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Abstract Objective To explore the relationship between 35 trace metals in scalp hair and the glioma risk as well as the potential mediating roles of 27 plasma inflammatory cytokines. Methods A case–control study involving 228 participants was performed in southeastern China. Trace metals in scalp hair were analyzed using inductively coupled plasma mass spectrometry, and multiplex cytokines were detected based on Luminex® technology. The least absolute shrinkage and selection operator (LASSO) regression in combination with four machine learning methods were used to select trace metals associated with gliomas. The joint exposure effect of trace metals was estimated using the generalized weighted quantile sum (gWQS) regression and quantile‐based g‐computation (qgcomp) algorithms. Results Both LASSO regression and random forest algorithms identified five trace metals (gadolinium [Gd], lithium [Li], thulium [Tm], thorium [Th], and molybdenum [Mo]) associated with gliomas. After adjustments for potential confounders, Gd (odds ratio [OR] = 2.84, 95% confidence interval [CI]: 1.89–4.43) and Li (OR = 1.77, 95% CI: 1.04–3.02) concentrations were positively associated with glioma risk, while Tm (OR = 0.36, 95% CI: 0.17–0.73) and Th (OR = 0.45, 95% CI: 0.28–0.71) exhibited inverse associations. Both gWQS and qgcomp algorithms showed Gd contributed most to the mixture effect. Moreover, there was a significant interaction between Gd and Tm or Th on glioma risk (p

Abstract Background Increasingly intense weather anomalies associated with interannual climate variability patterns, like El Niño-southern oscillation (ENSO), could exacerbate the occurrence and transmission of infectious diseases. However, research in China remains limited in understanding the impacts and intermediate weather changes of ENSO on bacillary dysentery (BD). This study aimed to reveal the relationship between ENSO, weather conditions, and the incidence of BD, and to identify the potential meteorological pathways moderated by ENSO in the ENSO-BD connections. Methods BD disease data and meteorological data, as well as ENSO index, from 2005 to 2020 were obtained for 95 cities in the Yangtze River Basin. We first established the associations between ENSO events and BD, ENSO and weather, as well as weather and BDs using two-stage statistical models. Then, we applied a causal mediation analysis to identify the specific meteorological changes in the ENSO-BD relationship. Results In the Yangtze River Basin, both El Niño (IRR: 1.06, 95%CI: 1.04 ~ 1.08) and La Niña (IRR: 1.03, 95%CI: 1.02 ~ 1.05) events were found to increase the risk of BD. Variations of ENSO index were associated with changes in local weather conditions. Both the increases in regional temperatures and rainfall were associated with a higher risk of BD. In the casual mediation analyses, we identified that higher temperatures and excessive rainfall associated with La Niña and El Niño events mediated the ENSO’s effect on BD, with mediation proportions of 38.58% and 34.97%, respectively. Conclusions Long-term climate variability, like ENSO, can affect regional weather conditions and lead to an increased risk of BD. We identified the mediating weather patterns in the relationship between ENSO and BD, which could improve targeted health interventions and establish an advanced early warning system in response to the BD epidemic.

Abstract Purpose The relationship between exposure doses of 2.5-micrometer Particulate Matter (PM2.5), Inhalable particles (PM10), Sulfur Dioxide (SO2), Nitrogen Dioxide (NO2) and Ozone (O3) in the first trimester and spontaneous abortion of pregnant women was evaluated by global average method and nearest monitoring station method, respectively. Method Retrospective analysis of the clinical data of pregnant women with spontaneous abortion and full-term pregnant women in the Department of Obstetrics and Gynecology of two third-class hospitals in a valley city in Northwest China. According to the age factor, the eligible pregnant women were matched at a ratio of 1 : 4. The global average method and the nearest monitoring station method were used to evaluate the exposure of pollutants. The rank-sum test and conditional logistic regression were used to analyze the correlation between air pollutants and spontaneous abortion. Results Although the global average method and the nearest monitoring station method are slightly different in the assessment of exposure dose, they do not affect the correlation evaluation with spontaneous abortion. The exposure of pregnant women to PM2.5(OR1 = 1.156, OR2 = 1.036), SO2 (OR1 = 1.432, OR2 = 1.429) and NO2 (OR1 = 1.121, OR2 = 1.159) in the first trimester is related to the occurrence of spontaneous abortion.(OR1: the global average method, OR2: the nearest monitoring station method) Conclusion The exposure of PM2.5, SO2 and NO2 in the first trimester in valley cities is associated with the occurrence of spontaneous abortion in pregnant women.

Abstract Objectives To investigate the relationships between life events and psychological distress in the postepidemic era as well as the effects of fear of COVID-19 (FCV-19) and impermanence on these relationships to enrich the study of the underlying psychological mechanisms of postepidemic psychological distress and to provide a theoretical basis for scientific prevention and intervention in individuals with psychological distress. Methods A survey of 504 adults (71.3% female; age M = 26.87, SD = 10.70) was conducted via the Social Readjustment Rating Scale, the FCV-19 Scale, the Impermanence Scale, the Anxiety Scale and the Depression Scale, and a structural equation model was established to explore the relationships between variables. Results The present study revealed the following: (1) there is a significant positive correlation between life events and psychological distress; (2) FCV-19 completely mediates the relationship between life events and psychological distress; and (3) impermanence moderates the mediation, regulating the path by which life events affect FCV-19 and the path by which FCV-19 affects psychological distress. Conclusions In the postepidemic era, impermanence can effectively mitigate the impact of life events on FCV-19 and the impact of FCV-19 on psychological distress.

Abstract Human respiratory syncytial virus (RSV) is a major cause of acute respiratory infection. In 2020, RSV was eliminated from New Zealand due to non-pharmaceutical interventions (NPI) used to control the spread of SARS-CoV-2. However, in 2021, following a brief quarantine-free travel agreement with Australia, there was a large-scale nationwide outbreak of RSV that led to reported cases more than five-times higher than typical seasonal patterns. We generated 1470 viral genomes of both RSV-A and RSV-B sampled between 2015–2022 from across New Zealand. Using a phylodynamics approach, we used these data to better understand RSV transmission patterns in New Zealand prior to 2020, and how RSV became re-established in the community following the relaxation of COVID-19 restrictions. We found that in 2021, there was a large epidemic of RSV due to an increase in importations, leading to several large genomic clusters of both RSV-A ON1 and RSV-B BA9 genotypes. However, while a number of viral importations were detected, there was also a major reduction in RSV genetic diversity compared to pre-pandemic years. These data reveal the impact of NPI used during the COVID-19 pandemic on other respiratory infections and highlight the important insights that can be gained from viral genomes.

Abstract Eco-friendly Sn-based perovskites show significant potential for high-performance second near-infrared window light-emitting diodes (900 nm – 1700 nm). Nevertheless, achieving efficient and stable Sn-based perovskite second near-infrared window light-emitting diodes remains challenging due to the propensity of Sn2+ to oxidize, resulting in detrimental Sn4+-induced defects and compromised device performance. Here, we present a targeted strategy to eliminate Sn4+-induced defects through moisture-triggered hydrolysis of tin tetrahalide, without degrading Sn2+ in the CsSnI3 film. During the moisture treatment, tin tetrahalide is selectively hydrolyzed to Sn(OH)4, which provides sustained protection. As a result, we successfully fabricate second near-infrared window light-emitting diodes emitting at 945 nm, achieving a performance breakthrough with an external quantum efficiency of 7.6% and an operational lifetime reaching 82.6 h.

Abstract Background Remimazolam tosilate represents the novel ultrashort-acting benzodiazepine drug. This work focused on exploring whether remimazolam tosilate was effective and safe in anesthesia for short otolaryngology surgery in adults, and optimize its medication regimen, thus providing a theoretical basis for its widespread clinical application. Methods The present unicentric, double-blind, randomized controlled study enrolled altogether 85 otolaryngology surgery patients aged 18–60 years, and they were divided as remimazolam (RM, 42 cases) or midazolam (MD, 43 cases) group. Efficacy outcomes included successful sedation time, sedation effect (Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) score), bispectral index values (BIS), and postoperative recovery. The safety outcomes were patient vital signs at each time point (before induction (T0), 2 min and 5 min after trial drug treatment (T1 and T2 separately), during successful intubation (T3), at the end of surgery (T4), during extubation (T5), and at the time of exiting the room (T6)), any adverse reactions (AEs) during perioperative period, and patient satisfaction with anesthesia experience. Results Demographics were not significantly different in both groups (P > 0.05). RM group had significantly decreased successful sedation time relative to MD group (P 0.05), but RM group exhibited decreased discharge time compared with MD group (P

Abstract Background Papillary thyroid cancer (PTC) is a malignant tumor that poses a serious threat to human health. LncRNA CASC9 serves as an oncogene in numerous tumors. The purpose of this study was to explore the mechanism of lncRNA CASC9 regulating doxorubicin (Dox) resistance in PTC. Methods The expression of CASC9, miR-28-3p and BCL-2 in PTC tissues or dox-resistant cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot (WB). CCK-8, colony formation assay, flow cytometry and transwell assay were used to measure the semi-inhibitory concentration (IC50) of dox, cell proliferation, apoptosis and migration, respectively. Dual luciferase reporter gene assays were performed to verify the targeting relationship between miR-28-3p and CASC9 or BCL-2. Rescue experiments were applied to verify the mechanism of CASC9. Finally, the role of CASC9 was verified by xenograft modeling in vivo. Results We discovered that CASC9 was enhanced in PTC tissues, cells and Dox-resistant cells (BCPAP/Dox and K1/Dox). Furthermore, CASC9 inhibition markedly restrained the proliferation, migration and facilitated apoptosis of Dox cells. In vivo experiments also showed that silencing of CASC9 inhibited tumor growth. Meanwhile, knockdown of CASC9 sensitized PTC cells to Dox. CASC9 enhanced tumor progression by activating the PI3K/AKT signaling pathway. Furthermore, bioinformatics analysis identified miR-28-3p as a downstream target of CASC9. MiR-28-3p inhibitor reversed the impact of CASC9 knockdown in BCPAP/Dox and K1/Dox. Further studies showed that CASC9 positively regulated BCL-2 expression through miR-28-3p. miR-28-3p weakened Dox resistance, proliferation, migration and accelerated apoptosis of PTC cells via BCL-2. Conclusion CASC9, as an oncogenic lncRNA, has a promotional effect on Dox resistance and PTC progression via miR-28-3p/BCL-2 axis and PI3K/AKT signaling pathway.

Abstract Background GM3 synthase deficiency (GM3SD) is an autosomal recessive disorder resulting from mutations in the ST3GAL5 gene. It is characterized by intellectual disability, microcephaly, psychomotor and developmental delay, hearing and visual impairments, and changes in skin pigmentation. This study aims to broaden the genetic mutation spectrum of GM3SD through the report of a de novo mutation and a comprehensive summary of GM3SD phenotype to aid in genetic counseling and prenatal diagnosis. Results Compound heterozygous variants in ST3GAL5 (NM_003896.4: c.1000delC, p.Arg334Glufs*15 and c.207-1G > T, p.Cys70Glufs*81) were identified via trio-whole exome sequencing (trio-WES) and confirmed pathogenic through functional experiments. Notably, c.207-1G > T was a newly discovered variant. Additionally, previously reported GM3SD mutations were classified into R288X and non-R288X, revealing that R288X mutations were more likely to manifest developmental, emotional abnormalities, and severe feeding difficulties. Conclusions This study reveals a novel mutation in ST3GAL5 and provides a comprehensive overview of GM3SD phenotype, aiding in the diagnosis and genetic counseling of GM3SD in clinical practice.

Abstract Purpose It is a central goal in current ecology to investigate the effects of global changes on ecosystem productivity, which includes above- and below-ground plant productivity as well as soil microbial productivity, but most studies focus on aboveground plant productivity. As plant and microbial communities have different attributes, it is intuitive to hypothesize that belowground plant root productivity will respond to global changes more similarly as aboveground stem/leaf productivity than soil microbial productivity; however, this hypothesis remains largely unexplored. Methods Here we conducted a long-term nitrogen deposition experiment in the Eurasian steppe, manipulating nine rates (0–50 g N m− 2 yr− 1) at two frequencies under two management strategies (fencing or mowing). Results Belowground plant productivity was found to respond similarly as soil microbial productivity rather than aboveground plant productivity, contrary to the hypothesis. And this pattern was more obvious under mowing than fencing, because mowing decreased soil water content and caused another pressure beyond the decreased pH induced by N addition. Conclusions Overall, our results demonstrated the importance of microhabitat (below- or above-ground) relative to community attribute (plants or microorganisms) in determining productivity response to nitrogen deposition, emphasizing the necessity to integratively study the response of both above- and below-ground productivities to global changes.

Abstract Background Homocysteine (Hcy) is a pro-inflammatory molecule that has the potential to induce oxidative damage to cells and stimulate the release of inflammatory mediators. Hcy has been observed to enhance the production of inflammatory agents in vascular endothelial cells. However, the impact of Hcy on intestinal mucosal inflammation remains largely unexplored. Therefore, the objective of this study was to examine the potential of Hcy to stimulate the synthesis of inflammatory mediators and elucidate the underlying mechanisms in the intestinal mucosa. Methods A total of 99 patients diagnosed with inflammatory bowel disease (IBD) and 10 healthy individuals were included in this study to assess the impact of homocysteine (Hcy) on the levels of leukotriene E4 (LTE4) and prostaglandin E2 (PGE2). The underlying mechanism responsible for the generation of LTE4 and PGE2 induced by Hcy was investigated using colitis rats and Caco-2 cells. 32 Sprague–Dawley rats were categorized into four groups: normal control, TNBS model, normal with Hcy injection, and TNBS model with Hcy injection. The mRNA expressions of 5-LOX, COX-2, and NF-κB were assessed using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Caco-2 cells were subjected to treatment with varying concentrations (10, 20, 50, 100 μmol/L) of Hcy and incubated for different durations (1, 3, 6 h). The alterations in NF-κB activity, as well as the levels of Hcy, LTE4, and PGE2, were measured using enzyme-linked immunosorbent assay (ELISA). Results The excretion of Hcy, LTE4, and PGE2 in urine exhibited significant increases in patients with inflammatory bowel disease (IBD), Crohn's disease (CD), and ulcerative colitis (UC). In addition, Hcy demonstrated a significant increase in the expression of 5-LOX, COX-2, and NF-κB, as well as elevated levels of LTE4 and PGE2 in rats with colitis. Furthermore, Hcy was found to induce NF-κB activation and nuclear translocation, thereby contributing to the enhanced synthesis of LTE4 and PGE2 in Caco-2 cells. Conclusions Hcy was found to enhance the expression of 5-LOX and COX-2 by activating NF-κB, thereby augmenting the production of LTE4 and PGE2, which ultimately exacerbates colonic inflammation in individuals with inflammatory bowel disease (IBD).

Abstract Epidermal growth factor receptor (EGFR)-activating mutations are critical factors in the development of EGFR-driven non-small-cell lung cancer (NSCLC), and molecular targeted therapies have focused on inhibiting these mutations. EGFR tyrosine kinase inhibitors (TKIs) have remarkable inhibitory effects on NSCLC with EGFR mutations. However, acquired resistance limits the clinical application of EGFR-TKIs, highlighting the need for discovery of novel therapeutic strategies. 1,4,5,6-tetrahydroxy-7,8-diprenylxanthone is a natural product derived from Garcinia xanthochymus, has shown potential anti-tumor activity, but the underlying mechanism needs further elucidation. In this study, we developed Ba/F3 and NIH/3T3 cells harboring EGFR L858R/T790M/C797S mutation, and then found that 1,4,5,6-tetrahydroxy-7,8-diprenylxanthone exerted inhibitory effects against cells with EGFR L858R/T790M/C797S mutation. Additionally, 1,4,5,6-tetrahydroxy-7,8-diprenylxanthone exhibited potent anti-tumor activity against cells harboring the triple-mutant EGFR by promoting apoptosis and inducing changes in cell cycle distribution. Furthermore, 1,4,5,6-tetrahydroxy-7,8-diprenylxanthone was found to significantly reduce tumor growth via suppressing the phosphorylation of EGFR in tumor tissues. These effects are associated with binding of 1,4,5,6-tetrahydroxy-7,8-diprenylxanthone to EGFR resulting in the suppression of extracellular signal-regulated kinase (Erk) phosphorylation. In conclusion, our results suggest that 1,4,5,6-tetrahydroxy-7,8-diprenylxanthone may be a potential novel candidate for further investigation and treatment of NSCLC with the triple-mutant EGFR.

Abstract Efficient harnessing of solar energy presents a significant challenge in environmental cleanup efforts. This study develops a highly effective carbon quantum dots-modified hollow core-shell TiO2-LaFeO3 heterojunction photocatalyst (CDs-TLFO). Structural analysis confirmed that nanosheets are loaded with CQDs, forming a hollow core-shell structure with intimate interconnection. Photocatalytic experiments reveal that CDs-TLFO degrads tetracycline hydrochloride (TC) 2.02 times faster than TLFO alone, and significantly outperformes h-TiO2 and LaFeO3 (11.28 and 2.78 times, respectively). This enhancement is attributed to CQDs acting as electron acceptors with upconversion properties, enhancing the separation of e–-h+ pairs and boosting visible light absorption. Integration of CQDs onto the TLFO surface creates numerous active sites and enhances visible light absorption. SEM and TEM tests confirm that the catalyst has a hollow core-shell structure. ESR tests and radical trapping experiments indicate that the high degradation efficiency of the catalyst mainly owns to the synergistic effect of hydroxyl radicals (·OH) and superoxide radicals (·O2 −). The reusability and stability of the catalysts are investigated, potential TC degradation pathways are proposed as well as the photocatalytic reaction mechanism is revealed. This research introduces promising avenues for environmental cleanup and offers a straightforward, energy-efficient, and environmentally friendly method for producing CDs-TLFO heterojunction materials with superior photocatalytic capabilities.

Abstract The cascade of correlated topological quantum states in the newly discovered vanadium-based kagome superconductors, AV3Sb5 (A = K, Rb, and Cs), with a Z2 topological band structure has sparked immense interest. Here, we report the discovery of superconductivity and electronic nematic order in high-quality single-crystals of a new titanium-based kagome metal, CsTi3Bi5, that preserves the translation symmetry, in stark contrast to the charge density wave superconductor AV3Sb5. Transport and magnetic susceptibility measurements show superconductivity with an onset superconducting transition temperature T c of approximately 4.8 K. Using the scanning tunneling microscopy/spectroscopy and Josephson scanning tunneling spectroscopy, we demonstrate that the single crystals of CsTi3Bi5 exhibit two distinct superconducting gaps. Furthermore, the superconducting gaps break the six-fold crystal rotational symmetry down to two-fold. At low energies, we find that the quasiparticle interference patterns exhibit rotational-symmetry-breaking C2 patterns, revealing a nematic ordered normal state with the same nematic direction as in the superconducting state. Our findings uncover a novel superconducting state in CsTi3Bi5 and provide new insights for the intrinsic electron liquid crystal phases in kagome superconductors.

Abstract Background Lysosomal homeostasis and functions are essential for the survival of neural cells. Impaired lysosomal biogenesis and acidification in Alzheimer’s disease (AD) pathogenesis leads to proteolytic dysfunction and neurodegeneration. However, the key regulatory factors and mechanisms of lysosomal homeostasis in AD remain poorly understood. Methods ROCK1 expression and its co-localization with LAMP1 and SQSTM1/p62 were detected in post-mortem brains of healthy controls and AD patients. Lysosome-related fluorescence probe staining, transmission electron microscopy and immunoblotting were performed to evaluate the role of ROCK1 in lysosomal biogenesis and acidification in various neural cell types. The interaction between ROCK1 and TFEB was confirmed by surface plasmon resonance and in situ proximity ligation assay (PLA). Moreover, we performed AAV-mediated ROCK1 downregulation followed by immunofluorescence, enzyme-linked immunosorbent assay (ELISA) and behavioral tests to unveil the effects of the ROCK1–TFEB axis on lysosomes in APP/PS1 transgenic mice. Results ROCK1 level was significantly increased in the brains of AD individuals, and was positively correlated with lysosomal markers and Aβ. Lysosomal proteolysis was largely impaired by the high abundance of ROCK1, while ROCK1 knockdown mitigated the lysosomal dysfunction in neurons and microglia. Moreover, we verified ROCK1 as a previously unknown upstream kinase of TFEB independent of m-TOR or GSK-3β. ROCK1 elevation resulted in abundant extracellular Aβ deposition which in turn bound to Aβ receptors and activated RhoA/ROCK1, thus forming a vicious circle of AD pathogenesis. Genetically downregulating ROCK1 lowered its interference with TFEB, promoted TFEB nuclear distribution, lysosomal biogenesis and lysosome-mediated Aβ clearance, and eventually prevented pathological traits and cognitive deficits in APP/PS1 mice. Conclusion In summary, our results provide a mechanistic insight into the critical role of ROCK1 in lysosomal regulation and Aβ clearance in AD by acting as a novel upstream serine kinase of TFEB.

Abstract Background Individuals with low socioeconomic status (SES) bear a disproportionate share of the cognitive impairment (CI) burden, there are growing evidence focusing on socioeconomic inequalities in CI among older persons. However, data in the underdeveloped regions is limited. This study aims to measure socioeconomic inequalities in CI among individuals aged 65 years or older in Gansu, China, and determine the contributions of socioeconomic factors to the inequalities. Methods Data from the Gansu Aging Study in 2022 including 3241 participants. Participates’ SES was assessed by using education, income, and occupation. Multivariate logistic regression was conducted to identify the associated between SES and CI, and decomposition analysis was further applied to decompose the contribution of each determinant to the observed inequalities in CI. The SES inequalities in CI were illustrated and quantified by the concentration curve index. Results Overall, 24.2% of participants suffered from CI in the study. The likelihood of CI was lower among those with a medium SES (OR = 0.04, 95% CI:0.03, 0.07), good SES (OR = 0.06, 95% CI: 0.04, 0.09) compared to those with lower levels of SES. Older adults with mild depression (OR = 3.66, 95% CI:2.70,4.95), moderate-severe (OR = 2.82, 95% CI:2.05,3.88) were more likely to have CI in comparison to those with no depression and regular social activities were protective factors for CI (OR = 0.28, 95% CI:0.11,0.75). The concentration index indicated that CI was more concentrated in households with poor SES. Subsequently, SES explained 34.65% of socioeconomic inequality in CI. Conclusion This study suggested that, approximately one-quarter of older persons suffered from CI in Gansu, China. Low SES was substantially associated with risk of CI. Although interventions to modify traditional risk factors may decrease the risk of CI, disparities by SES may remain without addressing SES itself.

Abstract The interaction between the shock wave and boundary layer of transonic wings can trigger periodic self-excited oscillations, resulting in transonic buffet. Buffet severely restricts the flight envelope of civil aircraft and is directly related to their aerodynamic performance and safety. Developing efficient and reliable techniques for buffet onset prediction is crucial for the advancement of civil aircraft. In this study, utilizing a comprehensive database of supercritical airfoils generated through numerical simulations, a convolutional neural network (CNN) model is firstly developed to perform buffet classification based on the flow fields. After that, employing explainable machine learning techniques, including Gradient-weighted Class Activation Mapping (Grad-CAM), random forest algorithms, and statistical analysis, the research investigates the correlations between supervised CNN features and key physical characteristics related with the separation region, shock wave, leading edge suction peak, and post-shock loading. Finally, physical buffet onset metric is established with good generalization and accuracy, providing valuable guidance for engineering design in civil aircraft.

Abstract Colorectal cancer (CRC) is a common malignant tumor of the digestive tract in China; its incidence rates and mortality rates have been on the rise in recent years, ranking third in terms of incidence and second in mortality. Rational dietary intervention plays an important role in human health, and prevention and adjuvant treatment of CRC through dietary supplementation is the most ideal and safest way to treat the disease at present. More importantly, dietary protein is the basis of our diet and the key nutrient to maintain the normal function of the human body. Therefore, this narrative review delivered an overview of the common causes and therapeutic treatments for CRC. It emphasized the importance of dietary interventions, with a particular focus on elucidating the distinct regulatory impacts of plant proteins, animal proteins, and their mixed proteins.

Abstract Septic cardiomyopathy (SCM), a complication initiated by sepsis, presents a significant clinical challenge, leading to increased mortality rates. However, the mechanisms of SCM have not been fully uncovered. Our study involved analyzing RNA sequencing (RNA-seq) data from rat heart tissue, along with utilizing molecular docking and molecular dynamics (MD) simulations, to discover key targets and potential pharmacological actions of the calcitonin gene-related peptide (CGRP) against SCM. A lipopolysaccharide-induced SCM model was established in rats (LPS 10 mg/kg, intraperitoneal (i.p.)). Thereafter, the myocardial tissues from the three groups of rats (Ctrl group, LPS group, and CGRP group) (n = 5) were extracted and underwent RNA-seq, followed by bioinformatics analyses. The qPCR-validated hub targets potentially interacting with CGRP were identified. Following this, homology modeling was utilized to obtain the 3D structure of hub targets, and molecular docking was conducted to evaluate the interaction between CGRP and hub targets. MD simulations (300 ns) were performed to confirm the findings further. Our findings demonstrated that CGRP significantly lowered mortality in SCM rats. 633 DEGs were affected by LPS, contrasted with the Ctrl group. 96 DEGs were affected by CGRP compared to the LPS group. In total, ten fully annotated CGRP-triggered hub genes were obtained. The molecular docking and MD simulations indicate that the relationship between CGRP and eight hub genes is extremely strong. This research offers a thorough examination of the possible objectives and fundamental molecular processes of CGRP in combating SCM, laying the groundwork for investigating the potential protective mechanisms of CGRP against SCM.

Introduction: Synthetic lethality (SL) provides an opportunity to leverage different genetic interactions when designing synergistic combination therapies. To further explore SL-based combination therapies for cancer treatment, it is important to identify and mechanistically characterize more SL interactions. Artificial intelligence (AI) methods have recently been proposed for SL prediction, but the results of these models are often not interpretable such that deriving the underlying mechanism can be challenging. Objectives: This study aims to develop an interpretable AI framework for SL prediction and subsequently utilize it to design SL-based synergistic combination therapies. Methods: We propose a knowledge and data dual-driven AI framework for SL prediction (KDDSL). Specifically, we use gene knowledge related to the SL mechanism to guide the construction of the model and develop a method to identify the most relevant gene knowledge for the predicted results. Results: Experimental and literature-based validation confirmed a good balance between predictive and interpretable ability when using KDDSL. Moreover, we demonstrated that KDDSL could help to discover promising drug combinations and clarify associated biological processes, such as the combination of MDM2 and CDK9 inhibitors, which exhibited significant anti-cancer effects in vitro and in vivo. Conclusion: These data underscore the potential of KDDSL to guide SL-based combination therapy design. There is a need for biomedicine-focused AI strategies to combine rational biological knowledge with developed models.

A straw interlayer added to soil can effectively reduce soil salinity effects on plant growth, however, the effects of soil moisture, salt and microbial community composition on plant growth under a straw interlayer are unclear. A rhizobox study was conducted to investigate the role of straw interlayer thickness on soil moisture, salt migration, microbial community composition, as well as root growth in sunflower. The study included four treatments: Control (no straw interlayer); S3 (straw interlayer of 3.0 cm); S5 (straw interlayer of 5.0 cm); S7 (straw interlayer of 7.0 cm). Straw interlayer treatments increased soil moisture by 8.2–11.0% after irrigation and decreased soil salt content after the bud stage in 0–40 cm soil. Total root length, total root surface area, average root diameter, total root volume and the number of root tips of sunflower plants were higher under straw interlayer treatments than in the control, and were the highest under the S5 treatment. This stimulated root growth was ascribed to the higher abundance of Chloroflexi and Verrucomicrobia bacteria in soil with a straw interlayer, which was increased by 55.7 and 54.7%, respectively, in the S5 treatment. Addition of a straw interlayer of 5 cm thickness is a practical and environmentally feasible approach for improving sunflower root growth in saline-alkali soil.

Peripheral nervous system (PNS) injuries often lead to significant sensory and motor impairments. Traditional artificial nerve conduits, lacking anisotropic structures, have been associated with prolonged repair time and failures in nerve regeneration. This study aimed to address these challenges by developing a novel approach for rapid repair of peripheral nerve injuries (PNI). A 3D oriented fibers scaffold featuring distinct radial (RFs) and longitudinal (LFs) fibers orientations was engineered using coaxial electrospinning and gas directional foaming techniques. This scaffold was then integrated with a shape memory conduit to form a directional multi-channel nerve conduit with micro/nanostructures. The results revealed that the grooved surface of the fibers significantly improved cellular directional guidance, effectively facilitating the migration of SCs from the periphery towards the center and from the base to the apex of the scaffold. In a rat model with a 10 mm nerve defect, the ND-PLATMC/LF ND-PCL scaffold significantly enhanced nerve regeneration and motor function recovery within 4 weeks. These results suggest the potential of this innovative scaffold for efficient repair of the nerve injuries.

Dielectric capacitors with high power density and fast charge-discharge speed play an essential role in the development of pulsed power systems. The increased demands for miniaturization and practicality of pulsed power equipment also necessitate the development of dielectric materials that possess high energy density while maintaining ultrahigh efficiency (η). In particular, ultrahigh efficiency signifies minimal energy loss, which is essential for practical applications but challenging to effectively mitigate. Here, we demonstrate a strategy of incorporating heterovalent elements into Ba(Zr0·1Ti0.9)O3, which contributes to achieving relaxor ferroelectric ceramics and reducing lattice strain, thereby improving the comprehensive energy storage performance. Finally, optimal energy storage performance is attained in 0.85Ba(Zr0·1Ti0.9)O3-0.15Bi(Zn2/3Ta1/3)O3 (BZT-0.15BiZnTa), with an ultrahigh η of 97.37% at 440 kV/cm (an advanced level in the lead-free ceramics) and an excellent recoverable energy storage density (Wrec) of 3.74 J/cm3. Notably, the BZT-0.15BiZnTa ceramics also exhibit exceptional temperature stability, maintaining fluctuations in Wrec within ∼10% and η consistently exceeding 90% across the wide temperature range of −55 °C to160 °C, and under a high electric field of 250 kV/cm. All these features demonstrate that the relaxor and lattice strain engineering strategies have been successful in achieving high-performance lead-free ceramics, paving the way for designing high-efficiency dielectric capacitors with a wide temperature range.

Abstract The absence of validated correlates of protection (CoPs) hampers the rational design and clinical development of new tuberculosis vaccines. In this review, we provide an overview of the potential CoPs in tuberculosis vaccine research. Major hindrances and potential opportunities are then discussed. Based on recent progress, it is reasonable to anticipate that success in the ongoing efforts to identify CoPs would be a game-changer in tuberculosis vaccine development.

In China's agricultural catastrophe insurance market, issues of non-equilibrium are prominent. To understand the causes of non-equilibrium in agricultural catastrophe insurance and to develop prevention strategies, this study employs an Evolutionary Game Model, incorporating disaster and insurance data for three types of cereal crops in Henan Province to analyse the Evolutionarily Stable Strategies in the agricultural catastrophe insurance market. The research also considers government policies and disaster reinsurance as implicit participants in the model. The findings reveal significant differences in the impact of non-equilibrium in the agricultural catastrophe insurance market and the choice of game strategies, dependent on the scale of farm operations, the type of crops cultivated, and regional variations. Significantly, decision-making evolutionary paths vary between small and medium-scale farmers, with rice growers emphasising income insurance more. In regions prone to frequent catastrophes, the insurance rates for agricultural catastrophe insurance exhibit greater flexibility. By scientifically delineating agricultural catastrophe risk zones, appropriately expanding the scale of cultivation, reducing insurance rates, and adjusting agricultural catastrophe insurance products, a balanced development in the agricultural catastrophe insurance market can be promoted.

177Lu- prostate specific membrane antigen (PSMA) radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China. Based on domestic clinical practice and experimental data and referred to international experience and viewpoints, the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Abstract Background Coronary artery bypass grafting (CABG) is often performed with hypothermic cardiopulmonary bypass (CPB) to reduce metabolic demands and protect the myocardium. However, hypothermia can increase bleeding risks and other complications. Methods This is a prospective, multi-center, randomized controlled trial. From September 2023 to December 2024, a total of 336 eligible patients planning to undergo on-pump CABG will be enrolled. All participants will be randomly divided into mild hypothermia CPB group (target oxygenator arterial outlet blood temperature at 32–33℃) or normothermia CPB group (target oxygenator arterial outlet blood temperature at 35–36℃). The primary endpoint is Universal Definition of Perioperative Bleeding (UDPB) class 2–4. Secondary endpoints are class of UDPB, levels of coagulation and inflammatory factors, in-hospital mortality, perioperative related complications, ICU length of stay, and hospital length of stay. Discussion This clinical trial aims to compare the effects of different target temperature during CPB on postoperative bleeding and to explore optimal temperature strategy to provide new clinical evidence. Trial registration Chictr.org.cn : ChiCTR2300075405. The trial was prospectively registered on 4 September 2023.

Abstract Optical fiber sensors (OFSs) have attracted more and more attention in the field of in-situ ocean observation because of their advantages of the small size, light weight, low cost, and intrinsic immunity to electromagnetic interference. Here, we comprehensively reviewed the development of various advanced physical and chemical OFSs for in-situ measurement of ocean key parameters, including temperature, salinity, pressure, acoustics, flow velocity and turbulence, potential of hydrogen (pH), heavy metal ions, nitrates, and gases. Moreover, the performances of different kinds of OFSs and their practical sea trial reports for in-situ measurement in the marine environment are provided. As we discussed, the field of OFS is rapidly evolving and is poised to make essential breakthroughs in marine monitoring, leading to better utility of marine resources.

Abstract While the elevation of serum uric acid (SUA) is acknowledged as a risk factor for chronic kidney disease, the independent extent to which variations in SUA levels are correlated with temporal changes in estimated glomerular filtration rate (eGFR) remains uncertain. In light of this uncertainty, our research endeavored to elucidate the temporal associations between change in SUA and rapid eGFR decline in China. In this longitudinal study of China’s middle-aged and elderly between 2011 and 2015, we analyzed 5421 individuals with complete SUA and eGFR data. Logistic regression was applied to evaluate the risk factors associated with a rapid eGFR decline (defined by a 5 mL/min/1.73 m2 decrease or falling to less than 15 mL/min/1.73 m2 by 2015), adjusted for age, gender, marital, residence, income, BMI, hypertension, diabetes, dyslipidemia, CRP, Hba1c, baseline eGFR and baseline SUA. Linear regression was used to evaluate the relationship between variations in SUA and changes in eGFR. After multivariable adjustments, the risk factors of a rapid eGFR decline included aging (OR per 1-year increase: 1.1, 95% CI 1.08–1.12, P

Abstract Magnesium (Mg) plays a pivotal role as an essential component of plant chlorophyll and functions as a critical coenzyme. However, research exploring the regulatory mechanisms of magnesium ions on the synthesis of secondary metabolites is still in its early stages. Sophora tonkinensis is a widely utilized medicinal plant in China, recognized for its diverse secondary metabolites with active properties. This study investigates variations in these ingredients in tissue-cultured seedlings under varying magnesium concentrations. Simultaneously, an omics data analysis was conducted on tissue-cultured seedlings subjected to treatments with magnesium and low magnesium. These comprehensive omics analyses aimed to elucidate the mechanisms through which magnesium influences active components, growth, and development. Magnesium exerts a pervasive influence on various metabolic pathways, forming an intricate network. Research findings indicate that magnesium impacts diverse metabolic processes, including the absorption of potassium and calcium, as well as photosynthetic activity. Consequently, these influences lead to discernible changes in the levels of pharmacologically active compounds and the growth and developmental status.This study is the first to employ a multi-omics data analysis in S. tonkinensis. This methodology allows us to uncover the overarching impact of metabolic networks on the levels of various active ingredients and specific phenotypes.

Abstract Background While physicians are considered to be more susceptible to developing depressive symptoms, empirical data are lacking. The study aims to compare the risk of depressive symptoms between emergency physicians and the general population in China based on national data. Methods This was a national cross-sectional study. 10 457 emergency physicians and 101 120 participants from the general population were investigated from July 2018 to August 2018 and January 2019 to February 2019, respectively. PHQ-9 was used to measure depressive symptoms, and a score ≥ 10 indicates major depression. Propensity score matching was adopted to balance the characteristics between emergency physicians and the general population. Multinomial logistic regression model was used to examine the association between occupational groups and the severity of depressive symptoms. Binary logistic regression model was performed to explore the risk factors of major depression among emergency physicians. Results The prevalence of major depression among emergency physicians was 35.7%, whereas among the general population was 13.9%. Emergency physicians had a 3.65 times higher risk of major depression than the general population. And emergency physician was significantly associated with mild (OR: 3.12, 95% CI 2.95–3.30), moderate (OR: 4.94, 95% CI 4.60–5.30), moderately severe (OR: 9.48, 95% CI 8.61–10.44), and severe depressive symptoms (OR: 14.18, 95% CI 12.47–16.13) compared with none depressive symptoms. Even after matching, the results remained consistent. Factors associated with major depression among emergency physicians included bachelor degree or above (OR: 1.22, 95% CI 1.06–1.40), worked long years (OR: 1.26, 95% CI 1.08–1.46 for 1–5 years; OR: 1.56, 95% CI 1.32–1.84 for ≥ 6 years), experienced workplace violence (OR: 2.51, 95% CI 2.16–2.94), worked more night shifts per month (OR: 1.33, 95% CI 1.16–1.51 for 6–10 times; OR: 1.83, 95% CI 1.58–2.11 for ≥ 11 times), smoked (OR: 1.64, 95% CI 1.47–1.84), and effort-reward imbalance (OR: 4.18, 95% CI 3.62–4.85). Conclusions Emergency physicians had a higher risk of depressive symptoms than the general population. There is a need for greater awareness of the mental health issues faced by emergency physicians.

Abstract Background Resilience is a protective feature against anxiety and depression disorders. However, the precise relationship and structure of resilience and anxiety and depression remain poorly understood. This study sought to investigate the link among resilience’ components and anxiety as well as depression. Methods 1,279 clinical nurses were recruited. 10-item Connor-Davidson Resilience Scale, Generalized Anxiety Disorder 7, and Patient Health Questionnaire 9 were employed to evaluate resilience, anxiety, and depression, respectively. The regularized partial-correlation network was generated utilizing data from cross-sectional survey and the bridge expected influence index was utilized to quantify bridge components. Results The rates of anxiety and depression within clinical nurses were 67.3% and 67.2%, accordingly. Four strongest bridge edges appeared in the resilience-anxiety network, like “Adapt to change”- “Fear that something might happen”, and “Stay focused under pressure”- “Uncontrollable worry”. Two strongest bridge edges appeared in the resilience-depression network, like “Adapt to change”- “Concentration difficulties” and “Stay focused under pressure”- “Fatigue”. “Adapt to change” was recognized as bridging nodes in both the resilience-anxiety network and the resilience-depression network. Conclusions Interventions targeting the bridge component “Adapt to change” within resilience, may mitigate the intensity of anxiety and depression symptoms among clinical nurses.

Abstract Lung squamous cell carcinoma (LUSC) is associated with high mortality and has few therapeutic options. Chemotherapy remains the main treatment for LUSC patients, but multi-drug resistance has become the dominant challenge in the failure of chemotherapy in various cancers. Therefore, the effective therapeutic strategy for LUSC patients is an urgent unmet need. Here, we found vasohibin-2 (VASH2) was a prognostic biomarker for LUSC patients, and VASH2 promoted the malignant biological behaviors of LUSC cells and chemoresistance by increasing the detyrosination of α-tubulin. The high level of detyrosinated-tubulin was negatively associated with patient prognosis. Blocking the tubulin carboxypeptidase (TCP) activity of VASH2 inhibited the xenograft tumor growth and improved the treatment efficacy of paclitaxel in vivo. Results revealed that VASH2-induced increase in tubulin detyrosination boosted the binding of kinesin family member 3C (KIF3C) to microtubules and enhanced KIF3C-dependent endosomal recycling of EGFR, leading to the prolonged activation of PI3K/Akt/mTOR signaling. This study demonstrated that VASH2 was not only a prognostic biomarker but also a promising therapeutic target in LUSC, which offers a novel insight that combination of chemotherapy and EpoY, a TCP inhibitor, may be a promising treatment strategy for LUSC patients.

The separation and recovery of uranium from natural water is of great significance to the exploitation of unconventional uranium resources. In our paper, a novel polyacrylonitrile(PAN)/Hummers oxidized lotus seedpod carbon composite was prepared, and adsorption of U(Ⅵ) ion from U(Ⅵ)-CO3 solution under weakly alkaline condition was also studied. Batch adsorption experimental results show that at room temperature, pH=8.0, ρ(U(Ⅵ))=50 mg/L, cT(CO3)=2 mmol/L, the adsorption reaches equilibrium after 840 min, and the maximum adsorption capacity is about 51.92 mg/g. The increase of the pH values, calcium ion concentration, magnesium ion concentration and carbonate concentration inhibit the U(Ⅵ) adsorption. Thermodynamic results indicate that it is a spontaneous, endothermic chemical adsorption process. Characterization results show that the composite displays good structure stability during U(Ⅵ) adsorption process, meanwhile, the phenolic —OH and —COOH(C=O) are the main adsorption sites on the composite surfaces. In the presence of calcium/magnesium ions, the order of adsorption affinity of U(Ⅵ) on the composite material is as follows: Mg-U(Ⅵ)-CO3 system＞Ca-U(Ⅵ)-CO3 system. The results can provide the new materials for the separation and extraction of uranium from natural uranium-containing water.

Based on the tectonic genesis and seismic data of fault-controlled fractured-vuggy reservoirs, the typical fractured-vuggy structure features were analyzed. A 3D large-scale visual physical model of “tree-like” fractured-vuggy structure was designed and made. The experiments of bottom-water flooding and multi-media synergistic oil displacement after bottom-water flooding were conducted with different production rates and different well-reservoir configuration relationships. The formation mechanisms and distribution rules of residual oil during bottom-water flooding under such fractured-vuggy structure were revealed. The producing characteristics of residual oil under different production methods after bottom-water flooding were discovered. The results show that the remaining oil in “tree-like” fractured-vuggy structure after bottom-water flooding mainly include the remaining oil of non-well controlled fault zones and the attic remaining oil at the top of well controlled fault zones. There exists obvious water channeling of bottom-water along the fault at high production rate, but intermittent drainage can effectively weaken the interference effect between fault zones to inhibit water channeling. Compared with the vertical well, horizontal well can reduce the difference in flow conductivity between fault zones and show better resistance to water channeling. The closer the horizontal well locates to the upper part of the “canopy”, the higher the oil recovery is at the bottom-water flooding stage. However, comprehensive consideration of the bottom-water flooding and subsequent gas injection development, the total recovery is higher when the horizontal well locates in the middle part of the “canopy” and drills through a large number of fault zones. After bottom water flooding, the effect of gas huff and puff is better than that of gas flooding, and the effect of gas huff and puff with large slug is better than that of small slug. Because such development method can effectively develop the remaining oil of non-well controlled fault zones and the attic remaining oil at the top of well controlled fault zones transversely connected with oil wells, thus greatly improving the oil recovery.

Abstract Continuous development of photonic crystals (PCs) over the last 30 years has carved out many new scientific frontiers. However, creating tunable PCs that enable flexible control of geometric configurations remains a challenge. Here we present a scheme to produce a tunable plasma photonic crystal (PPC) ‘kaleidoscope’ with rich diversity of structural configurations in dielectric barrier discharge. Multi-freedom control of the PPCs, including the symmetry, dielectric constant, crystal orientation, lattice constant, topological state, and structures of scattering elements, has been realized. Four types of lattice reconfigurations are demonstrated, including transitions from periodic to periodic, disordered to ordered, non-topological to topological, and striped to honeycomb Moiré lattices. Furthermore, alterations in photonic band structures corresponding to the reconstruction of various PPCs have been investigated. Our system presents a promising platform for generating a PPC ‘kaleidoscope’, offering benefits such as reduced equipment requirements, low cost, rapid response, and enhanced flexibility. This development opens up new opportunities for both fundamental and applied research. Graphical Abstract

Abstract Background Dementia with Lewy Bodies (DLB) is a complex neurodegenerative disorder that often overlaps clinically with Alzheimer’s disease (AD), presenting challenges in accurate diagnosis and underscoring the need for novel biomarkers. Lipidomic emerges as a promising avenue for uncovering disease-specific metabolic alterations and potential biomarkers, particularly as the lipidomics landscape of DLB has not been previously explored. We aim to identify potential diagnostic biomarkers and elucidate the disease's pathophysiological mechanisms. Methods This study conducted a lipidomic analysis of plasma samples from patients with DLB, AD, and healthy controls (HCs) at Xuanwu Hospital. Untargeted plasma lipidomic profiling was conducted via liquid chromatography coupled with mass spectrometry. Machine learning methods were employed to discern lipidomic signatures specific to DLB and to differentiate it from AD. Results The study enrolled 159 participants, including 57 with AD, 48 with DLB, and 54 HCs. Significant differences in lipid profiles were observed between the DLB and HC groups, particularly in the classes of sphingolipids and phospholipids. A total of 55 differentially expressed lipid species were identified between DLB and HCs, and 17 between DLB and AD. Correlations were observed linking these lipidomic profiles to clinical parameters like Unified Parkinson’s Disease Rating Scale III (UPDRS III) and cognitive scores. Machine learning models demonstrated to be highly effective in distinguishing DLB from both HCs and AD, achieving substantial accuracy through the utilization of specific lipidomic signatures. These include PC(15:0_18:2), PC(15:0_20:5), and SPH(d16:0) for differentiation between DLB and HCs; and a panel includes 13 lipid molecules: four PCs, two PEs, three SPHs, two Cers, and two Hex1Cers for distinguishing DLB from AD. Conclusions This study presents a novel and comprehensive lipidomic profile of DLB, distinguishing it from AD and HCs. Predominantly, sphingolipids (e.g., ceramides and SPHs) and phospholipids (e.g., PE and PC) were the most dysregulated lipids in relation to DLB patients. The lipidomics panels identified through machine learning may serve as effective plasma biomarkers for diagnosing DLB and differentiating it from AD dementia.

Abstract Background: Haematological patients with severe thrombocytopenia and high thrombotic risk face challenges related to balancing bleeding and thrombosis risks. This study investigated factors associated with bleeding and thrombosis in high-risk haematological oncology patients with severe thrombocytopenia not receiving anticoagulant therapy and characterized their clinical features when both events occurred. Methods: A total of 446 haematological oncology patients with Caprini scores ≥ 5 were included from July 2022 to June 2023 at Mianyang City Central Hospital. Those not receiving prophylactic anticoagulants due to an admission platelet count

Abstract Background Despite the high cure rate of differentiated thyroid cancer (DTC), patients endure side effects from treatment and psychological distress, impacting their quality of life. The potential of mobile health (mHealth) interventions to address these issues remains unexplored. The purpose of this study is to develop an mHealth intervention based on the Multi-Theoretical Model of Health Behavior Change (MTM) and evaluate its impact on reducing anxiety, depression, fear of cancer progression, and enhancing quality of life in DTC patients. Methods A single-blind, single-center, prospective, randomized controlled trial was conducted. One hundred and eleven consecutive DTC patients from Harbin Medical University’s Fourth Hospital were enrolled from March 2023 to March 2024. Participants were randomized into a control group and an intervention group that received a 3-month mHealth intervention based on MTM theory. Outcomes were assessed using web-based questionnaires at baseline and conclusion. Results One hundred four patients with DTC completed the study, with 7 lost to follow-up (6.3%). The intervention group experienced a significant drop in PHQ-4 scores post-MTM-mHealth intervention (P

Abstract Hysteresis is an inherent property of first-order transition materials that poses challenges for solid-state refrigeration applications. Extensive research has been conducted, but the intrinsic origins of hysteresis remain poorly understood. Here, we report a study of the kinetic origin of hysteresis and the enhanced barocaloric effect (BCE) in MnCoGe-based alloys with ~2% nonmagnetic In atoms. First-principles calculations demonstrate that substituting In atoms at Ge sites rather than Co sites results in a lower energy barrier, indicating a narrower hysteresis for the former. Combining neutron powder diffraction (NPD) with magnetic and calorimetric measurements completely verified the theoretical prediction. Electron local function (ELF) calculations further reveal the atomic coordination origin of regulated hysteresis due to weaker Co–Ge bonds when In atoms replace Ge, which is opposite to Co sites. Moreover, we experimentally investigate the BCE and find that although MnCo(Ge0.98In0.02) has a lower barocaloric entropy change ΔSP than does Mn(Co0.98In0.02)Ge, the reversible ΔSrev of the former is advantageous owing to a smaller hysteresis. The maximum ΔSrev of MnCo(Ge0.98In0.02) is 1.7 times greater than that of Mn(Co0.98In0.02)Ge. These results reveal the atomic-scale mechanism regulating hysteresis and provide insights into tailoring the functional properties of novel caloric refrigeration materials.

Abstract Biomarkers are not only of significant importance for cancer diagnosis and selection of treatment plans but also recently increasingly used for the evaluation of malignancy development and tumor heterogeneity. Large-size tumors from clinical patients can be unique and valuable sources for the study of cancer progression, particularly to the extent of intratumoral heterogeneity. In the present study, we obtained a series of post-surgery puncture samples from a breast cancer patient with a 4 × 3.5 × 2 cm tumor in its original size. Immunohistochemistry for Ki-67, COX-2, and CA IX was performed and the expression levels within the breast cancer tumor mass were evaluated in the reconstructed 3D models. To further evaluate the intratumoral heterogeneity, we performed high throughput whole transcriptome sequencing of 12 samples from different spatial positions within the tumor tissue. Comparing the reconstructed 3D distribution of biomarkers with projected tumor growth models, asymmetric and heterogeneous expansion of tumor mass was found to be possibly influenced by factors such as blood supply, inflammation and/or hypoxia stimulations, as suggested from the correlation between the results of Ki-67 and CA IX or COX-2 staining. Furthermore, high-throughput RNA sequencing data provided additional information for profiling the intratumoral heterogeneity and expanded the understanding of cancer progression. Digital technology for medical imaging once properly integrated with molecular pathology examinations will become particularly helpful in dissecting out in-depth information for precision medicine. We prospect that this approach, facilitated by rapidly advancing artificial intelligence, could provide new insights for clinical decision-making in the future. Strategies for the continuous development from the present study for better performance and application were discussed.

Abstract Maximizing materials utilization efficiency via enhancing their reconfigurability and multifunctionality offers a promising avenue in addressing the global challenges in sustainability. To this end, significant efforts have been made in developing reconfigurable multifunctional smart materials, which can exhibit remarkable behaviors such as morphing and self-healing. However, the difficulty in efficiently manipulating and controlling matter at the building block level with manageable cost and complexity, which is crucial to achieving superior responsiveness to environmental clues and stimuli, has significantly hindered the further development of such smart materials. Here we introduce a concept of Robo-Matter, which can be activated and controlled through external information exchange at the building block level, to enable a high-level of controllability, mutability and versatility for reconfigurable multifunctional smart materials. Using specially designed micro-robot building blocks with symmetry-breaking active motion modes, tunable anisotropic interactions, and interactive coupling with a programmable spatial-temporal dynamic light field, we demonstrate an emergent Robot-Matter duality, which enables a spectrum of desirable behaviors spanning from matter-like properties such as ultra-fast self-assembly and adaptivity, to robot-like properties including active force output, smart healing, smart morphing and infiltration. Our work demonstrates a promising direction for designing next-generation smart materials and large-scale robotic swarms.

Abstract The traditional Chinese medicinal plant Fallopia multiflora (hereafter AYY) is well known for its anti-hyperlipidaemia, immunomodulating, and hepatoprotective effects, attributed to its abundance of anthraquinones and stilbene glycosides, which are distinct to its variety F. multiflora var. angulata (hereafter CYY) in proportion and composition. In this study, telomere-to-telomere (T2T) genomes were assembled for AYY and CYY using PacBio HiFi reads and Hi-C data. The genome sizes, percentages of repetitive sequences, and numbers of protein-coding genes of AYY and CYY assemblies were 1,458.37 Mb/70.48%/84,768 and 1,174.38 Mb/67.36%/69,100, respectively. Comprehensive assessments confirmed high continuity (contig N50: 112.58 Mb and 94.83 Mb; number of gaps: 9 and 5), completeness (BUSCOs: 97.30% and 97.60%; LAI: 16.93 and 16.77), and correctness (QV: 51.42 and 52.60) of AYY and CYY assemblies. These T2T genomes of F. multiflora provide valuable resources for studying the biosynthesis of specialized metabolites and facilitating precise genetic improvement.

Abstract Preeclampsia (PE) is a common placental-origin complication of pregnancy and a major cause of morbidity and mortality among pregnant women and fetuses. However, its pathogenesis has not been elucidated. Effective strategies for prevention, screening, and treatment are still lacking. Studies have indicated that dysfunction of placental trophoblast cells, such as impaired syncytialization, proliferation, and epithelial-mesenchymal transition processes, plays a crucial role in the development of PE. Glucose transporter 1 (GLUT1) is a key protein regulating glucose transport in placental tissues. However, the effect of GLUT1 on the function of trophoblast cells in PE is not well understood. In this study, we found that GLUT1 expression is reduced in PE placental tissues. GLUT1 promotes the syncytialization process by increasing the glucose uptake ability of BeWo cells. Additionally, GLUT1 promotes the proliferation, migration, and invasion capabilities of HTR-8/SVneo cells by regulating MAPK and PI3K/AKT signaling pathways. Overall, these findings provide a new insight into understanding the biological functions of GLUT1, clarifying the pathogenesis of PE, and identifying diagnostic and therapeutic targets for PE.

Abstract Objective The aim was to explore the effectiveness of the International Myeloma Working Group Frailty Index (IMWG-FI), Mayo Score, UK Myeloma Research Alliance Risk Profile (MRP), and Intergroupe Francophone du Myélome (IFM) simplified frailty scale for classifying frailty in elderly multiple myeloma (MM) patients and compare the validity of different frailty tools. Methods Eighty-four newly diagnosed MM patients aged ≥ 60 years in HeBei University Hospital were evaluated by the IMWG-FI, Mayo score, MRP score and IFM scale, and consistency and survival analyses were performed using Cohen's kappa coefficients and the Kaplan‒Meier method, respectively. Results A total of 64 patients (76.2%) were identified as frail by at least one frailty tool; 14 (21.9%) were identified as frail by all four tools, and although moderate concordance was achieved between the IMWG-FI and MRP and the Mayo Score (0.432–0.474, P

Abstract Materials capable of dynamic persistent luminescence (PersL) within the visible spectrum are highly sought after for applications in display, biosensing, and information security. However, PersL materials with eye-detectable and excitation-wavelength-dependent characteristics are rarely achieved. Herein, a nonstoichiometric compound CaGaxO4:Bi (x

Abstract Background Malaria is a serious public health concern. Artemisinin and its derivatives are first-line drugs for the treatment of Plasmodium falciparum malaria. In mammals, artemisinin exhibits potent anti-inflammatory and immunoregulatory properties. However, it is unclear whether artemisinin plays a regulatory role in the innate immunity of mosquitoes, thereby affecting the development of Plasmodium in Anopheles when artemisinin and its metabolites enter mosquitoes. This study aims to determine the effect of dihydroartemisinin (DHA), a first-generation semisynthetic derivative of artemisinin, on innate immunity and malaria vector competence of Anopheles stephensi. Methods Anopheles stephensi was fed Plasmodium-infected mice treated with DHA via gavage, Plasmodium-infected blood containing DHA in vitro, or DHA-containing sugar, followed by Plasmodium yoelii infection. The engorged female mosquitoes were separated and dissected 8 and 17 days after infection. Plasmodium oocysts and sporozoites were counted and compared between the control and DHA-treated groups. Additionally, total RNA and proteins were extracted from engorged mosquitoes 24 and 72 h post infection (hpi). Real-time polymerase chain reaction (PCR) and western blotting were performed to detect the transcriptional levels and protein expression of immune molecules in mosquitoes. Finally, the Toll signaling pathway was inhibited via RNA interference and the infection density was analyzed to confirm the role of the Toll signaling pathway in the effect of DHA on the vector competence of mosquitoes. Results DHA treatment via different approaches significantly reduced the number of Plasmodium oocysts and sporozoites in mosquitoes. The transcriptional levels of anti-Plasmodium immune genes (including TEP1, LRIM1, and APL1C), Toll pathway genes (including Tube, MyD88, and Rel1), and the effector defensin 1 were upregulated by DHA treatment at 24 and 72 hpi. TEP1 and Rel1 protein expression was significantly induced under DHA treatment. However, Rel1 knockdown in DHA-treated mosquitoes abrogated DHA-mediated refractoriness to Plasmodium infection. Conclusions DHA treatment effectively inhibited the development of P. yoelii in A. stephensi by upregulating mosquitoes’ Toll signaling pathway, thereby influencing the susceptibility of Anopheles to Plasmodium. Graphical Abstract

Abstract Background Apart from the conventional utilization of ICL implantation for the correction of refractive errors, its recent applications extend to correcting refractive errors post laser refractive surgery. Notably, the development of cataracts stands out as a prevalent postoperative complication, often associated with low vault. Previous cases have demonstrated successful management of cataracts with ICL through the combination of FLACS and ICL removal coupled with IOL implantation, resulting in favorable postoperative visual outcomes. Herein, we present a case of cataract with low vault ICL following LASIK and its subsequent management. Case presentation A 46-year-old male presented with vision loss in the right eye for 9 months, and he had undergone LASIK 22 years prior and had ICL implantation in both eyes 2 years ago to correct refractive error. One day after ICL implantation, both eyes exhibited the UDVA of 1.2 and 1.0, well-positioned ICLs, and approximate vault of 150 μm and 200 μm. Six months ago, the patient became aware of blurred vision in the right eye for a duration of 3 months. Examination revealed cloudy lens cortex in the right eye. During the current review, the UDVA of the right eye was 0.6, where nasal wedge-shaped clouding was evident and worsened, while the left eye lens remained transparent. AS-OCT demonstrated the vault of 54 μm in the right eye and 83 μm in the left eye. Considering the patient’s history of LASIK and the presence of right eye cataract, a monovision approach was adopted. The patient underwent FLACS combined with ICL extraction and monofocal IOL lens implantation in the right eye. At 10 days postoperatively, the patient exhibited the UDVA of 1.0. Conclusions Our report confirms the feasibility of FLACS in managing cataracts in patients with low vault ICL following LASIK. This procedure does not pose significantly greater challenges than in typical cataract cases, although meticulous care remains essential throughout every step of the surgery, particularly during laser scanning and positioning. With adequate preoperative preparation and precise calculation of the IOL power, surgical outcomes can meet expectations fully.