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Abstract Deep close distance coal seam mining is affected by the goaf of upper coal and remaining coal pillar, and the roadway of lower coal is difficult to maintain stability. By means of theoretical analysis, physical simulation test and numerical simulation, this paper analyzes the failure characteristics of roadway in deep close distance coal seam and the evolution law of stress field, and optimizes the reasonable layout of lower coal roadway. The results show that: (1) The analytical formula of the evolution of the floor principal stress difference with depth is derived theoretically, and the distribution law of the shear stress of the rock mass in the floor of the coal seam is obtained. (2) The airway below the goaf can maintain good stability. High stress accumulation phenomenon occurs in the transport roadway below the coal pillar, which can not keep stable. (3) Due to the stress difference under the goaf and the coal pillar, the shear stress increases and the rock mass is damaged, and the left gang of the transport roadway is prone to instability destruction. (4) By comparing the distribution characteristics of plastic zones of transport roadway at different locations, it is determined that the transport roadway is more appropriate to be arranged 45 m below the coal pillar from the goaf.

Abstract Introduction Lung adenocarcinoma (LUAD), a common subtype of NSCLC, has a high mortality rate. Telomere genes are influenced by radiation therapy, affecting treatment response. Additionally, immune cell presence in the tumor microenvironment plays a crucial role in cancer prognosis. However, the role of Radioresistant-Related Telomere Genes (RRTGs) in LUAD prognosis and immune infiltration remains unclear. Methods In this research, we utilized diverse bioinformatics techniques to examine our personally tested information along with publicly accessible datasets. We conducted a comprehensive study on the genetic and transcriptional differences, predictive significance, and expression profiles of RRTGs. Afterwards, a RRTGs score was developed to forecast the overall survival (OS) and ascertain its reliable predictive capacity for patients with LUAD. Following this, dependable nomograms were developed to enhance the practicality of RRTGs scoring in a clinical setting. Furthermore, the investigation delved into the associations among RRTGs, infiltration of immune cells, prognosis, and clinical treatments of patients. Gene Set Enrichment Analysis (GSEA) was conducted to explore the potential mechanisms by which RRTGs influence the regulation of LUAD. Then, Western blot, qRT-PCR and Immunohistochemistry were used to detect the expression levels of RRTGs in cell lines and LUAD tumor tissues. Results Our research indicates that certain genes related to telomeres have a notable correlation with the prognosis of patients diagnosed with LUAD. The RRTGs score, which includes three key genes (ARRB1, PLK1, and DSG2), was developed to forecast the OS and its dependable predictive capability for individuals diagnosed with LUAD was ascertained. Afterwards, extremely reliable nomograms were developed to improve the practicality of the RRTGs score. Moreover, as illustrated, genetic characteristics can be utilized to assess the infiltration of immune cells in tumors, as well as clinical attributes and prognosis. RRTGs score characterizes tumor mutational burden, immune activity, and notable survival probabilities in addition. Furthermore, GSEA results revealed that RRTGs may influence LUAD by modulating immune-related pathways in high-risk groups and regulating cell cycle and DNA repair processes in low-risk groups. The RRTGs (ARRB1 and PLK1) were upregulated in A549 cells and radiosensitive NSCLC tissues compared to radioresistant A549 cells and NSCLC tissues. Conclusion In conclusion, this research emphasizes the significance of RRTGs in the outlook of LUAD. The findings contributed to a better understanding of the link between radiotherapy, telomere-related genes, and prognosis in LUAD, and identified potential therapeutic targets for patients with LUAD.

Abstract Background Identification of drug–target interactions is an indispensable part of drug discovery. While conventional shallow machine learning and recent deep learning methods based on chemogenomic properties of drugs and target proteins have pushed this prediction performance improvement to a new level, these methods are still difficult to adapt to novel structures. Alternatively, large-scale biological and pharmacological data provide new ways to accelerate drug–target interaction prediction. Methods Here, we propose DrugMAN, a deep learning model for predicting drug–target interaction by integrating multiplex heterogeneous functional networks with a mutual attention network (MAN). DrugMAN uses a graph attention network-based integration algorithm to learn network-specific low-dimensional features for drugs and target proteins by integrating four drug networks and seven gene/protein networks collected by a certain screening conditions, respectively. DrugMAN then captures interaction information between drug and target representations by a mutual attention network to improve drug–target prediction. Results DrugMAN achieved the best performance compared with cheminformation-based methods SVM, RF, DeepPurpose and network-based deep learing methods DTINet and NeoDT in four different scenarios, especially in real-world scenarios. Compared with SVM, RF, deepurpose, DTINet, and NeoDT, DrugMAN showed the smallest decrease in AUROC, AUPRC, and F1-Score from warm-start to Both-cold scenarios. This result is attributed to DrugMAN’s learning from heterogeneous data and indicates that DrugMAN has a good generalization ability. Taking together, DrugMAN spotlights heterogeneous information to mine drug–target interactions and can be a powerful tool for drug discovery and drug repurposing.

Abstract Owing to the rapid increase in electric vehicle integration and the uncoordinated charging behaviour of electric vehicles, the overloading risk of distribution transformers has deteriorated. This impact caused by large‐scale electric vehicle integration can be effectively reduced through the orderly guidance of electric vehicle charging behaviours. Here, a dispatching strategy for charging loads is proposed to address the problems of the uncoordinated charging demand in electric vehicles and overloading risk of distribution transformers in residential areas. First, an edge‐side dynamic index of the electric vehicle hosting capacity is proposed to guide the optimal dispatching of charging loads. Subsequently, an optimal dispatching model of the charging loads is established based on edge computing. The edge‐side dispatching strategy for the charging loads is then further updated considering the participation willingness of electric vehicle users. Finally, the effectiveness of the proposed control strategy is validated using a modified residential distribution network in Tianjin. The results show that the proposed strategy can effectively decrease the overloading risk of distribution transformers while realizing the efficient operation of electric vehicles on the edge side.

Abstract Offline reinforcement learning (RL) has been widely used in safety-critical domains by avoiding dangerous and costly online interaction. A significant challenge is addressing uncertainties and risks outside of offline data. Risk-sensitive offline RL attempts to solve this issue by risk aversion. However, current model-based approaches only extract state transition information and reward information using dynamics models, which cannot capture risk information implicit in offline data and may result in the misuse of high-risk data. In this work, we propose a model-based offline policy optimization approach with a risk dynamics model (MOOR). Specifically, we construct a risk dynamics model using a quantile network that can learn the risk information of data, then we reshape model-generated data based on errors of the risk dynamics model and the risk information of data. Finally, we use a risk-averse algorithm to learn the policy on the combined dataset of offline and generated data. We theoretically prove that MOOR can identify risk information of data and avoid utilizing high-risk data, our experiments show that MOOR outperforms existing approaches and achieves state-of-the-art results in risk-sensitive D4RL and risky navigation tasks.

Abstract The optimal treatment strategy for proximal humerus fractures (PHFs) is debatable owing to the relatively high failure rate of locking plates. Optimizing implants may enhance the fixation stability of PHFs and reduce the rate of mechanical failures. We developed a finite element (FE) model to simulate the treatment of PHFs with Proximal Humerus Internal Locking System (PHILOS) plates. The model evaluated the average bone strain around the screw tips under vertical loading (as an alternative to the risk of cyclic screw cutout failure verified through biomechanical testing) to minimize this strain and maximize predicted fixation stability. After determining the optimal screw configuration, further FE analysis and in vitro biomechanical testing were conducted on both standard and optimized PHILOS screw orientation to assess whether the optimized plates have biomechanical advantages over the standard plates. The FE-based optimized configuration exhibited significantly lower bone strain around the implant than the standard PHILOS screw orientation (− 17.24%, p

Abstract Objective To evaluate the efficacy of sentinel lymph node biopsy (SLNB) in cT1/2N0 minor salivary gland cancer (mSGC) located within the oral cavity. Methods A retrospective analysis was conducted on patients diagnosed with cT1/2N0 oral mSGC, who were categorized into two groups based on neck management approaches. The impact of SLNB versus observation on regional control and overall survival was assessed using a Cox model. Results A total of 177 patients were included in the study, with 53 cases undergoing SLNB. All patients had at least one sentinel lymph node, with the majority having two sentinel lymph nodes. The sentinel lymph nodes were predominantly situated in level I, followed by level II. Four patients had positive sentinel lymph nodes, all of whom had primary tumors in the tongue or the floor of the mouth, and were classified as cT2 stage. This yielded a sensitivity and specificity of 100%, a false negative rate of 0%, and a negative predictive value of 100% for SLNB in predicting occult metastasis. In terms of regional control, SLNB exhibited a reduced hazard ratio of 0.90 (95% confidence interval: 0.64–0.96) compared to observation. However, SLNB did not confer a superior overall survival benefit compared to observation. Conclusion In patients with cT1/2N0 oral mSGC, SLNB proved to be both technically feasible and oncologically safe. When contrasted with observation, SLNB was associated with enhanced regional control, particularly recommending its use for cases of cT2 mSGC arising from the tongue or the floor of the mouth.

Abstract The endothelium-dependent vascular injury, a primary pathological feature of angiotensin II (Ang II)-induced hypertension. This study aimed to explore the role and underlying mechanisms of G protein-coupled receptor 39 (GPR39) in the pathogenesis of Ang II-induced hypertension. For in vivo studies, GPR39 knockout (KO) mice (C57BL/6 J, male) were generated and administered Ang II for 4 weeks. GPR39 expression was upregulated in the aorta of hypertensive patients and mice. The ablation of GPR39 mitigated vascular fibrosis, augmented endothelium-dependent vasodilation, and inhibited endothelial inflammation, oxidative stress, and apoptosis in mice. Additionally, GPR39 KO decreased NOD-like receptor protein 3 (Nlrp3) gene expression in Ang II-stimulated endothelial cells. Notably, Nlrp3 activation counteracted the therapeutic benefits of GPR39 KO. We identified the potential ligand of GPR39 using structure-based high throughput virtual screening (HTVS) and validated its antihypertensive function in vitro and in vivo. The small molecule ligand Z1780628919 of GPR39 can also reduce Ang II-induced hypertension and improve vascular function. GPR39 KO and the small molecule ligand Z1780628919 potentially downregulates Nlrp3, thereby mitigating vascular fibrosis, endothelial inflammation, oxidative stress, and apoptosis. This effect contributes to the alleviation of Ang II-induced hypertension and the rectification of vascular dysfunctions. These findings suggest new avenues for therapeutic intervention.

Hard X-ray microscopes with 20–30 nm spatial resolution ranges are an advanced tool for the inspection of materials at the nanoscale. However, the limited efficiency of the focusing optics, for example, a Fresnel zone plate (ZP) lens, can significantly reduce the power of a nanoprobe. Despite several reports on ZP lenses that focus hard X-rays with 20 nm resolution – mainly constructed by zone-doubling techniques – a systematic investigation into the limiting factors has not been reported. We report the structural effects on the focusing and imaging efficiency of 20–30 nm-resolution ZPs, employing a modified beam-propagation method. The zone width and the duty cycle (zone width/ring pitch) were optimized to achieve maximum efficiency, and a comparative analysis of the zone materials was conducted. The optimized zone structures were used in the fabrication of Pt-hydrogen silsesquioxane (HSQ) ZPs. The highest focusing efficiency of the Pt-HSQ-ZP with a resolution of 30 nm was 10% at 7 keV and >5% in the range 6–10 keV, whereas the highest efficiency of the Pt-HSQ-ZP with a resolution of 20 nm was realized at 7 keV with an efficiency of 7.6%. Optical characterization conducted at X-ray beamlines demonstrated significant enhancement of the focusing and imaging efficiency in a broader range of hard X-rays from 5 keV to 10 keV, demonstrating the potential application in hard X-ray focusing and imaging.

Due to the typically high flow rate of nozzles on large sprinkler machines, direct use for pesticide application can lead to pesticide waste and non-point source pollution. To fulfill the multifunctional needs of large sprinkler machines for irrigation, fertilization, and pesticide application, this study installed atomizing micro-sprinklers on the machines to enable their pesticide application capabilities. Based on the spraying patterns of the atomizing micro-sprinklers, three types were selected for this study: hollow cone, solid cone, and fan-shaped micro-sprinklers. Three working pressure levels were set at 0.2 MPa, 0.3 MPa, and 0.5 MPa, with the height of the micro-sprinklers above the ground set at three levels: 0.8 m, 1.2 m, and 1.5 m. A completely randomized design was used for the experiment, which included hydraulic performance tests and software simulation. The results indicated that the spray volume of the hollow cone, solid cone, and fan-shaped atomizing micro-sprinklers approximately presented a hollow conical, solid conical, and normal distribution, respectively. The spray intensity (average and maximum values) of the atomizing micro-sprinklers increased with the increase in pressure, while the median showed an initial increase followed by a decrease as pressure increased. Under the same pressure conditions, the spray intensity of the different atomizing micro-sprinklers decreased with the increase in height above the ground, while the spray width increased with height. By comparing the spraying characteristics of micro-sprinklers with various patterns, large sprinkler machines can select atomizing micro-sprinklers in different spraying statuses according to actual conditions and determine the optimal height of the atomizing micro-sprinklers above the ground to achieve efficient and uniform pesticide application effects. This reduces the evaporation and drift loss of liquid medicine. The research findings provide a scientific basis for achieving the pesticide application function of large sprinkler machines and expanding their usage capabilities.

Abstract Although the LiCoO2 (LCO) cathode material has been widely used in commercial lithium ion batteries (LIB) and shows high stability, LIB’s improvements have several challenges that still need to be overcome. In this paper, we have studied the in-operando structural properties of LCO within battery cells using Bragg Coherent X-ray Diffraction Imaging to identify ways to optimise the LCO batteries’ cycling. We have successfully reconstructed the X-ray scattering phase variation (a fingerprint of atomic displacement) within a ≈ (1.6 × 1.4 × 1.3) μm3 LCO nanocrystal across a charge/discharge cycle. Reconstructions indicate strained domains forming, expanding, and fragmenting near the surface of the nanocrystal during charging, with a determined maximum relative lattice displacements of 0.467 Å. While discharging, all domains replicate in reverse the effects observed from the charging states, but with a lower maximum relative lattice displacements of 0.226 Å. These findings show the inefficiency-increasing domain dynamics within LCO lattices during cycling.

Objective: Colorectal cancer (CRC) is a prevalent malignant tumor with a high fatality rate. CircPDIA4 has been shown to have a vital role in cancer development by acting as a facilitator. Nevertheless, the impact of the circPDIA4/miR-9-5p/SP1 axis on development of CRC has not been studied. Methods: Western blot, immunohistochemistry, and reverse transcription-quantitative polymerase chain reaction assays were used to analyze gene expression. The CCK-8 assay was used to assess cell growth. The Transwell assay was used to detect invasion and migration of cells. The luciferase reporter and RNA immunoprecipitation tests were used to determine if miR-9-5p and circPDIA4 (or SP1) bind to one another. An in vivo assay was used to measure tumor growth. Results: It was shown that circPDIA4 expression was greater in CRC cell lines and tissues than healthy cell lines and tissues. CircPDIA4 knockdown prevented the invasion, migration, and proliferation of cells in CRC. Additionally, the combination of circPDIA4 and miR-9-5p was confirmed, as well as miR-9-5p binding to SP1. Rescue experiments also showed that the circPDIA4/miR-9-5p/SP1 axis accelerated the development of CRC. In addition, SP1 combined with the promoter region of circPDIA4 and induced circPDIA4 transcription. CircPDIA4 was shown to facilitate tumor growth in an in vivo assay. Conclusions: The circPDIA4/miR-9-5p/SP1 feedback loop was shown to aggravate CRC progression. This finding suggests that the ceRNA axis may be a promising biomarker for CRC patient treatment.

Abstract Post-transcriptional regulation mediated by RNA binding proteins is crucial for male germline development. Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), an RNA binding protein, is specifically expressed in human and mouse male gonads and is involved in manifold biological processes and tumorigenesis. However, the function of IGF2BP1 in mammalian spermatogenesis remains poorly understood. Herein, we generated an Igf2bp1 conditional knockout mouse model using Nanos3-Cre. Germ cell deficiency of Igf2bp1 in mice caused spermatogenic defects in an age-dependent manner, resulting in decreased numbers of undifferentiated spermatogonia and increased germ cell apoptosis. Immunoprecipitation-mass spectrometry analysis revealed that ELAV-like RNA binding protein 1, a well-recognized mRNA stabilizer, interacted with IGF2BP1. Single cell RNA-sequencing showed distinct mRNA profiles in spermatogonia from conditional knockout versus wide type mice. Further research showed that IGF2BP1 plays a vital role in the modulation of spermatogenesis by regulating Lin28a mRNA, which is essential for clonal expansion of undifferentiated spermatogonia. Thus, our results highlight the crucial effects of IGF2BP1 on spermatogonia for the long-term maintenance of spermatogenesis.

Abstract Pulmonary embolism is a rare but serious complication in Mycoplasma pneumoniae pneumonia patients, leading to serious sequelae and even death. We aim to retrospectively analyze the clinical features of Mycoplasma pneumoniae pneumonia with pulmonary consolidation in children and to explore the independent risk factors for progression to pulmonary embolism. Clinical data of 207 children with Mycoplasma pneumoniae pneumonia complicated with pulmonary consolidation were collected, and the patients were divided into the pulmonary embolism group (69 patients) and the control group (138 patients). Multivariate logistic regression was used to analyze the risk factors and the predictive efficacy was evaluated by receiver operating characteristic curve. Multivariate logistic regression analysis showed that fever days, D-dimer, immunoglobulin A, chest pain, extra-respiratory symptoms, plastic bronchitis and cutaneous mucosal system complications were the independent risk factors. Fever days ≥ 7.5, D-dimer ≥ 0.895 mg/L, immunoglobulin A ≥ 1.015 g/L, chest pain, extra-respiratory symptoms, plastic bronchitis and cutaneous mucous system complications significantly increased the risk of pulmonary embolism in children with Mycoplasma pneumoniae pneumonia complicated with pulmonary consolidation.

Abstract The contradiction between high piezoelectricity and uniquely poor temperature stability generated by polymorphic phase boundary is a huge obstacle to high-performance (K, Na)NbO3 -based ceramics entering the application market as Pb-based substitutes. We possess the phase boundary by mimicking Pb(Zr, Ti)O3’s morphotropic phase boundary structure via the synergistic optimization of diffusion phase boundary and crystal orientation in 0.94(Na0.56K0.44)NbO3−0.03Bi0.5Na0.5ZrO3−0.03(Bi0.5K0.5)HfO3 textured ceramics. As a result, a prominent comprehensive performance is obtained, including giant d 33 of 550 ± 30 pC/N and ultrahigh temperature stability (d 33 change rate less than 1.2% within 25-150 °C), representing a significant breakthrough in lead-free piezoceramics, even surpassing the Pb-based piezoelectric ceramics. Within the same temperature range, the d 33 change rate of the commercial Pb(Zr, Ti)O3−5 ceramics is only about 10%, and more importantly, its d 33 (~ 350 pC/N) is much lower than that of the (K, Na)NbO3-based ceramics in this work. This study demonstrates a strategy for constructing the phase boundary with MPB feature, settling the problem of temperature instability in (K, Na)NbO3-based ceramics.

Abstract Memory reprocessing during sleep is a well-established phenomenon in numerous studies. However, it is unclear whether the intensity of memory reprocessing is consistently maintained throughout the night or exhibits dynamic changes. This study investigates the temporal dynamics of negative emotional memory reprocessing during sleep, with a specific focus on slow oscillation (SO)-spindle coupling and its role in memory reprocessing. In the first experiment (N = 40, mean age = 22.5 years), we detected the negative emotional memory reprocessing strength in each sleep cycle, we found that the 2nd sleep cycle after negative emotional memory learning constitute the most sensitive window for memory reprocessing, furthermore, SO-spindle coupling signals in this window plays a role in stabilizing negative emotional memory. To verify the role of SO-spindle coupling in negative emotional memory reprocessing, we utilized transcranial alternating current stimulation (tACS) to disrupt SO-spindle coupling during the 2nd sleep cycle (N = 21, mean age = 19.3 years). Notably, the outcomes of the tACS intervention demonstrated a significant reduction in the recognition of negative emotional memories. These findings offer new insights into the mechanisms that regulate emotional memory consolidation during sleep and may have implications for addressing psychiatric disorders associated with pathological emotional memory.

Abstract Background In the era of immunotherapy, neoadjuvant immunochemotherapy (NAIC) for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC) is used clinically but lacks of high‐level clinical evidence. This study aimed to compare the safety and long‐term efficacy of NAIC followed by minimally invasive esophagectomy (MIE) with those of neoadjuvant chemotherapy (NAC) followed by MIE. Methods A prospective, single‐center, open‐label, randomized phase III clinical trial was conducted at Henan Cancer Hospital, Zhengzhou, China. Patients were randomly assigned to receive either neoadjuvant toripalimab (240 mg) plus paclitaxel (175 mg/m2) + cisplatin (75 mg/m2) (toripalimab group) or paclitaxel + cisplatin alone (chemotherapy group) every 3 weeks for 2 cycles. After surgery, the toripalimab group received toripalimab (240 mg every 3 weeks for up to 6 months). The primary endpoint was event‐free survival (EFS). The pathological complete response (pCR) and overall survival (OS) were key secondary endpoints. Adverse events (AEs) and quality of life were also assessed. Results Between May 15, 2020 and August 13, 2021, 252 ESCC patients ranging from T1N1‐3M0 to T2‐3N0‐3M0 were enrolled for interim analysis, with 127 in the toripalimab group and 125 in the chemotherapy group. The 1‐year EFS rate was 77.9% in the toripalimab group compared to 64.3% in the chemotherapy group (hazard ratio [HR] = 0.62; 95% confidence interval [CI] = 0.39 to 1.00; P = 0.05). The 1‐year OS rates were 94.1% and 83.0% in the toripalimab and chemotherapy groups, respectively (HR = 0.48; 95% CI = 0.24 to 0.97; P = 0.037). The patients in the toripalimab group had a higher pCR rate (18.6% vs. 4.6%; P = 0.001). The rates of postoperative Clavien‐Dindo grade IIIb or higher morbidity were 9.8% in the toripalimab group and 6.8% in the chemotherapy group, with no significant difference observed (P = 0.460). The rates of grade 3 or 4 treatment‐related AEs did not differ between the two groups (12.5% versus 12.4%). Conclusions The interim results of this ongoing trial showed that in resectable ESCC, the addition of perioperative toripalimab to NAC is safe, may improve OS and might change the standard treatment in the future.

This study describes two new species within the genus Paranemachilus. Paranemachilus luegvetensis sp. nov. and Paranemachilus liui sp. nov. can be distinguished from all recognized congeners by a combination of morphological characteristics and substantial genetic divergences. Paranemachilus luegvetensis sp. nov. is characterized by scaled cheeks; the whole body covered in scales, except for the head; 11–12 branched pectoral fin rays; 4–5 preoperculomandibular canal pores; body depth 13.5%–16.8% of standard length; and preanus length 68.3%–73.9% of standard length. Paranemachilus liui sp. nov. is characterized by scaled cheeks; the whole body covered in scales except for the head; 11–13 branched pectoral fin rays; 11–15 supraorbital canal pores at the base of the anterior nostrils; 7–9 preoperculomandibular canal pores; preanus length 67.4%–74.3% of standard length; snout length 21.4%–28.7% of lateral head length.

Abstract Robbsia andropogonis is one of the most destructive leaf spot disease pathogens of numerous host plants and causes heavy economic damage. In the present study, the complete genome of R. andropogonis strain BLB1, causing the leaf spot disease of areca palm, was generated using a hybrid method combining ONT PromethION long reads and BGISEQ-500 short reads. The resulting genome consists of seven replicons totaling 6,828,120 bp, and 5,808 genes were annotated, including 788 virulence-related genes. Function analysis showed that genes involved in metabolism were the most abundant group. Impressively, the bacteria were well-equipped with four, two, and four sets of type three, four, and six secretion systems, respectively, highlighting the virulence features of R. andropogonis BLB1. As the first complete genome sequence of the species of genus Robbsia, the BLB1 genome provides a solid foundation for investigation of mechanisms underlying the pathogen virulence and disease control, and will promote further discovery and characterization of the genus Robbsia.

Abstract Etoposide is a second-line chemotherapy agent widely used for metastatic colorectal cancer. However, we discovered that etoposide treatment induced greater motility potential in four colorectal cancer cell lines. Therefore, we used microarrays to test the mRNA of these cancer cell lines to investigate the mechanisms of etoposide promoting colorectal cancer metastasis. Differentially expressed genes (DEGs) were identified by comparing the gene expression profiles in samples from etoposide-treated cells and untreated cells in all four colorectal cancer cell lines. Next, these genes went through the Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analysis. Among the top 10 genes including the upregulated and downregulated, eight genes had close interaction according to the STRING database: FAS, HMMR, JUN, LMNB1, MLL3, PLK2, STAG1 and TBL1X. After etoposide treatment, the cell cycle, metabolism-related and senescence signaling pathways in the colorectal cancer cell lines were significantly downregulated, whereas necroptosis and oncogene pathways were significantly upregulated. We suggest that the differentially expressed genes LMNB1 and JUN are potential targets for predicting colorectal cancer metastasis. These results provide clinical guidance in chemotherapy, and offer direction for further research in the mechanism of colorectal cancer metastasis.

Abstract Objective A hybrid manufacturing technique that combines selective laser melting (SLM) and computer numerical control (CNC) has been developed for the fabrication of implant-platform/framework interfaces (PFIs) for mandibular and maxillary full-arch implant-supported titanium frameworks. The aim of this study was to compare the discrepancies in specimens fabricated using the hybrid technique (termed SLM/m hereafter) with those in specimens fabricated by conventional CNC milling. Materials and methods Based on a mandibular four-PFI CAD model and a maxillary six-PFI CAD model, four groups of titanium frameworks (eight per group, totaling 32) were fabricated according to the fabrication technique (SLM/m or milling) and number of PFIs (four or six). The frameworks were scanned by a structured light scanner and aligned with the CAD model in Geomagic Control X. Discrepancy was defined as the difference between the PFIs of the scanned framework and those of the CAD model. Discrepancies were measured and evaluated by multilevel analysis using a mixed-effects model (α = 0.05), followed by independent samples t-tests (α = 0.0125). Furthermore, the manufacturing times and raw-material costs were recorded and compared. Results The maximum discrepancy values for the four-PFI and six-PFI hybrid frameworks were 52.2 and 64.3 μm, respectively. Multilevel analysis revealed that the fabrication technique and the number of PFIs had no significant effect on the discrepancy value. However, a significant interaction between the two factors was observed (P = 0.020). The discrepancies for the four-PFI hybrid frameworks were significantly lower than those for the four-PFI milled frameworks (P = 0.001). No significant difference in discrepancies between the six-PFI hybrid frameworks and six-PFI milled frameworks was observed (P = 0.697). Furthermore, the hybrid frameworks required only 11% of the raw materials and 25% of the milling time required for the conventionally milled frameworks. Conclusion SLM/m hybrid frameworks are viable, accurate alternatives to CNC-milled frameworks, with the added benefit of substantial cost reduction.

Abstract Plants such as herbs, vegetables, fruits, and cereals are closely related to human life. Developing effective testing methods to ensure their safety and quantify their active components are of significant importance. Recently, nanomaterials with enzyme-like activity (known as nanozymes) have been widely developed in various assays, including colorimetric, fluorescence, chemiluminescence, and electrochemical analysis. This review presents the latest advances in analyzing phytochemicals and hazardous substances in plant samples based on nanozymes, including some active ingredients, organophosphorus pesticides, heavy metal ions, and mycotoxins. Additionally, the current shortcomings and challenges of the actual sample analysis were discussed.

Abstract Background A Tonsil-Oral-Scrubbing (TOSc) method was developed to sample the sow’s oropharyngeal and tonsillar area without snaring and has shown comparable porcine reproductive and respiratory syndrome virus (PRRSV) RNA detection rates with tonsil scraping in infected sows. This study investigated the effect of specific TOSc collection factors on the PRRSV RT-rtPCR results (detection rates and Ct values). Those factors include whether the sow was snared or not snared at TOSc collection (“snared” vs. “not snared”); whether the sow was laying down or standing at collection (“laying down” vs. “standing”); and type of collectors used for TOSc collection (“TOSc prototype” vs. “Spiral-headed AI catheter (SHAC)”). Volume of fluid was compared between “snared” and “not snared” groups, and collection time was compared between “laying down” and “standing” groups as well. Results The effect for each factor was assessed in three independent studies following the same design: TOSc was collected twice from each studied sow, once with the baseline level for a factor (“not snared”, or “standing”, or “TOSc prototype”), and another time followed by the other level of the paired factor (“snared”, “laying down”, or “SHAC”, correspondingly). Results showed that “not snared” TOSc had numerically higher PRRSV RNA detection rate (60.7% vs. 52.5%, p = 0.11), significantly lower median Ct values (31.9 vs. 32.3, p

Abstract Rotavirus group C is an important cause of sporadic cases and outbreaks of gastroenteritis worldwide. Whole-Genome sequences of human rotavirus C (RVC) in public databases are limited. We performed genome sequencing to analyze a RVC outbreak of acute gastroenteritis in China. Samples from 22 patients were screened for pathogens using RT-PCR, and six samples were positive for rotavirus. Whole-Genome sequencing analysis showed that the outbreak strain SJZ217 belongs to the G4-P[2]-I2-R2-C2-M3-A2-N2-T2-E2-H2 genotype and shares almost identical genomic sequences with Chungnam isolated in Korea. Phylogenetic analysis revealed strain SJZ217 also fell into a cluster with rotavirus C strains from Japan and Europe. Reassortment in the VP4 fragment was observed. These results helped to understand the genetic diversity and possible spread of RVC strains.

Abstract Background The β-1,3-glucanase gene is widely involved in plant development and stress defense. However, an identification and expression analysis of the grape β-1,3-glucanase gene (VviBG) family had not been conducted prior to this study. Results Here, 42 VviBGs were identified in grapevine, all of which contain a GH-17 domain and a variable C-terminal domain. VviBGs were divided into three clades α, β and γ, and six subgroups A–F, with relatively conserved motifs/domains and intron/exon structures within each subgroup. The VviBG gene family contained four tandem repeat gene clusters. There were intra-species synteny relationships between two pairs of VviBGs and inter-species synteny relationships between 20 pairs of VviBGs and AtBGs. The VviBG promoter contained many cis-acting elements related to stress and hormone responses. Tissue-specific analysis showed that VviBGs exhibited distinct spatial and temporal expression patterns. Transcriptome analysis indicated that many VviBGs were induced by wounds, UV, downy mildew, cold, salt and drought, especially eight VviBGs in subgroup A of the γ clade. RT-qPCR analysis showed that these eight VviBGs were induced under abiotic stress (except for VviBG41 under cold stress), and most of them were induced at higher expression levels by PEG6000 and NaCl than under cold treatment. Conclusions The chromosome localization, synteny and phylogenetic analysis of the VviBG members were first conducted. The cis-acting elements, transcriptome data and RT-qPCR analysis showed that VviBG genes play a crucial role in grape growth and stress (hormone, biotic and abiotic) responses. Our study laid a foundation for understanding their functions in grape resistance to different stresses.

Abstract Background With the increasing incidence of renal lesions, pretreatment differentiation between benign and malignant lesions is crucial for optimized management. This study aimed to develop a machine learning model utilizing radiomic features extracted from various regions of interest (ROIs), intratumoral ecological diversity features, and clinical factors to classify renal lesions. Methods CT images (arterial phase) of 1,795 renal lesions with confirmed pathology from three hospital sites were split into development (1184, 66%) and test (611, 34%) cohorts by surgery date. Conventional radiomic features were extracted from eight ROIs of arterial phase images. Intratumoral ecological diversity features were derived from intratumoral subregions. The combined model incorporating these features with clinical factors was developed, and its performance was compared with radiologists’ interpretation. Results Combining intratumoral and peritumoral radiomic features, along with ecological diversity features yielded the highest AUC of 0.929 among all combinations of features extracted from CT scans. After incorporating clinical factors into the features extracted from CT images, our combined model outperformed the interpretation of radiologists in the whole (AUC = 0.946 vs 0.823, P

Abstract Depression has emerged as a significant global health concern, exerting a profound impact on individuals, as evidenced by its high prevalence and associated suicide rates. Considering its pervasive nature, the absence of optimal treatment modalities remains a challenge. Acupuncture has garnered substantial clinical and experimental validation for its efficacy in addressing diverse forms of depression, including postpartum, post-stroke, and adolescent depression. This article endeavors to elucidate the distinctive attributes and underlying mechanisms of acupuncture in the contemporary treatment of depression. Research has demonstrated that acupuncture exerts diverse physiological effects in animal models of depression, encompassing modulation of the brain, serum, and brain-gut axis. These effects are attributed to various mechanisms, including anti-inflammatory and anti-oxidative actions, promotion of neuronal plasticity, neuroprotection, neurotrophic effects, modulation of neurotransmitters, regulation of endocrine and immune functions, and modulation of cell signal pathways. Currently, the therapeutic mechanism of acupuncture involves the engagement of multiple targets, pathways, and bidirectional regulation. Hence, acupuncture emerges as a promising alternative medical modality, exhibiting substantial research prospects and meriting comprehensive worth further study and dissemination.

AIM: To explore the DNA methylation of COL4A1 in ultraviolet-B (UVB)-induced age-related cataract (ARC) models in vitro and in vivo. METHODS: Human lens epithelium B3 (HLEB3) cells and Sprague Dawley rats were exposure to UVB respectively. The MTT assay was utilized to evaluate cell proliferation. Flow cytometry was employed for analysis of cell apoptosis and cell cycle. COL4A1 expression in HLEB3 cells and anterior lens capsules were assessed using Western blot and reverse transcription-polymerase chain reaction (RT-PCR). The localization of COL4A1 in HLEB3 cells was determined by immunofluorescence. The methylation status of CpG islands located in COL4A1 promoter was verified using bisulfite-sequencing PCR (BSP). DNMTs and TETs mRNA levels was examined by RT-PCR. RESULTS: UVB exposure decreased HLEB3 cells proliferation, while increased the apoptosis rate and cells were arrested in G0/G1 phase. COL4A1 expression was markedly inhibited in UVB treated cells compared to the controls. Hypermethylation status was detected in the CpG islands within COL4A1 promoter in HLEB3 cells subjected to UVB exposure. Expressions of DNMTs including DNMT1/2/3 were elevated in UVB treated HLEB3 cells compared to that in the controls, while expressions of TETs including TET1/2/3 showed the opposite trend. Results from the UVB treated rat model further confirmed the decreased expression of COL4A1, hypermethylation status of the CpG islands at promoter of COL4A1 and abnormal expression of DNMT1/2/3 and TET1/2/ in UVB exposure group. CONCLUSION: DNA hypermethylation of COL4A1 promoter CpG islands is correlated with decreased COL4A1 expression in UVB induced HLEB3 cells and anterior lens capsules of rats.

Soft tissue integration around titanium (Ti) implants is weaker than that around natural teeth, compromising long-term success of Ti implants. Carbon monoxide (CO) possesses distinctive therapeutic properties, rendering it as a highly promising candidate for enhancing STI. However, achieving controlled CO generation at the STI interface remains challenging. Herein, a controlled CO-releasing dual-function coating was constructed on Ti surfaces. Under near-infrared (NIR) irradiation, the designed surface could actively accelerate CO generation for antibiosis against both aerobic and anaerobic bacteria. More importantly, in the absence of NIR, the slow release of CO induces macrophage polarization from pro-inflammatory phenotype towards pro-regenerative phenotype. In a rat implantation model with induced infection, the designed surface effectively controlled the bacterial infection, alleviates accompanying inflammation and modulated immune microenvironment, leading to enhanced STI. Single-cell sequencing revealed that the coating alters the cytokine profile within the soft tissue, thereby influencing cellular functions. Differentially expressed genes in macrophages are highly enriched in the PIK3-Akt pathway. Furthermore, the cellular communication between fibroblasts and macrophages was significantly enhanced through the CXCL12/CXCL14/CXCR4 and CSF1-CSF1R ligand-receptor pair. These findings indicate that our coating showed an appealing prospect for enhancing STI around Ti implants, which would ultimately contribute to the improved long-term success of Ti implants.

Diabetic ulcers (DUs) are persistent and challenging complications of diabetes. The consequences of DUs include a decline in functional status, increased risk of infection, hospitalization, and even death. Our study revealed a significant decrease in the levels of cortistatin (CST) in the skin tissue of patients with DUs and diabetic rats. This finding led us to hypothesize that the administration of exogenous CST is an effective strategy to promote wound healing in patients with DUs. We herein successfully prepared CST-loaded pDMA-pEPEMA nanoparticles (CST@NPs) designed to exhibit localized, acid-responsive behavior for enhanced wound healing. These CST@NPs were sensitive to acidic environments, triggering the rapid release of CST. In vitro experiments showed that CST@NPs effectively alleviated oxidative stress and reduced apoptosis in human umbilical vein endothelial cells (HUVECs). Our findings further demonstrated that CST@NPs accelerated re-epithelialization of the wound, enhanced collagen deposition, and stimulated angiogenesis, while alleviating the local inflammatory response. Both in vivo and in vitro results indicate that CST@NPs possess precise and rapid response capabilities in acidic environments, ensuring effective CST release to promote diabetic wound healing. In summary, this acid-responsive nanoparticle system presents a highly efficient therapeutic strategy for the treatment of chronic diabetic wounds.

Abstract Background The aim was to investigate the clinical characteristics, treatment and prognosis of neonatal influenza. Methods The clinical data of 21 neonates who were diagnosed with influenza and admitted to the neonatal intensive care unit of Henan Provincial Children’s Hospital, China, between January 2023 and January 2024 were retrospectively analyzed. Results A total of 21 patients were admitted, including 14 with influenza A and 7 with influenza B. Eighteen of these patients were reported to have been exposed to family members with respiratory symptoms before hospitalization. Among all the patients’ mothers, only 1 received the influenza vaccine during pregnancy. Fifteen newborns had fever, 13 appetite loss, 10 cough, 9 shortness of breath, 9 nasal obstruction, 3 runny nose, 3 vomiting, 2 severe wheezing, 2 choking, 2 diarrhea, 1 bloating, and 1 sputum in the throat. The pulmonary auscultation sounds were coarse in 19 neonates, weak in 2, moist rales were appreciated in 5 and wheezing in 4 of them. The peripheral total white blood cell count was normal in 18 patients and elevated in 3. The C-reactive protein level was normal in all subjects, and the procalcitonin level was elevated in 1. Nineteen patients had pneumonia on chest imaging. All patients were treated with oseltamivir and finally recovered. Conclusion Influenza A is the most common type of neonatal influenza. The clinical symptoms are atypical, and fever is the main symptom. Treatment with oseltamivir is safe and effective, and the prognosis is mostly favorable.

Abstract Photodynamic therapy (PDT) as a clinical method relies on appropriate light delivery to activate photosensitizers, usually necessitates the utilization of cumbersome surgical instruments and high irradiation intensity, along with the requirement for hospitalization. To extend the applicability of PDT beyond hospital for better patient mobility, we design a wearable and self-powered metronomic PDT (mPDT) system for chronic wound infection treatment. A flexible alternative current electroluminescent (ACEL) device is constructed through sandwiching an emissive layer between conductive hydrogel electrodes. This ACEL device works as a therapeutic patch by loading photosensitizer (PS) in its bottom hydrogel electrode, thus aviods the intravenous administration to patients. Under the triboelectric nanogenerator generated AC pulse, the electroluminescence produced from emissive layer can be absorbed by the PS-loaded electrode to generate reactive oxygen species for mPDT. Benefited from its arbitrary tailorability, this device can be customized into on-demand shapes and sizes. Using diabetic infected wound as a model condition, this ACEL mPDT device effectively eliminates drug-resistant bacteria and accelerates wound healing. Thus, the body-worn optoelectronic device successfully avoids the utilization of extracorporeal physical light and power sources, providing a promising strategy for convenient, user-friendly, and prolonged treatment of superficial diseases.

Abstract Background The spatiotemporal epidemiological evidence supporting joint endoscopic screening for esophageal cancer (EC) and gastric cancer (GC) remains limited. This study aims to identify combined high-risk regions for EC and GC and determine optimal areas for joint and separate endoscopic screening. Methods We analyzed the association of incidence trends between EC and GC in cancer registry areas across China from 2006 to 2016 using spatiotemporal statistical methods. Based on these analyses, we divided different combined risk regions for EC and GC to implement joint endoscopic screening. Results From 2006 to 2016, national incidence trends for both EC and GC showed a decline, with an average annual percentage change of -3.15 (95% confidence interval [CI]: -5.33 to -0.92) for EC and -3.78 (95% CI: -4.98 to -2.56) for GC. A grey comprehensive correlation analysis revealed a strong temporal association between the incidence trends of EC and GC, with correlations of 79.00% (95% CI: 77.85 to 80.14) in males and 77.62% (95% CI: 76.50 to 78.73) in females. Geographic patterns of EC and GC varied, demonstrating both homogeneity and heterogeneity across different regions. The cancer registry areas were classified into seven distinct combined risk regions, with 33 areas identified as high-risk for both EC and GC, highlighting these regions as priorities for joint endoscopic screening. Conclusion This study demonstrates a significant spatiotemporal association between EC and GC. The identified combined risk regions provide a valuable basis for optimizing joint endoscopic screening strategies for these cancers.

Abstract Wireless sensor nodes (WSNs) play an important role in many fields, including environmental monitoring. However, unattended WSNs face challenges in consuming power continuously even in the absence of useful information, which makes energy supply the bottleneck of WSNs. Here, we realized zero-power infrared switches, which consist of a metasurface and two-phase microfluidic flow. The metasurface can recognize the infrared signal from the target and convert it into heat, which triggers the two-phase microfluidic flow switch. As the target is not present, the switch is turned off. The graphene/MoS2/graphene 2D material heterostructure (thickness

Objective: Illumination of the integrative effects of herbs in a formula is a bottleneck that limits the development of traditional Chinese medicine (TCM). In the present study, we developed a transcriptome-based multi-scale network pharmacology model to explore the combined effects of different herbs. Materials and Methods: First, we curated gene signatures at different biological scales, from the molecular to higher tissue levels, including tissues, cells, pathological processes, biological processes, pathways, and targets. Second, using the Xiexin Tang (XXT) formula as an example, we collected transcriptomic data in response to the treatment of XXT or its three compositive herbs on Michigan cancer foundation7 cells. Third, we linked each herbal drug to different biological scales by calculating the correlation scores between herb-induced gene expression profiles and gene signatures. Finally, the combined mechanisms of the three constituent herbs in XXT were deciphered by comparing their multi-scale effects with those of the formula. Results: The results showed that although XXT or single herbs regulated a large number of signatures on each biological scale, the phenotypic effects of these herbal drugs are concentrated onto the “Blood” tissue, types of hemocytes, and hemorrhagic injury-related pathological processes. At the molecular level, these herbs consistently regulate processes such as the cell cycle and blood coagulation-related pathways, as well as protein targets related to the immunoinflammatory response and blood coagulation, such as proteinase-activated receptor 2, integrin beta-3, inhibitor of nuclear factor kappa-B kinase subunit beta, and coagulation factor XII. The analysis of the combinational modes demonstrated that different herbs can cooperate by acting on the same objects and/or regulating different objects in related functions, and cooperative behaviors change at different biological scales. Conclusions: Our model can dissect the combined effects of herbal formulae from a multi-scale perspective and should be beneficial for the development and exploitation of TCM.

Abstract Objective To investigate pantothenate kinases 1 (PANK1) expression in kidney renal clear cell carcinoma (KIRC) tissues, analyze its correlation with clinicopathological features and prognosis, and explore its impact on invasion, migration, and apoptosis in KIRC cells. Methods GEPIA (gene expression profiling interactive analysis), UALCAN and LinkedOmics, were employed to analyze PANK1 expression in KIRC tissues and its correlation with clinical characteristics. Comparative analyses were performed between KIRC (Caki-1 and 786-O) and noncancerous renal cells (HK-2 and RPTEC). Transfection with PANK1 activation particles was conducted, followed by Wound healing, Transwell assay, Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) staining, quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and Western blotting. Results PANK1 was down-regulated in KIRC tissues and cells compared to normal tissues and noncancerous cells. Correlation analyses linked PANK1 expression with clinicopathological features in KIRC, with high PANK1 expression associated with a favorable outcome. High PANK1 expression correlated positively with E-cadherin (CDH1), tight junction protein 1 (TJP1), Fas cell surface death receptor (FAS), caspase-8 (CASP8), and CASP9, while showing a negative correlation with vimentin (VIM), snail family transcriptional repressor 1 (SNAIL1), twist family BHLH transcription factor 1 (TWIST1), and TWIST2. PANK1 overexpression increased CDH1, TJP1, FAS, CASP8, and CASP9 while downregulating SNAIL1, VIM, TWIST1, and TWIST2, inhibiting invasion and migration, and promoting apoptosis in KIRC cells. Conclusion PANK1 down-regulation in KIRC tissues correlated with clinicopathological features and prognosis. Its overexpression modulated epithelial-mesenchymal transition (EMT)-related gene, inhibited invasion, promoted apoptosis in KIRC cells, highlighting its role in disease progression and therapeutic potential.

Abstract Cytokine-mediated STAT5 protein activation is vital for lymphocyte development and function. In vitro tyrosine phosphorylation of a C-terminal tyrosine is critical for activation of STAT5A and STAT5B; however, the importance of STAT5 tyrosine phosphorylation in vivo has not been assessed. Here we generate Stat5a and Stat5b tyrosine-to-phenylalanine mutant knockin mice and find they have greatly reduced CD8+ T-cell numbers and profoundly diminished IL-2-induced proliferation of these cells, and this correlates with reduced induction of Myc, pRB, a range of cyclins and CDKs, and a partial G1→S phase-transition block. These mutant CD8+ T cells also exhibit decreased IL-2-mediated activation of pERK and pAKT, which we attribute in part to diminished expression of IL-2Rβ and IL-2Rγ. Our findings thus demonstrate that tyrosine phosphorylation of both STAT5A and STAT5B is essential for maximal IL-2 signaling. Moreover, our transcriptomic and proteomic analyses elucidate the molecular basis of the IL-2-induced proliferation of CD8+ T cells.

Abstract Background Major depressive disorder (MDD) is a highly heterogeneous disease, with differences in clinical manifestations among depression patients based on onset ages and genders. The neural mechanisms underlying these differences remain unclear. In this study, we utilized resting state functional imaging data from a large sample database and adopted the ReHo method to investigate gender differences in local brain function in MDD patients across different onset age groups. Methods The study included 364 MDD patients and 695 healthy participants who were part of the REST-meta-MDD project. Regional homogeneity (ReHo) assessed gender disparities in MDD and healthy individuals within groups delineated by gender and onset age (young group: 18–29 years; middle-aged group: 30–45 years). Results Among the young MDD groups, there were significant gender differences in the right superior frontal gyrus, right inferior frontal gyrus, left superior temporal gyrus, and right superior parietal lobule, with male MDD patients having higher ReHo values compared to females. When compared to healthy males, male MDD patients exhibited elevated ReHo values in the right superior parietal lobule. In the middle-aged groups, a marked ReHo difference was observed in the bilateral cerebellum posterior lobe, with female MDD patients showing higher ReHo values. Conclusions The functional mechanisms of MDD differ between genders and show distinct variations across different onset age groups. These findings underscore the importance of developing personalized interventions that address the unique needs of MDD patients, tailored to their gender and age, and necessitate the development of antidepressant medications targeted at each gender-age subgroup.

Abstract Diabetic macular edema (DME) has emerged as the foremost cause of vision loss in the population with diabetes. Early detection of DME is paramount, yet the prevailing screening, relying on two-dimensional and labor-intensive fundus photography (FP), results in frequent unwarranted referrals and overlooked diagnoses. Self-imaging optical coherence tomography (SI-OCT), offering fully automated, three-dimensional macular imaging, holds the potential to enhance DR screening. We conducted an observational study within a cohort of 1822 participants with diabetes, who received comprehensive assessments, including visual acuity testing, FP, and SI-OCT examinations. We compared the performance of three screening strategies: the conventional FP-based strategy, a combination strategy of FP and SI-OCT, and a simulated combination strategy of FP and manual SD-OCT. Additionally, we undertook a cost-effectiveness analysis utilizing Markov models to evaluate the costs and benefits of the three strategies for referable DR. We found that the FP + SI-OCT strategy demonstrated superior sensitivity (87.69% vs 61.53%) and specificity (98.29% vs 92.47%) in detecting DME when compared to the FP-based strategy. Importantly, the FP + SI-OCT strategy outperformed the FP-based strategy, with an incremental cost-effectiveness ratio (ICER) of $8016 per quality-adjusted life year (QALY), while the FP + SD-OCT strategy was less cost-effective, with an ICER of $45,754/QALY. Our results were robust to extensive sensitivity analyses, with the FP + SI-OCT strategy standing as the dominant choice in 69.36% of simulations conducted at the current willingness-to-pay threshold. In summary, incorporating SI-OCT into FP-based screening offers substantial enhancements in sensitivity, specificity for detecting DME, and most notably, cost-effectiveness for DR screening.

Abstract Porcine Epidemic Diarrhea Virus (PEDV) poses a significant threat to neonatal piglets, particularly due to the limited efficacy of existing vaccines and the scarcity of efficacious therapeutic drugs. Gegen Qinlian Decoction (GQD) has been employed for over two millennia in treating infectious diarrhea. Nonetheless, further scrutiny is required to improve the drug’s efficacy and elucidate its underlying mechanisms of action. In this study, a modified GQD (MGQD) was developed and demonstrated its capacity to inhibit the replication of PEDV. Animal trials indicated that MGQD effectively alleviated pathological damage in immune tissues and modulated T-lymphocyte subsets. The integration of network analysis with UHPLC-MS/MS facilitated the identification of active ingredients within MGQD and elucidated the molecular mechanisms underlying its therapeutic effects against PEDV infections. In vitro studies revealed that MGQD significantly impeded PEDV proliferation in IPEC-J2 cells, promoting cellular growth via virucidal activity, inhibition of viral attachment, and disruption of viral biosynthesis. Furthermore, MGQD treatment led to increased expression levels of IFN-α, IFN-β, and IFN-λ3, while concurrently decreasing the expression of TNF-α, thereby enhancing resistance to PEDV infection in IPEC-J2 cells. In conclusion, our findings suggest that MGQD holds promise as a novel antiviral agent for the treatment of PEDV infections.

Abstract Background FGFR genomic aberrations occur in approximately 5–10% of human cancers. Erdafitinib has previously demonstrated efficacy and safety in FGFR-altered advanced solid tumors, such as gliomas, thoracic, gastrointestinal, gynecological, and other rare cancers. However, its efficacy and safety in Asian patients remain largely unknown. We conducted a multicenter, open-label, single-arm phase IIa study of erdafitinib to evaluate its efficacy in Asian patients with FGFR-altered advanced cholangiocarcinoma, non-small cell lung cancer (NSCLC), and esophageal cancer. Methods Patients with pathologically/cytologically confirmed, advanced, or refractory tumors who met molecular and study eligibility criteria received oral erdafitinib 8 mg once daily with an option for pharmacodynamically guided up-titration to 9 mg on a 28-day cycle, except for four NSCLC patients who received erdafitinib 10 mg (7 days on/7 days off) as they were recruited before the protocol amendment. The primary endpoint was investigator-assessed objective response rate per RECIST v1.1. Secondary endpoints included progression-free survival, duration of response, disease control rate, overall survival, safety, and pharmacokinetics. Results Thirty-five patients (cholangiocarcinoma: 22; NSCLC: 12; esophageal cancer: 1) were enrolled. At data cutoff (November 19, 2021), the objective response rate for patients with cholangiocarcinoma was 40.9% (95% CI, 20.7–63.6); the median progression-free survival was 5.6 months (95% CI, 3.6–12.7) and median overall survival was 40.2 months (95% CI, 12.4–not estimable). No patient with RET/FGFR-altered NSCLC achieved objective response and the disease control rate was 25.0% (95% CI, 5.5–57.2%), with three patients with stable disease. The single patient with esophageal cancer achieved partial response. All patients experienced treatment-emergent adverse events, and grade ≥ 3 treatment-emergent adverse events were reported in 22 (62.9%) patients. Hyperphosphatemia was the most frequently reported treatment-emergent adverse event (all-grade, 85.7%). Conclusions Erdafitinib demonstrated efficacy in a population of Asian patients in selected advanced solid tumors, particularly in those with advanced FGFR-altered cholangiocarcinoma. Treatment was tolerable with no new safety signals. Trial registration This trial is registered with ClinicalTrials.gov (NCT02699606); study registration (first posted): 04/03/2016.

Objective To explore the effects of expressive writing on repetitive negative thinking (RNT) and anxiety and depression in new recruits, and to compare the effectiveness of different writing intervals on the training effects. Methods A total of 262 new recruits of a troop were sampled using cluster sampling and then divided into 3 groups based on their own organizational company. There were 2 groups receiving RNT-focused expressive writing, including 6-week group (n=90), once a week for 6 consecutive weeks, and 6-day group (n=83) once a day for 6 consecutive days, as well as a control group without any intervention (control group, n=89). Perseverative Thinking Questionnaire (PTQ), Self-Rating Depression Scale (SDS), and Self-Rating Anxiety Scale (SAS) were used to survey all participants at following 3 time points: before intervention (T0), at the end of intervention (T1) and 1 month after intervention (T2). Results There were no significant differences in demographic information and psychological indicators among the 3 groups before the intervention. After intervention, the scores of RNT, depression, and anxiety were significantly lower in the 6-week group at T1 and T2 than the baseline levels (T0) (P < 0.01). The 6-day group showed a tendency of increasing and then decreasing in the 3 scores, the scores of RNT and depression were significantly higher at T1 than T0 (P < 0.01), then all 3 scores fell back at T2, and the scores of depression and anxiety at T2 were significantly lower than at T0 (P < 0.01). No significant changes were observed in these psychological indicators in the control group before and after training. Conclusion RNT-focused expressive writing for 6 weeks can reduce RNT and relieve emotions such as depression and anxiety in new recruits, but similar effects are not observed in the 6-day consecutive writing program. So, we recommend a 6-week writing intervention to promote mental health in new recruits.

Abstract Background Surgical penile prosthesis implantation (PPI) procedures have only recently been introduced to mainland China, with the overall number of such procedures having been conducted to date remaining relatively low. Accordingly, relatively little remains known with respect to the annual trends in PPI. Accordingly, this study was developed with the goal of clarifying these trends across different hospitals in mainland China, while also providing a single-center overview of post-PPI patient outcomes. Results To identify males in mainland China who had undergone PPI, a retrospective review of data from January 2019 – October 2023 was conducted. This approach revealed an increase in the total PPI caseload from 120 in 2019 to 413 within the first 10 months of 2023. Over this same interval, the number of surgeons performing PPI rose from 33 to 74. A retrospective review of the 112 patients who had undergone PPI at Shanghai General Hospital from 2019–2023 revealed that these patients had a median age of 39 [27–63] years, and PPI treatment led to a significant increase in median International Index of Erectile Function-5 (IIEF-5) scores from a baseline value of 10.23 ± 1.26 to a post-treatment value of 22.6 ± 2.73. The underlying causes of erectile dysfunction for these patients included vasculogenic factors (58/112; 51.8%), diabetes mellitus (21/112; 18.8%), and injuries to the spinal cord or pelvis (14/112; 12.5%). The overall rates of satisfaction with the PPI reported by patients and their partners were 93.0% and 90.4%, respectively, and the 3-year PPI survival rate for this cohort was 87%. Conclusion These data highlight a rising trend in the number of PPI being performed in China, with these steadily increasing rates since 2019 emphasizing the increasingly high levels of acceptance of this procedure by patients and clinicians as a means of treating erectile dysfunction. However, the expertise is restricted to a small number of surgeons. Even so, it is a safe and efficacious approach to managing severe erectile dysfunction for patients in China, and when performed by experienced surgeons based on standardized protocols, low complication rates can be achieved while providing patients and their sexual partners with high levels of satisfaction.

Abstract Purpose Analyzing the correlation between patients’ basic information, three-dimensional parameters after calcaneal fractures, and the prognosis of calcaneal fractures. Methods A retrospective analysis was conducted on 43 patients with calcaneal fractures who underwent surgical treatment in the Foot and Ankle Surgery, Xi’an Honghui Hospital, from September 2019 to August 2022. Patient demographics including gender and age were collected, as well as the preoperative posterior articular surface collapse area, number of fracture fragments, length, width, height, and volume of the calcaneus obtained from preoperative three-dimensional imaging. Patients were followed up for VAS, AOFAS, and SF-36 scores. Correlation analysis was performed on the obtained data. Results All 43 included patients received complete follow-up, including 40 males and 3 females, with an average follow-up time of 35.37 ± 10.73 months, and an average age of 43.98 ± 12.08 years. All patients’ VAS, AOFAS, and SF-36 scores at the last follow-up showed no correlation with patient age, gender, or the area of posterior articular collapse, number of fracture fragments, length, width, height, or volume of the calcaneus. Conclusions The prognosis of calcaneal fractures is unrelated to three-dimensional factors such as patient age, gender, length, width, height, volume of the calcaneus, area of the posterior joint, and number of fracture fragments.

Abstract High frequencies of stem-like memory T cells in infusion products correlate with superior patient outcomes across multiple T cell therapy trials. Herein, we analyzed a published CRISPR activation screening to identify transcriptional regulators that could be harnessed to augment stem-like behavior in CD8+ T cells. Using IFN-γ production as a proxy for CD8+ T cell terminal differentiation, LMO4 emerged among the top hits inhibiting the development of effectors cells. Consistently, we found that Lmo4 was downregulated upon CD8+ T cell activation but maintained under culture conditions facilitating the formation of stem-like T cells. By employing a synthetic biology approach to ectopically express LMO4 in antitumor CD8+ T cells, we enabled selective expansion and enhanced persistence of transduced cells, while limiting their terminal differentiation and senescence. LMO4 overexpression promoted transcriptional programs regulating stemness, increasing the numbers of stem-like CD8+ memory T cells and enhancing their polyfunctionality and recall capacity. When tested in syngeneic and xenograft tumor models, LMO4 overexpression boosted CD8+ T cell antitumor immunity, resulting in enhanced tumor regression. Rather than directly modulating gene transcription, LMO4 bound to JAK1 and potentiated STAT3 signaling in response to IL-21, inducing the expression of target genes (Tcf7, Socs3, Junb, and Zfp36) crucial for memory responses. CRISPR/Cas9-deletion of Stat3 nullified the enhanced memory signature conferred by LMO4, thereby abrogating the therapeutic benefit of LMO4 overexpression. These results establish LMO4 overexpression as an effective strategy to boost CD8+ T cell stemness, providing a new synthetic biology tool to bolster the efficacy of T cell-based immunotherapies.

As the second largest carbon emitter in China, iron and steel enterprises have great potential for carbon emission reduction.In order to facilitate the supervision and control of carbon emissions by relevant departments, carbon emission prediction research is carried out.Taking a steelmaking plant as the research object, firstly, the carbon dioxide emissions in the steelmaking process were analyzed, and 10 energy substances that caused carbon emissions were determined.The basic energy data of the steelmaking plant from 2001 to 2023 were collected, and the carbon emissions were calculated from the basic energy data according to the carbon emission accounting method.Secondly, based on the long short-term memory network to predict the carbon emissions in the next 7 years, the training error and test error were close to 0.01, and the actual error was 1 323 307.46 tons of carbon dioxide.Then, the Mann-Kendall trend test was used to evaluate the overall carbon emission trend of the steelmaking plant.Finally, some reasonable suggestions were put forward for steelmaking plants in order to actively respond to the goal of low-carbon environmental protection.

A high-resolution meteorological dataset (≤10 km) over the Tibetan Plateau (TP) is the foundation for investigating and predicting the weather and climate over Asia. The TP Subregional Dynamical Downscaling (TPSDD) dataset is a newly developed high-spatial-temporal resolution gridded dataset for land‒air exchange processes and lower atmospheric structure studies over the whole TP region, taking the climate characteristics of each TP subregion into consideration. The dataset spans from 1981 to 2020, covering the TP with a temporal resolution of 2 hr and spatial resolution of 10 km. Meteorological elements of the dataset include near-surface land–air exchange parameters, such as downward/upward longwave/shortwave radiation flux, sensible heat flux, latent heat flux, etc. In addition, the vertical distributions of 3-dimensional wind, temperature, humidity, and pressure from the surface to the lower stratosphere are also included. Independent evaluations were conducted to verify the performance of the TPSDD dataset by comparing TPSDD/reanalysis with surface and vertical observations through the calculation of statistical parameters. The results demonstrate the accuracy and superiority of this dataset against reanalysis data, which provides great potential for future climate change research.

Abstract The kink structure in band dispersion usually refers to a certain electron-boson interaction, which is crucial in understanding the pairing in unconventional superconductors. Here we report the evidence of the observation of a kink structure in Fe-based superconductor CsCa2Fe4As4F2 using angle-resolved photoemission spectroscopy. The kink shows an orbital selective and momentum dependent behavior, which is located at 15 meV below Fermi level along the $$\Gamma -{{\rm{{M}}}}$$ Γ − M direction at the band with d xz orbital character and vanishes when approaching the $$\Gamma -{{\rm{{X}}}}$$ Γ − X direction, correlated with a slight decrease of the superconducting gap. Most importantly, this kink structure disappears when the superconducting gap closes, indicating that the corresponding bosonic mode (~ $$9\pm 1$$ 9 ± 1 meV) is closely related to superconductivity. However, the origin of this mode remains unidentified, since it cannot be related to phonons or the spin resonance mode (~15 meV) observed by inelastic neutron scattering. The behavior of this mode is rather unique and challenges our present understanding of the superconducting paring mechanism of the bilayer FeAs-based superconductors.