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Abstract To address the issue of excessive mid-span deflection in rigid frame-continuous girder bridges during the later stages of normal use and to provide a basis for setting the pre-camber of this bridge type. This study focused on a specific rigid frame-continuous girder bridge. Based on the outcomes of finite element analysis, a GM(1,1) model developed using grey theory was utilized to forecast the vertical deflection of the primary girder in the construction phase of a rigid frame-continuous girder bridge, resulting in notable outcomes. The results suggest that the GM(1,1) model grounded in grey theory offers precise estimations of the vertical deflection of the primary girder during the prestressing tendon tensioning stage, displaying a minimal deviation of merely 1.73 mm compared to actual measurements. Consequently, applying the GM(1,1) model based on grey theory for projecting the vertical deflection of the primary girder in the construction process of rigid frame-continuous girder bridges can advance the accuracy of construction management. Through comparative analysis of measured values estimated values and theoretical values at the construction site, it is evident that the predictive model effectively controls the displacement, thus serving as a reference for construction control in similar projects.

During construction at low temperatures, fresh concrete is susceptible to early freeze damage, which can permanently damage the concrete structure. Therefore, this study aimed to enhance the early-age strength and durability properties of the cement paste at −5 ℃ by incorporating calcium nitrite (CN) antifreeze and nano-silica (NS). First, the effects of CN and NS on the fresh properties of the cement paste were measured by setting time and bleeding rate tests. Subsequently, the mechanical properties and chloride content after salt solution erosion were tested for each group of specimens, and the change in slurry densification was further observed by ultrasonic pulse velocity and resistivity tests. Finally, the hydration products and microstructure of the specimens were analyzed using XRD and SEM tests. The results showed that the addition of CN and NS could reduce the setting time of cement paste and avoid the bleeding phenomenon of cement paste under negative temperature environment. The decrease in curing temperature and the use of NS both inhibited the promotion of C3A hydration by nitrite ions, which led to a decrease in nitrite-AFm content. However, NS can compensate for the reduced nitrite-AFm content by promoting the production of hydrated C-S-H through nucleation and pozzolanic effects. Ultimately, the strength and resistance of the slurry to chloride erosion are improved.

H5, H7, and H9 are pivotal avian influenza virus (AIV) subtypes that cause substantial economic losses and pose potential threats to public health worldwide. In this study, a novel triplex fluorescence reverse transcription-loop-mediated isothermal amplification (TLAMP) assay was developed in which traditional LAMP techniques were combined with probes for detection. Through this innovative approach, H5, H7, and H9 subtypes of AIV can be simultaneously identified and differentiated, thereby offering crucial technical support for prevention and control efforts. Three primer sets and composite probes were designed based on conserved regions of the haemagglutinin gene for each subtype. The probes were labelled with distinct fluorophores at their 3′ ends, which were detached to release the fluorescence signal during the amplification process. The detection results were interpreted based on the colour of the TLAMP products. Then, the reaction conditions were optimized, and three primer sets and probes were combined in the same reaction system, resulting in a TLAMP detection assay for the differential diagnosis of AIV subtypes. Sensitivity testing with in vitro-transcribed RNA revealed that the detection limit of the TLAMP assay was 205 copies per reaction for H5, 360 copies for H7, and 545 copies for H9. The TLAMP assay demonstrated excellent specificity, no cross-reactivity with related avian viruses, and 100% consistency with a previously published quantitative polymerase chain reaction (qPCR) assay. Therefore, due to its simplicity, rapidity, sensitivity, and specificity, this TLAMP assay is suitable for epidemiological investigations and is a valuable tool for detecting and distinguishing H5, H7, and H9 subtypes of AIV in clinical samples.

Starting in 2015, the widespread prevalence of hydropericardium-hepatitis syndrome (HHS) has led to considerable financial losses within China’s poultry farming industry. In this study, pathogenicity assessments, whole-genome sequencing, and analyses were conducted on 10 new isolates of the novel genotype FAdV-4 during a HHS outbreak in Guangxi Province, China, from 2019 to 2020. The results indicated that strains GX2019-010 to GX2019-013 and GX2019-015 to GX2019-018 were highly virulent, while strain GX2020-019 exhibited moderate virulence. Strain GX2019-014 was characterized as a wild-type strain with low virulence, displaying no pathogenic effects when 0.5 mL containing 106 TCID50 virus was inoculated into the muscle of specific pathogen-free (SPF) chickens at 4 weeks of age, while 107 TCID50 and 108 TCID50 resulted in mortality rates of 80 and 100%, respectively. The whole genomes of strains GX2019-010 to GX2019-013, GX2019-015 to GX2019-018, and GX2020-019 showed high homology with other Chinese newly emerging highly pathogenic FAdV-4 strains, whereas GX2019-014 was closer to nonmutant strains and shared the same residues with known nonpathogenic strains (B1-7, KR5, and ON1) at positions 219AA and 380AA of the Fiber-2 protein. Our work enriches the research on prevalent strains of FAdV-4 in China, expands the knowledge on the virulence diversity of the novel genotype FAdV-4, and provides valuable reference material for further investigations into the key virulence-associated genetic loci of FAdV-4.

The global energy transition is increasingly driven by hydrogen energy, making digital green innovation crucial for hydrogen energy enterprises. This article explores effective strategies for these enterprises to select digital green innovation partners and provides actionable guidance for their transformation and development. First, an evaluation index system is developed using fuzzy set theory, grounded in the principles of digital green innovation partner selection for hydrogen energy enterprises. Next, a dual-combination weighting evaluation method is proposed, integrating combination weighting theory and field theory to build a decision model that supports partner selection for these companies. The model is then applied in a real-world case analysis of Baotailong, demonstrating its practical effectiveness in addressing digital green innovation challenges within hydrogen energy enterprises. The study concludes that a green and digital transformation approach, guided by a fuzzy decision-making model, enables hydrogen energy companies to identify suitable innovation partners. This approach not only aligns with the broader trends of socio-economic development but also enhances the companies’ core competitiveness.

Abstract An enzyme-free sandwich amperometric immunosensor based on bimetallic Pt/Ag nanoparticle (Pt/AgNPs)-functionalized chitosan (Chi)-modified multiwalled carbon nanotubes (MWCNTs) as dual signal amplifiers and Chi-modified MWCNTs (MWCNTs-Chi) as substrate materials was developed for ultrasensitive detection of fowl adenovirus group I (FAdV-I). MWCNTs have a large specific surface area, and many accessible active sites were formed after modification with Chi. Hence, MWCNTs-Chi, as a substrate material for modifying glassy carbon electrodes (GCEs), could immobilize more antibodies (fowl adenovirus group I-monoclonal antibody, FAdV-I/MAb). Multiple Pt/AgNPs were attached to the surface of MWCNTs-Chi to generate MWCNTs-Chi-Pt/AgNPs with high catalytic ability for the reaction of H2O2 and modified active sites for fowl adenovirus group I-polyclonal antibody (FAdV-I/PAb) binding. Amperometric i–t measurements were employed to characterize the recognizability of FAdV-I. Under optimal conditions, and the developed immunosensor exhibited a wide linear range (100.93 EID50 mL−1 to 103.43 EID50 mL−1), a low detection limit (100.67 EID50 mL−1) and good selectivity, reproducibility and stability. This immunosensor can be used in clinical sample detection.

Abstract The clinical applications of the association of cortical thickness and white matter fiber with freezing of gait (FoG) are limited in patients with Parkinson’s disease (PD). In this retrospective study, using white matter fiber from diffusion-weighted imaging and cortical thickness from structural-weighted imaging of magnetic resonance imaging, we investigated whether a machine learning-based model can help assess the risk of FoG at the individual level in patients with PD. Data from the Parkinson’s Disease Progression Marker Initiative database were used as the discovery cohort, whereas those from the Fujian Medical University Union Hospital Parkinson’s Disease database were used as the external validation cohort. Clinical variables, white matter fiber, and cortical thickness were selected by random forest regression. The selected features were used to train the support vector machine(SVM) learning models. The median area under the receiver operating characteristic curve (AUC) was calculated. Model performance was validated using the external validation cohort. In the discovery cohort, 25 patients with PD were defined as FoG converters (15 men, mean age 62.1 years), whereas 60 were defined as FoG nonconverters (38 men, mean age 58.5 years). In the external validation cohort, 18 patients with PD were defined as FoG converters (8 men, mean age 66.9 years), whereas 37 were defined as FoG nonconverters (21 men, mean age 65.1 years). In the discovery cohort, the model trained with clinical variables, cortical thickness, and white matter fiber exhibited better performance (AUC, 0.67–0.88). More importantly, SVM-radial kernel models trained using random over-sampling examples, incorporating white matter fiber, cortical thickness, and clinical variables exhibited better performance (AUC, 0.88). This model trained using the above mentioned features was successfully validated in an external validation cohort (AUC, 0.91). Furthermore, the following minimal feature sets that were used: fractional anisotropy value and mean diffusivity value for right thalamic radiation, age at baseline, and cortical thickness for left precentral gyrus and right dorsal posterior cingulate gyrus. Therefore, machine learning-based models using white matter fiber and cortical thickness can help predict the risk of FoG conversion at the individual level in patients with PD, with improved performance when combined with clinical variables.

Abstract The vibration controlled transient elastography (VCTE) technique was used to assess the effectiveness of a Biejia Decoction pill in combination with Entecavir in the treatment of hepatitis B liver fibrosis/cirrhosis. We randomly selected 120 patients to receive entecavir and 119 patients to receive both entecavir and Biejia Decoction Pill, which both with hepatitis B liver fibrosis/cirrhosis visited the Second Affiliated Hospital of Nanchang University between January 2019 and February 2022. The observation group got ETV (entecavir) and Biejia Decoction pills, whereas the control group received only standard ETV antiviral medication. Based on the grading of the VCTE detection value (LSM) initially diagnosed for patients with hepatitis B liver fibrosis/cirrhosis, we divided the patients into two subgroups of liver fibrosis and cirrhosis. In addition, patients with liver fibrosis were divided into mild and moderate subgroups according to their VCTE values. Patients were measured for liver hardness after three, six, nine, and twelve months of treatment with VCTE. Biejia Decoction Pill combined with ETV on HBV liver fibrosis/cirrhosis was evaluated by comparing patients' changes in liver hardness and HBV-DNA negative conversion rates before and after treatment in each group at the same baseline. The LSM (liver elasticity value) of the observation group and the control group after treatment was lower than that before treatment, and the difference was statistically significant (P

Penile shrapnel injuries are an exceedingly rare occurrence and a medical emergency. Herein, we present a case of penile shrapnel wounds in an adolescent male and discuss the management and complications associated with penetrating injuries to penile. We reported that an 18-year-old Chinese armed police soldier underwent debridement, shrapnel removal and suturing under spinal anesthesia. Six days postoperatively, he was discharged from the hospital smoothly. The patient reported normal erectile function and urination following discharge. With a follow-up of three months, the patient exhibited no symptoms of dysuria or erectile dysfunction. It is explicitly stated that prompt surgery intervention described in this report resulted in optimal prognosis. Penile shrapnel injury is a rare phenomenon typically associated with emergency drill and military training involving explosive shells. With regard to penetrating penile injury, timely surgical exploration is essential because it avoids penile plaque formation, penile fibrosis and angulation, and accelerates the return to erectile and urination function.

To investigate the effects of nano-SiO2 (NS) and polyvinyl alcohol (PVA) fibers on the durability and mechanical properties of cementitious composites subjected to saline freeze–thaw cycling, a series of PVA fiber-reinforced cementitious composite (PFRCC) specimens were prepared using various fiber contents, and a series of NS and PVA fiber-reinforced cementitious composite (NPFRCC) specimens were prepared using various combinations of NS and fiber contents. Durability and fracture toughness tests were subsequently conducted on the specimens after different numbers of saline freeze–thaw cycles. The results indicate that the degradation of material properties can be divided into slow and accelerated damage stages before/after 50 freeze–thaw cycles. The durability and fracture toughness of the specimen series tended to increase, then decrease with increasing NS and PVA contents, suggesting optimum levels. When the PVA fiber content was 0.5%, PFRCC specimens had the best durability after saline freeze–thaw cycles; when the NS and PVA fiber contents were 1.0% and 0.5%, respectively, NPFRCC specimens had the best durability and fracture properties, and the initiation toughness, destabilization toughness, and fracture energy after 100 saline freeze–thaw cycles were 120.69%, 160.02%, and 451.31%, respectively. The results of this study may guide future exploration of the durability and mechanical properties of concrete subjected to freeze–thaw action.

The objective of this paper is to investigate the effect of calcium nitrite (CN) on improving the mechanical properties and microstructures of early-frozen cement paste. Cement pastes containing 1%, 1.5%, 2%, 2.5%, and 3% CN were prepared. One batch of samples was frozen at −6 °C for 7 days and then cured at 20 °C, and the other batch of samples was directly cured at 20 °C as a control. The compressive strength, ultrasonic pulse velocity, and resistivity of all specimens at different target ages were measured under these two curing conditions. The hydration products and microstructures of typical samples were observed using XRD and scanning SEM. The results showed that the addition of 1.5% CN could promote cement hydration and enhance slurry densification, thereby increasing the compressive strength, ultrasonic pulse velocity, and electrical resistivity of the slurry, and positively affecting the early freezing resistance of the slurry. However, when the CN dosage exceeded 1.5%, the internal structure of the slurry was loose and porous due to the generation of a large amount of nitrite–AFm, which negatively affects the properties of the cement paste. In addition, the effectiveness of CN is only limited to temperature environments above −6 °C. Concrete antifreeze suitable for lower temperatures still requires further research.

Interferon-alpha inducible protein 6 (IFI6) is an important interferon-stimulated gene. To date, research on IFI6 has mainly focused on human malignant tumors, virus-related diseases and autoimmune diseases. Previous studies have shown that IFI6 plays an important role in antiviral, antiapoptotic and tumor-promoting cellular functions, but few studies have focused on the structure or function of avian IFI6. Avian reovirus (ARV) is an important virus that can exert immunosuppressive effects on poultry. Preliminary studies have shown that IFI6 expression is upregulated in various tissues and organs of specific-pathogen-free chickens infected with ARV, suggesting that IFI6 plays an important role in ARV infection. To analyze the function of avian IFI6, particularly in ARV infection, the chicken IFI6 gene was cloned, a bioinformatics analysis was conducted, and the roles of IFI6 in ARV replication and the innate immune response were investigated after the overexpression or knockdown of IFI6 in vitro. The results indicated that the molecular weight of the chicken IFI6 protein was approximately 11 kDa and that its structure was similar to that of the human IFI27L1 protein. A phylogenetic tree analysis of the IFI6 amino acid sequence revealed that the evolution of mammals and birds was clearly divided into two branches. The evolutionary history and homology of chickens are similar to those of other birds. Avian IFI6 localized to the cytoplasm and was abundantly expressed in the chicken lung, intestine, pancreas, liver, spleen, glandular stomach, thymus, bursa of Fabricius and trachea. Further studies demonstrated that IFI6 overexpression in DF-1 cells inhibited ARV replication and that the inhibition of IFI6 expression promoted ARV replication. After ARV infection, IFI6 modulated the expression of various innate immunity-related factors. Notably, the expression patterns of MAVS and IFI6 were similar, and the expression patterns of IRF1 and IFN-β were opposite to those of IFI6. The results of this study further advance the research on avian IFI6 and provide a theoretical basis for further research on the role of IFI6 in avian virus infection and innate immunity.

BackgroundTelomere length (TL) has been regarded as a biomarker of aging, and TL shortening is associated with numerous chronic illnesses. The mounting evidence has shown that inflammatory cytokines are involved in maintaining or shortening TL, the causality of cytokines with TL remains unknown. Therefore, we performed a two-sample Mendelian randomization (MR) analysis to estimate the underlying correlations of circulating inflammatory cytokines with TL.MethodsGenetic instrumental variables for inflammatory cytokines were identified through a genome-wide association study (GWAS) involving 8,293 European individuals. Summary statistics of TL were derived from a UK Bio-bank cohort comprising 472,174 samples of individuals with European descent. We employed the inverse-variance weighted (IVW) approach as our main analysis, and to ensure the reliability of our findings, we also conducted additional analyses including the weighted median, MR-Egger, MR pleiotropy residual sum and outlier test, and weighted model. Lastly, the reverse MR analyses were performed to estimate the likelihood of inverse causality between TL and the cytokines identified in the forward MR analysis. Cochran’s Q test were employed to quantify the degree of heterogeneity.ResultsAfter applying Bonferroni correction, a higher circulating level of Interleukin-7 (IL-7) was suggestively associated with TL maintaining (OR:1.01, 95%CI:1.00-1.02, P=0.032 by IVW method). The study also revealed suggestive evidence indicating the involvement of Interleukin-2 receptor, alpha subunit (IL-2Rα) level was negatively associated with TL maintaining (OR:0.98, 95%CI:0.96-1.00, P=0.045 by IVW method), and the weighted median approach was consistent (OR:0.99, 95%CI:0.97-1.00, P=0.035). According to the findings of reverse MR analysis, no significant causal relationship between TL and cytokines was explored. Our analysis did not reveal any substantial heterogeneity in the Single nucleotide polymorphisms or horizontal pleiotropy.ConclusionsOur MR analysis yielded suggestive evidence supporting the causality between circulating IL-7 and IL-2Rα and telomere length, necessitating further investigations to elucidate the mechanisms by which these inflammatory cytokines may impact the progression of telomeres.

Interferon-inducible transmembrane protein 3 (IFITM3) is an antiviral factor that plays an important role in the host innate immune response against viruses. Previous studies have shown that IFITM3 is upregulated in various tissues and organs after avian reovirus (ARV) infection, which suggests that IFITM3 may be involved in the antiviral response after ARV infection. In this study, the chicken IFITM3 gene was cloned and analyzed bioinformatically. Then, the role of chicken IFITM3 in ARV infection was further explored. The results showed that the molecular weight of the chicken IFITM3 protein was approximately 13 kDa. This protein was found to be localized mainly in the cytoplasm, and its protein structure contained the CD225 domain. The homology analysis and phylogenetic tree analysis showed that the IFITM3 genes of different species exhibited great variation during genetic evolution, and chicken IFITM3 shared the highest homology with that of Anas platyrhynchos and displayed relatively low homology with those of birds such as Anser cygnoides and Serinus canaria. An analysis of the distribution of chicken IFITM3 in tissues and organs revealed that the IFITM3 gene was expressed at its highest level in the intestine and in large quantities in immune organs, such as the bursa of Fabricius, thymus and spleen. Further studies showed that the overexpression of IFITM3 in chicken embryo fibroblasts (DF-1) could inhibit the replication of ARV, whereas the inhibition of IFITM3 expression in DF-1 cells promoted ARV replication. In addition, chicken IFITM3 may exert negative feedback regulatory effects on the expression of TBK1, IFN-γ and IRF1 during ARV infection, and it is speculated that IFITM3 may participate in the innate immune response after ARV infection by negatively regulating the expression of TBK1, IFN-γ and IRF1. The results of this study further enrich the understanding of the role and function of chicken IFITM3 in ARV infection and provide a theoretical basis for an in-depth understanding of the antiviral mechanism of host resistance to ARV infection.

Avian reovirus (ARV) infection is prevalent in farmed poultry and causes viral arthritis and severe immunosuppression. The spleen plays a very important part in protecting hosts against infectious pathogens. In this research, transcriptome and translatome sequencing technology were combined to investigate the mechanisms of transcriptional and translational regulation in the spleen after ARV infection. On a genome-wide scale, ARV infection can significantly reduce the translation efficiency (TE) of splenic genes. Differentially expressed translational efficiency genes (DTEGs) were identified, including 15 upregulated DTEGs and 396 downregulated DTEGs. These DTEGs were mainly enriched in immune regulation signaling pathways, which indicates that ARV infection reduces the innate immune response in the spleen. In addition, combined analyses revealed that the innate immune response involves the effects of transcriptional and translational regulation. Moreover, we discovered the key gene IL4I1, the most significantly upregulated gene at both the transcriptional and translational levels. Further studies in DF1 cells showed that overexpression of IL4I1 could inhibit the replication of ARV, while inhibiting the expression of endogenous IL4I1 with siRNA promoted the replication of ARV. Overexpression of IL4I1 significantly downregulated the mRNA expression of IFN-β, LGP2, TBK1 and NF-κB; however, the expression of these genes was significantly upregulated after inhibition of IL4I1, suggesting that IL4I1 may be a negative feedback effect of innate immune signaling pathways. In addition, there may be an interaction between IL4I1 and ARV σA protein, and we speculate that the IL4I1 protein plays a regulatory role by interacting with the σA protein. This study not only provides a new perspective on the regulatory mechanisms of the innate immune response after ARV infection but also enriches the knowledge of the host defense mechanisms against ARV invasion and the outcome of ARV evasion of the host’s innate immune response.

Background: Bladder cancer (BC) is a common urological malignancy that still lacks effective treatments. Abietic acid (AA) is an abietane diterpene that possesses various biological activities, including antitumor activity. This study aimed at evaluating the effects of AA on BC cells. Materials and methods: The 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay was used to assess the effects of AA on the viability of BC cells. Annexin-V and FITC staining was used to assess cellular death. The type of cell death was determined by the administration of various specific cell death inhibitors. Commercial kits were used to measure the levels of reactive oxygen species (ROS), intracellular iron, malondialdehyde (MDA), and glutathione (GSH). Real-time polymerase chain reaction (RT-PCR) and western blot analysis were used to assay mRNA and protein levels, respectively. The role of glutathione peroxidase 4 (GPX4) in the antitumor effects of AA was evaluated using the forced expression of GPX4 in BC cells. The impact of HO-1 on the antitumor effects of AA was examined by gene silencing and pharmacological inhibition of the protein. Finally, the antitumor effects of AA were evaluated in xenograft models. Results: AA selectively inhibited the viability of BC cells but not normal cells. AA-induced ferroptosis in BC cells was evidenced by the upregulation of ROS, intracellular iron, and MDA. AA treatment led to the downregulation of GPX4 and the upregulation of HO-1 in BC cells. Forced expression of GPX4 or inhibition of HO-1 resulted in decreased ferroptosis triggered by AA in BC cells. AA also showed synergistic effects with various chemotherapeutic agents against BC and inhibited the growth of BC cells in vivo. Conclusion: This study revealed AA-induced ferroptosis in BC cells both in vitro and in vivo. AA might be applied as a promising agent for the treatment of BC.

IntroductionIntraductal carcinoma of the prostate (IDC-P) is a special pathological type of prostate cancer that is highly aggressive with poor prognostic outcomes.ObjectiveTo establish an effective predictive model for predicting IDC-P.MethodsData for 3185 patients diagnosed with prostate cancer at three medical centers in China from October 2012 to April 2022 were retrospectively analyzed. One cohort (G cohort) consisting of 2384 patients from Zhejiang Provincial People’s Hospital was selected for construction (Ga cohort) and internal validate (Gb cohort)of the model. Another cohort (I cohort) with 344 patients from Quzhou People’s Hospital and 430 patients from Jiaxing Second People’s Hospital was used for external validation. Univariate and multivariate binary logistic regression analyses were performed to identify the independent predictors. Then, the selected predictors were then used to establish the predictive nomogram. The apparent performance of the model was evaluated via externally validated. Decision curve analysis was also performed to assess the clinical utility of the developed model.ResultsUnivariate and multivariate logistic regression analyses showed that alkaline phosphatase (ALP), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), prostate specific antigen (PSA) and lactate dehydrogenase were independent predictors of IDC-P. Therefore, a predictive nomogram of IDC-P was constructed. The nomogram had a good discriminatory power (AUC = 0.794). Internal validation (AUC = 0.819)and external validation (AUC = 0.903) also revealed a good predictive ability. Calibration curves showed good agreement between the predicted and observed incidences of IDC-P.ConclusionWe developed a clinical predictive model composed of alkaline phosphatase (ALP), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), prostate specific antigen (PSA) and lactate dehydrogenase (LDH) with a high precision and universality. This model provides a novel calculator for predicting the diagnosis of IDC-P and different treatment options for patients at an early stage.

Avian reovirus (ARV) infection can lead to severe immunosuppression, complications, and secondary diseases, causing immense economic losses to the poultry industry. In-depth study of the mechanism by which the innate immune system combats ARV infection, especially the antiviral effect mediated by interferon, is needed to prevent and contain ARV infection. In this study, ARV strain S1133 was used to artificially infect 7-day-old specific pathogen–free chickens. The results indicated that ARV rapidly proliferated in the immune organs, including the spleen, bursa of Fabricius, and thymus. The viral load peaked early in the infection and led to varying degrees of pathological damage to tissues and organs. Real-time quantitative PCR revealed that the mRNA levels of interferon and multiple interferon-stimulated genes (ISGs) in the spleen, bursa of Fabricius, and thymus were upregulated to varying degrees in the early stage of infection. Among the ISGs, IFIT5, and Mx were the most upregulated in various tissues and organs, suggesting that they are important ISGs for host resistance to ARV infection. Further investigation of the role of IFIT5 in ARV infection showed that overexpression of the IFIT5 gene inhibited ARV replication, whereas inhibition of the endogenously expressed IFIT5 gene by siRNA promoted ARV replication. IFIT5 may be a positive feedback regulator of the innate immune signaling pathways during ARV infection and may induce IFN-α production by promoting the expression of MAD5 and MAVS to exert its antiviral effect. The results of this study help explain the innate immune regulatory mechanism of ARV infection and reveal the important role of IFIT5 in inhibiting ARV replication, which has important theoretical significance and practical application value for the prevention and control of ARV infection.

Abstract Background Hospital-acquired infections (HAIs) are an emerging global problem that increases in-hospital mortality, length of stay, and cost. We performed a 6-year retrospective study to provide valuable insight into appropriate antibiotic use in HAI cases. We also aimed to understand how hospitals could reduce pathogen drug resistance in a population that overuses antibiotics. Methods All data (2012–2017) were obtained from the hospital information warehouse and clinical microbiology laboratory. Results We isolated 1392 pathogen strains from patients admitted to the orthopedics department during 2012–2017. Escherichia coli (14.7%, 204/1392), Enterobacter cloacae (13.9%, 193/1392), and Staphylococcus aureus (11.3%, 157/1392) were the most common pathogens causing nosocomial infections. The dominant Gram-negative bacterium was E. coli, with high resistance to ampicillin, levofloxacin, cotrimoxazole, gentamicin, and ciprofloxacin, in that order. E. coli was least resistant to amikacin, cefoperazone-sulbactam. The most dominant Gram-positive bacterium was S. aureus, highly resistant to penicillin and ampicillin, but not resistant to fluoroquinolones and cotrimoxazole. Analysis of risk factors related to multidrug-resistant bacteria showed that patients with open fractures (Gustillo III B and IIIC) were significantly more susceptible to methicillin-resistant S. aureus infections (p

Avian reovirus (ARV) can induce many diseases as well as immunosuppression in chickens, severely endangering the poultry industry. Interferons (IFNs) play an antiviral role by inducing the expression of interferon-stimulated genes (ISGs). The effect of ARV infection on the expression of host ISGs is unclear. Specific-pathogen-free (SPF) chickens were infected with ARV strain S1133 in this study, and real time quantitative PCR was used to detect changes in the dynamic expression of IFNs and common ISGs in joints of SPF chickens. The results showed that the transcription levels of IFNA, IFNB, and several ISGs, including myxovirus resistance (MX), interferon-induced transmembrane protein 3 (IFITM3), protein kinase R (PKR), oligoadenylate synthase (OAS), interferon-induced protein with tetratricopeptide repeats 5 (IFIT5), interferon-stimulated gene 12 (ISG12), virus inhibitory protein (VIPERIN), interferon-alpha-inducible protein 6 (IFI6), and integrin-associated protein (CD47), were upregulated in joints on days 1–7 of infection (the levels of increase of MX, IFIT5, OAS, VIPERIN, ISG12, and IFI6 were the most significant, at hundreds-fold). In addition, the expression levels of the ISGs encoding zinc finger protein 313 (ZFP313), and DNA damage–inducible transcript 4 (DDIT4) increased suddenly on the 1st or 2nd day, then decreased to control levels. The ARV viral load in chicken joints rapidly increased after 1 day of viral challenge, and the viral load remained high within 6 days of viral challenge. The ARV viral load sharply decreased starting on day 7. These results indicate that in SPF chicken joints, many ISGs have mRNA expression patterns that are basically consistent with the viral load in joints. IFNA, IFNB, and the ISGs MX, IFITM3, PKR, OAS, IFIT5, ISG12, VIPERIN, IFI6, and CD47 play important roles in defending against ARV invasion, inhibiting ARV replication and proliferation, and promoting virus clearance. These results enrich our understanding of the innate immune response mechanisms of hosts against ARV infection and provide a theoretical basis for prevention and control of ARV infection.

Agricultural practices, such as applying excessive water and nitrogen fertilizer to increase the crop yield, can be a significant source of greenhouse gas emissions (GHGs). Therefore, techniques and proper management are needed to mitigate these emissions without yield reduction. The experiment used three subsurface drip irrigation (SDI) depths with emitters buried at 0.05, 0.10, and 0.15 m below the soil surface, along with two nitrogen fertilizer (Urea, N > 46.2%) application levels of 300 kg N ha−1 (N300) and 240 kg N ha−1 (N240) to investigate the effect of vertical and horizontal water and fertilizer distribution on N2O emissions under different SDI techniques in greenhouse conditions. The results indicated that soil N2O emissions from SDI10 and SDI15 decreased by 7.06% and 10.69%, respectively, compared to SDI5. N2O, WFPS, NH4+-N, and NO3−-N were significantly reduced with the increased radial distance from the emitter. N2O was positively correlated to WFPS and NH4+-N while negatively correlated to NO3−-N. The NH4+-N and NO3−-N concentrations decreased with depth and increased with fertilization events. Furthermore, N2O, WFPS, NH4+-N, and NO3−-N were increased under N300 compared to N240 (p > 0.05). The findings demonstrated that the Chinese cabbage yield was significantly enhanced under SDI15 compared to SDI5 and SDI10. Furthermore, N300 can increase the cabbage yield more than N240 among all treatments.

Abstract Background Nearly 30% of clear cell renal cell carcinoma (ccRCC) patients present with metastasis at the time of diagnosis, and the prognosis for these patients is poor. Therefore, novel potential prognostic biomarkers and therapeutic targets for ccRCC could be helpful. Emerging evidence indicates that lncRNAs play important roles in cancer tumorigenesis and could be used as potential biomarkers or therapeutic targets. PANDAR (promoter of CDKN1A antisense DNA damage activated RNA) is a relatively novel lncRNA that plays an important role in the development of multiple cancers. However, the clinical significance and molecular mechanism of PANDAR in ccRCC are still elusive. In the present study, we attempted to elucidate the role of PANDAR in ccRCC. Methods The relative expression level of lncRNA PANDAR was quantified by real-time qPCR in 62 paired ccRCC tissues and in renal cancer cell lines, and its association with overall survival was assessed by statistical analysis. The biological functions of lncRNA PANDAR on ccRCC cells were determined both in vitro and in vivo. Results PANDAR expression was significantly upregulated in tumor tissues and cell lines compared with normal counterparts. Moreover, PANDAR served as an independent predictor of overall survival, and increased PANDAR expression was positively correlated with an advanced TNM stage. Further experiments demonstrated that PANDAR silencing can significantly inhibit cell proliferation and invasion, induce cell cycle arrest in the G1 phase and significantly promote apoptosis in 7860 and Caki-1 cell lines. In addition, in vivo experiments confirmed that downregulation of PANDAR inhibited the tumorigenic ability of 7860 cells in nude mice. Silencing of PANDAR also inhibited the expression of Bcl-2 and Mcl-1 and upregulated the expression of Bax in vivo. Conclusions Our results suggest that PANDAR is involved in ccRCC progression and may serve as a potential prognostic biomarker and therapeutic target.

Coherent anti-Stokes Raman scattering (CARS) is able to enhance molecular signals by vibrational coherence compared to weak Raman signal. The surface or tip enhancement are successful technologies, which make it possible for Raman to detect single molecule with nanometer resolution. However, due to technical difficulties, tip-enhanced CARS (TECARS) is not as successful as expected. For single molecular detection, high sensitivity and resolution are two main challenges. Here, we reported the first single atom layer TECARS imaging on Graphene with the highest resolution about 20nm, which has ever been reported. The highest EFTECARS∕CARS is about 104, the similar order of magnitude with SECARS (EF of tip is usually smaller than that of substrates). Such resolution and sensitivity is promising for medical, biology and chemical applications in the future.

Abstract This paper reports on a 22-year-old male presenting with persistent chest pain accompanied by mediastinal emphysema. We firstly considered mediastinal emphysema induced by community acquired pneumonia. Pathogen detection was performed but no positive results were found. Based on the results of a subsequent lung CT scan, paraquat poisoning was suspected. Although there was no trace of paraquat in the blood, the nebulizer masks used by patient at home was found to be positive for paraquat. The diagnosis was ultimately established as paraquat poisoning via inhalation with mediastinal emphysema. This case report explores the clinical manifestations, diagnostic challenges, and treatment complexities of inhaled paraquat poisoning, emphasizing the importance of recognizing this rare poisoning route and its atypical symptoms.

Abstract Rejection seriously affects the success of kidney transplantations. However, the molecular mechanisms underlying this rejection remain unclear. The GSE21374 and GSE36059 datasets were downloaded from the Gene Expression Omnibus (GEO) database. Next, the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm was used to infer the proportions of 22 immune cells. Moreover, infiltrating immune cell-related genes were identified using weighted gene co-expression network analysis (WGCNA), and enrichment analysis was conducted to observe their biological functions. Extreme Gradient Boosting (XGBoost) and Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression algorithms were used to screen hub genes. Quantitative real-time PCR was conducted to verify the number of immune cells and hub gene expression levels. The rejection and non-rejection groups showed significantly different distributions (P

Abstract Background Blood biomarkers predictive of the progression of idiopathic pulmonary fibrosis (IPF) would be of value for research and clinical practice. We used data from the IPF-PRO Registry to investigate whether the addition of “omics” data to risk prediction models based on demographic and clinical characteristics improved prediction of the progression of IPF. Methods The IPF-PRO Registry enrolled patients with IPF at 46 sites across the US. Patients were followed prospectively. Median follow-up was 27.2 months. Prediction models for disease progression included omics data (proteins and microRNAs [miRNAs]), demographic factors and clinical factors, all assessed at enrollment. Data on proteins and miRNAs were included in the models either as raw values or based on clusters in various combinations. Least absolute shrinkage and selection operator (Lasso) Cox regression was applied for time-to-event composite outcomes and logistic regression with L1 penalty was applied for binary outcomes assessed at 1 year. Model performance was assessed using Harrell’s C-index (for time-to-event outcomes) or area under the curve (for binary outcomes). Results Data were analyzed from 231 patients. The models based on demographic and clinical factors, with or without omics data, were the top-performing models for prediction of all the time-to-event outcomes. Relative changes in average C-index after incorporating omics data into models based on demographic and clinical factors ranged from 1.7 to 3.2%. Of the blood biomarkers, surfactant protein-D, serine protease inhibitor A7 and matrix metalloproteinase-9 (MMP-9) were among the top predictors of the outcomes. For the binary outcomes, models based on demographics alone and models based on demographics plus omics data had similar performances. Of the blood biomarkers, CC motif chemokine 11, vascular cell adhesion protein-1, adiponectin, carcinoembryonic antigen and MMP-9 were the most important predictors of the binary outcomes. Conclusions We identified circulating protein and miRNA biomarkers associated with the progression of IPF. However, the integration of omics data into prediction models that included demographic and clinical factors did not materially improve the performance of the models. Trial registration ClinicalTrials.gov; No: NCT01915511; registered August 5, 2013; URL: www.clinicaltrials.gov .

Abstract Ensuring operational integrity in large-scale equipment hinges on effective fault prediction and health management. Prognostics and health management (PHM) face the challenge of accurately predicting remaining useful life (RUL) using multivariate sensor data. Traditional methods often require extensive prior knowledge for indicator construction and processing. Deep learning offers a promising alternative. This study presents a multi-channel multi-scale deep learning approach. Initially, an improved Savitzky‒Golay filter (ISG) addresses challenges posed by large and rapidly changing data volumes, enhancing data preprocessing. Subsequently, a framework integrates convolutional neural networks (CNNs) with long short-term memory (LSTM) to capture hierarchical signal information and make integrated predictions. The CNN extracts spatial features from multi-channel input data, while the LSTM captures temporal dependencies. By fusing outputs from both components, the framework enhances predictive accuracy and robustness for complex operational datasets. Experimental validation on the C-MAPSS dataset tests various fusion methods and CNN depths, determining parameters and evaluating filtering effectiveness. Comparative analyses show promising performance, particularly under dynamic conditions. While not optimal for predicting multiple fault types, it outperforms classical algorithms, especially in single fault type prediction tasks.

Abstract This study investigates the potential molecular mechanisms by which O-GlcNAc modification of YTHDF2 regulates the cell cycle and participates in intervertebral disc degeneration (IDD). We employed transcriptome sequencing to identify genes involved in IDD and utilized bioinformatics analysis to predict key disease-related genes. In vitro mechanistic validation was performed using mouse nucleus pulposus (NP) cells. Changes in reactive oxygen species (ROS) and cell cycle were assessed through flow cytometry and CCK-8 assays. An IDD mouse model was also established for in vivo mechanistic validation, with changes in IDD severity measured using X-rays and immunohistochemical staining. Bioinformatics analysis revealed differential expression of YTHDF2 in NP cells of normal and IDD mice, suggesting its potential as a diagnostic gene for IDD. In vitro cell experiments demonstrated that YTHDF2 expression and O-GlcNAcylation were reduced in NP cells under H2O2 induction, leading to inhibition of the cell cycle through decreased stability of CCNE1 mRNA. Further, in vivo animal experiments confirmed a decrease in YTHDF2 expression and O-GlcNAcylation in IDD mice, while overexpression or increased O-GlcNAcylation of YTHDF2 promoted CCNE1 protein expression, thereby alleviating IDD pathology. YTHDF2 inhibits its degradation through O-GlcNAc modification, promoting the stability of CCNE1 mRNA and the cell cycle to prevent IDD formation.

Abstract Background To improve the capacity of county medical and health services, China encourages all localities to pilot the close-type county medical alliance. In Shandong Province, medical alliances have been piloted in 47 counties, ranking first in the country. The objective of this study is to comprehensively evaluate the implementation of close-type county medical alliance in Shandong Province, identify the differences between different county regions, and analyze the reasons, so as to provide a reference for the construction of a new county medical and health service system with clear goals, powers and responsibilities, and division of labor. Methods The implementation of the close-type county medical alliance was comprehensively evaluated in 47 national pilot counties in Shandong Province using entropy weight TOPSIS method and non-integer rank sum ratio method. Variance analysis was used for comparison of the comprehensive evaluation results. Results The weight coefficient of evaluation indicators was highest for information interconnection, at 18.06%, and lowest for orderly referral of patients, at 3.64%. There was no difference in results of the comprehensive evaluation of entropy weight TOPSIS method and non-integer rank sum ratio method. Comprehensively order the implementation status of each pilot county according to the relative paste progress, 13 counties Y 5 , Y 11 , Y 14 , Y 16 , Y 20 , Y 25 , Y 26 , Y 27 , Y 28 , Y 32 , Y 33 , Y 40 and Y 42 were ranked highest, whereas county Y 37 was ranked lowest. Non-integer rank sum ratio method graded counties into three grades: excellent, good and average. Kruskal-Wallis nonparametric test showed that the difference between the grades was statistically significant (H $$\:\:=\:$$ 37.099, p $$\:

Abstract Background Peripheral immunity and neuroinflammation interact with each other and they play important roles in the pathophysiology of idiopathic Parkinson’s disease (IPD). There have been very few real-world reports on the relationship between peripheral immune inflammation and motor phenotypes of IPD. This study aimed to investigate the potential correlation between peripheral inflammatory indicators and motor subtypes in patients with IPD. Methods This observational, prospective case-control study examined patients with IPD and healthy controls (HC) matched for age and sex between September 2021 and July 2023 at the Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University. The levels of peripheral inflammatory indicators were collected from each patient with IPD and HCs. Differences in the levels of peripheral inflammatory indicators among groups were compared. Binary logistic regression analysis was used to explore the inflammatory mechanism underlying the motor subtype of IPD. Results A total number of 94 patients with IPD were recruited at the Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University between September 2021 and July 2023, including 49 males and 45 females, and 37 healthy volunteers matched for age and sex were also enrolled as the control group. Of the 94 patients with IPD, 42.6% performed as the TD motor subtype and 57.4% performed as the AR motor subtype. NLR and the plasma levels of IL-1βand TNF-α in the IPD group were higher than those in the HC group (P

Abstract (−)-Epigallocatechin-3-gallate (EGCG) is reported to have benefits for the treatment of Alzheimer’s disease by binding with acetylcholinesterase (AChE) to enhance the cholinergic neurotransmission. Organophosphorus pesticides (OPs) inhibited AChE and damaged the nervous system. This study investigated the combined effects of EGCG and OPs on AChE activities in vitro & vivo. The results indicated that EGCG significantly reversed the inhibition of AChE caused by OPs. In vitro, EGCG reactived AChE in three group tubes incubated for 110 min, and in vivo, it increased the relative activities of AChE from less than 20% to over 70% in brain and vertebral of zebrafish during the exposure of 34 h. The study also proposed the molecular interaction mechanisms through the reactive kinetics and computational analyses of density functional theory, molecular docking, and dynamic modeling. These analyses suggested that EGCG occupied the key residues, preventing OPs from binding to the catalytic center of AChE, and interfering with the initial affinity of OPs to the central active site. Hydrogen bonding, conjugation, and steric interactions were identified as playing important roles in the molecular interactions. The work suggests that EGCG antagonized the inhibitions of OPs on AChE activities and potentially offered the neuroprotection against the induced damage.

Abstract The dynamic disulfide linkage plays a vital role in various biological processes as well as drugs and biomaterials. The conversion of thiols to their corresponding disulfides is a hallmark of sulfur chemistry, but notoriously difficult to control. Achieving optimal reactivity and selectivity continues to pose significant challenges. Here, we describe a click chemistry for disulfide formation from thiols in both batch and flow-mode using SO2F2, which display exceptional selectivity toward disulfide formation through an effective nucleophilic substitution cascade. This reaction’s unique characteristics satisfy the stringent click-criteria with its high thermodynamic driving force, straightforward conditions, wide scope, quantitative yields, exceptional chemoselectivity, and non-chromatographic purification process. The modular synthesis of symmetrical, unsymmetrical, cyclic and polydisulfides is demonstrated, along with the formation of disulfide cross-linked hydrogels.

Abstract Although live streaming is indispensable, live-streaming e-business requires accurate and timely sales-volume prediction to ensure a healthy supply–demand balance for companies. Practically, because various factors can significantly impact sales results, the development of a powerful, interpretable model is crucial for accurate sales prediction. In this study, we propose SaleNet, a deep-learning model designed for sales-volume prediction. Our model achieved correct prediction results on our private, real operating data. The mean absolute percentage error (MAPE) of our model’s performance fell as low as 11.47% for a + 1.5-days forecast. Even for a 1-week forecast (+ 6 days), the MAPE was only 19.79%, meeting actual business needs and practical requirements. Notably, our model demonstrated robust interpretability, as evidenced by the feature contribution results which are consistent with prevailing research findings and industry expertise. Our findings provided a theoretical foundation for predicting shopping behavior in live-broadcast e-commerce and offered valuable insights for designing live-broadcast content and optimizing the user experience.

Background: A milestone goal of the Healthy China Program (2019–2030) is to achieve 5-year cancer survival at 43.3% for all cancers combined by 2022. To assess the progress towards this target, we analyzed the updated survival for all cancers combined and 25 specific cancer types in China from 2019 to 2021. Methods: We conducted standardized data collection and quality control for cancer registries across 32 provincial-level regions in China, and included 6,410,940 newly diagnosed cancer patients from 281 cancer registries during 2008–2019, with follow-up data on vital status available until December 2021. We estimated the age-standardized 5-year relative survival overall and by site, age group, and period of diagnosis using the International Cancer Survival Standard Weights, and quantified the survival changes to assess the progress in cancer control. Results: In 2019–2021, the age-standardized 5-year relative survival for all cancers combined was 43.7% (95% confidence interval [CI], 43.6–43.7). The 5-year relative survival varied by cancer type, ranging from 8.5% (95% CI, 8.2–8.7) for pancreatic cancer to 92.9% (95% CI, 92.4–93.3) for thyroid cancer. Eight cancers had 5-year survival of over 60%, including cancers of the thyroid, breast, testis, bladder, prostate, kidney, uterus, and cervix. The 5-year relative survival was generally lower in males than in females. From 2008 to 2021, we observed significant survival improvements for cancers of the lung, prostate, bone, uterus, breast, cervix, nasopharynx, larynx, and bladder. The most significant improvement was in lung cancer. Conclusions: Progress in cancer control was evident in China. This highlights the importance of a comprehensive approach to control and prevent cancer.

Abstract Background The triglyceride glucose (TyG) index is a cutting-edge and highly effective marker of insulin resistance, a crucial factor in the development and exacerbation of diabetic kidney disease (DKD). To date, there has been limited research on how the triglyceride-glucose (TyG) index affects the outlook for patients suffering from DKD. Methods In this multicenter retrospective cohort study, the analysis recruited 2,203 DKD patients from the National Health and Nutrition Examination Survey (NHANES) dataset, which covers the US from 2001 to 2018. The research applied a Cox proportional hazards model with multiple variables to investigate the association of the TyG index with mortality outcomes. Restricted cubic splines (RCS) and methods for analyzing threshold effects were employed to identify possible non-linear relationships. Results Over nearly 19 years of follow-up, this study captured data on 753 all-cause and 231 cardiovascular disease-specific fatalities. Sophisticated statistical methods, including RCS and smoothing curve adjustments via penalized splines, helped identify distinctive patterns: The baseline TyG index was observed to have a U-shaped pattern related to overall mortality and an L-shape with cardiovascular diseases(CVD) mortality among individuals with DKD. Notably, TyG index below 9.15 for overall mortality and 9.27 for CVD mortality were linked to reduced death rates (HR = 0.65, 95% CI = 0.52–0.82 for all-cause; HR = 0.58, 95% CI = 0.43–0.83 for CVD). On the other hand, TyG index exceeding these benchmarks (greater than 9.15 for all-cause and 9.27 for CVD) correlated with increased all-cause mortality risks (HR = 1.21, 95% CI = 1.02–1.43) and showed a non-significant change in CVD mortality risks (HR = 1.07, 95% CI = 0.83–1.38). Conclusions This study emphasizes the non-linear linkage involving the TyG index and death rates due to CVD and other factors in patients with DKD, demonstrating its effectiveness in estimating potential adverse events within this demographic.

Abstract High-power terahertz (THz) quantum cascade laser, as an emerging THz solid-state radiation source, is attracting attention for numerous applications including medicine, sensing, and communication. However, due to the sub-wavelength confinement of the waveguide structure, direct beam brightness upscaling with device area remains elusive due to several mode competition and external optical lens is normally used to enhance the THz beam brightness. Here, we propose a metallic THz photonic crystal resonator with a phase-engineered design for single mode surface emission over a broad area. The quantum cascade surface-emitting laser is capable of delivering an output peak power over 185 mW with a narrow beam divergence of 4.4° × 4.4° at 3.88 THz. A high beam brightness of 1.6 × 107 W sr−1m−2 with near-diffraction-limited M2 factors of 1.4 in both vertical and lateral directions is achieved from a large device area of 1.6 × 1.6 mm2 without using any optical lenses. The adjustable phase shift between the lattices enables a stable and high-intensity surface emission over a broad device area, which makes it an ideal light extractor for large-scale THz emitters. Our research paves the way to high brightness solid-state THz lasers and facilitates new applications in standoff THz imaging, detection, and diagnosis.

Abstract Non-Hodgkin lymphoma (NHL) is a common malignancy in the hematologic system, and traditional therapy has limited efficacy for people with recurrent/refractory NHL (R/R NHL), especially for patients with diffuse large B cell lymphoma (DLBCL). Chimeric antigen receptor (CAR) T-cell therapy is a novel and effective immunotherapy strategy for R/R hematopoietic malignancies, but relapses can occur due to the loss of CAR-T cells in vivo or the loss of antigen. One strategy to avoid antigen loss after CAR-T cell therapy is to target one more antigen simultaneously. Tandem CAR targeting CD19 and CD22 has demonstrated the reliability of tandem CAR-T cell therapy for R/R B-ALL. This study explores the therapeutic potential of tandem CD19/20 CAR-T in the treatment of R/R B cell NHL. The efficacy and safety of autologous CD19/20 CAR-T cells in eleven R/R B cell NHL adult patients were evaluated in an open-label, single-arm trial. Most patients achieved complete response, exhibiting the efficacy and safety of tandem CD19/20 CAR-T cells. The TCR repertoire diversity of CAR-T cells decreased after infusion. The expanded TCR clones in vivo were mainly derived from TCR clones that had increased expression of genes associated with immune-related signaling pathways from the infusion product (IP). The kinetics of CAR-T cells in vivo were linked to an increase in the expression of genes related to immune response and cytolysis/cytotoxicity.

Abstract SuFEx click chemistry demonstrates remarkable molecular assembly capabilities. However, the effective utilization of alkyl sulfonyl fluoride hubs in SuFEx chemistry, particularly in reactions with alcohols and primary amines, presents considerable challenges. This study pioneers an intramolecular chalcogen bonding activated SuFEx (S-SuFEx) click chemistry employing alkyl sulfonyl fluorides with γ-S as the activating group. The ChB-activated alkyl sulfonyl fluorides can react smoothly with phenols, alcohols, and amines, exhibiting enhanced reactivity compared to SO2F2. Excellent yields have been achieved with all 75 tested substrates. Pioneering the application of S-SuFEx chemistry, we highlight its immense potential in organic-inorganic linking, considering the critical role of interfacial covalent bonding in material fabrication. The S-SuFEx hub 1c, incorporating a trialkoxy silane group has been specifically designed and synthesized for organic-inorganic linking. In a simple step, 1c efficiently anchors various organic compounds onto surfaces of inorganic materials, forming functionalized surfaces with properties such as antibacterial activity, hydrophobicity, and fluorescence.

Abstract TWAS have shown great promise in extending GWAS loci to a functional understanding of disease mechanisms. In an effort to fully unleash the TWAS and GWAS information, we propose MTWAS, a statistical framework that partitions and aggregates cross-tissue and tissue-specific genetic effects in identifying gene-trait associations. We introduce a non-parametric imputation strategy to augment the inaccessible tissues, accommodating complex interactions and non-linear expression data structures across various tissues. We further classify eQTLs into cross-tissue eQTLs and tissue-specific eQTLs via a stepwise procedure based on the extended Bayesian information criterion, which is consistent under high-dimensional settings. We show that MTWAS significantly improves the prediction accuracy across all 47 tissues of the GTEx dataset, compared with other single-tissue and multi-tissue methods, such as PrediXcan, TIGAR, and UTMOST. Applying MTWAS to the DICE and OneK1K datasets with bulk and single-cell RNA sequencing data on immune cell types showcases consistent improvements in prediction accuracy. MTWAS also identifies more predictable genes, and the improvement can be replicated with independent studies. We apply MTWAS to 84 UK Biobank GWAS studies, which provides insights into disease etiology.

Abstract. Background:. Studies that comprehensively address the characteristics of centenarian deaths are rare. The present study aimed to depict the characteristics of centenarian deaths in China and their changing trends. Methods:. Data on centenarian deaths between 2013 and 2020 were obtained from the national mortality surveillance system of China, including date, place of death (PoD), and underlying cause of death (CoD). Descriptive analyses were performed to understand the epidemiological characteristics, and a joinpoint regression model was adopted to examine the changing trends in the proportions of different PoDs, CoDs among centenarians, and centenarian deaths accounting for all deaths and deaths among people aged 65 years and older. Results:. There were 46,938 registered centenarian deaths between 2013 and 2020 that included 34,311 females (73.10%) and 12,627 males (26.90%). January (12.05%), February (9.99%), and December (9.74%) were the top three months with the highest number of deaths. The proportions of deaths that occurred in homes, hospitals, and nursing homes were 81.71%, 13.63%, and 2.68%, respectively. The proportion of deaths in nursing homes increased by 9.60% (95% confidence intervals [CIs], 6.4–12.9%) from 2014 to 2020. Heart disease (35.72%) was the leading cause of death, followed by respiratory diseases (17.63%), cerebrovascular disease (15.60%), and old age (11.22%). The proportion of respiratory diseases decreased by 4.8% (95% CI, –8.8 to –0.7%), and the proportion of deaths from old age decreased by 2.3% (95% CI, –4.4 to –0.1%) per year. Shanghai had the highest proportions of deaths in hospitals (39.38%) and nursing homes (14.68%). Sichuan had the highest proportion of deaths attributed to respiratory diseases (32.30%), while Jiangsu (26.58%) and Zhejiang (23.61%) had the highest proportions of deaths from old age. Conclusion:. Unlike other countries, centenarian deaths in China are characterized by a higher proportion of home and heart disease deaths, and this death pattern differs across provinces.

In response to the challenges of high rock strength in deep underground metal mines, difficulty in slotting, and low efficiency in excavation, based on the tunneling project at Xingshan Underground Iron Mine of Shougang Corporation, and utilizing precise per-hole blasting with digital electronic detonators, we propose a phased blasting scheme for slotting areas of straight-eye barrel-shaped grooves, combining segmentation within and between holes, as well as delays within each hole. In combination with numerical simulations and field tests, it presents a trench domain gradient detonation configuration with differential detonation in the hole area, between holes and within holes on the basis of the original conventional scheme, builds a three-dimensional(3D) model of the trench domain μsing LS-DYNA numerical simulation software, sets up the original conventional scheme and three gradient schemes for modelling, and provides a comparative analysis of the evolution of the effective peak stress in the dredged-trench zone for the original conventional blasting solution and the staged solution. The results of the numerical simulations show that the μse of short-delay inter-hole blasting can change the fluctuation pattern of the peak effective stress, and compared to the original conventional scheme, the peak effective stress state of the rock in the dredged-trench zone along the direction of the shell hole is increased by 40% to 57%, while the peak effective stress state of the rock in the radiμs of 0-30 cm at the bottom of the shell hole is increased by 84% to 92%. In addition to the numerical simulation results, field experiments were carried out to verify the results. It is clear that the combination of short-delay differential detonation between holes can improve debris crowding in mine excavation, and short-delay differential detonation within holes can improve throwing capacity, improve debris throwing after blasting in the upper part of the shell hole, and avoid affecting the blasting of subsequent shell holes. Incorporating the two in hard rock blasting can significantly improve the blasting effect and increase the hollowing progress by 28%. And better results can be obtained in rock point-excavation by μsing short delay between holes and long delay within hole settings. The results of this paper could provide a reference for similar mine production.

Abstract Introduction Children and adolescents, after natural and man-made disasters, often exhibit various psychological, emotional, and behavioral issues, showing a range of clinical symptoms related to post-traumatic stress disorder (PTSD) and depression. This review used a network meta-analysis (NMA) approach to compare and rank psychological interventions for PTSD and depression in children and adolescents after exposure to natural and man-made disasters. Methods Randomized studies of psychosocial interventions for PTSD and depression in children and adolescents exposed to natural and man-made disasters were identified. PTSD and depression symptoms at postintervention and 1–12 month follow-up are the outcomes. The standardized mean differences (SMDs) between pairs of interventions at postintervention and follow-up were pooled. Mean effect sizes with 95% credible intervals (CI) were calculated, and the ranking probabilities for all interventions were estimated using the surface under the cumulative ranking curve. Study quality was assessed with version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). Results In total, 26 studies with 4331 participants were included in this NMA. Eye movement desensitization and reprocessing therapy (EMDR) (SMD = − 0.67; 95% CI − 1.17 to − 0.17), exposure therapy (ET) (SMD = − 0.66; 95% CI − 1.11 to − 0.22), and cognitive behavioral therapy (CBT) (SMD = − 0.62; 95% CI − 0.90 to − 0.34) were significantly more effective for PTSD at postintervention than inactive intervention. EMDR (SMD = − 0.72; 95% CI − 1.11 to − 0.33) and ET (SMD = − 0.62; 95% CI − 0.97 to − 0.27) were associated with a higher reduction in PTSD symptoms at follow-up than inactive intervention. EMDR (SMD = − 0.40; 95% CI − 0.78 to − 0.03) and play therapy (PT) (SMD = − 0.37; 95% CI − 0.62 to − 0.12) were significantly more effective for depression at postintervention than inactive intervention. For all psychological interventions in reducing depression symptoms at follow-up compared with inactive intervention, the differences were not significant. Conclusion EMDR appears to be most effective in reducing PTSD and depression in children and adolescents exposed to natural and man-made disasters. In addition, ET and CBT are potentially effective in reducing PTSD symptoms at postintervention, while PT is beneficial in managing depression symptoms at the treatment endpoint.

Abstract In modern tunnel construction, TBM (Tunnel Boring Machine) plays a very important role. In response to the needs of tunnel wall reinforcement and TBM automated construction for tunnel construction, a shotcrete mechanism mounted on the TBM is designed. In order to evaluate the kinematic performance of the mechanism, this paper studies the forward and inverse kinematics and spatial architecture of the TBM shotcrete robot. Firstly, based on the D–H parameter method, the number of joints and links is determined and structural analysis is performed to obtain the robot's forward kinematics equation, achieving the mapping between joint space and pose space. Then, by determining the joint variables, the mapping of the end tool in Cartesian space is achieved. Finally, based on the Monte Carlo random sampling method, the workspace of the robot is constructed, and its reachability and flexibility within the robot workspace are evaluated. The performance of the device is verified by building a prototype, which meets the requirements well. Through the research in this paper, it can provide theoretical basis and guidance for the design and control of the shotcrete robot.

Abstract Oxygen is necessary for life and plays a key pivotal in maintaining normal physiological functions and treat of diseases. Hemoglobin-based oxygen carriers (HBOCs) have been studied and developed as a replacement for red blood cells (RBCs) in oxygen transport due to their similar oxygen-carrying capacities. However, applications of HBOCs are hindered by vasoactivity, oxidative toxicity, and a relatively short circulatory half-life. With advancements in nanotechnology, Hb encapsulation, absorption, bioconjugation, entrapment, and attachment to nanomaterials have been used to prepare nanomaterial-related HBOCs to address these challenges and pend their application in several biomedical and therapeutic contexts. This review focuses on the progress of this class of nanomaterial-related HBOCs in the fields of hemorrhagic shock, ischemic stroke, cancer, and wound healing, and speculates on future research directions. The advancements in nanomaterial-related HBOCs are expected to lead significant breakthroughs in blood substitutes, enabling their widespread use in the treatment of clinical diseases. Graphical Abstract

Objective: To assess the performance and advantages of HyperArc for radiotherapy of multiple brain metastases with dosimetric parameters with respect to coplanar volumetric modulated arc radiotherapy (c-VMAT), and characterize implicit correlations between tumor features and dosimetric parameters. Methods: This retrospective study involved 40 patients with multiple brain metastases (4–16 tumors, 12.8–240.8 cm3) who received simultaneous radiotherapy at the Department of Radiation Oncology, Shenzhen People's Hospital from January 2019 to December 2022. Both HyperArc and c-VMAT plans were designed by the same and qualified physicist using the Eclipse system with Truebeam. A single isocenter and a 6 ​MV flattening filter-free (6FFF) photon beam were used for radiotherapy of multiple brain metastases in each plan. Dosimetric parameters of tumors and organs at risk (OARs) were compared between HyperArc and c-VMAT plans. Correlations between tumor features (number and volume) and dosimetric parameters were revealed and analyzed. Furthermore, monitor units (MUs) of both plan types were recorded to assess rays utilization and delivery efficiency. Results: Compared to c-VMAT plans, HyperArc plans achieved higher maximum dose (Dmax) (5.23%, t ​= ​7.87, P ​ ​0.05). Conclusions: This study demonstrates the promising performance of HyperArc for radiotherapy of multiple brain metastases, including better dose conformity for the tumors, more rapid dose drop and less dose spillage outside the tumors area, effective reduction of dose bridges among close tumors, and sparing OARs. It also reveals the correlations between the number or volume of tumors and dose parameters, which can help optimize the use of HyperArc and predict clinical benefits.

Introduction: The level of atmospheric CO2 has continuously been increasing and the resulting greenhouse effects are receiving attention globally. Carbon removal from the atmosphere occurs naturally in various ecosystems. Among them, saline environments contribute significantly to the global carbon cycle. Carbonate deposits in the sediments of salt lakes are omnipresent, and the biological effects, especially driven by halophilic microalgae and bacteria, on carbonate formation remain to be elucidated. Objectives: The present study aims to characterize the carbonates formed in saline environments and demonstrate the mechanisms underlying biological-driven CO2 removal via microalgal-bacterial consortium. Methods: The carbonates naturally formed in saline environments were collected and analyzed. Two saline representative organisms, the photosynthetic microalga Dunaliella salina and its mutualistic halophilic bacteria Nesterenkonia sp. were isolated from the inhabiting saline environment and co-cultivated to study their biological effects on carbonates precipitation and isotopic composition. During this process, electrochemical parameters and Ca2+ flux, and expression of genes related to CaCO3 formation were analyzed. Genome sequencing and metagenomic analysis were conducted to provide molecular evidence. Results: The results showed that natural saline sediments are enriched with CaCO3 and enrichment of genes related to photosynthesis and ureolysis. The co-cultivation stimulated 54.54% increase in CaCO3 precipitation and significantly promoted the absorption of external CO2 by 49.63%. A pH gradient was formed between the bacteria and algae culture, creating 150.22 mV of electronic potential, which might promote Ca2+ movement toward D. salina cells. Based on the results of lab-scale induction and 13C analysis, a theoretical calculation indicates a non-negligible amount of 0.16 and 2.3 Tg C/year carbon sequestration in China and global saline lakes, respectively. Conclusion: The combined effects of these two typical representative species have contributed to the carbon sequestration in saline environments, by promoting Ca2+ influx and increase of pH via microalgal and bacterial metabolic processes.

Misfolding and aggregation of specific proteins are associated with liquid-liquid phase separation (LLPS), and these protein aggregates can interfere with normal cellular functions and even lead to cell death, possibly affecting gene expression regulation and cell proliferation. Therefore, understanding the role of LLPS in disease may help to identify new mechanisms or therapeutic targets and provide new strategies for disease treatment. There are several ways to disrupt LLPS, including screening small molecules or small molecule drugs to target the upstream signaling pathways that regulate the LLPS process, selectively dissolve and destroy RNA droplets or protein aggregates, regulate the conformation of mutant protein, activate the protein degradation pathway to remove harmful protein aggregates. Furthermore, harnessing the mechanism of LLPS can improve drug development, including preparing different kinds of drug delivery carriers (microneedles, nanodrugs, imprints), regulating drug internalization and penetration behaviors, screening more drugs to overcome drug resistance and enhance receptor signaling. This review initially explores the correlation between aberrant LLPS and disease, highlighting the pivotal role of LLPS in preparing drug development. Ultimately, a comprehensive investigation into drug-mediated regulation of LLPS processes holds significant scientific promise for disease management.