophagy. Consequently, this reduction in mitophagy results in diminished mitochondrial reactive oxygen species (mitoROS) production, thereby alleviating the HIF1α-mediated downregulation of glycolytic genes HK1, HKDC1, and LDHB. Additionally, we illustrate that RABIF regulates glucose uptake by controlling RAB10 expression. Importantly, the knockout of RABIF or blockade of mitophagy sensitizes HCC cells to sorafenib. This study uncovers a previously unrecognized role of RABIF crucial for HCC growth and identifies it as a potential therapeutic target.

Abstract Quantum walks provide a speed-up in computational power for various quantum algorithms and serve as inspiration for the construction of complex graph representations. Many pioneering works have been dedicated to expanding the experimental state space and the complexity of graphs. However, these experiments are mostly limited to small experimental scale, which do not reach a many-body level and fail to reflect the multi-particle quantum interference effects among non-adjacent modes. Here, we present a quantum walk with three photons on a two-dimensional triangular lattice, which is mapped to a 19 × 19 × 19 high-dimensional state space and constructs a complex graph with 6859 nodes and 45,486 edges. By utilizing the statistical signatures of the output combinations and incorporating machine learning techniques, we successfully validate the nonclassical properties of the experiment. Our implementation provides a paradigm for exponentially expanding the state space and graph complexity of quantum walks, paving the way for surmounting the classical regime in large-scale quantum simulations.

Abstract Background Ferroptosis, a newly identified form of regulated cell death triggered by small molecules or specific conditions, plays a significant role in virus-associated carcinogenesis. However, whether tumours arising after high-risk HPV integration are associated with ferroptosis is unexplored and remains enigmatic. Methods High-risk HPV16 integration was analysed by high­throughput viral integration detection (HIVID). Ferroptosis was induced by erastin, and the levels of ferroptosis were assessed through the measurement of lipid-reactive oxygen species (ROS), malondialdehyde (MDA), intracellular Fe2+ level and transmission electron microscopy (TEM). Additionally, clinical cervical specimens and an in vivo xenograft model were utilized for the study. Results Expression of HPV16 integration hot spot c-Myc negatively correlates with ferroptosis during the progression of cervical squamous cell carcinoma (CSCC). Further investigation revealed that the upregulated oncogene miR-142-5p in HPV16-integrated CSCC cells served as a critical downstream effector of c-Myc in its target network. Inhibiting miR-142-5p significantly decreased the ferroptosis-suppressing effect mediated by c-Myc. Through a combination of computational and experimental approaches, HOXA5 was identified as a key downstream target gene of miR-142-5p. Overexpression of miR-142-5p suppressed HOXA5 expression, leading to decreased accumulation of intracellular Fe2+ and lipid peroxides (ROS and MDA). HOXA5 increased the sensitivity of CSCC cells to erastin-induced ferroptosis via transcriptional downregulation of SLC7A11, a negative regulator of ferroptosis. Importantly, c-Myc knockdown increased the anti-tumour activity of erastin by promoting ferroptosis both in vitro and in vivo. Conclusions Collectively, these data indicate that HPV16 integration hot spot c-Myc plays a novel and indispensable role in ferroptosis resistance by regulating the miR-142-5p/HOXA5/SLC7A11 signalling axis and suggest a potential therapeutic approach for HPV16 integration-related CSCC.

In current practice of bolt reaming and anchoring of roadways in soft coal and rock mass, resin cartridges bend easily under the strong pushing and stirring of bolts, and the resin accumulates in the bolt-reamed area and does not participate in the stirring. As a result, bolts encounter high drilling resistance and cannot reach the bottom of drillholes. The effective anchorage length is far less than the actual anchorage length. Bolts are not centered, and the shear is misaligned at the joint surface in the reaming area, which leads to cracking of the whole anchoring solid and large shear deformation of bolts. This study systematically analyzes the characteristics of roadway bolt reaming and anchoring. The influences of resin stirring force, bolt pull-out force, and reaming–anchoring solid strength on reaming–anchoring performance were analyzed theoretically. The main purpose is to develop a device that enhances reaming and anchoring. The mechanism through which the device strengthens the reaming–anchoring solid was analyzed theoretically. Numerical simulation and experiments were carried out to verify the improved performance of the small-pore reaming and anchoring using the proposed technology. The results showed that the stirring migration rate of the resin cartridge is greatly improved by adding the device to bolts. The reaction rate of the anchoring mixture, stirring pressure, pull-out force of the reaming and anchoring system, bolt concentricity, and shear and compressive strengths of the anchoring solid are also enhanced in the reaming area. This ensures that the resin cartridge in the reaming area is completely stirred, which greatly improves the shear resistance of the reaming–anchoring solid. Meanwhile, the drilling performance, torsional force, and stirring efficiency of bolts are maximized and prevail over those of conventional bolts.

Abstract Objective To evaluate the feasibility, safety and efficacy of robot-assisted laparoscopic modified ureteroplasty using a lingual mucosa graft (LMG) or an appendiceal flap (AF) for complex ureteral strictures and summarize our experience. Methods A total of 16 patients with complex ureteral strictures (range: 1.5–5 cm) who underwent robotic-assisted laparoscopic-modified ureteroplasty and were admitted to our hospital from May 2022-October 2023 were retrospectively analyzed. We used modified presuture methods in patients who needed the posteriorly augmented anastomotic technique to reduce anastomotic tension. Perioperative variables and outcomes were recorded for each patient. Results The operation under robot-assisted laparoscopy was successfully performed in all sixteen patients (12 with LMG ureteroplasty and 4 with AF ureteroplasty) without conversion to open surgery. The mean length of the ureteral structure was 2.90 ± 0.90 cm (range: 1.5–5 cm), the mean operation duration was 209.69 ± 26.74 min (range: 170–255 min), the median estimated blood loss was 75 (62.5) ml (range: 50–200 ml), and the duration of postoperative hospitalization was 10.44 ± 2.10 d (range: 7–14 d). The follow-up time in this group was 6 ~ 21 months. The success rate of the surgery was 100%. Conclusion Robot-assisted laparoscopic modified ureteroplasty using AF or LMG is a safe and feasible operation for complex ureteral strictures and deserves to be popularized.

Abstract Background Large variations in respiratory system compliance and resistance may cause the accuracy of tidal volume (VT) delivery beyond the declared range. This study aimed at evaluating the accuracy of VT delivery using a test lung model to simulate pulmonary mechanics under normal or disease conditions. Methods In vitro assessment of the VT delivery accuracy was carried out on two commercial ventilators. Measurements of the inspired and expired VT from the ventilator and FlowAnalyser were compared to evaluate the separated and combined influences of compliance and resistance on the delivered VT accuracy. To do this, the errors of five delivered volumes (30 ml, 50 ml, 100 ml, 300 ml, and 500 ml) were checked under 29 test conditions involving a total of 27 combinations of resistance and compliance. Results For the tested ventilator S1 with a flow sensor near the expiratory valve, the average of expired VT errors (ΔVTexp) in three measurements (4 test conditions for each measurement) correlated to test lung compliance (r=-0.96, p = 0.044), and the average of inspired VT errors (ΔVTins) correlated to compliance (r = 0.89, p = 0.106); for the tested ventilator S2 with a flow sensor located at the Y piece, no clear relationship between compliance and ΔVTexp or ΔVTins was found. Furthermore, on two ventilators tested, the current measurements revealed a poor correlation between test lung resistance and ΔVTins or ΔVTexp, and the maximum values of ΔVTexp and ΔVTins correspond to the maximum resistance of 200 cmH2O/(L/s), at which the phenomenon of the flap fluttering in the variable orifice flow senor was observed, and the recorded peak inspiratory pressure (Ppeak) was much higher than the Ppeak estimated by the classical equation of motion. In contrast, at the lower resistance values of 5, 20, 50 and 100 cmH2O/(L/s), the recorded Ppeak was very close to the estimated Ppeak. Overall, the delivered VT errors were in the range of ± 14% on two ventilators studied. Conclusions Depending on the placement site of the flow sensor in the ventilator circuit, the compliance and resistance of the test lung have different influences on the accuracy of VT delivery, which is further attributed to different fluid dynamics effects of the compliance and resistance. The main influence of compliance is to raise the peak inspiratory pressure Ppeak, thereby increasing the compression volume within the ventilator circuit; whereas a high resistance not only contributes to elevating Ppeak, but more importantly, it governs the gas flow conditions. Ppeak is a critical predictive indicator for the accuracy of the VT delivered by a ventilator.

Abstract Branched-chain amino acid transaminase 2 (BCAT2) encodes a crucial protein involved in the initial catalysis of branched-chain amino acid (BCAA) catabolism, with emerging evidence suggesting its association with tumor progression. This study explores BCAT2 in a pan-cancer multi-omics context and evaluates its prognostic significance. We utilized a multi-database approach, analyzing cBioPortal for genetic alterations, RNA-Seq data from TCGA and GTEx for expression patterns, and RSEM for transcript analysis. Protein expression and interaction networks were assessed using the Human Protein Atlas, UniProt, and STRING. Prognostic value was determined through Cox regression analysis of TCGA clinical survival data, while immune cell infiltration across various cancers was examined using TCGA data and the TIMER2 platform. Our results revealed that BCAT2 alterations are primarily amplifications and is upregulated in various tumors, correlating with poor survival rates in several tumor types, including GBMLGG, LGG, and UVM. Elevated BCAT2 protein levels were common in pan-cancer, interacting with a range of metabolic enzymes. Additionally, BCAT2 expression significantly influenced CD4+ T cells, CD8+ T cells, and Treg cells infiltration, with varied correlations across cancer types. These findings indicate BCAT2 as a potential biomarker for cancer diagnosis and therapy, potentially regulating key metabolic and immune factors to mediate tumor progression and the microenvironment.

Abstract Kadsura heteroclita (Roxb) Craib also named Xuetong in Tujia ethnomedicine in China, has been traditionally employed in rheumatoid arthritis (RA) treatment. Our preceding investigations have elucidated that Xuetongsu (XTS), a triterpenoid compound predominant in Xuetong, showed excellent anti-RA-fibroblast-like synoviocytes (RAFLS) proliferation effect. However, XTS belongs to the trace components of the Xuetong plant, which poses certain limitations to the research. In this study, we designed a method that enhanced the extraction yield of XTS and explored the mechanism of its inhibition of RAFLS cell proliferation and migration in the treatment of RA. The results displayed that XTS reduced RAFLS cell proliferation, with an IC50 value of 4.68 ± 0.65 µM. A series of experimental techniques were utilized to show that XTS induce apoptosis in RAFLS cells at concentrations ranging from 4.5 to 18 µM, including wound healing assay, flow cytometry, and western blot analysis. Moreover, XTS at dosages of 0.42–0.84 mg/kg markedly attenuated paw swelling and synovial hyperplasia in arthritic rats, primarily through the inhibition of RAFLS migration and promotion of RAFLS apoptosis via High mobility group box 1 (HMGB-1)/Matrix metalloproteinase-9 (MMP-9)/MMP-13 signaling pathway and Bcl-2/Bax/Caspase-3 signaling pathway, respectively.

Abstract Feature enhancement is important in mechanical equipment fault diagnosis. A limited set of characteristic parameters is insufficient for diagnosing bearing signals with multiple fault types. The presence of noise increases the difficulty of extracting fault features from images. To address the challenge of diagnosing rolling bearing faults in complex environments, this study presents an enhanced weighted image fusion framework aimed at enhancing fault features within the images, which enables accurate diagnosis of bearing faults using a limited number of features. The proposed method encompasses four distinct stages. In the first stage, a symmetrized dot pattern method is employed to transform one-dimensional time-series data into two-dimensional images, visualizing the signal in a 2D format. In the second stage, image binarization and an improved weighted fusion method are utilized to simplify subsequent processing and enhance the image features. The third stage involves extracting the image’s contrast and maximum singular value to improve the Canberra distance calculation. Finally, the enhanced Canberra distance is used for classifying bearing faults. Performance testing of the image feature enhancement is conducted on various datasets containing rolling bearings. Comparative experiments with alternative enhancement methods demonstrate the superiority of the proposed improved weighted image fusion framework. Comparative experiments with the original Canberra distance validate the effectiveness of the enhanced Canberra distance. Additionally, experiments conducted in noisy environments confirm the robustness of the proposed approach. Furthermore, the image feature enhancement method is applied to other bearing datasets, and the experimental results demonstrate its effectiveness in enhancing fault feature representation and achieving accurate diagnosis of rolling bearings.

Abstract Background Up to 17% of cancer survivors have been reported to develop second primary cancers (SPC), which cause significant physical and economic distress and often complicate clinical decision-making. However, understanding of SPC remains limited and superficial. Human leukocyte antigen (HLA) is characterized by its polymorphism and has been associated with various diseases. This study aims to explore the role of HLA diversity in SPC incidence. Methods We analyzed a cohort of 47,550 cancer patients from the UK Biobank. SNP-derived HLA alleles were used and SPC-related HLA alleles were identified using logistic regression, followed by stepwise filtering based on the Akaike information criterion (AIC) and permutation tests. Additionally, we examined the association between extragenetic factors and the risk of SPC in patients carrying hazardous HLA alleles. Results During a median follow-up of 3.11 years, a total of 2894 (6.09%) participants developed SPC. We identified three protective HLA alleles (DRB1*04:03 and DPA1*02:02 for males and DRB5*01:01 for females) and two hazardous alleles (A*26:01 for males and DPB1*11:01 for females) about SPC. The presence of the protective alleles was associated with a reduced SPC risk (males: hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.59–0.89; females: HR 0.81, 95% CI 0.70–0.93), while the hazardous alleles were linked to an increased risk (males: HR 1.27, 95% CI 1.03–1.56; females: HR 1.35, 95% CI 1.07–1.70). The hazardous allele A*26:01 indicated skin-lung organ-specific SPC occurrence in males. Animal fat and vitamin C were associated with SPC risk in males carrying the hazardous alleles, while free sugar and vegetable fat were linked to SPC risk in females. Conclusions These results suggest that HLA alleles may serve as biomarkers for the susceptibility and organ-specific occurrence of SPC, while dietary modulation may mitigate hazardous alleles-related SPC risk, potentially aiding in the early prediction and prevention of SPC.

Abstract The current throughput of conventional organic chemical synthesis is usually a few experiments for each operator per day. We develop a robotic system for ultra-high-throughput chemical synthesis, online characterization, and large-scale condition screening of photocatalytic reactions, based on the liquid-core waveguide, microfluidic liquid-handling, and artificial intelligence techniques. The system is capable of performing automated reactant mixture preparation, changing, introduction, ultra-fast photocatalytic reactions in seconds, online spectroscopic detection of the reaction product, and screening of different reaction conditions. We apply the system in large-scale screening of 12,000 reaction conditions of a photocatalytic [2 + 2] cycloaddition reaction including multiple continuous and discrete variables, reaching an ultra-high throughput up to 10,000 reaction conditions per day. Based on the data, AI-assisted cross-substrate/photocatalyst prediction is conducted.

Abstract Background Research has elucidated that homeobox B9 (HOXB9), an important transcriptional activator, plays a pivotal role in promoting the invasion and metastasis of hepatocellular carcinoma (HCC) cells. However, the mechanism by which HOXB9 promotes the invasion and metastasis of HCC cells is incompletely understood and needs further exploration. Methods HOXB9 and snail family transcriptional repressor 2 (SNAI2) expression were analyzed using qRT-PCR and western blotting. The invasion and metastasis of hepatocellular carcinoma (HCC) cells were investigated using in vitro and in vivo assays. The H3K27me3 enrichment and HOXB9 interaction with microRNA 203a (MIR203A) or SNAI2 were detected using ChIP-qPCR. Transcriptional activities of SNAI2 and MIR203A promoter were detected using dual-luciferase reporter assays. Co-IP and GST pull-down assays were performed to confirm the binding between HOXB9 and EZH2. Results HOXB9 and SNAI2 were highly expressed in HCC tissues and their expression was positively intercorrelated and associated with poor prognosis in patients with HCC. In vitro and in vivo experiments confirmed that HOXB9 can upregulate the expression of SNAI2 to promote the invasion and metastasis of HCC cells. Furthermore, HOXB9 elevated SNAI2 expression by inhibiting MIR203A expression, a tumor suppressor gene, in HCC cells. Mechanistically, HOXB9 recruited enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) through interaction with its WD-binding domain, which increased EZH2-mediated histone H3 lysine 27 trimethylation (H3K27me3) at the MIR203A promoter region, in turn repressing the transcriptional activity and expression of MIR203A and consequently increasing the SNAI2 level in HCC cells. Finally, empirical evidence from in vitro and in vivo studies confirmed that mitigation of the HOXB9-mediated enhancement of epigenetic silencing of MIR203A inhibited SNAI2 expression, impeding the invasion and metastasis of HCC cells. Conclusions Our study reveals a novel mechanism by which HOXB9 promotes the invasion and metastasis of HCC cells and expands the understanding of the function of HOXB9 in tumor progression and provides a novel therapeutic strategy for curtailing HCC invasion and metastasis.

Abstract Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide. Its complexity is influenced by various signal transduction networks that govern cellular proliferation, survival, differentiation, and apoptosis. The pathogenesis of CRC is a testament to the dysregulation of these signaling cascades, which culminates in the malignant transformation of colonic epithelium. This review aims to dissect the foundational signaling mechanisms implicated in CRC, to elucidate the generalized principles underpinning neoplastic evolution and progression. We discuss the molecular hallmarks of CRC, including the genomic, epigenomic and microbial features of CRC to highlight the role of signal transduction in the orchestration of the tumorigenic process. Concurrently, we review the advent of targeted and immune therapies in CRC, assessing their impact on the current clinical landscape. The development of these therapies has been informed by a deepening understanding of oncogenic signaling, leading to the identification of key nodes within these networks that can be exploited pharmacologically. Furthermore, we explore the potential of integrating AI to enhance the precision of therapeutic targeting and patient stratification, emphasizing their role in personalized medicine. In summary, our review captures the dynamic interplay between aberrant signaling in CRC pathogenesis and the concerted efforts to counteract these changes through targeted therapeutic strategies, ultimately aiming to pave the way for improved prognosis and personalized treatment modalities in colorectal cancer.

Abstract Resistance to gemcitabine in pancreatic ductal adenocarcinoma (PDAC) leads to ineffective chemotherapy and, consequently, delayed treatment, thereby contributing to poor prognosis. Glycolysis is an important intrinsic reason for gemcitabine resistance as it competitively inhibits gemcitabine activity by promoting deoxycytidine triphosphate accumulation in PDAC. However, biomarkers are lacking to determine which patients can benefit significantly from glycolysis inhibition under the treatment of gemcitabine activity, and a comprehensive understanding of the molecular mechanisms that promote glycolysis in PDAC will contribute to the development of a strategy to sensitize gemcitabine chemotherapy. In this study, we aimed to identify a biomarker that can robustly indicate the intrinsic resistance of PDAC to gemcitabine and guide chemotherapy sensitization strategies. After establishing gemcitabine-resistant cell lines in our laboratory and collecting pancreatic cancer and adjacent normal tissues from gemcitabine-treated patients, we observed that circRNA hsa_circ_0008383 (namely cNEK6) was highly expressed in the peripheral blood and tumor tissues of patients and xenografts with gemcitabine-resistant PDAC. cNEK6 enhanced resistance to gemcitabine by promoting glycolysis in PDAC. Specifically, cNEK6 prevented K48 ubiquitination of small ribonucleoprotein peptide A from the BTRC, a ubiquitin E3 ligase; thus, the accumulated SNRPA stopped PP2Ac translation by binding to its G-quadruplexes in 5′ UTR of mRNA. mTORC1 pathway was aberrantly phosphorylated and activated owing to the absence of PP2Ac. The expression level of cNEK6 in the peripheral blood and tumor tissues correlated significantly and positively with the activation of the mTORC1 pathway and degree of glycolysis. Hence, the therapeutic effect of gemcitabine is limited in patients with high cNEK6 levels, and in combination with the mTORC1 inhibitor, rapamycin, can enhance sensitivity to gemcitabine chemotherapy.

Abstract Background Extracting the premolars is an effective strategy for patients with bimaxillary dentoalveolar protrusion. Clear aligners (CAs) close the extraction spaces through shortening the length of aligners. The contraction force generated by the terminal of aligners makes the posterior teeth tip mesially, which is known as the roller coaster effect. This phenomenon is even worse in the 2nd premolar extraction cases. Posterior anchorage preparation is commonly used to protect the angulation of molars, taking the form of presetting distal tipping value. However, the distal tipping design aggravates the anchorage loss of anterior teeth simultaneously. This study aimed to explore the different anchorage loss of the posterior teeth when the 1st or 2nd premolars were extracted using CAs, respectively in maxillary and mandibular arches, further providing guidance for anchorage preparation design in clinical practice. Methods Two bimaxillary finite element models with different extraction patterns were established to simulate the anterior en-masse retraction process of the CAs. In Model 1, the maxillary and mandibular 1st premolars were extracted, while in Model 2, the 2nd premolars were extracted. Finite element analysis methods were utilized to analyze the tipping angle of the anterior and posterior teeth. Results Compared between two models, the anterior teeth exhibited a greater lingual inclination tendency and the posterior teeth exhibited a slighter mesial tipping tendency in Model 1 regarding individual tooth. The closer to the extraction spaces, the greater the tip, and the distal tipping tendency of the 1st premolars was more evident than the mesial tipping tendency of the 1st molars in Model 2. Compared between the maxillary and mandibular arches, the mesial tipping tendency of individual posterior tooth was more evident in the maxilla. In addition, the highest hydrostatic stress of the periodontal ligaments was concentrated on the cervical and apical parts directly adjacent to the extraction spaces, and it exhibited relatively uniform distribution in Model 1. Conclusions The individual posterior tooth showed the same mesial tipping direction but to different degree when the 1st or the 2nd premolars were extracted during clear aligner treatment. Presetting anchorage preparation design for the posterior teeth is essential to alleviate the roller coaster effect, especially in the 2nd premolar extraction cases. Furthermore, larger anchorage preparation value should be proposed for the maxillary posterior teeth.

Background: Oxaliplatin is commonly used to treat gastrointestinal malignancies. However, its applications are limited due to potential adverse drug reactions (ADRs), particularly severe anaphylactic shock. There is no method to predict or prevent ADRs caused by oxaliplatin. Therefore, we aimed to investigate the genetic HLA predisposition and immune mechanism of oxaliplatin-induced ADRs. Methods: A retrospective review was performed for 154 patients with ADRs induced by oxaliplatin during 2016–2021 recorded in our ADR notification system. HLA genotyping was conducted for 47 patients with oxaliplatin-induced ADRs, 1100 general population controls, and 34 oxaliplatin-tolerant controls in 2019–2023. The in vitro basophil activation test (BAT) was performed and oxaliplatin-specific IgE levels were determined. Results: The incidence of oxaliplatin-induced ADRs and anaphylactic shock in our cohort was 7.1% and 0.15%, respectively. Of the 154 patients, 67.5% suffered rash/eruption; 26.0% of the patients who could not undergo oxaliplatin rechallenge were considered to show oxaliplatin-induced immune-mediated hypersensitivity reactions (HRs). The genetic study found that the HLA-DRB∗12:01 allele was associated with oxaliplatin-induced HRs compared to the general population controls (sensitivity = 42.9%; odds ratio [OR] = 3.4; 95% CI = 1.4–8.2; P = 0.008) and tolerant controls (OR = 12; 95% CI = 2.3–63.7; P = 0.001). The in vitro BAT showed higher activation of CD63+ basophils in patients with oxaliplatin-induced HRs compared to the tolerant controls (P

Abstract Background Cervical squamous cell carcinoma (CSCC) is a prevalent gynecological malignancy worldwide. Current treatments for CSCC can impact fertility and cause long-term complications, underscoring the need for new therapeutic strategies. Oncolytic virotherapy has emerged as a promising option for cancer treatment. Previous research has demonstrated the oncolytic activity of the coxsackievirus B3 strain 2035 A (CVB3/2035A) against various tumor types. This study aims to evaluate the clinical viability of CVB3/2035A for CSCC treatment, focusing on its oncolytic effect in patient-derived CSCC organoids. Methods The oncolytic effects of CVB3/2035A were investigated using human CSCC cell lines in vitro and mouse xenograft models in vivo. Preliminary tests for tumor-selectivity were conducted on patient-derived CSCC tissue samples and compared to normal cervical tissues ex vivo. Three patient-derived CSCC organoid lines were developed and treated with CVB3/2035A alone and in combination with paclitaxel. Both cytotoxicity and virus replication were evaluated in vitro. Results CVB3/2035A exhibited significant cytotoxic effects in human CSCC cell lines and xenograft mouse models. The virus selectively induced oncolysis in patient-derived CSCC tissue samples while sparing normal cervical tissues ex vivo. In patient-derived CSCC organoids, which retained the immunohistological characteristics of the original tumors, CVB3/2035A also demonstrated significant cytotoxic effects and efficient replication, as evidenced by increased viral titers and presence of viral nucleic acids and proteins. Notably, the combination of CVB3/2035A and paclitaxel resulted in enhanced cytotoxicity and viral replication. Conclusions CVB3/2035A showed oncolytic activity in CSCC cell lines, xenografts, and patient-derived tissue cultures and organoids. Furthermore, the virus exhibited synergistic anti-tumor effects with paclitaxel against CSCC. These results suggest CVB3/2035A could serve as an alternative or adjunct to current CSCC chemotherapy regimens.

Abstract Distributed optical fiber sensor (DAS) is an emerging acquisition technique and has begun to be widely applied in seismic exploration owing to its advantages in acquisition and deployment. Nonetheless, DAS record has a low signal-to-noise ratio (SNR) due to the intense background noise. How to suppress the DAS background noise and increase the SNR of the DAS records has gradually become one of the hot issues in the field of seismic data processing. To solve the challenging tasks in intense DAS noise suppression, a multiscale sparse asymmetric attention convolutional neural network (MSAACNN) is proposed. The network uses dilated convolutions to expand the receptive field and map more feature information. Moreover, asymmetric convolutions are introduced to form an asymmetric unit, aiming to strengthen the feature extraction ability and realize the interaction between feature information of different scales. Finally, a pyramid attention module is used to enhance the primary features and improve the network denoising performance. The experimental results show that MSAACNN can effectively suppress the complex background noise in DAS records, compared with the traditional denoising methods and typical convolutional neural network (CNN) architecture. Additionally, the recovered signal components in the processing results are clear and complete, with significantly improved SNR.

Abstract Rapid glucose supply is crucial for animal survival during stress response. How the timescale of stress-induced glucose release precisely controlled by hypothalamic corticotropin-releasing hormone (CRH) neurons remains unclear. Here, we show that stress-induced hyperglycemia can be divided into at least two stages in male mice: the first fast stage is mediated by hypothalamus (paraventricular to ventromedial hypothalamus)-sympathetic (raphe pallidus nucleus to intermediolateral nucleus)-liver (HSL) axis activity; the second delayed stage is mediated by adrenal activity. Blocking the activity of HSL axis impairs predatory evoked flight responses, indicating that the HSL pathway activity is necessary for stress coping. We further reveal the intracellular signal cascade for CRH signal in the hypothalamus, which is mediated by GABAA receptor β3 subunit phosphorylation at S408/409, results in prevention of GABAA receptor membrane recruitment. Thus, we uncovered the precise timescale of glucose supply during stress which is mediated by adrenal independent HSL and adrenal dependent pathway respectively.

Utilizing first-order beam dynamics models is adequate for studying the beam properties during the conceptual design of a cyclotron-based proton therapy beamline. After finishing lattice design, particle-matter interaction simulations for passive elements (e.g., degrader, collimators, energy slit) are required. The cascade simulation is used for lattice updates in each iteration, which is complicated. In addition, when the models involve particle tracking and particle-matter interaction, their optimization process is time-consuming. Therefore, this study proposes a start-to-end modeling method using Monte Carlo Beam Delivery Simulation (BDSIM) software that considers more realistic factors, such as particle-matter interaction and the realistic vacuum chamber, to precisely evaluate working parameters, along with an efficient optimization method that utilizes multi-objective Bayesian optimization (MOBO) to improve transmission efficiency. Taking the Huazhong University of Science and Technology proton therapy facility (HUST-PTF) as an example, beam loss along the beamline is located, quantified, and subsequently reduced by tuning the quadrupole strengths based on MOBO. The results show that: (i) By considering the particle-matter interaction and the realistic vacuum chamber, the precision in the prediction of the beam properties is improved; (ii) After optimization, the transmission efficiency of the entire beamline is relatively increased by an average of 6.52 % under different energy settings, especially 11.39 % at 70 MeV.

Wampee (Clausena lansium) is an important evergreen fruit tree native to southern China that has a long history of use for medicinal purposes. Here, a chromosome-level genome of C. lansium was constructed with a genome size of 282.9 Mb and scaffold N50 of 30.75 Mb. The assembled genome contains 48.70% repetitive elements and 24,381 protein-coding genes. Comparative genomic analysis showed that C. lansium diverged from Aurantioideae 15.91–24.95 million years ago. Additionally, some expansive and specific gene families related to methyltransferase activity and S-adenosylmethionine-dependent methyltransferase activity were also identified. Further analysis indicated that N-methyltransferase (NMT) is mainly involved in alkaloid biosynthesis and O-methyltransferase (OMT) participates in the regulation of coumarin accumulation in wampee. This suggested that wampee's richness in alkaloids and coumarins might be due to the gene expansions of NMT and OMT. The tandem repeat event was one of the major reasons for the NMT expansion. Hence, the reference genome of C. lansium will facilitate the identification of some useful medicinal compounds from wampee resources and reveal their biosynthetic pathways.

Viral covert mortality disease (VCMD) in cultured shrimp is caused by covert mortality nodavirus (CMNV). The infected shrimp mainly die successively in the deep-water areas at the bottom of farming ponds, which is difficult to observe; as such, the term "covert mortality disease" was coined by local farmers. The disease is known as running mortality syndrome by Southeast Asian farmers because a small number of diseased shrimp die daily in the infected ponds, and more continue to die until harvest time. The infected shrimp mostly show symptoms such as carapace softening, hepatopancreas color fading, atrophy, empty stomach, slow growth, etc. In the acute infection stage, the infected shrimp show opaque abdominal muscles. The prevalence of VCMD has caused severe economic losses in the shrimp farming industry over the past decade. CMNV can infect many major cultured shrimp species, including Penaeus vannamei, P. japonicus, P. chinensis, Macrobrachium rosenbergii, and Exopalaemon carinicauda. Moreover, the virus infects the co-inhabiting organisms in shrimp ponds, which makes it difficult to remove from shrimp farming areas due to its wide host range among invertebrates and its transport by many vectors. To elucidate the prevalence of CMNV in the main cultured shrimp species in China in recent years, an epidemiological investigation of CMNV, including clinical sample collection from shrimp and other organisms inhabiting the shrimp ponds, was carried out in the main shrimp culture areas of China from 2021 to 2022, and the collected samples were systematically analyzed using molecular biology, histopathology, and transmission electron microscopy approaches. During this period, 1, 299 samples were collected from Tianjin, Shandong, Jiangsu, Hainan, Hubei, and Xinjiang and included P. vannamei, M. rosenbergii, P. japonicus, P. chinensis, Procambarus clarkia, and other organisms living in shrimp culture ponds. The collected samples were analyzed using CMNV TaqMan probe real-time quantitative reverse transcription PCR (TaqMan RT-qPCR). The results showed that CMNV could be detected in the main cultured shrimp species, including P. vannamei, M. rosenbergii, and P. japonicus. A percentage of the samples collected from Shandong, Jiangsu, Hainan, Xinjiang, Guangxi, and Tianjin were observed to be CMNV-positive in the TaqMan RT-qPCR assays. In addition to cultured shrimp, CMNV was detected in organisms living in the shrimp ponds, such as Artemia collected in 2021 and Perinereis aibuhitensis collected in 2022. The CMNV-positive rate of samples collected in 2021 was 10.04% (69/687), and that of samples collected in 2022 was 11.44% (70/612). Epidemiological investigation showed that CMNV infection in outdoor pond culture usually caused a certain degree of cumulative death, whereas CMNV infection in indoor culture mainly caused the softening and reduced growth of infected shrimp and did not cause a large number of infected shrimp to die. High CMNV loads were detected in samples of Artemia used as fresh bait for shrimp and in samples of P. aibuhitensis living in shrimp pond soils. Accordingly, a high CMNV infection rate was observed in cultured P. vannamei feeding on CMNV-positive Artemia and in that farmed in ponds containing CMNV-positive P. aibuhitensis. The results indicated that CMNV vectors such as Artemia and P. aibuhitensis may pose a high risk of CMNV transition, threatening the health of the shrimp in the culture system. Recent studies on the pathogenesis of CMNV infection indicated that the virus mainly infected epithelial tissues, nerve tissues, and connective tissues in the hepatopancreas, appendages, mid-gut, gills, eye stalks, and nerves of shrimp. Therefore, histopathological and in situ hybridization analyses were performed on samples identified as CMNV-positive using TaqMan RT-qPCR in this study. Eosinophilic virus inclusion bodies were observed in the hepatopancreas and foremidgut tissues, and pathological lesions were observed in the appendicular nerves of diseased Penaeus shrimp. Moreover, obvious purple hybridization signals from the CMNV RNA probe were seen in tissues with lesions, which further confirmed the positive detection results for CMNV in shrimp samples obtained using TaqMan RT-qPCR in this study. The results of this study showed that, compared with previous years, there was still a high CMNV-positive detection rate in many areas of crustacean culture in 2022, and the epidemic risk of this virus was still high. Multiple CMNV-positive results were obtained in the co-inhabiting and feed organisms in crustacean farming ponds. These results remind fishery authorities and stakeholders in the prawn breeding industry to further strengthen the monitoring and early detection of CMNV to prevent and control the spread of the virus in seedlings, reduce the risk of epidemic hazards, and promote the sustainable and healthy development of the crustacean aquaculture industry.

Lithium-ion batteries (LIBs) are widely used as important energy storage and energy supply devices. The porous design and heteroatomization modification of carbon-based anode materials are crucial for achieving high-capacity and reversible energy storage in LIBs. Sol-gel method and pyrolysis treatment were used to obtain silica/silver composite particles used as templates. Polyphosphazene-coated silica/silver composite composite carbon materials (SiO2/Ag@PZS-C) were synthesized through in-situ self-assembly and carbonization of polyphosphazene. The electrochemical behavior and lithium storage mechanism of SiO2/Ag@PZS-C was also studied. The results reveal that the composite exhibited high specific capacity, stable cycling and superior rate performance. The double modification of silver nanoparticles and polyphosphazene carbon significantly improves the conductivity of silica and reduces the volume change. Moreover, the carbon shell of polyphosphazene facilitated the formation of a stable solid electrolyte interface film (SEI), preventing direct contact between the active material and the electrolyte, thereby substantially enhancing lithium storage performance.

Introduction: Posterior tibial slope (PTS) plays a vital role in knee stability. PTS of more than 12° may be considered with increased strain on the native anterior cruciate ligament (ACL) fibers. To handle the instability caused by changes in PTS degree, Proximal Tibial Anterior Closing Wedge Osteotomy (PT-ACWO) is adopted by surgeons. Methods: Between October 2015 and October 2019, our department conducted a retrospective analysis of patients who experienced anterior cruciate ligament reconstruction (ACLR) graft failures, with a particular focus on pathological PTS. The time from initial ACLR to revision ranged from 1 to 10 years, with a mean of 2.5 years. Radiological assessments of PTS were conducted, and outcomes were quantified using the International Knee Documentation Committee (IKDC) score, Lysholm score, and Tegner activity scale. The surgical technique and the use of 3D Patient-Specific Instrumentation (PSI) were outlined. Preoperative imaging included the use of Kirschner wires to establish tibial plateau reference points, and 3D-PSI was employed to guide the location and depth of the tibial osteotomy, which was performed obliquely. In a notable instance, a novel tibial tunnel was mapped out, and ortho-bridge system (OBS) fixation was utilized to ensure adequate space for the new tunnel. Results: In a cohort of seven patients with a mean follow-up of 28.1 months, a significant reduction in PTS was noted postoperatively (median [interquartile range, IQR], from 15.27° [13.46°, 16.60°] to 6.25° [5.89°, 6.78°]; P = 0.002). IKDC score improved to 85.10 (80.25, 88.10), P

The reactions of the angular ligand 4,4′-oxybis(N-(pyridin-3-yl)benzamide) (L1) and 1,4-naphthalenedicarboxylic acid (1,4-H2NDC) with divalent metal salts yielded three distinct coordination polymers (CPs): {[Zn2(L1)(1,4-NDC)2]·MeOH}n, 1, {[Cu(L1)(1,4-NDC)(H2O)]·3H2O}n, 2, and {[Cd(L1)(1,4-NDC)]·2H2O}n, 3. Complex 1 features a 2-fold interpenetrated 3D framework with the (412·63)-pcu topology, while complex 2 reveals a 1D triple-strained helical chain and complex 3 displays a 3-fold interpenetrated 3D framework with (66)-dia topology. Additionally, the reactions of the flexible ligand N,N′-bis(3-methylpyridyl) adipoamide (L2) afforded {[Co4(L2)0.5(1,4-NDC)3(H2O)3(µ3-OH)2]·EtOH·2H2O}n, 4, {[Zn2(L2)(1,4-NDC)2]·2CH3OH}n, 5, and [Cd(L2)(adipic)(H2O)]n (H2adipic = adipic acid), 6, exhibiting a self-catenated 3D framework with the (420·68)-8T32 topology, a 2D layer with the (413·62) − (4,4)IIb topology, and a 2D layer with the (44·62)-sql topology, respectively. The structural diversity observed in complexes 1–6 highlights the pivotal influence of the metal center on the degree of entanglement in CPs within mixed-ligand systems. The thermal stability and luminescent properties of complexes 1–3, 4, and 6 are also discussed.

Abstract Some cases of chronic rhinosinusitis (CRS) require surgical treatment and postoperative nasal packing, but bleeding and adhesion are common complications after nasal surgery. Biodegradable drug-loaded implants hold great therapeutic options for the treatment of CRS, but little data are available regarding the safety and efficacy of a novel drug-loaded haemostatic sponge (DLHS) in the sinus. The aim of this study was to investigate the safety and efficacy of DLHS in the sinus. We conducted a prospective, randomized, controlled, double-blind clinical trial. In this clinical trial, 49 patients were enrolled and randomly divided into 2 groups: group A (n = 25) had the DLHS containing 1 mg budesonide and 0.67 mg sodium hyaluronate placed into the sinus, and group B (n = 24) had the Nasopore placed after ESS. Endoscopic follow-up was performed for 12 weeks, and the findings were classified using the discharge, inflammation, polyps/oedema (DIP) endoscopic appearance scores. All patients completed questionnaires to evaluate their sinonasal symptoms by using the sinonasal outcome test-22 (SNOT-22) Chinese version and visual analogue scale (VAS). Serum cortisol concentration in group A was measured prior to surgery and at days 1, 3, 7, and 14 after nasal surgery. Comparing group A and group B, at 2 weeks, no significant differences were observed in either objective or subjective parameters. The mean value of VAS for rhinorrhoea and DIP for oedema and the mean value of nasal adhesion were significantly lower in Group A than in Group B at 6 and 12 weeks, but a significant difference did not occur in SNOT-22 and VAS for dysosmia between the two groups at 6 and 12 weeks. The mean serum cortisol concentrations in group A at the follow-up were within normal limits without remarkable fluctuations. This study demonstrates the safety and efficacy of a novel biodegradable DLHS with the possibility of being used in CRS patients, and this sponge may reduce inflammation and minimize adhesions via controlled local drug delivery without measurable systemic exposure.