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Abstract Aim The purpose of this study was to interpret real-world clinical data to analyze the surgical safety and survival outcomes of patients with initial unresectable hepatocellular carcinoma (uHCC) after conversion therapy. Methods A retrospective analysis was performed on 2984 hepatocellular carcinoma (HCC) patients hospitalized in Shandong Cancer Hospital Affiliated to Shandong First Medical University from June 1st, 2019 to June 1st, 2023. Clinicopathological features, response to systemic and/or loco-regional treatments, surgical resection rate after conversion therapy, surgical safety, and postoperative recurrence were analyzed. Results A total of 38 patients were successfully converted to obtain surgical resection. 35 patients underwent radical resection. A high objective response rate (ORR) (52.6% under RECIST v1.1 and 78.9% under mRECIST criteria) was observed in patients under conversion therapy, and the disease control rate (DCR) was 100%. Pathologic complete response (pCR) was 42.9%. Treatment-related adverse events (TRAEs) of any grade were observed in 37 patients (97.4%). Safety of conversion or direct surgery continues to improve. The median follow-up time was 19.3 months. The 1-year Disease-free survival (DFS) rate of patients with direct surgery and patients with conversion surgery were 91.4% and 86.8%, respectively. Conclusions With conversion therapy, a small percentage (1.81%) of uHCC patients are likely to be converted to radical resection. Local combined systemic therapy is a relatively safe and effective conversion therapy, and the safety of surgery is gradually improved after successful conversion. Preliminary follow-up data showed satisfactory survival benefits for patients undergoing conversion surgery. Trial registration This was a retrospective study and it did not interfere with treatment decisions.

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

Abstract Microplastics (MPs) can enter the body via plastic products. Given modern plastic exposure, we seek to assess MP exposure in large populations through epidemiological tools. In this quasi-experimental study, every participant filled out a questionnaire, and those who satisfied any of the following requirements were not allowed to continue in the study: Diabetes, ulcerative colitis, Crohn’s disease, infectious diseases. Participants in the exposure and control groups were provided three hot meals in disposable plastic tableware (DPT) (n = 30) or non-DPT (n = 30), respectively. After a month of observation, individuals in the exposure group discontinued the three meals provided in DPT (n = 27) for 1 month as the post-exposure group. Each Participant in the three groups received a questionnaire survey and fecal sample collection. We compared the differences in MP levels between different groups and used the Bland–Altman analysis method to evaluate the consistency of the results obtained by different measurement methods. Statistically significant differences in the total quantity (P (0.80 matching degree) = 0.020; P (0.65 matching degree)

Using the example of the Far Eastern Federal District, the article examines the role of Confucius Institutes, educational institutions that China has established in various countries since 2004 to teach Chinese language and culture. The relevance of the research is linked to the growing criticism of the dual function of these organizations. On the one hand, these Institutes are considered as a soft power instrument capable of creating China’s positive image and increasing its global influence through cultural and educational contacts. On the other hand, there are cases of Confucius Institutes acquiring hard power functions, allowing China to implement its strategic goals in other areas unrelated to education and culture. This has prompted reproaches from partner countries. These moments are especially relevant in the Russian Far East, given its close proximity to China, the considerable length of the Russian-Chinese border, and the critical demographic situation in the Russian Far East. The goal of the research is to identify whether regional factors support the criticism leveled at the Confucius Institutes and, subsequently, to propose measures to mitigate China’s hard power influence in the region. By analyzing the Institutes’ activities in the Russian Far East, the authors reveal three main aspects confirming their hard power functioning. The Confucius Institutes promote China’s ‘peaceful’ expansion; they increase the internationalization of Chinese education and contribute to the development of national culture. The authors conclude that when analyzing the pros and cons of Confucius Institutes, it is important to take into account the economic and political situation in the region where they operate. Otherwise, they risk being accused of serving as a Trojan horse. The article is based on recent Russian and Chinese sources, including academic writings and mass media publications, as well as the authors’ empirical research.

Objective In the process of proliferation and division, normal human cells reach the mortality stage M1 and mortality stage M2, which makes the cells stop division and apoptosis. This irreversible physiological process is also an inherent anti-tumor mechanism. The limited ability of cell proliferation limits its role in basic research, clinical application, bioengineering and other fields. The development of immortalized cell lines with stable, continuous proliferation and normal structure and function has become a hot and difficult point in the research of cell biology.Immortalized cells are important sources for the production of engineered blood cells.This review discusses the molecular research process of immortalization technology which is widely used at present and describes the technology of immortalized cell de-immortalization.

Abstract A single-blind, randomized controlled trial comparing oxycodone and fentanyl for patient-controlled intravenous analgesia (PCIA) after laparoscopic hysteromyomectomy found comparable pain relief between the two groups. The study included 60 participants, with NRS scores for pain at rest and when moving showing no significant differences between oxycodone and fentanyl groups at various time points postoperatively. Self-rating depression scale scores were also similar between the groups at 48 h. However, patients’ satisfaction with PCIA was higher in the oxycodone group, with 73.3% reporting being very satisfied compared to 36.7% in the fentanyl group. Additionally, the oxycodone group had fewer incidences of headaches within 48 h postoperatively compared to the fentanyl group. These findings suggest that oxycodone may offer comparable pain relief, higher patient satisfaction, and fewer headaches for patients undergoing laparoscopic hysteromyomectomy compared to fentanyl, making it a suitable option for postoperative pain management in this population. Clinical trial registration number The study was registered with CHICTR.org, ChiCTR2100051924.

Dissimilar materials of TC4 titanium alloy and 316L stainless steel were joined by means of resistance spot welding with nickel interlayer in different thicknesses. A significant enhancement in terms of nugget morphology quality with less defects was achieved for the welded joints with nickel interlayer compared with that without interlayer. With increasing the nickel interlayer thickness from 50 μm to 300 μm, the effective nugget diameter increased gradually from ∼4.8 mm to ∼5.2 mm, which was lower than that of the interlayer-free welded joint being ∼5.9 mm. A thinner intermetallic compound layer with dual-layered structure features with thickness of ∼11 μm was formed at the nugget/titanium interface in the welded joint with nickel interlayer compared with that of the interlayer-free welded joint, meanwhile an intermetallic compound layer with thickness of ∼3 μm was formed at the nugget/stainless steel interface, which exhibited serrated structure features. The introduction of nickel interlayer in the welded joint could suppress the formation of the brittle Ti–Fe intermetallics such as Fe2Ti, and facilitate the formation of TiNi, Ti2Ni and TiNi3. A more homogeneous current density distribution and a lower peak temperature (1809 °C) during welding were achieved via employing nickel interlayer. With increasing nickel interlayer thickness from 0 μm to 300 μm, the tensile shear load of welded joints experienced an increased tendency first and then decreased, meanwhile the maximum tensile shear load of 3.7 kN was obtained with the interlayer thickness of 200 μm, which was 61% higher than that of the interlayer-free welded joint.

The dissimilar welding between aluminum alloys and ultra-high strength steels (UHSS) can realize the structural lightweighting in the manufacturing of vehicle bodies. However, brittle Al–Fe intermetallic compounds (IMCs) are easily formed during welding, limit the industrial application of Al/steel hybrid structure. In this paper, solid rivet resistance riveting welding (RRW) is adopted to join AA6061-T6 aluminum alloy to CR1180T UHSS. This method employs a solid steel rivet to pierce the aluminum alloy workpiece under a piercing current, then a welding current is conducted to weld the rivet to the steel sheet. The influence of rivet leg height, rivet diameter, taper of rivet leg and volume ratio of rivet cap to rivet leg on the joint performance of RRW Al/steel are investigated. The results show that a rivet with small dimension will make it difficult to form effective piercing and welding, and a rivet with too large dimension will increase the difficulty of piercing and welding. With suitable design of rivet dimensions and selection of piercing and welding parameters, the maximum average tensile-shear force of RRW joint reaches 10.8 kN.

Abstract Deterministic encryption (DET) allows for fast retrieval of encrypted information, but it would cause significant leakage of frequency information of the underlying data, which results in an array of inference attacks. Simply replacing DET with fully randomized encryption is often undesirable in the scenario of an encrypted database since it incurs a large overhead in query and storage. Frequency Smoothing Encryption (FSE) is a practical encryption scheme to protect frequency information. Current FSE constructions still fall short of efficiency and a reasonable security definition. We revisit FSE and propose two security definitions from both theoretical and practical perspectives. Furthermore, we adopt a novel partitioning strategy to construct a new FSE scheme to improve performance. Experimental results show that compared with others, our scheme achieves excellent query performance while attaining security against inference attacks.

Abstract Bio-inspired micro-air-vehicles (MAVs) usually operate in the atmospheric boundary layer at a low Reynolds number and complex wind conditions including large-scale turbulence, strong shear, and gusts. We develop an open jet facility (OJF) to meet the requirements of MAV flight experiments at very low speed and high turbulence intensity. Powered by a stage-driven fan, the OJF is capable of generating wind speeds covering 0.1 – 16.8 m/s, with a velocity ratio of 100:1. The contraction section of the OJF is designed using an adjoint-driven optimization method, resulting in a contraction ratio of 3:1 and a length-to-diameter ratio of 0.75. A modularized design of the jet nozzle can produce laminar or high-turbulence wind conditions. Flow field calibration results demonstrate that the OJF is capable of producing a high-quality baseline flow with steady airspeed as low as 0.1 m/s, uniform region around 80% of the cross-sectional test area, and turbulence intensity around 0.5%. Equipped with an optimized active grid (AG), the OJF can reproduce controllable, fully-developed turbulent wind conditions with the turbulence intensity up to 24%, energy spectrum satisfying the five-thirds power law, and the uniform region close to 70% of the cross-sectional area of the test section. The turbulence intensity, integral length scale, Kolmogorov length scale, and mean energy dissipation rate of the generated flow can be adjusted by varying the area of the triangular through-hole in the wings of the AG.

Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are closely related to the treatment of human diseases. Traditional biological experiments often require time-consuming and labor-intensive in their search for mechanisms of disease. Computational methods are regarded as an effective way to predict unknown lncRNA-miRNA interactions (LMIs). However, most of them complete their tasks by mainly focusing on a single lncRNA-miRNA network without considering the complex mechanism between biomolecular in life activities, which are believed to be useful for improving the accuracy of LMI prediction. To address this, a heterogeneous information network (HIN) learning model with neighborhood-level structural representation, called HINLMI, to precisely identify LMIs. In particular, HINLMI first constructs a HIN by integrating nine interactions of five biomolecules. After that, different representation learning strategies are applied to learn the biological and network representations of lncRNAs and miRNAs in the HIN from different perspectives. Finally, HINLMI incorporates the XGBoost classifier to predict unknown LMIs using final embeddings of lncRNAs and miRNAs. Experimental results show that HINLMI yields a best performance on the real dataset when compared with state-of-the-art computational models. Moreover, several analysis experiments indicate that the simultaneous consideration of biological knowledge and network topology of lncRNAs and miRNAs allows HINLMI to accurately predict LMIs from a more comprehensive perspective. The promising performance of HINLMI also reveals that the utilization of rich heterogeneous information can provide an alternative insight for HINLMI to identify novel interactions between lncRNAs and miRNAs.

AIM: To understand the current situation of parental perspectives, knowledge, and practices concerning myopia prevention and control for both pre- and school-aged children. METHODS: This study was a cross-sectional survey that involved children aged 0 to 15y and their parents. Participants were required to respond to an online questionnaire by scanning a quick response (QR) code. The questionnaire consisted of 25 tick-box questions and was open to response from December 22, 2022, to January 5, 2023. The dioptric traits of the children, the visual status and educational background of the parents, the parental perspectives towards myopia and its risks, and the parents' knowledge and practices related to myopia prevention and control were recorded and measured. The Chi-square test and binomial logistic regression were used for statistics. RESULTS: Totally 350 parents responded to the questionnaire. The prevalence and severity of myopia among the surveyed children exhibited a positive correlation with advancing age (P

Abstract Background The limited regenerative capacity of damaged neurons in adult mammals severely restricts neural repair. Although stem cell transplantation is promising, its clinical application remains challenging. Direct reprogramming, which utilizes cell plasticity to regenerate neurons, is an emerging alternative approach. Methods We utilized primary postnatal cortical astrocytes for reprogramming induced neurons (iNs) through the viral-mediated overexpression of the transcription factors Ngn2 and Pax6 (NP). Fluorescence-activated cell sorting (FACS) was used to enrich successfully transfected cells, followed by single-cell RNA sequencing (scRNA-seq) using the 10 × Genomics platform for comprehensive transcriptomic analysis. Results The scRNA-seq revealed that NP overexpression led to the differentiation of astrocytes into iNs, with percentages of 36% and 39.3% on days 4 and 7 posttransduction, respectively. CytoTRACE predicted the developmental sequence, identifying astrocytes as the reprogramming starting point. Trajectory analysis depicted the dynamic changes in gene expression during the astrocyte-to-iN transition. Conclusions This study elucidates the molecular dynamics underlying astrocyte reprogramming into iNs, revealing key genes and pathways involved in this process. Our research contributes novel insights into the molecular mechanisms of NP-mediated reprogramming, suggesting avenues for optimizing the efficiency of the reprogramming process.

Abstract The retina, an anatomical extension of the brain, forms physiological connections with the visual cortex of the brain. Although retinal structures offer a unique opportunity to assess brain disorders, their relationship to brain structure and function is not well understood. In this study, we conducted a systematic cross-organ genetic architecture analysis of eye-brain connections using retinal and brain imaging endophenotypes. We identified novel phenotypic and genetic links between retinal imaging biomarkers and brain structure and function measures from multimodal magnetic resonance imaging (MRI), with many associations involving the primary visual cortex and visual pathways. Retinal imaging biomarkers shared genetic influences with brain diseases and complex traits in 65 genomic regions, with 18 showing genetic overlap with brain MRI traits. Mendelian randomization suggests bidirectional genetic causal links between retinal structures and neurological and neuropsychiatric disorders, such as Alzheimer’s disease. Overall, our findings reveal the genetic basis for eye-brain connections, suggesting that retinal images can help uncover genetic risk factors for brain disorders and disease-related changes in intracranial structure and function.

Abstract Extremely large magnetoresistance (XMR) is highly applicable in spintronic devices such as magnetic sensors, magnetic memory, and hard drives. Typically, XMR is found in Weyl semimetals characterized by perfect electron–hole symmetry or exceptionally high electric conductivity and mobility. Our study explores this phenomenon in a recently developed graphene moiré system, which demonstrates XMR owing to its topological structure and high-quality crystal formation. We investigate the electronic properties of three-dimensional intertwined twisted graphene spirals (TGS), manipulating the screw dislocation axis to achieve a rotation angle of 7.3°. Notably, at 14 T and 2 K, the magnetoresistance of these structures reaches 1.7 × 107%, accompanied by a metal–insulator transition as the temperature increases. This transition becomes noticeable when the magnetic field exceeds a minimal threshold of approximately 0.1 T. These observations suggest the possible existence of complex, correlated states within the partially filled three-dimensional Landau levels of the 3D TGS system. Our findings open up possibilities for achieving XMR by engineering the topological structure of 2D layered moiré systems.

Abstract Dysfunction of the ubiquitin-proteasome system (UPS) is involved in the pathogenesis of various malignancies including colorectal cancer (CRC). Ubiquitin domain containing 1 (UBTD1), a ubiquitin-like protein, regulates UPS-mediated protein degradation and tumor progression in some cancer types. However, the biological function and mechanism of UBTD1 are far from being well elucidated, and its role in CRC has not been explored yet. In our study, we analyzed CRC patients’ clinical information and UBTD1 expression data, and found that the expression of UBTD1 in cancer tissue was significantly higher than that in adjacent normal tissue. Higher UBTD1 expression was significantly associated with poorer survival and more lymph node metastasis. Overexpression of UBTD1 could facilitate, while knockdown could inhibit CRC cell proliferation and migration, respectively. RNA-seq and proteomics indicated that c-Myc is an important downstream target of UBTD1. Metabolomics showed the products of the glycolysis pathway were significantly increased in UBTD1 overexpression cells. In vitro, we verified UBTD1 upregulating c-Myc protein and promoting CRC cell proliferation and migration via regulating c-Myc. UBTD1 promoted CRC cells’ glycolysis, evidenced by the increased lactate production and glucose uptake following UBTD1 overexpression. Mechanistically, UBTD1 prolonged the half-life of the c-Myc protein by binding to E3 ligase β-transducin repeat-containing protein (β-TrCP), thereby upregulated the expression of glycolysis rate-limiting enzyme hexokinase II (HK2), and enhanced glycolysis and promoted CRC progression. In conclusion, our study revealed that UBTD1 promotes CRC progression by upregulating glycolysis via the β-TrCP/c-Myc/HK2 pathway, suggesting its potential as a prognostic biomarker and therapeutic target in CRC.

Nonlinear photonics has unveiled new avenues for applications in metrology, spectroscopy, and optical communications. Recently, there has been a surge of interest in integrated platforms, attributed to their fundamental benefits, including compatibility with complementary metal-oxide semiconductor (CMOS) processes, reduced power consumption, compactness, and cost-effectiveness. This paper provides a comprehensive review of the key nonlinear effects and material properties utilized in integrated platforms. It discusses the applications and significant achievements in supercontinuum generation, a key nonlinear phenomenon. Additionally, the evolution of chip-based optical frequency combs is reviewed, highlighting recent pivotal works across four main categories. The paper also examines the recent advances in on-chip switching, computing, signal processing, microwave generation, and quantum applications. Finally, it provides perspectives on the development and challenges of nonlinear photonics in integrated platforms, offering insights into future directions for this rapidly evolving field.

Abstract Background Breast cancer patients undergoing chemotherapy via peripherally inserted central catheter often experience serious behavioral and psychological challenges, with uncertainty and cancer-related fatigue being prevalent issues that profoundly impact prognosis. Therefore, this study aimed to investigate the relationship between uncertainty and cancer-related fatigue by employing a chain mediation model to examine the potential mediating roles of psychological resilience and self-care. Methods A cross-sectional study was conducted with 223 breast cancer patients receiving peripherally inserted central catheter chemotherapy at two tertiary affiliated hospitals of China Medical University in Liaoning, China, from February 2021 to December 2022. Participants completed self-reported questionnaires to assess uncertainty, psychological resilience, self-care, and cancer-related fatigue. The collected data were subsequently analyzed using Pearson’s correlation analysis, hierarchical regression analysis, and mediation analysis. Results Uncertainty exhibited a significant positive correlation with cancer-related fatigue (p

Abstract The discovery of novel two-dimensional (2D) multiferroic materials is attractive due to their potential for the realization of information storage and logic devices. Although many approaches have been explored to simultaneously introduce ferromagnetic (FM) and ferroelectric (FE) orders into a 2D material, the resulting systems are often plagued by weak magnetoelectric (ME) coupling or limited room-temperature stability. Here, we present a superlattice strategy to construct non-centrosymmetric AM2X4 multiferroic monolayers, i.e., intercalating transition metal ions (A) into the tetragonal-like vacancies of transition metal dichalcogenide bilayers (MX2). Starting from 960 intercalated AM2X4 compounds, our high-throughput calculations have identified 21 multiferroics with robust magnetic order, large FE polarization, low transition barrier, high FE/FM transition temperature, and strong ME coupling. According to the origin of magnetism, we have classified them into twelve type-a, seven type-b, and two type-c multiferroics, which exhibit different ME coupling behavior. During the switching of polarization, the reversal of skyrmions chirality, the transition of the magnetic ground state from FM to antiferromagnetic, and the changes in spin-polarized electron distribution were observed in type-a, type-b, and type-c 2D multiferroic materials, respectively. These results substantially expand the family of 2D ferroic materials and pave an avenue for designing and implementing nonvolatile logic and memory devices.

Abstract Neural circuits with specific structures and diverse neuronal firing features are the foundation for supporting intelligent tasks in biology and are regarded as the driver for catalyzing next-generation artificial intelligence. Emulating neural circuits in hardware underpins engineering highly efficient neuromorphic chips, however, implementing a firing features-driven functional neural circuit is still an open question. In this work, inspired by avoidance neural circuits of crickets, we construct a spiking feature-driven sensorimotor control neural circuit consisting of three memristive Hodgkin-Huxley neurons. The ascending neurons exhibit mixed tonic spiking and bursting features, which are used for encoding sensing input. Additionally, we innovatively introduce a selective communication scheme in biology to decode mixed firing features using two descending neurons. We proceed to integrate such a neural circuit with a robot for avoidance control and achieve lower latency than conventional platforms. These results provide a foundation for implementing real brain-like systems driven by firing features with memristive neurons and put constructing high-order intelligent machines on the agenda.

Abstract Background Phytophthora sojae, a soil-borne oomycete pathogen, has been a yield limiting factor for more than 60 years on soybean. The resurgence of P. sojae (Phytophthora sojae) is primarily ascribed to the durable oospores found in soil and remnants of the disease. P. sojae is capable of infesting at any growth periods of the soybean, and the succeed infestation of P. sojae is predominantly attributed to long-lived oospores present in soil. Comprehending the molecular mechanisms that drive oospores formation and their significance in infestation is the key for effective management of the disease. However, the existing challenges in isolating and extracting significant quantities of oospores pose limitations in investigating the sexual reproductive stages of P. sojae. Results The study focused on optimizing and refining the culture conditions and extraction process of P. sojae, resulting in establishment of an efficient and the dependable method for extraction. Novel optimized approach was yielded greater quantities of high-purity P. sojae oospores than traditional methods. The novel approach exceeds the traditional approaches with respect to viability, survival ability, germination rates of new oospores and the pathogenicity of oospores in potting experiments. Conclusion The proposed method for extracting P. sojae oospores efficiently yielded a substantial quantity of highly pure, viable, and pathogenic oospores. The enhancements in oospores extraction techniques will promote the research on the sexual reproductive mechanisms of P. sojae and lead to the creation of innovative and effective approaches for managing oomycete diseases.

Abstract Background Mounting evidences shows that the ubiquitin‒proteasome pathway plays a pivotal role in tumor progression. The expression of 26S proteasome non-ATPase regulatory subunit 9 (PSMD9) is correlated with recurrence and radiotherapy resistance in several tumor types. However, the role and mechanism of PSMD9 in hepatocellular carcinoma (HCC) progression remain largely unclear. Methods PSMD9 was identified as a prognosis-related biomarker for HCC based on analysis of clinical characteristics and RNA-seq data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and the JP Project of the International Cancer Genome Consortium (ICGC-LIRI-JP). PSMD9 expression was analyzed in cancer tissues and adjacent noncancerous tissues via immunohistochemistry and Western blotting. Multiple in vivo and in vitro experimental techniques (such as CCK-8, colony formation, EdU, and Transwell assays; flow cytometry; Western blotting; quantitative RT-PCR; Coimmunoprecipitation assay and immunofluorescence confocal imaging) were used to assess the functions of PSMD9 in the pathogenesis of HCC. Results We found that the expression of PSMD9 was upregulated and associated with a poor prognosis in HCC patients. PSMD9 promoted HCC cell proliferation, migration, invasion and metastasis. Knockdown of PSMD9 significantly inhibited HCC cell proliferation by inducing G1/S cell cycle arrest and apoptosis. Mechanistically, we demonstrated that PSMD9 promoted HCC cell proliferation and metastasis via direct interaction with the E3 ubiquitin ligase c-Cbl, suppresses EGFR ubiquitination, influenced EGFR endosomal trafficking and degradation and subsequently activated ERK1/2 and Akt signaling. In addition, we showed that PSMD9 knockdown sensitized HCC cells to the tyrosine kinase inhibitor erlotinib in vitro and in vivo. Conclusions Collectively, our results indicate that PSMD9 drives HCC progression and erlotinib resistance by suppressing c-Cbl mediated EGFR ubiquitination and therefore can be a potential therapeutic target for HCC.

Abstract Gallbladder cancer (GBC) is the most common malignant tumor of the biliary system, with poor response to current treatments. Abnormal alternative splicing has been associated with the development of a variety of tumors. Combining the GEO database and GBC mRNA‐seq analysis, it is found high expression of the splicing factor polypyrimidine region‐ binding protein 3 (PTBP3) in GBC. Multi‐omics analysis revealed that PTBP3 promoted exon skipping of interleukin‐18 (IL‐18), resulting in the expression of ΔIL‐18, an isoform specifically expressed in tumors. That ΔIL‐18 promotes GBC immune escape by down‐regulating FBXO38 transcription levels in CD8+T cells to reduce PD‐1 ubiquitin‐mediated degradation is revealed. Using a HuPBMC mouse model, the role of PTBP3 and ΔIL‐18 in promoting GBC growth is confirmed, and showed that an antisense oligonucleotide that blocked ΔIL‐18 production displayed anti‐tumor activity. Furthermore, that the H3K36me3 promotes exon skipping of IL‐18 by recruiting PTBP3 via MRG15 is demonstrated, thereby coupling the processes of IL‐18 transcription and alternative splicing. Interestingly, it is also found that the H3K36 methyltransferase SETD2 binds to hnRNPL, thereby interfering with PTBP3 binding to IL‐18 pre‐mRNA. Overall, this study provides new insights into how aberrant alternative splicing mechanisms affect immune escape, and provides potential new perspectives for improving GBC immunotherapy.

With the increasing number of electric vehicles (EVs), a large amount of charging load will affect the safety and economic operation of the distribution network (DN). In this paper, an optimization dispatching strategy for integrated electricity and natural gas systems (IEGS) with fast charging stations (FCSs) is proposed to address the impact of fast charging loads. Firstly, the FCS load model is established based on the simulation of vehicle traveling and vehicle charging. Secondly, a natural gas supply model is established, which includes constraints such as the adjustment range, direction, and total number of supply flow adjustments. Then, an optimization dispatching strategy for IEGS based on energy storage and gas storage is proposed. Finally, the effectiveness of the proposed strategy is verified. The simulation results show that when the proposed strategy is applied, the voltage of FCS node will be stabilized within a good range. And the energy purchase cost will be reduced by more than 50%. The proposed method improves the carrying capacity of DN for FCSs.

BackgroundThere are gender differences in hypertension and the effect of gender on the relationship between systemic immune-inflammation index (SII) and mortality in hypertensive patients is unclear.MethodsHypertensive patients (n=7444) from ten cycles of the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018 were enrolled in this study. The maximally selected rank statistics method was employed to identify the optimal cut-off value for the SII. Survey-weighted Cox regression analysis was utilized to explore the links between SII and all-cause and cardiovascular mortality. Kaplan-Meier method and time-dependent receiver operating characteristic curve analysis was conducted to assess the predictive accuracy of SII for mortality.ResultsWhether SII was considered as a numerical variable or as a binary variable (higher- and lower-SII groups), higher SII levels were associated with a higher risk of all-cause and cardiovascular mortality in female hypertensive patients (all P < 0.001), but no such association was observed in the males. The area under the curve of the SII was 0.602, 0.595, and 0.569 for 3-, 5-, and 10-year all-cause mortality, respectively, in females, but was 0.572, 0.548, and 0.554 in males. High SII levels interacted with the poverty income ratio and physical activity to affect mortality in the male population (P for interaction < 0.05), and there was an interaction between race and SII in the female cardiovascular mortality rate (P for interaction < 0.05).ConclusionHigher levels of SII may be closely related to the high risk of all-cause and cardiovascular mortality in hypertensive patients, and the results showed that this relationship is more significant and stable in the female group. High SII interacts with PIR, physical activity, and race to affect the mortality rate in different gender populations.

IntroductionOsteoarthritis (OA) is a prevalent chronic degenerative disease, marked by a complex interplay of mechanical stress, inflammation, and metabolic imbalances. Recent studies have highlighted the potential of spermidine (SPD), a naturally occurring polyamine known for its anti-inflammatory and antioxidant properties, as a promising therapeutic agent for OA. This study delves into the therapeutic efficacy and mechanistic pathways of SPD in mitigating OA symptoms.MethodsForty Sprague-Dawley rats were randomly assigned to four groups, including the CG (sham operation), model (anterior cruciate ligament transection [ACLT], and treatment (ACLT + two different doses of SPD) groups. In vivo, correlations between OA severity and different interventions were assessed by ELISA, X-rays, CT imaging, histological staining, and immunohistochemistry. In vitro, IL-1β was used to trigger chondrocyte inflammation, and SPD’s cytotoxicity was assessed in primary rat chondrocytes. Next, inflammatory markers, extracellular matrix (ECM) proteins, and pathway marker proteins were detected in chondrocytes administered IL-1β alone, SPD, or aryl hydrocarbon receptor (AhR) silencing, by qRT-PCR, Griess reaction, ELISA, Western blot, and immunofluorescence. Morphological alterations and pyroptosis in chondrocytes were examined by transmission electron microscopy (TEM) and flow cytometry.ResultsOur research reveals that SPD exerts significant anti-inflammatory and antipyroptotic effects on IL-1β-treated chondrocytes and in anterior cruciate ligament transection (ACLT) rat models of OA, primarily through interaction with the Aryl hydrocarbon receptor (AhR). Specifically, SPD’s binding to AhR plays a crucial role in modulating the inflammatory response and cellular pyroptosis by inhibiting both the AhR/NF-κB and NLRP3/caspase-1/GSDMD signaling pathways. Furthermore, the knockdown of AhR was found to negate the beneficial effects of SPD, underscoring the centrality of the AhR pathway in SPD’s action mechanism. Additionally, SPD was observed to promote the preservation of cartilage integrity and suppress ECM degradation, further supporting its potential as an effective intervention for OA.DiscussionCollectively, our findings propose SPD as a novel therapeutic approach for OA treatment, targeting the AhR pathway to counteract the disease’s progression and highlighting the need for further clinical evaluation to fully establish its therapeutic utility.

The experiment was conducted on gully slopes with slopes ranging from 80° to 90° to investigate the relationship between erosion rates, spatial and temporal changes in microtopography, and drivers of erosion on gully slopes in different seasons. To precisely characterize the microtopography of slopes where debris slides occur, we used the RIEGL VZ-400 3D laser scanner to scan the observation site and acquire point cloud data on the slope’s microtopography. Using the “data conversion module” of ArcGIS software, the point cloud data were transformed into raster data. Through the “3D analysis,” “hydrological analysis,” and “grid calculator” modules, the basic microgeomorphological indicators were extracted from the gully slope grid data, and the erosion rate and microterrain evolution mechanism of the gully slope in different seasons were also determined. The results revealed the following: (1) in the Pisha sandstone area, erosion was relatively strong in the first quarter, with 65% of the area being eroded. The average erosion rates over the four quarters followed the order of first quarter > fourth quarter > second quarter > third quarter, from fastest to slowest. (2) As the soil on the gully slope thawed, melt water increased soil moisture. This phenomenon sharply increased surface roughness in the first quarter. The correlation coefficients between the erosion rate and temperature in the first and fourth quarters were 0.75 and 0.82, respectively. Temperature mainly affected the erosion rate through surface roughness. The direct path coefficient of this effect was 0.72. (3) In the first and fourth quarters, temperature and wind speed were the main factors influencing the erosion rate; the relationship between surface roughness and other factors was evident, making surface roughness the best topographic factor for assessing slope erosion in the Pisha sandstone area. The results of this study aim to provide theoretical references for understanding the gravity erosion mechanism of gully slopes in the Pisha sandstone area and contribute to the high-quality development of the Yellow River Basin.

Objective: Ischemic stroke (IS) is a significant health concern with high disability and fatality rates despite available treatments. Immune cells and cuproptosis are associated with the onset and progression of IS. Investigating the interaction between cuproptosis-related genes (CURGs) and immune cells in IS can provide a theoretical basis for IS treatment. Methods: We obtained IS datasets from the Gene Expression Omnibus (GEO) and employed machine learning to identify CURGs. The diagnostic efficiency of the CURGs was evaluated using receiver operating characteristic (ROC) curves. KEGG and gene set enrichment analysis (GSEA) were also conducted to identify biologically relevant pathways associated with CURGs in IS patients. Single-cell analysis was used to confirm the expression of 19 CURGs, and pathway activity calculations were performed using the AUCell package. Additionally, a risk prediction model for IS patients was developed, and core modules and hub genes related to IS were identified using weighted gene coexpression network analysis (WGCNA). We classified IS patients using a method of consensus clustering. Results: We established a precise diagnostic model for IS. Enrichment analysis revealed major pathways, including oxidative phosphorylation, the NF-kappa B signaling pathway, the apoptosis pathway, and the Wnt signaling pathway. At the single-cell level, compared to those in non-IS samples, 19 CURGs were primarily overexpressed in the immune cells of IS samples and exhibited high activity in natural killer cell-mediated cytotoxicity, steroid hormone biosynthesis, and oxidative phosphorylation. Two clusters were obtained through consensus clustering. Notably, immune cell types including B cells, plasma cells, and resting NK cells, varied between the two clusters. Furthermore, the red module and hub genes associated with IS were uncovered. The expression patterns of CURGs varied over time. Conclusion: This study developed a precise diagnostic model for IS by identifying CURGs and evaluating their interaction with immune cells. Enrichment analyses revealed key pathways involved in IS, and single-cell analysis confirmed CURG overexpression in immune cells. A risk prediction model and core modules associated with IS were also identified.

Identifying the stability and sensitivity of land ecosystems to climate change is vital for exploring nature-based solutions. However, the underlying mechanisms governing ecosystem stability and sensitivity, especially in regions with overlapping ecological projects, remain unclear. based on Mann-Kendall, stability analysis method, and multiple regression method, this study quantified the stability and sensitivity of gross primary productivity (GPP) to climate variables [temperature, vapor pressure deficit (VPD), soil moisture, and radiation] in China from 1982 to 2019. Our findings revealed the following: (1) GPP demonstrated an increased trend with lower stability in Eastern regions, whereas a decreasing trend with higher stability was observed in Western and Southwest China. Notably, the stability of GPP was highest (74.58%) in areas with five overlapping ecological projects: Grain to Green, Natural Forest Resource Protection Project, Three-River Ecological Conservation and Restoration Project, Return Grazing to Grassland Project, and Three-North Shelter Forestation Project. (2) In regions with minimal or no overlapping ecological projects, temperature and radiation jointly dominated GPP variations. In contrast, water-related factors (VPD and soil moisture) significantly affected GPP in areas with multiple overlapping ecological projects. (3) In the southwestern and northeastern regions, GPP exhibited the highest sensitivity to climate change, whereas, in the eastern coastal areas and Tibet, GPP showed low sensitivity to climate change. In the Loess Plateau, where five ecological projects overlap extensively, carbon sinks primarily demonstrate a monotonic increasing trend, high stability, and low sensitivity to climate change. This study aimed to assess the stability of the land ecosystems and delineate their sensitivity to climate changes, thereby laying the groundwork for understanding ecosystem resilience.

BackgroundThe systemic immune-inflammation index (SII) is a novel inflammatory marker used to assess the immune-inflammatory status of the human body. The systemic immune inflammation has an interplay and mutual relationship with neurological disorders. Serum neurofilament light chain (sNfL) is widely regarded as a potential biomarker for various neurological diseases. The study aimed to examine the association between SII and sNfL.MethodsThis cross-sectional investigation was conducted in a population with complete data on SII and sNfL from the 2013–2014 National Health and Nutrition Examination Survey (NHANES). The SII was calculated by dividing the product of platelet count and neutrophil count by the lymphocyte count. Multivariate linear regression models and smooth curves were used to explore the linear connection between SII and sNfL. Sensitivity analyses, interaction tests, and diabetes subgroup smoothing curve fitting were also performed.ResultsA total of 2,025 participants were included in our present research. SII showed a significant positive association with the natural logarithm-transformed sNfL (ln-sNfL) in crude model [0.17 (0.07, 0.28)], partially adjusted model [0.13 (0.03, 0.22)], and fully adjusted model [0.12 (0.02, 0.22)]. In all participants, the positive association between SII and ln-sNfL served as a linear relationship, as indicated by a smooth curve. Interaction tests showed that age, gender, BMI, hypertension, and diabetes did not have a significant impact on this positive association (p for interaction >0.05). The subgroup analysis of diabetes was conducted using smooth curve fitting. It was found that compared to the group without diabetes and the group in a pre-diabetic state, the effect was more pronounced in the group with diabetes.ConclusionOur findings suggest that there is a positive association between SII and sNfL. Furthermore, in comparison to individuals without diabetes and those in a pre-diabetic state, the positive association between SII and sNfL was more pronounced in individuals with diabetes. Further large-scale prospective studies are needed to confirm the association between SII and sNfL.

BackgroundCancer immunotherapy has made significant progress in recent years, with numerous studies worldwide. Immunotherapy has had a transformative impact on oncology and autoimmune diseases. In the biomedical arena, hydrogels with good properties are widely used in cancer immunotherapy. Our study used bibliometrics to analyze the changing trends in using hydrogels for cancer immunotherapy.MethodsFrom 2013 to 2023, a systematic search was conducted in the Web of Science Core Collection database to identify reviews and articles discussing the applications of hydrogels in cancer immunotherapy. The software CiteSpace was used to visually perform the bibliometric analysis in terms of research trends, countries, institutions, authors, journals, and keywords. Individual authors’ productivity was assessed with the Lotka’s law. The most relevant publication sources were identified by Bradford’s law.ResultsA total of 422 English-language publications related to hydrogels in cancer immunotherapy were collected. The number of annual publications increased rapidly after 2021 and remained constant for the past two years. China published the most articles in this field. The institution with the maximum number of published articles was the Chinese Academy of Sciences in China. Chen. Q was the most prolific author, and Liu. Z was the second most published author. In terms of journal contributions, the journal “Biomaterials” had the highest number of publications (n = 30). Biomaterials, Advanced Functional Materials and Journal of Controlled Release were the most influential journals. Keyword analysis revealed that cancer immunotherapy, drug delivery, immunogenic cell death, tumor microenvironment, injectable hydrogels, and immune checkpoint blockade were the primary research hotspots. In recent 3 years, adoptive T-cell therapy, black phosphorus, cell capture, adaptive cell therapy, tumor microenvironment, photodynamic therapy, and sustained release were the research hotspots in this field. Our study summarizes the objective of hydrogels in cancer immunotherapy in recent years, providing a reference for potential researchers in related field.ConclusionThis bibliometric analysis shows the progress and trend of research on hydrogels in cancer immunotherapy. This study provides a significant avenue for future investigation into current concerns and trends in research within this field.

BackgroundHyperthyroidism is an endocrine disorder with a relatively low global prevalence but significantly higher incidence among females compared to males. The onset age primarily ranges from 30 to 50, although it is not limited to this age group. Challenges in the treatment of hyperthyroidism include individualized treatment plan formulation, management of side effects, and prediction of disease progression, necessitating comprehensive consideration to achieve more effective therapy and management. Mendelian randomization studies can reveal more precise therapeutic targets between blood and urine biomarkers and hyperthyroidism, providing more decadent treatment options for the condition.MethodsThe study will build upon the omics Mendelian randomization (MR) framework by conducting MR analysis using 35 blood and urine biomarkers separately for two distinct databases of hyperthyroidism. Subsequently, the results will undergo meta-analysis and multiple corrections to ensure accuracy and reliability. Finally, positive findings will undergo reverse MR validation to verify causal relationships with hyperthyroidism.ResultsIn the British database, the MR analysis of Total bilirubin levels about hyperthyroidism yielded an odds ratio (OR) of 1.097 (95% CI: 0.951-1.265, P = 0.205). Conversely, in the Thyroid Omics Association database, the MR analysis revealed an OR of 1.283 (95% CI: 1.122-1.467, P = 0.0002) for the same relationship. Meta-analysis of the MR analysis results from both databases, following multiple corrections, resulted in an OR of 1.192 (95% CI: 1.081-1.314, P = 0.015). Additionally, the direction of beta values in the MR analysis results from both databases was consistent.ConclusionThe urine biomarker total bilirubin levels may contribute to an increased risk of hyperthyroidism and accelerate its progression, thus representing a risk factor for the condition.

BackgroundSex is a crucial factor in the development, progression, and treatment of cancer, making it vital to examine cancer incidence trends by sex for effective prevention strategies. ObjectiveThis study aimed to assess the incidence of cancer in China between 2007 and 2021, with a focus on sex-based trends. MethodsA population-based cancer registry comprising 14.14 million individuals was maintained between 2007 and 2021 by the Beijing Municipal Health Big Data and Policy Research Center. The age-standardized rates (ASRs) of cancers were calculated using the Segi population. The average annual percentage of change (AAPC) was evaluated using the joinpoint regression model, while the Bayesian age-period-cohort model was used to predict cancer incidence in the next 10 years. ResultsFrom 2007 to 2021, the study included 651,342 incident patients with cancer, of whom 51.2% (n=333,577) were women. The incidence indicated by the ASR for all cancers combined was 200.8 per 100,000 for women and 184.4 per 100,000 for men. The increase in incidence indicated by AAPC for all malignancies combined significantly increased in women between 2007 and 2021 (AAPC=3.1%; P

Acute liver injury (ALI) is an abnormal liver function caused by oxidative stress, inflammation and other mechanisms.The interaction between intestine and liver plays an important role in ALI, and natural polysaccharides can participate in the regulation of ALI by regulating the composition of intestinal flora. In this study, Ganoderma lucidum polysaccharide was used as the research object, and ICR mice were used to construct an acute liver injury model induced by carbon tetrachloride (CCl4). 16S rRNA sequencing technology was used to analyze the flora structure abundance and detect the changes of intestinal flora. The effective reading of 8 samples was obtained by 16S rRNA sequencing technology, and a total of 1233 samples were obtained. The results of alpha diversity analysis showed that the sequencing depth was sufficient, the abundance of species in the samples was high and the distribution was uniform, and the sequencing data of the samples was reasonable. Nine species with significant differences were screened out by abundence analysis of intestinal flora structure at genus level. Beta diversity analysis showed that species composition was different between the model group and the treatment group. Ganoderma lucidum polysaccharide can maintain the integrity of mucosal barrier by promoting the proliferation of intestinal epithelial cells and anti-oxidative stress injury, thereby improving the intestinal mucosal inflammation of mice, regulating intestinal flora, and effectively alleviating CCl4-induced acute liver injury.

Nylon 54 is a novel, biodegradable polyamide with excellent thermal resistance and water absorption properties. It can be polymerized using bio-based cadaverine and succinic acid as monomers. Traditional separation methods isolate individual monomers from the fermentation broth through acidification or alkalization, resulting in significant amounts of waste salts; however, synchronous separation of dibasic acids and diamines has not been reported. This study investigated an integrated process for the separation and extraction of nylon 54 salts from a co-fermentation broth without acidification or alkalization. We meticulously optimized the operational parameters of the integrated process to achieve maximum separation efficiency. Following microfiltration, ultrafiltration, and decolorization, the bacterial eliminating rate was ≥99.83%, and the protein concentration was ≤40 mg/L. The absorbance of the decolorized solution was ≤0.021 at 430 nm, and the recovery rate of nylon 54 salt reached 97%. Then, the pretreated solution was passed through sequential chromatographic columns, which effectively removed organic acid by-products (such as acetic acid and lactic acid), SO42−, and NH4+ from the fermentation broth, resulting in a cadaverine yield of 98.01% and a succinic acid yield of 89.35%. Finally, by concentrating and crystallizing the eluent, the simulated fermentation broth yielded nylon 54 salt with a purity of 99.16% and a recovery rate of 58%, and the real fermentation broth yielded nylon 54 salt with a purity of 98.10% and a recovery rate of 56.21%. This integrated process offers a sustainable and environmentally friendly pathway for the complete biosynthesis of nylon 54 salt and has the potential to be extended to the preparation of other nylon salts.

The DSQ water tube tiltmeter at Yunnan Yanziyan observation station frequently records high-frequency disturbances in various components, manifested in the form of thickened observation curve pulsation, and the replacement of amplification boxes, coils, lines, data acquisition, etc. failed to eliminate this high-frequency disturbance. After comparing with actual meteorological observation data, it was found that there was a certain degree of synchronization between tidal disturbances and atmospheric pressure fluctuations. After further diagnosis, investigation, and analysis, it had been determined that the cause of high-frequency disturbance was that the bowl cover of the DSQ water tube tiltmeter lacked air pipes, resulting in independent cavities above the liquid levels at both ends of the tiltmeter. The pressure balance at both ends of the liquid level was disrupted, causing high-frequency disturbances. After punching the bowl cover, high-frequency disturbances were eliminated. The process and method of diagnosing and eliminating high-frequency disturbances are of great significance for improving the quality of solid tide observation using the DSQ water tube tiltmeter, and have reference value for improving and managing similar instruments.

Abstract Notable-HCC (NCT05185531) is a phase 1b trial, aiming to evaluate the safety and preliminary effectiveness of neoadjuvant PD-1 blockade plus stereotactic body radiotherapy (SBRT) in early-stage resectable hepatocellular carcinoma (HCC). Twenty patients with HCC of BCLC stage 0-A received 3 $$\times $$ × Gy SBRT and two cycles of tislelizumab, an anti-PD-1 monoclonal antibody before the curative HCC resection. Primary endpoints were the surgery delay, radiographic and pathological tumor response after the neoadjuvant therapy, safety and tolerability. During the neoadjuvant therapy, treatment-related adverse events (TRAEs) of grade 1-2 occurred in all 20 patients (100%), eight patients (40%) had grade 3 TRAEs, no grade 4 to 5 TRAE occurred, and all resolved without corticosteroids treatment. Per mRECIST, the objective response rate was 63.2% (12/19), with 3 complete response; the disease control rate was 100%. Two (10.5%) patients achieved complete pathological response. No surgery delay occurred. The neoadjuvant therapy did not increase the surgical difficulty or the incidence of complications. Secondary endpoints of disease-free survival and overall survival were not mature at the time of the analysis. Our pilot trial shows that neoadjuvant therapy with anti-PD-1 + SBRT is safe and promotes tumor responses in early-stage resectable HCC.

Abstract Firstly, the Canny operator combined with circle fitting is used to position the working surface. Secondly, the median filter and the Laplacian operator are selected for preprocessing. Due to uneven illumination, surface texture, or environmental dust, the extracted scratches exhibit fragmentation, and traditional morphological operations cannot handle scratches well, so an improved Canny operator combined with probabilistic Hough transform is proposed for scratch connection. A bidirectional connection is introduced to optimize the edge detection process of the Canny operator, and a parallel algorithm is introduced to shorten the detection time. Finally, the standard Hough transform needs to traverse the entire parameter space, and the calculation is complicated, and the probability Hough transform is selected. The experimental results show that compared with the traditional Canny algorithm, the precision, recall, and F1‐score of the improved Canny algorithm are increased by 3.2%, 13.2%, and 6.0%, respectively. After adding parallel processing, the average detection time was reduced by 45 ms. Finally, the accuracy of scratches extracted using this algorithm reached 97.96%, the leak rate, and mistake rate of this study are only 3.33% and 2.00%, which provides a more accurate and efficient theoretical support for the research on brake disc scratch detection.

Bessel beams have multiple applications owing to their propagation-invariant properties, including particle trapping, optical coherence tomography, and material processing. However, traditional Bessel-beam shaping techniques require bulky components, which limits the development of miniaturized optical systems for integration with other devices. Here, we report a novel femtosecond laser direct writing strategy for fabricating mesoscale (from submicrometer to subcentimeter) binary optical elements with microscale resolution. This strategy utilizes femtosecond beams with a long focal depth to increase throughput while reducing the constraints on critical sample positioning. As a demonstration, we manufactured and characterized a 2.2 mm diameter binary axicon. The experimentally measured quasi-Bessel beam intensity distribution and the numerical results were remarkably consistent, demonstrating a suitable tradeoff between the overall size, efficiency, and structural fidelity. Furthermore, a compact Bessel lens containing binary axicons was constructed and successfully used for femtosecond laser mask-less ablation of periodic grating-type surface plasmon polariton excitation units. The demonstrated approach shows significant potential for fabricating customizable integrated optical components.

Vaccines have an essential role in preventing infectious diseases and reducing the burden of disease. The differences in vaccine lists and prices, and the National Immunization Program (NIP) and vaccine development between China and the United States (US) in conjunction with epidemiologic data on infectious diseases were systematically compared. The epidemiologic data of infectious diseases in 2019 were extracted from the China National Health Commission and the US Centers for Disease Control and Prevention (CDC). The vaccine list was identified from the China National Medical Products Administration and US Food and Drug Administration databases. Vaccine prices were obtained via the China government procurement platform and the US CDC. The NIP vaccines for China and the US were obtained from the China and US CDCs. Vaccine candidates investigated in 2015-2022 were identified from the China Clinical Trial Registry Platform and the US clinicaltrials.gov database. Differences in the incidence of infectious diseases between China and the US were detected with both countries facing a lack of available vaccines for prevention of many diseases. The number of listed vaccines and preventable diseases in China was 59 and 36, respectively, which was higher than the US (45 and 31, respectively). The median price of NIP vaccines in China was significantly lower than the price in the US (median: $3.8 vs. $20; P

Abstract As immovable stone cultural heritage is kept in the open air, they are more susceptible to damage, and damage detection is very important for the protection and restoration of cultural heritage. This is especially true for gold-overlaid stone cultural heritage, which is usually more complicated than ordinary stone carvings. However, the detection of cultural heritage damages is mainly based on expert visual inspection, which is often subjective, time-consuming, and laborious. This paper uses the Mask R-CNN algorithm to rapidly and accurately detect the gold foil shedding of stone cultural heritage through two-dimensional images. The research data are from the high-precision images of the Dazu Thousand-Hand Bodhisattva Statue (World Heritage, UNESCO) in Chongqing, China. After cleaning and augmentation, 1900 images are input into Mask R-CNN model for training. Finally, the average precision value (AP) for detecting gold foil shedding is found to be 0.967. In order to test the performance of the model, the new images that do not participate in the training period are used, and it is found that the model can still accurately detect the gold foil shedding even if there are interference factors. This is the first attempt to detect the damages of gold-overlaid stone cultural heritage based on a deep learning algorithm, and it has achieved good results.

Abstract With the exponential growth of various data interactions on network systems, network intrusions are also increasing. The emergence of edge computing technology brings a new solution to network security. However, due to the difficulty of processing massive and unbalanced data at the edge, higher accuracy requirements are necessary for deployed detection models. This paper proposes a multi-classification model for network intrusion detection based on reconstruction and feature matching. This model can be deployed on small-scale edge nodes, effectively identifying various attack behaviors through the utilization of reconstruction errors and adaptive scaling. Furthermore, we proposed a model transfer method based on feature matching to enhance the training and detection efficiency of multi-classification models under different data distribution conditions. The proposed model has been evaluated on the CICIDS2017 dataset in terms of accuracy, recall, precision and F1 score. The model demonstrates high accuracy for normal flows in the network, majority class attacks, and minority class attacks, achieving an overall multi-class accuracy of 99.81%, outperforming similar models. Furthermore, this model demonstrates faster convergence and training speed after feature matching, exhibiting better robustness and outstanding performance at the edge.

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb), which threatens human health and safety all over the world. Hundreds of thousands of people die from TB every year. Timely early diagnosis and treatment of patients is the most important measure to control the source of infection and curb the epidemic of tuberculosis. The existing diagnostic methods have the disadvantages of poor sensitivity and long culture time. Competitive endogenous RNAs (ceRNAs) can regulate the expression of corresponding target genes by competing for the same microRNA (miRNA) response elements (MREs) as mRNA. Recent studies have found that circRNA has the advantages of long half-life, good stability and tissue specificity, and can be used as a biomarker for predicting, diagnosing and treating various diseases, and is an ideal candidate for biomarkers in body fluid biopsy. In this study, transcriptome sequencing was performed on whole blood samples to screen out TB-related mirna and mRNA differential expression, and to construct the ceRNA regulatory network. Through the analysis of ceRNA regulatory network, it was found that circRNA could competitively bind has-miR-607 and induce down-regulation of has-miR-607, thereby inhibiting the expression of IFNG. The hsa_circ_0000566, hsa_circ_0001844, hsa_circ_0005408, hsa_circ_0007587, hsa_circ_0086710, IFNG and has-miR-607 couble be used as new diagnostic targets for TB. The results of this study not only provide a new perspective for studying the potential role of ceRNA regulatory network in tuberculosis, but also provide a new target and method for the diagnosis of tuberculosis.

Immunotherapy has transformed the management of hepatocellular carcinoma (HCC), but effectiveness varies among patients. This study aimed to identify biomarkers and HCC subtypes responsive to immunotherapy. Patients were classified into Immunity-High (Immunity-H) and Immunity-Low (Immunity-L) subtypes using ssGSEA scores. Prognostic genes were identified through Cox regression, and immune cell infiltration was quantified with TIMER 2.0. Brother of CDO (BOC) expression, analyzed via immunohistochemistry, correlated with immunotherapy responses. Flow cytometry assessed immune cell infiltration relative to BOC levels, while CCK-8 and transwell assays evaluated BOC overexpression’s effects on cell proliferation and invasiveness. Clinically, immunity-H patients had better survival outcomes. Three hub genes—BOC, V-Set and Transmembrane Domain Containing 1 (VSTM1), and PRDM12—were identified as significantly associated with prognosis. Among these, BOC and VSTM1 demonstrated positive correlations with immune cell infiltration. Elevated expression of BOC was found to be predictive of favorable responses to immunotherapy and was associated with enhanced infiltration of T cells, dendritic cells, and B cells in the tumor microenvironment. Conversely, BOC overexpression in liver cancer cell lines led to decreased cell proliferation and invasiveness. This study underscores the prognostic significance of HCC subtypes defined by immunogenomic profiles and identifies BOC as a potential biomarker for immunotherapy selection and outcome prediction.

Background and objectives In clinical practice, some patients are diagnosed with diabetic nephropathy (DN) combined with acute tubulointerstitial nephritis (ATIN) through renal biopsy. There is relatively little research on the treatment and prognosis of such patients, and no consensus exists on the use of glucocorticoid for treatment. Therefore, our study explores the progression of DN combined with ATIN and the renal outcomes after treatment with glucocorticoid.Methods This study retrospectively analyzed patients diagnosed with DN combined with ATIN through renal biopsy at our center from January 1, 2015, to December 31, 2021. We collected general patient information, laboratory indicators, renal pathology indicators, and the glucocorticoid usage after kidney biopsy. Follow-up data were collected from medical records. Statistical analysis methods included t-tests, non-parametric tests, and chi-square tests. Univariate and multivariate Cox regression analyses were used to evaluate the risk factors for renal endpoint events in patients. Statistical significance was defined as p-values < 0.05.Results In this study, a total of 67 patients were included. The subjects were divided into two groups based on whether they received glucocorticoid treatment: 33 patients in the steroid group and 34 in the non-steroid group. In the steroid group, 19 patients reached the renal endpoint event, which was significantly higher than in the non-steroid group (57.58% vs. 29.41%, p = 0.038). Univariate Cox regression analysis showed that serum creatinine (HR = 1.008, p

Background This study aims to investigate the incidence and prognosis of malignancy in individuals with thrombospondin type-1 domain-containing 7A (THSD7A)-associated membranous nephropathy (MN).Methods First, we performed a systematic literature review of prevalence of malignancy in THSD7A-associated MN. Then, we conducted a retrospective analysis of 454 patients diagnosed with MN through renal biopsy at our hospital between January 2016 and December 2020. We assessed the presence of serum anti-THSD7A antibodies and performed immunohistochemical staining of renal tissue for THSD7A. Subsequently, we followed patients with THSD7A-associated MN for a minimum of 3–5 years, collecting their clinical, pathological characteristics, and prognosis. Additionally, we conducted a literature review on patients with THSD7A-associated MN in conjunction with malignancy.Results We identified a total of nine articles containing comprehensive data on THSD7A-associated MN and malignancy. Among 235 patients with THSD7A-positive MN, 36 individuals had concurrent malignancies, resulting in a malignancy prevalence of 13.3% (95% CI: 8.9–17.7%). In our center, we followed up with 15 patients diagnosed with THSD7A-associated MN and observed three cases of concomitant tumors: two cases of lung adenocarcinoma and one case of small cell lung cancer with multiple metastases. The prevalence of malignancy in our cohort was 20%. Notably, we detected positive THSD7A staining in both renal and lung cancer tissues in one patient with small cell lung cancer.Conclusions Patients with THSD7A-associated MN should undergo vigilant follow-up assessments, with a particular focus on actively seeking potential tumorigenic lesions to prevent misdiagnosis or oversight.

ABSTRACTGut microbiota plays an essential role in nonalcoholic fatty liver disease (NAFLD). However, the contribution of individual bacterial strains and their metabolites to childhood NAFLD pathogenesis remains poorly understood. Herein, the critical bacteria in children with obesity accompanied by NAFLD were identified by microbiome analysis. Bacteria abundant in the NAFLD group were systematically assessed for their lipogenic effects. The underlying mechanisms and microbial-derived metabolites in NAFLD pathogenesis were investigated using multi-omics and LC-MS/MS analysis. The roles of the crucial metabolite in NAFLD were validated in vitro and in vivo as well as in an additional cohort. The results showed that Enterococcus spp. was enriched in children with obesity and NAFLD. The patient-derived Enterococcus faecium B6 (E. faecium B6) significantly contributed to NAFLD symptoms in mice. E. faecium B6 produced a crucial bioactive metabolite, tyramine, which probably activated PPAR-γ, leading to lipid accumulation, inflammation, and fibrosis in the liver. Moreover, these findings were successfully validated in an additional cohort. This pioneering study elucidated the important functions of cultivated E. faecium B6 and its bioactive metabolite (tyramine) in exacerbating NAFLD. These findings advance the comprehensive understanding of NAFLD pathogenesis and provide new insights for the development of microbe/metabolite-based therapeutic strategies.