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Abstract Background MicroRNAs (miRNAs) are critical regulators of cancer progression, prompting our investigation into the specific function of miR-630 in pancreatic cancer stem cells (PCSCs). Analysis of miRNA and mRNA expression data in PCSCs revealed downregulation of miR-630 and upregulation of PRKCI, implying a potential role for miR-630 in PCSC function and tumorigenicity. Results Functional assays confirmed that miR-630 directly targets PRKCI, leading to the suppression of the Hedgehog signaling pathway and consequent inhibition of PCSC self-renewal and tumorigenicity in murine models. This study unveiled the modulation of the PRKCI-Hedgehog signaling axis by miR-630, highlighting its promising therapeutic potential for pancreatic cancer (PC) treatment. Conclusions MiR-630 emerges as a pivotal regulator in PCSC biology, opening up new avenues for targeted interventions in PC. The inhibitory effect of miR-630 on PCSC behavior underscores its potential as a valuable therapeutic target, offering insights into innovative treatment strategies for this challenging disease.

Abstract Cybercrime is a complex human behavior and social phenomenon. The COVID-19 pandemic has significantly altered socioeconomic activities, potentially causing changes in crime patterns. However, there has been limited research on how the interaction between the pandemic and socioeconomic factors affects cybercrime. Here we explore the spatiotemporal patterns of police-recorded cybercrime, including fraud and cyber-dependent crime, and employ a machine learning approach to assess the correlation of various factors on cybercrimes at the level of internal regions and police areas within the United Kingdom. Our results show that fraud and cyber-dependent crime are mainly concentrated in London and the southeast region of England. Moreover, following the implementation of the third national lockdown, these areas experienced a noticeable increase, while changes in other regions were not as pronounced. The spatial autocorrelation analysis further suggests that there are significant spatial heterogeneities among regions, with spatiotemporal hotspots centered around London and cold spots mainly concentrated in the northeast of England. Additionally, we found that the identified patterns of fraud and cyber-dependent crime are primarily associated with socioeconomic factors, followed by government containment measures and mobility factors. These findings can help law enforcement and regulatory agencies better understand the social-environmental factors contributing to the prevalence of cybercrime within those areas.

Abstract Head and neck squamous cell carcinoma (HNSCC) is notorious for poor prognoses, and effective biomarkers are urgently needed for early diagnosis of HNSCC patients. We investigate the role of alkaline ceramidase 1 (ACER1) and its relationship with immune infiltration in HNSCC. The differential expression and clinical prognostic significance of ACER1 in HNSCC patients are explored using bioinformatics methods and verified in human HNSCC samples. Genetic mutation, DNA methylation and drug sensitivity linked with ACER1 are examined. The potential biological function of ACER1 co-expression genes is assessed, and a series of functional assays are performed on ACER1in vitro. The results comprehensively reveal a relationship between ACER1 and immune infiltration in HNSCC patients. ACER1 expression is significantly downregulated in HNSCC tissues and closely correlated with better prognoses for HNSCC patients, and this prognostic significance is determined by distinct clinical characteristics. Genetic alteration and promoter hypomethylation of ACER1 are involved in progression of HNSCC, and ACER1 expression is significantly related to several drug sensitivities. Functional analysis shows that ACER1 co-expression genes are mainly enriched in the sphingolipid signaling pathway associated with inhibition of tumorigenesis, leading to better prognoses for HNSCC patients. In vitro, ACER1 overexpression inhibits proliferation and migration, induces apoptosis, and promotes adhesion of Fadu and SCC9 cells. In addition, high ACER1 expression is closely linked with infiltration levels of immune cells, and strongly associated with biomarkers of immune cells in HNSCC, suggesting the important role of ACER1 in regulating tumor immunity in HNSCC patients. In summary, ACER1 may be a useful indicator for diagnosis and prognosis, and may regulate immune infiltration in HNSCC patients, thus promising targeted immunotherapy for HNSCC.

Abstract The obese heart undergoes metabolic remodeling and exhibits impaired calcium (Ca2+) homeostasis, which are two critical assaults leading to cardiac dysfunction. The molecular mechanisms underlying these alterations in obese heart are not well understood. Here, we show that the Rab-GTPase activating protein AS160 is a lipid-responsive regulator of Ca2+ homeostasis through governing lysophosphatidylinositol metabolism and signaling. Palmitic acid/high fat diet inhibits AS160 activity through phosphorylation by NEK6, which consequently activates its downstream target Rab8a. Inactivation of AS160 in cardiomyocytes elevates cytosolic Ca2+ that subsequently impairs cardiac contractility. Mechanistically, Rab8a downstream of AS160 interacts with DDHD1 to increase lysophosphatidylinositol metabolism and signaling that leads to Ca2+ release from sarcoplasmic reticulum. Inactivation of NEK6 prevents inhibition of AS160 by palmitic acid/high fat diet, and alleviates cardiac dysfunction in high fat diet-fed mice. Together, our findings reveal a regulatory mechanism governing metabolic remodeling and Ca2+ homeostasis in obese heart, and have therapeutic implications to combat obesity cardiomyopathy.

Abstract The oviduct epithelium is the initial maternal contact site for embryos after fertilization, offering the microenvironment before implantation. This early gestation period is particularly sensitive to stress, which can cause reduced fertility and reproductive disorders in mammals. Nevertheless, the local impact of elevated stress hormones on the oviduct epithelium has received limited attention to date, except for a few reports on polyovulatory species like mice and pigs. In this study, we focused on the effects of chronic maternal stress on cattle, given its association with infertility issues in this monoovulatory species. Bovine oviduct epithelial cells (BOEC) differentiated at the air–liquid interface (ALI) were stimulated with 250 nmol/L cortisol for 1 or 3 weeks. Subsequently, they were assessed for morphology, bioelectrical properties, and gene expression related to oviduct function, glucocorticoid pathway, cortisol metabolism, inflammation, and apoptosis. Results revealed adverse effects of cortisol on epithelium structure, featured by deciliation, vacuole formation, and multilayering. Additionally, cortisol exposure led to an increase in transepithelial potential difference, downregulated mRNA expression of the major glucocorticoid receptor (NR3C1), upregulated the expression of cortisol-responsive genes (FKBP5, TSC22D3), and significant downregulation of oviductal glycoprotein 1 (OVGP1) and steroid receptors PGR and ESR1. The systematic comparison to a similar experiment previously performed by us in porcine oviduct epithelial cells, indicated that bovine cultures were more susceptible to elevated cortisol levels than porcine. The distinct responses between both species are likely linked to their divergence in the cortisol-induced expression changes of HSD11B2, an enzyme controlling the cellular capacity to metabolise cortisol. These findings provide insights into the species-specific reactions and reproductive consequences triggered by maternal stress.

Abstract Metabolic dysfunction-associated steatohepatitis (MASH) is a rising global disease signaling the urgent need for non-invasive tests (NITs). Recent work demonstrated that dynamic 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) imaging can identify MASH by measuring liver glucose transport rate, K1, and liver CT attenuation. By combining dynamic PET/CT with the serum-based fibrosis-4 (FIB-4) test, we were able to better distinguish clinical MASH from fibrotic subtypes, enabling determination of the core tenets of MASH: steatosis, inflammation, and fibrosis. Future studies using FDG-PET technology can further enable concomitant prediction of MASH severity and extrahepatic comorbidities such as cardiovascular disease.

Abstract Zingiber striolatum Diels is a unique medicine food homology plant native to China. In recent years, due to severe habitat destruction, studying the impact of climate change on the distribution of wild resources is of great significance for the ecological conservation and artificial cultivation of Z. striolatum. This study collected 141 valid species distribution records, and 37 environmental variables, and projected two future climate scenarios (SSP126 and SSP585) for two periods (2050s and 2090s). By employing Pearson analysis, Maximum Entropy Model (MaxEnt), and Geographic Information System (ArcGIS), we predicted the potential suitable habitats for Z. striolatum under present and future climates, as well as identified the dominant environmental variables influencing its distribution. The results indicated that the MaxEnt model performed well (AUC > 0.9) with high accuracy and reliability. The dominant environmental factors included Precipitation of driest quarter (39.0 ~ 473.8 mm), Precipitation of wettest quarter (593.2 ~ 1269.4 mm), Temperature annual range (9.8 ~ 28.6℃), and Mean diurnal range (6.5 ~ 9.6℃). The highly suitable areas for Z. striolatum were mainly distributed in western and southern Yunnan, northern and western Guangxi, Guangdong, Fujian, and central Hainan. Under future climate change, the centroid of the total suitable area for Z. striolatum is projected to shift towards the southwest (Yungui Plateau) at higher elevations.

Abstract Astrocytes, the predominant glial cells in the central nervous system, play essential roles in maintaining brain function. Reprogramming induced pluripotent stem cells (iPSCs) to become astrocytes through overexpression of the transcription factors, NFIB and SOX9, is a rapid and efficient approach for studying human neurological diseases and identifying therapeutic targets. However, the precise differentiation path and molecular signatures of induced astrocytes remain incompletely understood. Accordingly, we performed single-cell RNA sequencing analysis on 64,736 cells to establish a comprehensive atlas of NFIB/SOX9-directed astrocyte differentiation from human iPSCs. Our dataset provides detailed information about the path of astrocyte differentiation, highlighting the stepwise molecular changes that occur throughout the differentiation process. This dataset serves as a valuable reference for dissecting uncharacterized transcriptomic features of NFIB/SOX9-induced astrocytes and investigating lineage progression during astrocyte differentiation. Moreover, these findings pave the way for future studies on neurological diseases using the NFIB/SOX9-induced astrocyte model.

Abstract Angular random walk (ARW), rate random walk (RRW), and bias instability (BI) are the main noise types in inertial measurement units (IMUs) and thus determine the navigation performance of IMUs. BI is the flicker noise, which determines the noise level of an inertial sensor. The traditional error modeling approach involves modeling the ARW and BI processes as RRW or Gauss–Markov (GM) processes, and this approach is applied as a suboptimal filter in the global navigation satellite system (GNSS)/inertial navigation system (INS) extended Kalman filter (EKF). In this paper, the random error identification processes for white noise and colored noise for inertial sensors are separated using the Allan variance and power spectral density methods and the equivalence of the stochastic process differential equations of bias instability and a combination of multiple first-order GM processes are derived. A colored noise compensation method is proposed based on the enhanced EKF model. Experimental results demonstrate that, compared to traditional error models, our proposed model reduces positional drift error in dynamic testing from 195 to 49 m, enhancing positional accuracy by 40.2%. These findings confirm the potential and superiority of our method in complex navigation environments.

Rock abrasiveness is an important factor affecting the tool's lifetime and efficiency in breaking a rock. Characterizing rock abrasiveness helps in the design, optimization, and mean-life prediction of tools. X-ray diffraction, cast thin section analysis, and CERCHAR abrasiveness tests were performed on 18 different sandstones to characterize rock abrasiveness and explore new methods for characterization. The relationship between the mineral composition and microstructure of sandstone and abrasiveness was investigated. The results show that different structural maturities have varying effects on abrasiveness. In addition, the higher the structural maturity, the more the abrasiveness. Furthermore, in sandstones of the same structural maturity, the abrasiveness increases with equivalent quartz content (EQC). The texture coefficient (TC) and CERCHAR abrasiveness index (CAI) of sandstones with the same structural maturity showed a good linear relationship. Moreover, the correlation coefficients considering the combined parameters are above 0.85. Therefore, obtaining the microstructure and mineral composition of sandstone can effectively characterize rock abrasiveness. It also provides a new method for predicting the abrasiveness of the rock in the well.

Abstract The emulation of tactile sensory nerves to achieve advanced sensory functions in robotics with artificial intelligence is of great interest. However, such devices remain bulky and lack reliable competence to functionalize further synaptic devices with proprioceptive feedback. Here, we report an artificial organic afferent nerve with low operating bias (−0.6 V) achieved by integrating a pressure-activated organic electrochemical synaptic transistor and artificial mechanoreceptors. The dendritic integration function for neurorobotics is achieved to perceive directional movement of object, further reducing the control complexity by exploiting the distributed and parallel networks. An intelligent robot assembled with artificial afferent nerve, coupled with a closed-loop feedback program is demonstrated to rapidly implement slip recognition and prevention actions upon occurrence of object slippage. The spatiotemporal features of tactile patterns are well differentiated with a high recognition accuracy after processing spike-encoded signals with deep learning model. This work represents a breakthrough in mimicking synaptic behaviors, which is essential for next-generation intelligent neurorobotics and low-power biomimetic electronics.

Abstract Background CD74 is ectopically expressed in many tumors and can regulate tumor immunity. However, there are many gaps in the study of the prognostic value of CD74 expression and immune infiltration in hepatocellular carcinoma (HCC). Methods An online tumor database was searched to obtain data on gene/protein expression. Immune infiltration analysis was performed using the Tumor Immune Estimation Resource and Comprehensive Analysis on Multi-Omics of Immunotherapy in Pan-cancer databases. Single-cell data were obtained from the Tissue-specific Gene Expression and Regulation, Single-cell Transcriptomes of Tumor Immune Microenvironment and Tumor Immune Single-cell Hub 2 databases. Results CD74 was highly expressed in HCC patients. HCC patients with high CD74 expression who consumed alcohol or were negative for hepatitis virus had a better prognosis than patients with low CD74 expression. CD74 was mainly enriched in immune response regulation pathways. Both copy number variations in CD74 and CD74 expression patterns affected the infiltration levels of immune cells. Interestingly, CD74 regulated the differentiation of myeloid cells. CD74 in macrophages and dendritic cells (DCs) forms complex networks with malignant cells and hepatic progenitor cell (HPC)-like cells, respectively. High CD74 expression in HPC-like cells and malignant cells significantly decreased the fraction of C-type lectin domain family 9 A (CLEC9A)-cDC1+ DCs and IL-1B+ macrophages, respectively. Their crosstalk subsequently shaped the tumor microenvironment of HCC, possibly through the CD74-MIF axis. Importantly, patients with high CD74 expression presented higher immune scores and achieved good outcomes after receiving immunotherapy. Conclusion High CD74 expression is associated with the abundance of a variety of immune cell types, mediating interactions among tumor and immune cells and shaping the malignant behavior of HCC. In summary, CD74 may be a hallmark for determining the prognosis and immune cell infiltration levels of HCC patients.

Abstract Artificial wrinkles, especially those with responsive erasure/regeneration behaviors have gained extensive interest due to their potential in smart applications. However, current wrinkle modulation methods primarily rely on network rearrangement, causing bottlenecks in in situ wrinkle regeneration. Herein, we report a dually cross-linked network wherein [2]rotaxane cross-link can dissipate stress within the wrinkles through its sliding motion without disrupting the network, and quadruple H-bonding cross-link comparatively highlight the advantages of [2]rotaxane modulation. Acid stimulation dissociates quadruple H-bonding and destructs network, swiftly eliminating the wrinkles. However, the regeneration process necessitates network rearrangement, making in situ recovery unfeasible. By contrast, alkaline stimulation disrupts host–guest recognition, and subsequent intramolecular motion of [2]rotaxane dissipate energy to eliminate wrinkles gradually. The always intact network allows for the in situ recovery of surface microstructures. The responsive behaviors of quadruple H-bonding and mechanical bond are orthogonal, and their combination leads to wrinkles with multiple but accurate responsiveness.

Abstract Background Salt is an important factor that affects crop productivity. Plant hexokinases (HXKs) are key enzymes in the glycolytic pathway and sugar signaling transduction pathways of plants. In previous studies, we identified and confirmed the roles of GmHXK2 in salt tolerance. Results In this study, we analyzed the tissue-specific expression of GmHXK2 at different growth stages throughout the plant’s life cycle. The results showed that GmHXK2 was expressed significantly in all tissues at vegetative stages, including germination and seedling. However, no expression was detected in the pods, and there was little expression in flowers during the later mature period. Arabidopsis plants overexpressing the GmHXK2 (OE) had more lateral roots. The OE seedlings also produced higher levels of auxin and ascorbic acid (AsA). Additionally, the expression levels of genes PMM, YUC4/YUC6/YUC8, and PIN/LAX1,LAX3, which are involved respectively in the synthesis of AsA and auxin, as well as polar auxin transport, were upregulated in OE plants. This upregulation occurred specifically under exogenous glucose treatment. AtHKT1, AtSOS1, and AtNHX1 were up-regulated in OE plants under salt stress, suggesting that GmHXK2 may modulate salt tolerance by maintaining ion balance within the cells and alleviating damage caused by salt stress. Additionally, we further confirmed the interaction between GmHXK2 and the protein GmPMM through yeast two-hybridization and bimolecular fluorescence complementation assays, respectively. Conclusion The expression of GmHXK2 gene in plants is organ-specific and developmental stage specific. GmHXK2 not only regulates the synthesis of AsA and the synthesis and distribution of auxin, but also promotes root elongation and induces lateral root formation, potentially enhancing soil water absorption. This study reveals the crosstalk between sugar signaling and hormone signaling in plants, where GmHXK2 acts as a glucose sensor through its interaction with GmPMM, and sheds light on the molecular mechanism by which GmHXK2 gene is involved in salt tolerance in plants.

Abstract Hepatocellular carcinoma (HCC) poses a significant clinical challenge, necessitating the integration of immunotherapeutic approaches. Palbociclib, a selective CDK4/6 inhibitor, has demonstrated promising efficacy in preclinical HCC models and is being evaluated as a novel therapeutic option in clinical trials. Additionally, CDK4/6 inhibition induces cellular senescence, potentially influencing the tumor microenvironment and immunogenicity of cancer cells. In this study, we conducted comprehensive bioinformatic analyses using diverse HCC transcriptome datasets, including bulk and single-cell RNA-sequencing data from public databases. We also utilized human and mouse HCC cells to investigate functional aspects. Primary T cells isolated from mouse blood were employed to assess T cell immunity against HCC cells. Results revealed that CD8+ T-cell infiltration correlates with improved outcomes in HCC patients with suppressed CDK4/6 expression. Moreover, CDK4/6 expression was associated with alterations in the immune landscape and immune checkpoint expression within the liver tumor microenvironment. Furthermore, we found that treatment with Palbociclib and Doxorubicin induces cellular senescence and a senescence-associated secretory phenotype in HCC cells. Notably, pretreatment with Palbociclib augmented T cell-mediated cytotoxicity against HCC cells, despite upregulation of PD-L1, surpassing the effects of Doxorubicin pretreatment. In conclusion, our study elucidates a novel mechanism by which CDK4/6 inhibition enhances T-cell-associated cancer elimination and proposes a potential therapeutic strategy to enhance T-cell immunotherapy on HCC. Graphical abstract

Abstract The eukaryotic asparagine (N)-linked glycan is pre-assembled as a fourteen-sugar oligosaccharide on a lipid carrier in the endoplasmic reticulum (ER). Seven sugars are first added to dolichol pyrophosphate (PP-Dol) on the cytoplasmic face of the ER, generating Man5GlcNAc2-PP-Dol (M5GN2-PP-Dol). M5GN2-PP-Dol is then flipped across the bilayer into the lumen by an ER translocator. Genetic studies identified Rft1 as the M5GN2-PP-Dol flippase in vivo but are at odds with biochemical data suggesting Rft1 is dispensable for flipping in vitro. Thus, the question of whether Rft1 plays a direct or an indirect role during M5GN2-PP-Dol translocation has been controversial for over two decades. We describe a completely reconstituted in vitro assay for M5GN2-PP-Dol translocation and demonstrate that purified Rft1 catalyzes the translocation of M5GN2-PP-Dol across the lipid bilayer. These data, combined with in vitro results demonstrating substrate selectivity and rft1∆ phenotypes, confirm the molecular identity of Rft1 as the M5GN2-PP-Dol ER flippase.

Abstract Aims We aim to explore the associations between serum tyrosine (Tyr) to threonine (Thr) ratio and chronic heart failure (HF) with reduced or mildly reduced ejection fraction (EF) (HFrEF or HFmrEF). Methods and results The study recruited 418 subjects (77.5% males, mean age 65.2 ± 12.5 years), including 318 HF subjects (HFrEF or HFmrEF) and 100 cardiovascular subjects without acute or chronic HF [including heart failure with preserved ejection fraction (HFpEF)] as controls. Serum levels of 21 kinds of amino acids (AAs) were measured by mass spectrometry. Logistic regression analysis was conducted to measuring the association between the AAs levels and the presence of HF. Event‐free survival was determined by Kaplan–Meier curves and differences in survival were assessed using log‐rank tests. Cox regression analysis was used to assess the prognostic value of AAs in HF. Receiver‐operating characteristic (ROC) curve was performed to further confirm regression analysis. Along with the control, HFmrEF, and HFrEF subjects, serum tyrosine (Tyr) gradually increased (64.43 ± 15.28 μmol/L vs. 71.79 ± 18.74 μmol/L vs. 77.32 ± 25.90 μmol/L, P

Abstract The human nervous system inspires the next generation of sensory and communication systems for robotics, human‐machine interfaces (HMIs), biomedical applications, and artificial intelligence. Neuromorphic approaches address processing challenges; however, the vast number of sensors and their large‐scale distribution complicate analog data manipulation. Conventional digital multiplexers are limited by complex circuit architecture and high supply voltage. Large sensory arrays further complicate wiring. An ʻin‐electrolyte computingʼ platform is presented by integrating organic electrochemical transistors (OECTs) with a solid‐state polymer electrolyte. These devices use synapse‐like signal transport and spatially dependent bulk ionic doping, achieving over 400 times modulation in channel conductance, allowing discrimination of locally random‐access events without peripheral circuitry or address assignment. It demonstrates information processing from 12 tactile sensors with a single OECT output, showing clear advantages in circuit simplicity over existing all‐electronic, all‐digital implementations. This self‐multiplexer platform offers exciting prospects for circuit‐free integration with sensory arrays for high‐quality, large‐volume analog signal processing.

Abstract The main challenge for immune checkpoint blockade (ICB) therapy lies in immunosuppressive tumor microenvironment (TME). Repolarizing M2‐like tumor‐associated macrophages (TAMs) into inflammatory M1 phenotype is a promising strategy for cancer immunotherapy. Here, this study shows that the tumor suppressive protein SHISA3 regulates the antitumor functions of TAMs. Local delivery of mRNA encoding Shisa3 enables cancer immunotherapy by reprogramming TAMs toward an antitumoral phenotype, thus enhancing the efficacy of programmed cell death 1 (PD‐1) antibody. Enforced expression of Shisa3 in TAMs increases their phagocytosis and antigen presentation abilities and promotes CD8+ T cell‐mediated antitumor immunity. The expression of SHISA3 is induced by damage/pathogen‐associated molecular patterns (DAMPs/PAMPs) in macrophages via nuclear factor‐κB (NF‐κB) transcription factors. Reciprocally, SHISA3 forms a complex with heat shock protein family A member 8 (HSPA8) to activate NF‐κB signaling thus maintaining M1 polarization of macrophages. Knockout Shisa3 largely abolishes the antitumor efficacy of combination immunotherapy with Toll‐like receptor 4 (TLR4) agonist monophosphoryl lipid A (MPLA) and PD‐1 antibody. It further found that higher expression of SHISA3 in antitumoral TAMs is associated with better overall survival in lung cancer patients. Taken together, the findings describe the role of SHISA3 in reprogramming TAMs that ameliorate cancer immunotherapy.

BackgroundSplenic cysts are relatively rare benign tumors that are asymptomatic in most patients and are usually discovered incidentally by imaging. In our case, we report a splenic cyst in a child who underwent laparoscopic partial splenectomy.Case descriptionA 13-year-old boy was admitted to the hospital after an incidental finding of a splenic cyst on an abdominal ultrasound conducted 4 days prior. He was asymptomatic before admission. Upon admission, abdominal ultrasound and CT revealed a cystic lesion in the spleen, highly suspicious for a splenic cyst. Then, we used transumbilical single-site laparoscopic exploration and found a cyst measuring approximately 12 cm × 11 cm × 10 cm at the upper pole of the spleen, so we performed a partial splenectomy and diagnosed a primary epithelioid splenic cyst via postoperative pathology.ConclusionsSplenic cysts in children are very rare and can be treated conservatively in asymptomatic patients with a diameter of less than 5 cm, while surgery is required in symptomatic patients or those with a diameter greater than or equal to 5 cm. Transumbilical single-site laparoscopic partial splenectomy is a minimally invasive and effective treatment, especially for children.

ObjectiveThis study is aimed to evaluate the efficacy and safety of PD-1 inhibitors combined with neoadjuvant chemotherapy in patients with locally advanced hypopharyngeal and oropharyngeal cancer prior to surgical resection.MethodsThis retrospective analysis included 42 patients diagnosed with locally advanced hypopharyngeal and oropharyngeal cancer. The efficacy, safety, survival, and laryngeal preservation rate were evaluated.ResultsA total of 42 patients were included in this retrospective analysis, of whom 28 had hypopharyngeal cancer and 14 had oropharyngeal cancer. Of the 42 patients, 14 (33.3%) achieved a pathological complete response (PCR) at the primary site, 20 (47.6%) achieved a major pathological response (MPR), and 8 (19%) had an incomplete pathological response (IPR) at the primary lesion. A PCR at both the primary site and the neck lymph nodes was observed in 9 patients (21.4%). The laryngeal preservation rate was 92.9% (26/28) in patients with hypopharyngeal cancer. The median follow-up time was 10.5 months. The median progression-free survival (PFS) was 26.42 months (95% CI, 23.416–29.424), and the median overall survival (OS) was 27.1 months (95% CI, 24.316–29.884). The 1-year PFS rate was 83.1%, and the 1-year OS rate was 85.9%.ConclusionCombination therapy with PD-1 inhibitors and neoadjuvant chemotherapy has demonstrated superior efficacy and safety as a preoperative treatment for locally advanced hypopharyngeal and oropharyngeal cancer. Notably, this treatment regimen does not increase the risk of severe postoperative complications and has shown promising results in improving laryngeal preservation rates.

BackgroundHypertension is a common complication in patients with osteoarthritis (OA). There is increasing interest in the relationship between hypertension and OA. However, hypertension has been reported to negatively affect symptoms and quality of life in patients with OA. Therefore, treating hypertension is crucial for patients with OA. However, there is a lack of real-world studies on the effects of medications for treating hypertension on OA.MethodsData from the FAERS database from January 2004 to December 2023 were extracted for disproportionality analyses, and proportional reporting ratios (PRRs) were used to assess the association between medications for hypertension and all types of arthritis. Adverse event signals were identified and determined using reporting odds ratios (RORs) Adverse event signals were considered to have occurred if a drug-induced adverse event was recorded more than or equal to 3 and the lower limit of the ROR confidence interval was more than 1. We selected five classes of drugs including, calcium channel blockers (CCBs), angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), thiazide diuretics and β-blockers and representative drugs were analysed for osteoarthritis-related adverse reactions, and age and gender subgroups were analysed for drugs of significance. We also analysed the occurrence of AEs in relation to time using the Weibull distribution.ResultsIn terms of overall data, we found significant OA adverse reaction signals only for ARBs among the five drug classes.ARB AEs for spinal osteoarthritis (ROR 4.64, 95% CI 3.62–5.94), osteoarthritis (ROR 3.24 95% CI 2.82–3.72) and gouty arthritis (ROR 3.27 95% CI 1.22–8.75) were the three adverse reactions with the loudest signals. Next, we found that valsartan had strong osteoarthritis adverse reaction signals among the three ARBs, namely, irbesartan, cloxartan, and valsartan. We also analysed age and gender subgroups and found that osteoarthritis signals were strongest in the 18–65 and 65+ population, while females seem to be more prone to valsartan-related OA AEs.ConclusionARBs, especially valsartan, have significant positive signals for OA AEs. Therefore, ARB drugs, especially valsartan, should be used with caution when treating patients with OA combined with hypertension.

Field capacity (FC) is an important soil hydraulic concept in soil science and irrigation management. It is generally determined from soil water content in a soil layer when soil profile reaches a steady pressure head or negligible drainage flux from an initially saturated soil. However, the proposed criteria are mainly tested for uniform soils and vary with soil textures. To quantify FC in layered soils, a Richards equation-based model was used to describe water flow in fine-textured soils with a coarse interlayer. With calibrated soil hydraulic parameters for loam and sand from infiltration measurements, drainage from saturation was simulated in the loam with a sand interlayer. A relative drainage rate (δ) was defined as a function of water storage and drainage flux to analyze soil water status at FC. Soil water content in the upper loam layer of layered profiles was improved compared with that in the uniform loam, which was negatively correlated with buried depth but positively correlated with thickness of the sand layer for a specified δ. Under different buried depths and thicknesses, soil water content decreased with the decline of δ and decreased rapidly as δ reduced to 1 % d−1. The drainage flux at δ = 1 % d−1 changed within a range of 0.056–0.26 cm d−1, and soil water content reached to 0.278–0.346 cm3 cm−3, which accounted for 70–87 % of the saturated water content of loam. Although the FC in the upper fine-textured soil layer varied for different buried depths and thicknesses of coarse interlayer, the proposed dynamic method is reliable and universal to estimate the FC in the above layered soils at δ = 1 % d−1. An empirical equation was also developed to calculate the FC in fine-textured soils with different buried depths and thicknesses of a coarse interlayer based on the critical δ value.

Abstract Background Lp-PLA2 is linked to cardiovascular diseases and poor outcomes, especially in diabetes, as it functions as a pro-inflammatory and oxidative mediator. Objectives This research aimed to explore if there is a connection between the serum levels of Lp-PLA2 and the progression of coronary plaques (PP) in individuals with type 2 diabetes mellitus (T2DM) and those without the condition. Materials and methods Serum Lp-PLA2 levels were measured in 137 T2DM patients with PP and 137 T2DM patients with no PP, and in 205 non-diabetic patients with PP and 205 non-diabetic patients with no PP. These individuals met the criteria for eligibility and underwent quantitative coronary angiography at the outset and again after about one year of follow-up. The attributes and parameters of the participants at the outset were recorded. Results Increased serum levels of Lp-PLA2 were closely associated with coronary artery PP, and also significantly correlated with change of MLD, change of diameter stenosis and change of cumulative coronary obstruction in both diabetic and non-diabetic groups, with higher correlation coefficients in diabetic patients as compared with non-diabetic patients. Moreover, multivariate logistic regression analysis showed that serum Lp-PLA2 level was an independent determinant of PP in both groups, with OR values more significant in diabetic patients than in non-diabetic patients. Conclusions Levels of serum Lp-PLA2 show a significant association with the progression of coronary atherosclerotic plaque in patients with T2DM and those without, especially among individuals with diabetes.

Abstract The aim of this study was to explore the impact of chronic apical periodontitis (CAP) on atherosclerosis in apoE−/− mice fed high-fat diet (HFD). This investigation focused on the gut microbiota, metabolites, and intestinal barrier function to uncover potential links between oral health and cardiovascular disease (CVD). In this study, CAP was shown to exacerbate atherosclerosis in HFD-fed apoE−/− mice, as evidenced by the increase in plaque size and volume in the aortic walls observed via Oil Red O staining. 16S rRNA sequencing revealed significant alterations in the gut microbiota, with harmful bacterial species thriving while beneficial species declining. Metabolomic profiling indicated disruptions in lipid metabolism and primary bile acid synthesis, leading to elevated levels of taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA), and tauroursodeoxycholic acid (TDCA). These metabolic shifts may contribute to atherosclerosis development. Furthermore, impaired intestinal barrier function, characterized by reduced mucin expression and disrupted tight junction proteins, was observed. The increased intestinal permeability observed was positively correlated with the severity of atherosclerotic lesions, highlighting the importance of the intestinal barrier in cardiovascular health. In conclusion, this research underscores the intricate interplay among oral health, gut microbiota composition, metabolite profiles, and CVD incidence. These findings emphasize the importance of maintaining good oral hygiene as a potential preventive measure against cardiovascular issues, as well as the need for further investigations into the intricate mechanisms linking oral health, gut microbiota, and metabolic pathways in CVD development.

Adhesive small bowel obstruction (ASBO) causes a major burden in emergency medicine. Owing to in situ decompression, nasointestinal tube (NIT) placement has been increasingly used in clinical practice compared with traditional conservation (TC); however, the indications remain controversial. This study was designed to explore the indications for each treatment in ASBOs and then suggest the optimal strategy.After propensity score matching, 128 pairs were included (the NIT and TC groups). The occurrence of severe adverse events (SAEs), peri-treatment clinical parameters, and radiological features were compared between the successful and failed treatment groups.According to different stages of the entire treatment, the independent risk factors for adverse effects for ASBO were analysed in phase I and phase II. In phase I, normal red blood cells (RBC) levels (p = 0.011) and a balanced sodium ion level (p = 0.016) positively affected the outcomes of TC treatment. In phase II, for the TC group, the successful treatment rate reached 79.5% for patients with ASBOs whose normal RBC levels (p = 0.006) or decreasing white blood cells (WBC) levels (p = 0.014) after treatment. For the NIT group, the treatment success rate was 68.1% for patients whose electrolyte imbalance could be reversed or whose neutrophil count/lymphocyte ratio (NLR) levels was lower than 4.3 (p = 0.018).TC treatment is highly recommended for patients with normal RBC counts and sodium levels pretreatment. After dynamic monitoring of the treatment process, for both the TC and NIT groups, once ASBOs had elevated inflammatory biomarkers or irreversible electrolyte disturbances, surgical interference was preferred.

Abstract The transcription and replication processes of non-segmented, negative-strand RNA viruses (nsNSVs) are catalyzed by a multi-functional polymerase complex composed of the large protein (L) and a cofactor protein, such as phosphoprotein (P). Previous studies have shown that the nsNSV polymerase can adopt a dimeric form, however, the structure of the dimer and its function are poorly understood. Here we determine a 2.7 Å cryo-EM structure of human parainfluenza virus type 3 (hPIV3) L–P complex with the connector domain (CD′) of a second L built, while reconstruction of the rest of the second L–P obtains a low-resolution map of the ring-like L core region. This study reveals detailed atomic features of nsNSV polymerase active site and distinct conformation of hPIV3 L with a unique β-strand latch. Furthermore, we report the structural basis of L–L dimerization, with CD′ located at the putative template entry of the adjoining L. Disruption of the L–L interface causes a defect in RNA replication that can be overcome by complementation, demonstrating that L dimerization is necessary for hPIV3 genome replication. These findings provide further insight into how nsNSV polymerases perform their functions, and suggest a new avenue for rational drug design.

Abstract The essence of difference between hemostasis and thrombosis is that the clotting reaction is a highly fine-tuned process. Vascular protein disulfide isomerase (PDI) represents a critical mechanism regulating the functions of hemostatic proteins. Herein we show that histidine-rich glycoprotein (HRG) is a substrate of PDI. Reduction of HRG by PDI enhances the procoagulant and anticoagulant activities of HRG by neutralization of endothelial heparan sulfate (HS) and inhibition of factor XII (FXIIa) activity, respectively. Murine HRG deficiency (Hrg −/− ) leads to delayed onset but enhanced formation of thrombus compared to WT. However, in the combined FXII deficiency (F12 −/− ) and HRG deficiency (by siRNA or Hrg −/− ), there is further thrombosis reduction compared to F12 −/− alone, confirming HRG’s procoagulant activity independent of FXIIa. Mutation of target disulfides of PDI leads to a gain-of-function mutant of HRG that promotes its activities during coagulation. Thus, PDI-HRG pathway fine-tunes thrombosis by promoting its rapid initiation via neutralization of HS and preventing excessive propagation via inhibition of FXIIa.

Abstract Background Impaired collateral formation is a major factor contributing to poor prognosis in type 2 diabetes mellitus (T2DM) patients with atherosclerotic cardiovascular disease. However, the current pharmacological treatments for improving collateral formation remain unsatisfactory. The induction of endothelial autophagy and the elimination of reactive oxygen species (ROS) represent potential therapeutic targets for enhancing endothelial angiogenesis and facilitating collateral formation. This study investigates the potential of molybdenum disulfide nanodots (MoS2 NDs) for enhancing collateral formation and improving prognosis. Results Our study shows that MoS2 NDs significantly enhance collateral formation in ischemic tissues of diabetic mice, improving effective blood resupply. Additionally, MoS2 NDs boost the proliferation, migration, and tube formation of endothelial cells under high glucose/hypoxia conditions in vitro. Mechanistically, the beneficial effects of MoS2 NDs on collateral formation not only depend on their known scavenging properties of ROS (H2O2, •O2 -, and •OH) but also primarily involve a molecular pathway, cAMP/PKA-NR4A2, which promotes autophagy and contributes to mitigating damage in diabetic endothelial cells. Conclusions Overall, this study investigated the specific mechanism by which MoS2 NDs mediated autophagy activation and highlighted the synergy between autophagy activation and antioxidation, thus suggesting that an economic and biocompatible nano-agent with dual therapeutic functions is highly preferable for promoting collateral formation in a diabetic context, thus, highlighting their therapeutic potential. Graphical Abstract

A landslide inventory is essential for numerous applications, including disaster prevention and mitigation. The emergence of advanced satellite technologies and the proliferation of extensive satellite imagery have greatly enhanced the role of deep learning-based semantic segmentation networks in the development of comprehensive landslide inventories. In deep learning, especially in semantic segmentation tasks, the loss function is crucial to guide the training of neural networks. However, typical loss functions have several challenges and shortcomings, including difficulty in handling objects of different scales and neglecting spatial correlation. These drawbacks hinder semantic segmentation networks from solely concentrating on accurately predicting landslide categories with rich semantic information. The spatial details (e.g. small landslides and precise landslide boundary information) in the segmentation results may be lost, reducing the accuracy of landslide extraction. Most studies only focus on training and detection in the local region. Consequently, detecting new unexplored region and detrimental to emergency response is challenging. This study presents a level set loss-guided semantic segmentation network, which can be integrated with different semantic segmentation networks, to address these issues. Three out of five study areas (e.g. Bijie, Jiuzhaigou, and Taitung) are used for model training and accuracy evaluation, while the rest, which are newly unexplored regions (e.g. Hokkaido and Haiti), are used to test the transferability of the proposed loss function in different regions. The study results validate the effectiveness of the designed level set loss in various semantic segmentation networks and in different study areas for landslide extraction.

ABSTRACTMelatonin has various physiological effects, such as the maintenance of circadian rhythms, anti-inflammatory functions, and regulation of intestinal barriers. The regulatory functions of melatonin in gut microbiota remodeling have also been well clarified; however, the role of gut microbiota in regulating host melatonin production remains poorly understood. To address this, we studied the contribution of gut microbiota to host melatonin production using gut microbiota-perturbed models. We demonstrated that antibiotic-treated and germ-free mice possessed diminished melatonin levels in the serum and elevated melatonin levels in the colon. The influence of the intestinal microbiota on host melatonin production was further confirmed by fecal microbiota transplantation. Notably, Lactobacillus reuteri (L. R) and Escherichia coli (E. coli) recapitulated the effects of gut microbiota on host melatonin production. Mechanistically, L. R and E. coli activated the TLR2/4/MyD88/NF-κB signaling pathway to promote expression of arylalkylamine N-acetyltransferase (AANAT, a rate-limiting enzyme for melatonin production), and MyD88 deficiency in colonic epithelial cells abolished the influence of intestinal microbiota on colonic melatonin production. Collectively, we revealed a specific underlying mechanism of gut microbiota to modulate host melatonin production, which might provide novel therapeutic ideas for melatonin-related diseases.

ABSTRACTThe gut microbiota (GM) and its metabolites affect the host nervous system and are involved in the pathogeneses of various neurological diseases. However, the specific GM alterations under pathogenetic pressure and their contributions to the “microbiota – metabolite – brain axis” in Alzheimer’s disease (AD) remain unclear. Here, we investigated the GM and the fecal, serum, cortical metabolomes in APP/PS1 and wild-type (WT) mice, revealing distinct hub bacteria in AD mice within scale-free GM networks shared by both groups. Moreover, we identified diverse peripheral – central metabolic landscapes between AD and WT mice that featured bile acids (e.g. deoxycholic and isodeoxycholic acid) and unsaturated fatty acids (e.g. 11Z-eicosenoic and palmitoleic acid). Machine-learning models revealed the relationships between the differential/hub bacteria and these metabolic signatures from the periphery to the brain. Notably, AD-enriched Dubosiella affected AD occurrence via cortical palmitoleic acid and vice versa. Considering the transgenic background of the AD mice, we propose that Dubosiella enrichment impedes AD progression via the synthesis of palmitoleic acid, which has protective properties against inflammation and metabolic disorders. We identified another association involving fecal deoxycholic acid-mediated interactions between the AD hub bacteria Erysipelatoclostridium and AD occurrence, which was corroborated by the correlation between deoxycholate levels and cognitive scores in humans. Overall, this study elucidated the GM network alterations, contributions of the GM to peripheral – central metabolic landscapes, and mediatory roles of metabolites between the GM and AD occurrence, thus revealing the critical roles of bacteria in AD pathogenesis and gut – brain communications under pathogenetic pressure.

ABSTRACTStreptococcus mutans (S. mutans) is one of the major etiological agents of dental caries. Interfering with the expression of genes associated with cariogenicity of S. mutans is an effective ecological approach for caries prevention. Thus, understanding the role of genes related to cariogenicity in S. mutans is important. dltD is a conserved gene in Gram-positive bacteria, which is involved in D-alanylation of lipoteichoic acid to modify cell surface charge. In vivo caries experiments have shown significant decreases in the caries severity in rats infected with S. mutans dltD-deficient strain. Although the impact of dltD on bacterial surface charge and division in other Gram-positive bacteria is known, its role in S. mutans biological functions remains unclear. This study aimed to investigate the biological functions of dltD in S. mutans. We examined growth curves, morphology, autolysis, biofilm formation, and cell membrane properties of S. mutans wild strain and dltD-deficient strain. Our results revealed that dltD plays a key role in the growth and autolysis of S. mutans. dltD deletion increased biofilm autolysis, thereby reducing the number of viable bacteria within the biofilm. Furthermore, dltD may have an epistatic effect on cell division and surface charge. Its regulatory network needs to be further elucidated. This study shed light on therole of dltD in the growth of S. mutans, thereby enhancing our understanding of its function.

Abstract By modulating subwavelength structures and integrating functional materials, 2D artificial microstructures (2D AMs), including heterostructures, superlattices, metasurfaces and microcavities, offer a powerful platform for significant manipulation of light fields and functions. These structures hold great promise in high‐performance and highly integrated optoelectronic devices. However, a comprehensive summary of 2D AMs remains elusive for photonics and optoelectronics. This review focuses on the latest breakthroughs in 2D AM devices, categorized into electronic devices, photonic devices, and optoelectronic devices. The control of electronic and optical properties through tuning twisted angles is discussed. Some typical strategies that enhance light‐matter interactions are introduced, covering the integration of 2D materials with external photonic structures and intrinsic polaritonic resonances. Additionally, the influences of external stimuli, such as vertical electric fields, enhanced optical fields and plasmonic confinements, on optoelectronic properties is analysed. The integrations of these devices are also thoroughly addressed. Challenges and future perspectives are summarized to stimulate research and development of 2D AMs for future photonics and optoelectronics.

Purpose: This research focused on meticulously tracking and identifying adverse reactions associated with leuprorelin, a drug prescribed for conditions such as prostate cancer, endometriosis, uterine fibroids, and early-onset puberty. The main objective was to enhance patient safety and offer informed guidance on the appropriate use of this treatment. Methods: From the first quarter of 2004 to the fourth quarter of 2023, a comprehensive analysis was conducted on a significant number of adverse event reports (AERs) from the FDA Adverse Event Reporting System (FAERS) database. Data mining with dismutation analysis was conducted to quantify signals associated with adverse events (AEs) related to leuprorelin, utilizing powerful algorithms such as ROR, PRR, BCPNN, and EBGM. Results: A total of 102 positive reaction terms (PT) spanning 24 System Organ Classes (SOCs) were identified from an analysis of 60,709 reports associated with leuprorelin use. Notably, several previously unrecognized adverse reactions were uncovered, including Artificial Menopause, Ovarian Adhesion, Follicular Cystitis, Intercepted product preparation error, among others. These findings underscore the importance of exercising additional vigilance regarding the potential adverse effects of leuprorelin, such as Abscess Sterile, Injection site granuloma, Intercepted medication error, and Bulbospinal muscular atrophy congenital. Conclusions: This research has successfully uncovered new and unforeseen signals associated with adverse drug reactions (ADRs) following leuprorelin administration. The study provides valuable insights into the intricate connection between ADRs and leuprorelin usage. The results underscore the crucial significance of continuous surveillance and meticulous monitoring to promptly identify and manage AEs, ultimately enhancing patient safety and well-being while undergoing leuprorelin therapy.

BackgroundsAtrial fibrillation (AF) is a common complication of chronic heart failure (HF). Serum phenylalanine (Phe) levels are related to inflammation disorder. It is meaningful to study the circulating Phe with AF occurrence in HF.MethodsThe cross-sectional study recruited 300 patients (78.0% male; mean age, 65 ± 13 years) with HF (left ventricular ejection fraction of ≤50%, containing 70 AF patients) and 100 normal controls. Serum Phe value was measured by liquid chromatography–tandem mass spectrometry. Logistic regression analysis was conducted to measure the association between Phe and AF risk in HF. The association between Phe and high-sensitivity C-reactive protein (hsCRP) was assessed by simple correlation analysis. In the prospective study, the 274 HF subjects (76.6% male; mean age, 65 ± 13 years) were followed up for a mean year (10.99 ± 3.00 months).ResultsSerum Phe levels increased across the control, the HF without AF, and the HF with AF groups (77.60 ± 8.67 umol/L vs. 95.24 ± 28.58 umol/L vs. 102.90 ± 30.43 umol/L, ANOVA P

Hidden champions are SMEs with strong global competitiveness in specialized fields but low profile. China’s hidden champions show less internationalization compared to their global peers, despite niche market dominance. Consequently, an exploration of the internationalization trajectories and determinants for China’s hidden champions is essential. This study utilizes fsQCA to investigate the internationalization strategies of 91 hidden champions, from China, using the “Efficiency-Structure-Environment” analytical framework. Five principal causal pathways for international operations are illustrated, categorized into three main driving models: “Efficiency-Environment,”“Efficiency-Structure,” and “System Interaction,” with the first model being the most dominant. The study further classifies hidden champions by ownership, finding that both state-owned and private enterprises predominantly follow the “Efficiency-Structure” driving model. Additionally, when classified by certification types, all categories are found to align with the “System Integration” model. Notably, the international path for cultivation hidden champions is also well-explained by the “Efficiency Dominance” model. Lastly, the study delineates industry-specific models: general equipment manufacturers employ the “Efficiency-Structure” model, special equipment manufacturers use the “Structure-Environment” model, and the computer industry follows the “System Integration” model.

Background: Nickel is a common metallic element in orthopedic implanted devices and living environment exposures. It is associated with varieties of diseases. The purpose of this investigation was to explore the correlation between nickel exposure and the prevalence of arthritis. Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) database from 2017 to 2018. Multivariate logistic regression was utilized to analyze the relationship between urinary nickel levels and arthritis. In addition, hierarchical modeling further explored the interactions and trends between urinary nickel levels and arthritis. Propensity score matching (PSM) method was used to reduce the effect of confounders. Additionally, restricted cubic spline curve (RCS) was used to assess the possible nonlinear association between urinary nickel and arthritis. Results: The investigation was comprised of 139 arthritis patients and 547 healthy participants. After correction by PSM, there was a positive correlation between arthritis and Nickel exposure levels. The risk of developing arthritis was significantly increased when nickel exposure levels were in the Q4 interval (OR=2.25, 95 % CI=1.03–5.02). When stratified by age and sex, nickel exposure was significantly and positively associated with arthritis in the subgroup aged over 65 years. (OR=2.78,95 %CI=1.20–6.46). Also, the difference between nickel exposure and arthritis was significant in the different gender subgroups (interaction P

In order to study the frost resistance of alkali activated concrete (AAC), 15 AAC cube specimens and 15 cylindrical specimens were designed and manufactured. The frost thawing cycle test and mechanical performance test were used to study the frost resistance of AAC. The results showed that after freeze–thaw cycles, small pores appeared on the surface of the specimen, and the surface roughness increased, resulting in a darker appearance. As the number of freeze–thaw cycles increases, the highest mass loss rate of AAC reaches 1.88%. The cube compressive strength and axial compressive strength of AAC first increase and then decrease, while the elastic modulus gradually decreases. After 50 freeze–thaw cycles, the compressive strength of the specimen was greater than that of the normal temperature specimen. When the freeze–thaw cycles reached 200, the elastic modulus of the specimen degraded by 9.7%, the compressive strength decreased by 18.6%, and the axial compressive strength decreased by 31.2%. Based on the experimental results, a method for calculating the residual strength of AAC after freeze–thaw cycles and key parameters of the freeze–thaw damage constitutive equation were proposed.

Shrews play a crucial role as repositories for diverse pathogens linked to zoonotic infectious diseases. However, the genetic information regarding Cryptosporidium in Chinese shrews remains unexplored. The objectives of this study were twofold: to determine the occurrence rate of Cryptosporidium spp. in wild shrews residing in the southern part of Zhejiang Province, China, and to investigate their genetic characteristics. A total of 282 wild shrews were captured between April and October of 2023. The detection of Cryptosporidium in fecal samples, collected from each animal's rectum, was performed using PCR and sequencing of the partial small subunit of ribosomal RNA (SSU rRNA) gene. The 60-kDa glycoprotein (gp60) gene was utilized to further subtype the positive samples of C. viatorum and C. parvum. All animals were identified as Suncus murinus, and a positive result for Cryptosporidium was obtained in 14.2 % (40/282) of the samples. The following species and genotypes were identified: C. ratti (n = 19), C. parvum (n = 2), C. viatorum (n = 1), Cryptosporidium rat genotype IV (n = 13), and Cryptosporidium skunk genotype (n = 5). Furthermore, the subtypes IIdA15G1 and XVdA3 were detected within C. parvum and C. viatorum, respectively. Molecular evidence indicates that S. murinus is concurrently infected with rodent-adapted and zoonotic species/genotypes, actively contributing to the dissemination of cryptosporidiosis.

Abstract Photo‐rechargeable zinc‐ion batteries (PRZIBs) have attracted much attention in the field of energy storage due to their high safety and dexterity compared with currently integrated lithium‐ion batteries and solar cells. However, challenges remain toward their practical applications, originating from the unsatisfactory structural design of photocathodes, which results in low photoelectric conversion efficiency (PCE). Herein, a flexible MoS2/SnO2‐based photocathode is developed via constructing a sunflower‐shaped light‐trapping nanostructure with 3D hierarchical and self‐supporting properties, enabled by the hierarchical embellishment of MoS2 nanosheets and SnO2 quantum dots on carbon cloth (MoS2/SnO2 QDs@CC). This structural design provides a favorable pathway for the effective separation of photogenerated electron‐hole pairs and the efficient storage of Zn2+ on photocathodes. Consequently, the PRZIB assembled with MoS2/SnO2 QDs@CC delivers a desirable capacity of 366 mAh g−1 under a light intensity of 100 mW cm−2, and achieves an ultra‐high PCE of 2.7% at a current density of 0.125 mA cm−2. In practice, an integrated battery system consisting of four series‐connected quasi‐solid‐state PRZIBs is successfully applied as a wearable wristband of smartwatches, which opens a new door for the application of PRZIBs in next‐generation flexible energy storage devices.

Background: Numerous studies have shown a strong correlation between disulfidptosis and various cancers. However, the expression and function of RPN1, a crucial gene in disulfidptosis, remain unclear in the context of cancer. Methods: Gene expression and clinical information on lung adenocarcinoma were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. RPN1 expression was analyzed using the Timer2.0 and the Human Protein Atlas (HPA) databases. Prognostic significance was assessed using Cox regression analysis and Kaplan–Meier curves. Genetic mutations and methylation levels were examined using the cBioPortal and UALCAN platforms, respectively. The relationship between RPN1 and tumor mutation burden (TMB) and microsatellite instability (MSI) across different cancer types was analyzed using the Spearman correlation coefficient. The relationship between RPN1 and immune cell infiltration was analyzed using the Timer2.0 database, whereas variations in drug sensitivity were explored using the CellMiner database. Receiver operating characteristic curves validated RPN1’s diagnostic potential in glioma, and its correlation with immune checkpoint inhibitors (ICIs) was assessed using Spearman’s correlation coefficient. Single-sample gene set enrichment analysis elucidated a link between RPN1 and immune cells and pathways. In addition, a nomogram based on RPN1 was developed to predict patient prognosis. The functional impact of RPN1 on glioma cells was confirmed using scratch and Transwell assays. Result: RPN1 was aberrantly expressed in various cancers and affected patient prognosis. The main mutation type of RPN1 in the cancer was amplified. RPN1 exhibited a positive correlation with myeloid-derived suppressor cells, neutrophils, and macrophages, and a negative correlation with CD8+ T cells and hematopoietic stem cells. RPN1 expression was associated with TMB and MSI in various cancers. The expression of RPN1 affected drug sensitivity in cancer cells. RPN1 was positively correlated with multiple ICIs in gliomas. RPN1 also affected immune cell infiltration into the tumor microenvironment. RPN1 was an independent prognostic factor for gliomas, and the nomogram demonstrated excellent predictive performance. Interference with RPN1 expression reduces the migratory and invasive ability of glioma cells. Conclusion: RPN1 exerts multifaceted effects on different stages of cancer, including immune infiltration, prognosis, and treatment outcomes. RPN1 expression affects the prognosis and immune microenvironment infiltration in patients with glioma, making RPN1 a potential target for the treatment of glioma.

Abstract The Homeostatic Model Assessment for Triglyceride Glucose Index (TyG) and its related indices, including triglyceride glucose-waist circumference (TyG-WC), triglyceride glucose-waist-to-height ratio (TyG-WHtR) and triglyceride glucose-body mass index (TyG-BMI), has emerged as a practical tool for assessing insulin resistance in metabolic disorders. However, limited studies have explored the connection between TyG, TyG-related indices and osteoporosis. This population-based study, utilizing data from the National Health and Nutrition Examination Survey 2011–2018, involved 5456 participants. Through weighted multivariate linear regression and smoothed curve fitting, a significant positive correlation was found between TyG, TyG-related indices and total bone mineral density (BMD) after adjusting for covariates [β = 0.0124, 95% CI (0.0006, 0.0242), P = 0.0390; β = 0.0004, 95% CI (0.0003, 0.0004), P

Abstract The ITER project is one of the largest international cooperative scientific projects in the world, aiming to verify the feasibility of magnetic confinement controlled nuclear fusion technology and provide a technical basis for the subsequent construction of fusion energy power stations. The success or failure of ITER will greatly affect the commercialization process of fusion energy. The probabilistic safety assessment (PSA) was a powerful means to evaluate the risk and reliability of nuclear facility and achieved great success in safety assessment of fission power plants. Based on this, the PSA progress for ITER was proposed in this paper. And the in-vessel leakage accident was investigated to verify the effectiveness of proposed method. The result shows the maximum possible radiological consequences of ITER in-vessel leakage accident of ITER is 1.6E−3 mSv, and the frequencies of this consequence is 1.63E−8/year. The reason of this consequence was also discussed in this paper. Those result could provide some valuable reference for radiation risk assessment and safety supervision of fusion commercial reactor in the nuclear future.

A nonsmooth ecological model was proposed and analyzed, focusing on IPM, state-dependent feedback control strategies, and anti-predator behavior. The main objective was to investigate the impact of anti-predator behavior on successful pest control, pest outbreaks, and the dynamical properties of the proposed model. First, the qualitative behaviors of the corresponding ODE model were presented, along with an accurate definition of the Poincaré map in the absence of internal equilibrium. Second, we investigated the existence and stability of order-k (where k = 1, 2, 3) periodic solutions through the monotonicity and continuity properties of the Poincaré map. Third, we conducted numerical simulations to investigate the complexity of the dynamical behaviors. Finally, we provided a precise definition of the Poincaré map in situations where an internal equilibrium existed within the model. The results indicated that when the mortality rate of the insecticide was low or high, the boundary order-1 periodic solution of the model was stable. However, when the mortality rate of the insecticide was maintained at a moderate level, the boundary order-1 periodic solution of the model became unstable; in this case, pests and natural enemies could coexist.

Abstract Objective To investigate the association between circulating secretoneurin (SN) and angiographic coronary collateralization in stable angina patients with chronic coronary total occlusion (CTO). Methods SN concentrations in serum were measured in 641 stable angina patients with CTO by radioimmunoassay. The status of coronary collaterals from the contra-lateral vessel was visually estimated using the Rentrop grading system, and was categorized into poor (grade 0 or 1) or good (grade 2 or 3) collateralization. Results Serum SN levels were significantly higher in patients with good coronary collaterals compared to those with poor collaterals (175.23 ± 52.09 pmol/L vs. 143.29 ± 42.01 pmol/L, P

In the realm of graph-based recommendation algorithms, the concept of metapaths plays a pivotal role in capturing complex semantic relationships between various types of entities, thereby significantly enhancing the recommendation quality. However, existing metapath-based recommendation algorithms often struggle to fully utilize the rich information embedded in metapaths while maintaining conciseness. Certain methods employ intricate and time-intensive aggregation networks to extract information from metapaths, while other strategies, prioritizing efficiency, neglect to investigate metapath information thoroughly. To address the above issues, we propose a Simple and Efficient Metapath Aggregated Network (SEMAN) for Recommendation. We employ a metapath pre-aggregation strategy using simple average pooling and concatenation operators to ensure the overall efficiency of the model. Furthermore, to fully exploit metapath information, the complete pathway nodes, including intermediate nodes, and metapath structural information are separately represented as aggregated vectors. Finally, we have designed a metapath semantic fusion module based on a dual-layer attention mechanism to process the metapath pre-aggregated results from both user and item sides across different granular levels. The theoretical analysis of time complexity substantiates the high efficiency of our model. Extensive experiments on three real-world graph datasets show that our proposed model performs significantly better than the state-of-the-art baselines on both Recall and NDCG metrics.

Knowledge enhanced recommendation algorithms focus on how to leverage auxiliary information from knowledge graphs to enhance recommendation performance. However, existing methods for knowledge enhanced recommendation often overlook the issues of the non-uniform distribution of task-relevant information: (1) Item nodes often have neighbors unevenly distributed across interaction graphs and knowledge graphs. This uneven distribution of neighbor nodes might lead to the information from certain sources being ignored during message passing, thereby reducing the quality of the learned node embeddings. (2) The implicit inclusion of noise within graph data exacerbates the aforementioned issues, further hindering the effective utilization of knowledge graph information. In this paper, we introduce a novel algorithm called hierarchically coupled view-crossing contrastive learning for knowledge enhanced recommendation to address the challenges mentioned above. Specifically, we controllably couple knowledge graph information into each layer of message passing, and then use a weighted sum of the embeddings learned hierarchically as the final node representation. In addition, we devised a view-crossing contrastive learning approach to construct two additional contrastive learning loss functions for joint training with the main task and more effectively mitigate the adverse impact of noise than the traditional contrastive learning paradigms. Extensive experiments on three real-world graph datasets show that our proposed model performs significantly better than the state-of-the-art baselines and the results of experiments involving adversarial samples indicate the robustness of our model.

Abstract Introduction Kukoamine B mesylate (KB) is a mesylate chrysamine B targeting lipopolysaccharides and CpG DNA, two potential treatment targets in sepsis. Methods This first-in-human, randomized, double-blind, placebo-controlled, phase I study was conducted from July 2014 to May 2015 to explore the safety, tolerability, and pharmacokinetics of KB in healthy subjects. This study consisted of a pre-phase (four participants; KB at 0.005 mg/kg) and a dose escalation phase (eight participants/dose group, randomized 6:2 to KB or placebo; KB at 0.02, 0.04, 0.08, 0.12, 0.24, and 0.48 mg/kg). The primary endpoint was safety. Results Fifty-two participants were enrolled, including four in the pre-phase and 48 in the dose escalation phase. Among the 40 participants who received KB, 12 (30.0%) experienced adverse events (AEs), while two (16.7%) experienced AEs among 12 participants who received the placebo. The most common AEs in the KB group were headache (5.0%), influenza (5.0%) and positive white blood cell in urine (5.0%). After the administration of KB, the mean plasma elimination half was around 1.61–4.24 h. The relationship between the KB plasma exposure of KB and the administered dose was not linear. The percentage of cumulative urinary excretion of KB was similar among the different dose groups (21.7–35.2%) and the urinary excretion of KB decreased significantly about 8 h after administration. Conclusions Single-dose KB demonstrated favorable safety and tolerability in healthy subjects at the dose level of 0.005–0.48 mg/kg. KB exhibited a non-linear pharmacokinetic profile with a half-life of about 1.61–4.24 h, which mainly distributed in plasma. Trial Registration ClinicalTrials.gov identifier, NCT02219971.

Abstract Recently, the design of lightweight high entropy alloys (HEAs) with a mass density lower than 5 g/cm3 has attracted much research interest in structural materials. We applied a first principles-based high-throughput method to design lightweight HEAs in single solid-solution phase. Three lightweight quinary HEA families were studied: AlBeMgTiLi, AlBeMgTiSi and AlBeMgTiCu. By comprehensively exploring their entire compositional spaces, we identified the most promising compositions according to the following design criteria: the highest stability, lowest mass density, largest elastic modulus and specific stiffness, along with highest Pugh’s ratio. We found that HEAs with the topmost compositions exhibit a negative formation energy, a low density and high specific Young’s modulus, but a low Pugh’s ratio. Importantly, we show that the most stable composition, Al0.31Be0.15Mg0.14Ti0.05Si0.35 is energetically more stable than its metallic compounds and it significantly outperforms the current lightweight engineering alloys such as the 7075 Al alloy. These results suggest that the designed lightweight HEAs can be energetically more stable, lighter, and stiffer but slightly less ductile compared to existing Al alloys. Similar conclusions can be also drawn for the AlBeMgTiLi and AlBeMgTiCu. Our design methodology and findings serve as a valuable tool and guidance for the experimental development of lightweight HEAs.