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Calligraphy is the treasure of traditional Chinese culture and it is ubiquitous in China. Because of the unique aesthetic characteristics of calligraphy, the difficulty of calligraphy teaching lies in the assessment of calligraphy works. The major problems concerning calligraphy assessment are the low time efficiency of calligraphy assessment and low engagement of students in the assessing process. As an active learning method, peer assessment (PA) has been widely applied to education. This research aims to explore the application of PA to the calligraphy class. With reasonable training, elementary school students can act rationally as an assessing group. On the basis of students' scores, this study further takes the most reasonable scores based on clustering analysis as the final score. Through the comparative analysis of the students' scores and the teachers' scores, it shows that the students' scores of calligraphy writing can obtain results that are close to the teachers' scores. The significance of the study lies in enhancing the time-efficiency of calligraphy assessment and maintaining the learners' high levels of engagement in the assessing process. The results show that the use of PA in the assessment of calligraphy writing is an effective and accurate method of calligraphy assessment, which contributes to students' command of the key points of calligraphy marking and plays an integral role in guiding students' future calligraphy practice.

Abstract Previous reports showed that long non-coding RNA (lncRNA) participates in the development and progression of tumors. Nevertheless, the effect of LINC02139 and its mechanism on gastric cancer (GC) is still unknown. We revealed that LINC02139 is upregulated in GC cell lines and tissues and high LINC02139 expression was correlated with the advancement of GC in patients. Functionally, overexpression of LINC02139 promoted, while knockdown of LINC02139 impaired GC cell proliferation, migration, and invasion in vitro and impeded tumorigenesis in a tumor xenograft model in vivo. Mechanistically, LINC02139 directly bound to XIAP and increased the protein level by maintaining its protein stability through inhibition of the ubiquitination and proteasome-dependent degradation pathway. Importantly, the regulatory function of XIAP in LINC02139-mediated oncogenic effects was demonstrated. Both in vitro and in vivo experiments showed that LINC02139 and XIAP collaboratively modulate GC cell growth and apoptosis. Analysis of clinical GC tissues further confirmed the upregulation of XIAP and the positive association between LINC02139 and XIAP expression. These findings established LINC02139 as a driver of tumorigenesis and highlighted the crucial involvement of the LINC02139-XIAP axis in GC progression, suggesting its potential as a promising therapeutic target for combating GC advancement.

Abstract The prognostic value of prostate-specific antigen (PSA) kinetics in primary high-volume metastatic hormone-sensitive prostate cancer (mHSPC) patients treated with novel hormonal therapy agents is still unclear. Here, we retrospectively reviewed the data of 102 patients with primary high-volume mHSPC who received novel hormonal therapy agents. The median follow-up was 32.25 ± 14.51 months and the median nadir PSA (nPSA) was 0.20 (0.06, 11.71) ng/mL after treatment. The mean time to nPSA was 10.82 ± 7.27 months and 55 patients (53.9%) had a PSA-density (PSA-D) ≤ 0.08 at 3-months. Univariate and multivariate Cox regression analyses showed that the absence of visceral metastases, nPSA ≤ 0.2 and PSA-D ≤ 0.08 were independent prognostic factors for better PFS and OS (all P

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

Artificial intelligence is the unification of philosophy, cognitive science, mathematics, neurophysiology, psychology, computer science, information theory, cybernetics, and uncertainty theory. Therefore, it is feasible and necessary to utilize STEAM (Science, Technology, Engineering, Liberal Arts, and Mathematics) education to learn artificial intelligence courses. Computational thinking skills are of vital importance to high school students. This paper integrates artificial intelligence education with STEAM model with the aim of enhancing students' computational thinking skills. First, we investigate the feasibility of this model and set teaching objectives about artificial intelligence curricula. Second, artificial intelligence curricula with STEAM model is proposed to carry out interdisciplinary artificial intelligence knowledge acquisition. Finally, the effects of this model on students' computational thinking skills, learning motivation, and self-efficacy are evaluated. One hundred thirty-six participants are recruited from a high school in Beijing. The results reveal that the integration of artificial intelligence education with STEAM is able to promote computational thinking skills, learning motivation, and self-efficacy of the students in the experimental group. The main implication of this study is that artificial intelligence education in light of STEAM model can be used as a teaching guide for the combination of artificial intelligence curricula with multi-disciplinary knowledge at the primary and secondary levels.

Abstract Necrotizing fasciitis (NF) is a rare and life-threatening serious infectious disease, characterized by acute onset and rapid progress, leading to extensive necrosis of skin, soft tissue as well as fascia by a variety of aerobic and anaerobic bacteria, localized on external genitalia, scrotum, groin and perianal areas in males. There exist numerous common etiologies for NF, yet NF induced by malignant neoplasms is exceedingly rare. Several studies have reported that NF may be associated with tumor site (rectal/sigmoid colon cancer) and blood supply dysfunction caused by targeted therapy drugs (bevacizumab, aflibercept, ramucirumab). The perforation of colorectal cancer poses a unique risk factor for NF. However, in our two cases, the patient with rectal cancer received CapeOX (oxaliplatin + capecitabine) + bevacizumab + tislelizumab for 3 cycles without perforation but did develop NF. One month after debridement, the patient continued immunotherapy with tislelizumab alone for the fourth cycle and maintained for an additional 3 cycles without any recurrence of NF. Therefore, does the occurrence of NF correlate with the tumor site (rectum) and targeted immunotherapy? Another patient with hepatocellular carcinoma also developed NF after receiving 2 cycles of lenvatinib + sintilimab treatment. The third cycle of sintilimab immunotherapy was administered on the 13th day after operation, which was subsequently maintained for an additional 2 cycles without recurrence of NF. The absence of a direct correlation between hepatocellular carcinoma and rectal tumor location as well as immunotherapy, suggests that NF may be closely linked to targeted therapy.

Abstract Endothelial dysfunction is acknowledged as a marker for subclinical target organ damage (STOD) in hypertension, though its therapeutic potential has not yet been clarified. This study assessed whether early endothelial function improvement (EEFI) reduced STOD in patients with essential hypertension (EH). We conducted a retrospective cohort analysis of 456 EH patients initially free from STOD. Endothelial function was assessed using brachial artery flow-mediated dilation (FMD), with values ≤ 7.1% indicating dysfunction. Patients were initially categorized by endothelial status (dysfunction: n = 180, normal: n = 276), and further divided into improved or unimproved groups based on changes within three months post-enrollment. During a median follow-up of 25 months, 177 patients developed STOD. The incidence of STOD was significantly higher in patients with initial dysfunction compared to those with normal function. Kaplan–Meier analysis indicated that the improved group had a lower cumulative incidence of STOD compared to the unimproved group (p

Crop yield forecasting is an essential component of crop production assessment, impacting people at the global scale down to the level of individual farms. Until now, yield forecasting has predominantly relied on optical data, particularly the maximum value of vegetation indexes. However, this approach only presents a short forecasting window, and it is essential to obtain yield estimates as early as possible in the growing season and then further improve forecasting even after the vegetation index has reached its peak. So far, optical satellite data at high-temporal resolution (1–3 days) has been actively used for real time crop yield monitoring, whereas fewer operational models make a use of synthetic aperture radar (SAR). In this study, we explore whether SAR data can capture distinct aspects of crop dynamics, providing new insights for yield estimation depending on the crop's phenological stage. We assess the efficiency of dual- (Sentinel-1) and quad-polarimetric (UAVSAR, RADARSAT-2) data to explain inter-field crop yield variability for corn, soybean, and rice over a test area in Arkansas, US (258 fields, 2019). We used optical imagery acquired by Planet/Dove-Classic, Sentinel-2, and Landsat 8, to establish a baseline performance of satellite-based indicators to explain yield variability and assess dual- and quad-polarimetric SAR data for crop yield assessment. In terms of polarimetric indexes, the results showed that in general the results for rice were mostly stable and better than the other crops (R2adj ∼ 0.4 on average). The best results were obtained for the Sentinel-1 VHasc with R2adj = 0.47 and RADARSAT-2 phase difference with R2adj = 0.45. The results for corn performed the least with an R2adj 0.4. We also investigated the day of year (DOY) with the maximum correlation between optical and SAR-derived features and the final yields for corn, soybean, and rice. The maximum correlation for optical features occurs over a short time between DOY 155 (June 4) and 185 (July 5) for corn and rice, and DOY 190 (July 9) and DOY 211 (July 30) for soybean, with these results being consistent across various optical-based sensors. On the contrary, the maximum correlation for SAR-derived features varied significantly and was between DOY 120 (April 30) to DOY 225 (August 13). A study of the time series parameters cross-correlation showed that the optical parameters were highly correlated, but the SAR parameters showed strong temporal decorrelation. We conducted a comparison between C-band and L-band to assess their sensitivity at each stage of growth. In this experiment, we determined that for low vegetation, the C band will be more useful at the beginning of the growth cycle, while the L band provides more information in later stages of growth. Using a random forest regression model combining SAR parameters with common difference vegetation index (DVI), we improved the error by 50% in comparison to the error using the (DVI) for corn, soybean, and rice.

Cytokines, which are important to the tumor microenvironment (TME), play critical roles in tumor development, metastasis, and immune responses. Interleukin-17(IL-17) has emerged as a key biomarker in many malignancies; however, its precise involvement in gastric cancer is less fully understood. Elevated levels of IL-17 have been observed in stomach diseases such as Helicobacter pylori infection and autoimmune gastritis, indicating that a sustained Th17 response may precede the development of gastric cancer. While IL-17 is related to inflammatory processes that may lead to cancer, its specific influence on gastric cancer development and therapy needs to be completely understood. Specifically, the release of IL-17A by diverse immune cells has been associated with both tumor development and inhibition in gastric cancer. It may impact tumor development through mechanisms such as boosting cell proliferation, inducing angiogenesis, and enabling immune cell recruitment or, conversely, suppressing tumor growth via the activation of anti-tumor immune responses. The dual role of IL-17 in cancer, along with its various effects depending on the TME and immune cell composition, highlights the complexity of its activity. Current research reveals that although IL-17 might serve as a target for immunotherapy, its therapeutic potential is hindered by its various activities. Some studies have shown that anti-IL-17 drugs may be helpful, especially when paired with immune checkpoint inhibitors, whereas others point to concerns about the validity of IL-17 in gastric cancer therapy. The lack of clinical trials and the heterogeneity of human tumors underscore the necessity for individualized treatment approaches. Further studies are needed to identify the specific mechanisms of IL-17 in gastric cancer and to design targeted therapeutics appropriately.

Quantum cascade lasers (QCLs) in the mid-infrared (MIR) hold significant potential for widespread applications in both military and civilian contexts. However, the utility of present single-chip QCLs is hampered by issues such as low output power and subpar beam quality. This study addresses these limitations by employing spectral beam combining (SBC) based on a diffraction grating, with an aim to enhance both power and beam quality of MIR QCLs. Coaxial power synthesis of three single-chip QCLs (around 4.75 μm) is achieved experimentally, importantly, the beam quality did not decrease after combining, essentially maintaining the same quality as before combining. It is proposed that there are four main factors affecting the combining efficiency, namely operating optical power (or driving current) of the chips, individual differences in QCL chips, diffraction grating, and reflectivity of feedback mirror, and their effects on the combining efficiency are discussed separately. This study confirms that SBC is an effective way to obtain high-power and high-beam quality MIR QCL sources, and lays a research foundation for more beam spectral combining.

Abstract Background The time‐series data of the Normalized Difference Vegetation Index (NDVI) is a crucial indicator for global and regional vegetation monitoring. However, the current assessment of global and regional long‐term vegetation changes is subject to large uncertainties due to the lack of spatiotemporally continuous time‐series data sets. Methods In this study, a long time‐series monthly NDVI data set with a spatial resolution of 250 m from 1982 to 2020 was developed by combining Moderate Resolution Imaging Spectroradiometer (MODIS) and AVHRR (Advanced Very High‐Resolution Radiometer) time‐series NDVI products using the Random Forest (RF) downscaling model. Results Compared to the MODIS NDVI product, the fused product shows RMSE and mean absolute error ranging from 0 to 0.075 and from 0 to 0.05, respectively, with R2 values mostly above 0.7. Conclusions The long time‐series NDVI products generated in this study are reliable in terms of accuracy and have great potential for long‐term dynamic monitoring of terrestrial ecosystems on the Qinghai–Tibet Plateau.

Abstract Tropical Cyclones (TCs) are devastating natural disasters. Analyzing four decades of global TC data, here we find that among all global TC-active basins, the South China Sea (SCS) stands out as particularly difficult ocean for TCs to intensify, despite favorable atmosphere and ocean conditions. Over the SCS, TC intensification rate and its probability for a rapid intensification (intensification by ≥ 15.4 m s−1 day−1) are only 1/2 and 1/3, respectively, of those for the rest of the world ocean. Originating from complex interplays between astronomic tides and the SCS topography, gigantic ocean internal tides interact with TC-generated oceanic near-inertial waves and induce a strong ocean cooling effect, suppressing the TC intensification. Inclusion of this interaction between internal tides and TC in operational weather prediction systems is expected to improve forecast of TC intensity in the SCS and in other regions where strong internal tides are present.

Abstract Background Intravenous thrombolysis (IVT) before endovascular thrombectomy (EVT) is the standard treatment for patients with acute ischemic stroke caused by large vessel occlusion (AIS-LVO). However, the efficacy and safety of IVT before EVT in AIS-LVO patients with atrial fibrillation (AF) remains controversial. Thus, this study aims to assess the benefit of IVT plus EVT and direct EVT alone in AIS-LVO patients with AF. Method Relevant studies that evaluated the outcomes of IVT plus EVT versus direct EVT alone in AIS-LVO patients with AF were systematically searched in PubMed, Embase, and Cochrane Library from inception to August 10, 2023. The outcomes included successful reperfusion (score of 2b to 3 for thrombolysis in cerebral infarction), symptomatic intracerebral hemorrhage (sICH), good clinical outcome (modified Rankin scale score ≤ 2) at 3 months, and 3-month mortality. Result Eight eligible observational studies involving 6998 (3827 in the IVT plus EVT group and 3171 in the direct EVT group) patients with AIS-LVO complicated by AF were included. Compared with direct EVT, IVT plus EVT resulted in better 3-month clinical outcomes (odds ratio [OR] 1.27, 95% confidence interval [CI] 1.05–1.54) and lower 3-month mortality (OR 0.78, 95% CI 0.68–0.88). However, the incidence of sICH (OR 1.26, 95% CI 0.91–1.75) and the rate of successful reperfusion (OR 0.98, 95% CI 0.83–1.17) were not significantly different between treatment modalities. Conclusion IVT plus EVT leads to better functional outcomes and lower mortality in AIS-LVO patients with AF. Withholding IVT plus EVT from patients with AF alone may not be justified.

Abstract In recent years, there has been a rise in human activities in oceanic areas, making the land–atmosphere interactions over islands a major scientific concern on a global scale. Examining the observation data from offshore areas enables a more comprehensive understanding of the turbulent fluxes in offshore atmospheric environments, patterns of momentum, energy and material exchange between the atmosphere and underlying surface in an oceanic boundary layer, and development of a heterogeneous atmospheric boundary layer. The related findings will assist in developing theoretical models and parameterization schemes to simulate the influence of heterogeneous surfaces on land–atmosphere interactions on the South China Sea Islands. Existing studies on the turbulent fluxes over the South China Sea Islands were mainly conducted on the Nansha Islands, whereas studies on the waters of the South China Sea are scarce. In this study, we used 10 Hz high‐frequency turbulence measurements to calculate the latent and sensible heat fluxes over the South China Sea Islands using the eddy correlation method. These findings were then compared with data from the Dunhuang Gobi, Ordos desert, and Xilingol grassland regions in inland China, along with the observed net radiation and surface heat fluxes. The findings indicate that the energy fluxes over the South China Sea in summer exhibit prominent diurnal variations. The magnitude of either latent or soil heat flux is low, and the net radiation is predominantly transformed into sensible heat flux, which warms the atmosphere. Furthermore, the daily variation curves of sensible and latent heat fluxes are influenced by intermittent turbulence on the islands and reefs, resulting in a less smooth pattern compared with soil heat flux. Although the South China Sea Islands have small land areas and are surrounded by the sea, the land–atmosphere interactions over the underlying surface of this region are similar to those over the underlying surface of grasslands in inland China during summer. The daily mean sensible heat flux on the islands is higher than that in an inland area, and the time lag in its response to sunrise is longer than that in inland areas by approximately 1 h. The overall energy balance ratio is approximately 0.75, c which is in line with the average level, but an energy balance residual of approximately 25% still exists. Furthermore, extreme weather conditions, such as typhoons, can disrupt the diurnal variations of sensible and latent heat fluxes, and the cyclical patterns are subsequently restored.

BackgroundMetabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease. Body mass index (BMI) is the most used obesity index but has important limitations. The weight-adjusted waist index (WWI) is a novel obesity metric and accurately reflects body composition. We explored the association of WWI with all-cause and cardiovascular disease (CVD) mortality in MASLD.MethodsAdult participants with MASLD were included from NHANES 1999-2018. WWI was calculated by dividing the waist circumference (WC) by the square root of body weight. MASLD was diagnosed by the presence of hepatic steatosis and at least one cardiometabolic risk factor in the absence of other causes of steatosis. A fatty liver index ≥60 suggested the presence of hepatic steatosis. Mortality data was obtained by prospectively linking to the National Death Index. Multivariate Cox proportional hazards regression analyses were used to explore these associations and multiple adjustment models were constructed including crude, partial, and fully adjusted models.ResultsAfter adjusting for all covariates including BMI, WWI remained positively and linearly associated with all-cause and CVD mortality in MASLD (hazard ratios [HR] 1.247 and 1.218, respectively). Higher WWI was associated with a significantly increased risk of mortality (both p for trend

The incidence of colorectal cancer is relatively high in our country, with the majority of patients being diagnosed at an advanced stage. For individuals with advanced-stage colorectal cancer, conversion or neoadjuvant therapy is frequently necessitated to facilitate surgical intervention and achieve a curative effect. And about 10% to 30% of colon cancer patients are complicated with intestinal obstruction. Surgical intervention remains the primary treatment for managing intestinal obstructions, albeit with a considerable risk of perioperative mortality and an increased likelihood of postoperative complications. PDT, as a neoadjuvant treatment for colon cancer, can shrink the local tumor and relieve obstruction, and is effective in colon cancer combined with obstruction. Robotic surgery has the advantages of high stability and low trauma, and compared with laparoscopic colon cancer surgery, robotic surgery can achieve better results. Fluorescent laparoscopic clarifies the location and size of the tumor lesion, allowing for greater precision when removing colon cancer lesions in robotic surgery. Therefore, in the treatment of colon cancer, PDT can offer an opportunity for surgery after relieving obstruction in patients with obstructive colon cancer. Additionally, when combined with fluorescent laparoscopic robotic colon cancer surgery, it provides a novel treatment approach for patients with obstructive colon cancer. Preoperative photodynamic neoadjuvant therapy combined with robotic colon cancer surgery has not yet been reported. Here, we report a case of colon cancer with obstruction, preoperative TNM stage was T4N1, and the lesion had caused intestinal stenosis. After four sessions of PDT, the patient’s intestinal lumen was unobstructed and the lesion had regressed. After evaluation, fluorescent laparoscopic localization and visualization of lymph nodes combined with robotic colon cancer resection were performed. Postoperative pathology showed that the patient’s tumor regression grade was grade 1. The patient’s tumor was completely resected with good resection effect. No tumor invasion was found on both sides of the resection margin, and the patient did not relapse after surgery.

ABSTRACT: Low hatchability has been a persistent challenge in the goose industry. Establishing standard atlases and comprehending embryonic development patterns are essential to improving the hatching rates of goose eggs. However, comprehensive descriptions of normal atlases, embryonic development, and energy requirements in geese are lacking. In this study, a total of 120 fertile eggs from well-known large Shitou goose were incubated using 12 nesting purebred female geese. During hatching, both the temperature of the eggshells and the weight of eggs were recorded, and daily photographs of the embryos were captured to monitor their development closely. After hatching, counted the number of pores per unit area of eggshells by choosing eggs from without sperm, dead embryos, and normally hatched. Furthermore, 150 Shitou goose eggs were hatched by automatic incubator, with adjustments made based on observed normal developmental stages that incubated by female geese. The eggs were carefully opened to meticulously document embryonic morphology and create a detailed development map. Measurements were taken of the eye diameter, length of the lower beak, tarsometatarsus bone, and embryo length. Subsequently, an analysis was conducted to assess the calcium, phosphorus, crude protein, and crude fat content to study the energy requirements for embryo development. characteristics on the 7th, 15th, 23rd and 28th days of Shitou goose hatching corresponded to the 5th, 10th, 17th and 19th days of chicken egg incubation, respectively. These days were distinguished individually by “visible embryo's eye”, “closure”, “sealing the door”, and “flashing hair”. Besides, the hatch rate of the incubator reached 86.67%, and the cumulative water loss rate increased with embryo age. Notably, normally developing embryos displayed a significantly higher number of pores on the eggshell surface compared to dead embryos (P < 0.05). Additionally, embryonic body length, eyeball diameter, and lower beak length exhibited continuous growth until day 19 of incubation, while tarsometatarsus length increased steadily from days 12 to 31. Liver size measurement began on the 10th day of incubation, while both leg and chest muscles showed continuous growth from the 12th day. For energy demand, the embryo primarily relied on protein sourced from the egg yolk within the first 10 days of development. Afterward, the egg yolk provided both protein and fat for embryonic growth. In summary, this study has generated a comprehensive developmental map for Shitou goose embryos, offering valuable insights into their growth and morphological changes throughout the incubation period. This map can serve as a reference for optimizing machine incubation techniques to enhance goose egg hatching rates and provide fresh perspectives on the development of geese.

Abstract Aim The main focus of this study is to explore the molecular mechanism of IRF7 regulation on RPS18 transcription in M1‐type macrophages in pancreatic adenocarcinoma (PAAD) tissue, as well as the transfer of RPS18 by IRF7 via exosomes to PAAD cells and the regulation of ILF3 expression. Methods By utilising single‐cell RNA sequencing (scRNA‐seq) data and spatial transcriptomics (ST) data from the Gene Expression Omnibus database, we identified distinct cell types with significant expression differences in PAAD tissue. Among these cell types, we identified those closely associated with lipid metabolism. The differentially expressed genes within these cell types were analysed, and target genes relevant to prognosis were identified. Flow cytometry was employed to assess the expression levels of target genes in M1 and M2 macrophages. Cell lines with target gene knockout were constructed using CRISPR/Cas9 editing technology, and cell lines with target gene knockdown and overexpression were established using lentiviral vectors. Additionally, a co‐culture model of exosomes derived from M1 macrophages with PAAD cells was developed. The impact of M1 macrophage‐derived exosomes on the lipid metabolism of PAAD cells in the model was evaluated through metabolomics analysis. The effects of M1 macrophage‐derived exosomes on the viability, proliferation, division, migration and apoptosis of PAAD cells were assessed using MTT assay, flow cytometry, EdU assay, wound healing assay, Transwell assay and TUNEL staining. Furthermore, a mouse PAAD orthotopic implantation model was established, and bioluminescence imaging was utilised to assess the influence of M1 macrophage‐derived exosomes on the intratumoural formation capacity of PAAD cells, as well as measuring tumour weight and volume. The expression of proliferation‐associated proteins in tumour tissues was examined using immunohistochemistry. Results Through combined analysis of scRNA‐seq and ST technologies, we discovered a close association between M1 macrophages in PAAD samples and lipid metabolism signals, as well as a negative correlation between M1 macrophages and cancer cells. The construction of a prognostic risk score model identified RPS18 and IRF7 as two prognostically relevant genes in M1 macrophages, exhibiting negative and positive correlations, respectively. Mechanistically, it was found that IRF7 in M1 macrophages can inhibit the transcription of RPS18, reducing the transfer of RPS18 to PAAD cells via exosomes, consequently affecting the expression of ILF3 in PAAD cells. IRF7/RPS18 in M1 macrophages can also suppress lipid metabolism, cell viability, proliferation, migration, invasion and intratumoural formation capacity of PAAD cells, while promoting cell apoptosis. Conclusion Overexpression of IRF7 in M1 macrophages may inhibit RPS18 transcription, reduce the transfer of RPS18 from M1 macrophage‐derived exosomes to PAAD cells, thereby suppressing ILF3 expression in PAAD cells, inhibiting the lipid metabolism pathway, and curtailing the viability, proliferation, migration, invasion of PAAD cells, as well as enhancing cell apoptosis, ultimately inhibiting tumour formation in PAAD cells in vivo. Targeting IRF7/RPS18 in M1 macrophages could represent a promising immunotherapeutic approach for PAAD in the future.

Summary: Background: The survival rates of patients with nasopharyngeal carcinoma (NPC) have improved significantly, but there is no consensus on whether they can be considered cured. We aimed to determine whether a statistical cure could be achieved for patients with NPC in the contemporary therapeutic landscape. Methods: This retrospective multicenter study enrolled 6315 patients with nonmetastatic NPC from nonendemic and endemic regions of China from 2007 to 2020. We applied mixture and nonmixture cure models to estimate the cure probabilities and cure times by incorporating background mortality for the general population, matching by gender, age, and diagnosed year. Findings: With death as the uncured event, the probability of patients with NPC achieving a life expectancy at par with the general population was 78.1%. Considering progression as the uncured event, the likelihood of patients attaining a life expectancy without progression equivalent to that of the general population was 72.4%. For individuals, the probabilities of achieving cure were conditional and time-dependent, requiring approximately 7.1 and 4.7 years with 95% certainty, respectively. The corresponding cure times for uncured patients were 8.9 and 6.8 years, respectively. The cure probability was correlated with age, Eastern Cooperative Oncology Group score, TNM staging, Epstein–Barr virus DNA copies, and lactate dehydrogenase. The correlation was excellent between 5-year overall survival/progression-free survival and cure fractions. Interpretation: Statistical cure is potentially achievable among patients with NPC undergoing contemporary treatment modalities. The results hold significant potential implications for both clinical practice and patient perspectives. Funding: National High Level Hospital Clinical Research Funding; Beijing Xisike Clinical Oncology Research Foundation; Beijing hope run fund.

Abstract Patients with locally advanced head and neck squamous cell carcinoma (LA‐HNSCC) have poor survival outcomes. The real‐world efficacy of nimotuzumab plus intensity modulated radiotherapy (IMRT)‐based chemoradiotherapy in patients with LA‐HNSCC remains unclear. A total of 25,442 HNSCC patients were screened, and 612 patients were matched by propensity score matching (PSM) (1:1). PSM was utilized to balance known confounding factors. Patients who completed at least five doses of nimotuzumab were identified as study group. The primary end point was 3‐year overall survival (OS) rate. Log‐rank test examined the difference between two survival curves and Cloglog transformation test was performed to compare survival at a fixed time point. The median follow‐up time was 54.2 (95% confidence interval [CI]: 52.7–55.9) months. The study group was associated with improved OS (hazard ratio [HR] = 0.75, 95% CI: 0.57–0.99, p = 0.038) and progression‐free survival (PFS) (HR = 0.74, 95% CI: 0.58–0.96, p = 0.021). Subgroup analysis revealed that aged 50–60 year, IV, N2, radiotherapy dose ≥ 60 Gy, without previous surgery, and neoadjuvant therapy have a trend of survival benefit with nimotuzumab. Nimotuzumab showed favorable safety, only 0.2% had nimotuzumab‐related severe adverse events. Our study indicated the nimotuzumab plus chemoradiotherapy provides survival benefits and safety for LA‐HNSCC patients in an IMRT era.

Sequential working memory (SWM), referring to the temporary storage and manipulation of information in order, plays a fundamental role in brain cognitive functions. The serial position effect refers to the phenomena that recall accuracy of an item is associated to the order of the item being presented. The neural mechanism underpinning the serial position effect remains unclear. The synaptic mechanism of working memory proposes that information is stored as hidden states in the form of facilitated neuronal synapse connections. Here, we build a continuous attractor neural network with synaptic short-term plasticity (STP) to explore the neural mechanism of the serial position effect. Using a delay recall task, our model reproduces the the experimental finding that as the maintenance period extends, the serial position effect transitions from the primacy to the recency effect. Using both numerical simulation and theoretical analysis, we show that the transition moment is determined by the parameters of STP and the interval between presented stimulus items. Our results highlight the pivotal role of STP in processing the order information in SWM.

Thermal action is a crucial process in laser processing. The classical Fourier heat conduction theory, which assumes an infinite speed of heat propagation, is commonly applied to describe steady-state and mild transient thermal processes. However, under the influence of ultra-short pulse lasers, such as those with picosecond and femtosecond durations, the heat propagation speed within the material is finite and deviates from Fourier’s law. This article addresses the unique characteristics of heat conduction in materials subjected to ultra-short pulse laser exposure by integrating Fourier’s law with the Gaussian distribution of the actual pulse laser output power density and the material’s optical absorption properties. It introduces a time variable to establish a time-dependent heat conduction equation. This equation is numerically analyzed using a difference algorithm. Based on this, simulation and experimental studies on the processing of dental hard tissues with a 1064 nm ps laser were conducted. The results show that the experimental processing depths were slightly larger than the simulation results, which may be due to damage to the dental hard tissues and the thermomechanical effects during processing. The results offer a technical reference for adjusting laser parameters in the ultra-short pulse laser processing technique.

Research has indicated that general anesthesia may cause neuroapoptosis and long-term cognitive dysfunction in developing animals, however, the precise mechanisms orchestrating these outcomes remain inadequately elucidated within scholarly discourse. The purpose of this study was to investigate the impact of sevoflurane on the hippocampus of developing rats by analyzing the changes in microRNA and mRNA and their interactions. Rats were exposed to sevoflurane for 4 h on their seventh day after birth, and the hippocampus was collected for analysis of neuroapoptosis by Western blot and immunohistochemistry. High-throughput sequencing was conducted to analyze the variances in miRNA and mRNA expression levels, and the Morris water maze was employed to assess long-term memory in rats exposed to sevoflurane after 8 weeks. The results showed that sevoflurane exposure led to dysregulation of 5 miRNAs and 306 mRNAs in the hippocampus. Bioinformatic analysis revealed that these dysregulated miRNA-mRNA target pairs were associated with pathological neurodevelopment and developmental disorders, such as regulation of axonogenesis, regulation of neuron projection development, regulation of neuron differentiation, transmission of nerve impulse, and neuronal cell body. Further analysis showed that these miRNAs formed potential network interactions with 44 mRNAs, and two important nodes were identified, miR-130b-5p and miR-449c-5p. Overall, this study suggests that the dysregulation of the miRNA-mRNA signaling network induced by sevoflurane may contribute to neurodevelopmental toxicity in the hippocampus of rats and be associated with long-term cognitive dysfunction.

Considering the importance of combustion diagnosis in industrial manufacturing and many fields, efficient, quick, and real-time multidimensional reconstruction is necessary and indispensable. Hence, focusing on the combustion field dynamic and multi-dimensional reconstruction, a modified U-ConvLSTM model was proposed to combine with the TDLAS method to resolve the real-time reconstruction and short prediction. By dividing the combustion field into space and time slices, we used discretized spatiotemporal slices to complete the 2-D distribution reconstruction and then expanded them into higher dimensions. The simulation results demonstrate that our design can effectively reconstruct different 2-D distributions, achieving a reconstruction error of less than 5%. Three-step predictions also performed well, a PSNR no less than 30 dB, and an SSIM no less than 0.75. In general, our multidimensional combustion field reconstruction method, based on the spatiotemporal discretization U-ConvLSTM model, can enhance the accuracy of combustion field reconstruction and provide short-term predictions. This work will contribute to closed-loop control in industrial fields.

Abstract Background ABCC8 variants can cause hyperinsulinemia by activating or deactivating gene expression. This study used targeted exon sequencing to investigate genetic variants of ABCC8 and the associated phenotypic features in Chinese patients with hyperinsulinemic hypoglycemia (HH). Methods We enrolled eight Chinese children with HH and analyzed their clinical characteristics, laboratory results, and genetic variations. Results The age at presentation among the patients ranged from neonates to 0.6 years old, and the age at diagnosis ranged from 1 month to 5 years, with an average of 1.3 ± 0.7 years. Among these patients, three presented with seizures, and five with hypoglycemia. One patient (Patient 7) also had microcephaly. All eight patients exhibited ABCC8 abnormalities, including six missense mutations (c. 2521 C > G, c. 3784G > A, c. 4478G > A, c. 4532T > C, c. 2669T > C, and c. 331G > A), two deletion-insertion mutations (c. 3126_3129delinsTC and c. 3124_3126delins13), and one splicing mutation (c. 1332 + 2T > C). Two of these mutations (c. 3126_3129delinsTC and c. 4532T > C) are novel. Six variations were paternal, two were maternal, and one was de novo. Three patients responded to diazoxide and one patient responded to octreotide treatment. All there patients had diazoxide withdrawal with age. Two patients (patients 3 and 7) were unresponsive to both diazoxide and octreotide and had mental retardation. Conclusions Gene analysis can aid in the classification, treatment, and prognosis of children with HH. In this study, the identification of seven known and two novel variants in the ABCC8 gene further enriched the variation spectrum of the gene.

Flexible humidity sensors (FHSs) with fast response times and durability to high-humidity environments are highly desirable for practical applications. Herein, an FHS based on crosslinked sodium alginate (SA) and MXene was fabricated, which exhibited high sensitivity (impedance varied from 107 to 105 Ω between 10% and 90% RH), good selectivity, prompt response times (response/recover time of 4 s/11 s), high sensing linearity (R2 = 0.992) on a semi-logarithmic scale, relatively small hysteresis (~5% RH), good repeatability, and good resistance to highly humid environments (negligible changes in sensing properties after being placed in 98% RH over 24 h). It is proposed that the formation of the crosslinking structure of SA and the introduction of MXene with good conductivity and a high specific surface area contributed to the high performance of the composite FHS. Moreover, the FHS could promptly differentiate the respiration status, recognize speech, and measure fingertip movement, indicating potential in breath monitoring and non-contact human–machine interactions. This work provides guidance for developing advanced flexible sensors with a wide application scope in wearable electronics.

The 15-15Ti austenitic stainless steel is commonly used as a fast reactor cladding material due to its favorable comprehensive properties. To further enhance its high temperature strength, yttrium (Y) modified 15-15Ti (15-15Ti-Y) steel was developed. In this study, the tensile properties of 15-15Ti-Y were evaluated across the temperature range of 200–700 °C, and the constant load creep properties of 20 % cold worked (CW) 15-15Ti-Y were measured at temperatures of 550–700 °C under various applied stresses. The results indicated that Y addition led to enhanced intragranular precipitates and delayed intergranular precipitates, which resulted in a YS (YS) that was ∼ 100 MPa higher than that of Y-free steel at temperatures ranging from 200 to 600 °C, without compromising the plasticity and ductility. The creep fracture life of 15-15Ti-Y steel ranged from 21 to 5761 h, and the deformation and damage processes were found to adhere to the Norton power-law and Modified Monkman Grant relationship. The stress exponent revealed that the deformation was dislocation creep mechanism, while the creep damage tolerance parameter suggested that the creep fracture was caused by necking. These findings provide data and theoretical support for the application of Y-modified 15-15Ti steel as a fast reactor cladding material in high temperature environments.

Background Interferons (IFNs) are essential for activating an effective immune response and play a central role in immunotherapy-mediated immune cell reactivation for tumor regression. Type III IFN (λ), related to type I IFN (α), plays a crucial role in infections, autoimmunity, and cancer. However, the direct effects of IFN-λ on the tumor immune microenvironment have not been thoroughly investigated.Methods We used mouse MB49 bladder tumor models, constructed a retroviral vector expressing mouse IFN-λ3, and transduced tumor cells to evaluate the antitumor action of IFN-λ3 in immune-proficient tumors and T cell-deficient tumors. Furthermore, human bladder cancer samples (cohort 1, n=15) were used for immunohistochemistry and multiplex immunoflurescence analysis to assess the expression pattern of IFN-λ3 in human bladder cancer and correlate it with immune cells’ infiltration. Immunohistochemistry analysis was performed in neoadjuvant immunotherapy cohort (cohort 2, n=20) to assess the correlation between IFN-λ3 expression and the pathological complete response rate.Results In immune-proficient tumors, ectopic Ifnl3 expression in tumor cells significantly increased the infiltration of cytotoxic CD8+ T cells, Th1 cells, natural killer cells, proinflammatory macrophages, and dendritic cells, but reduced neutrophil infiltration. Transcriptomic analyses revealed significant upregulation of many genes associated with effective immune response, including lymphocyte recruitment, activation, and phagocytosis, consistent with increased antitumor immune infiltrates and tumor inhibition. Furthermore, IFN-λ3 activity sensitized immune-proficient tumors to anti-PD-1/PD-L1 blockade. In T cell-deficient tumors, increased Ly6G–Ly6C+I-A/I-E+ macrophages still enhanced tumor cell phagocytosis in Ifnl3 overexpressing tumors. IFN-λ3 is expressed by tumor and stromal cells in human bladder cancer, and high IFN-λ3 expression was positively associated with effector immune infiltrates and the efficacy of immune checkpoint blockade therapy.Conclusions Our study indicated that IFN-λ3 enables macrophage-mediated phagocytosis and antitumor immune responses and suggests a rationale for using Type III IFN as a predictive biomarker and potential immunotherapeutic candidate for bladder cancer.

Objective: Accurate prognostic predictions and personalized decision-making on induction chemotherapy (IC) for individuals with locally advanced nasopharyngeal carcinoma (LA-NPC) remain challenging. This research examined the predictive function of tumor burden-incorporated machine-learning algorithms for overall survival (OS) and their value in guiding treatment in patients with LA-NPC. Methods: Individuals with LA-NPC were reviewed retrospectively. Tumor burden signature-based OS prediction models were established using a nomogram and two machine-learning methods, the interpretable eXtreme Gradient Boosting (XGBoost) risk prediction model, and DeepHit time-to-event neural network. The models' prediction performances were compared using the concordance index (C-index) and the area under the curve (AUC). The patients were divided into two cohorts based on the risk predictions of the most successful model. The efficacy of IC combined with concurrent chemoradiotherapy was compared to that of chemoradiotherapy alone. Results: The 1 221 eligible individuals, assigned to the training (n = 813) or validation (n = 408) set, showed significant respective differences in the C-indices of the XGBoost, DeepHit, and nomogram models (0.849 and 0.768, 0.811 and 0.767, 0.730 and 0.705). The training and validation sets had larger AUCs in the XGBoost and DeepHit models than the nomogram model in predicting OS (0.881 and 0.760, 0.845 and 0.776, and 0.764 and 0.729, P < 0.001). IC presented survival benefits in the XGBoost-derived high-risk but not low-risk group. Conclusion: This research used machine-learning algorithms to create and verify a comprehensive model integrating tumor burden with clinical variables to predict OS and determine which patients will most likely gain from IC. This model could be valuable for delivering patient counseling and conducting clinical evaluations.

Abstract To assess whether Roberts’ age-adjusted warfarin loading protocol is effective in Chinese patients and whether the SAMeTT2R2 score can predict international normalized ratio (INR) control. Roberts’ protocol for warfarin titration was applied to patients with non-valvular atrial fibrillation (NVAF) complicated with ischemic stroke at the Department of Neurology between 2014 and 2019. Clinical and sociodemographic variables were recorded. A minimum of 1-year follow-up was used to calculate the time in therapeutic range (TTR) of the INR. A total of 94 acute ischemic stroke patients with NVAF were included in the study. Seventy-seven (81.9%) of the patients had attained stable INR (2.0–3.0) at the fifth dose, and 90.0% of the patients had achieved stable INR on the ninth day. Seventeen (18.1%) of the patients had an INR > 4 during dose-adjustment period. Patients with INR > 4 had significantly lower body weight (53.8 vs. 63.1 kg, P = 0.014), lower rate of achievement of stable INR (35.3% vs. 92.2%, P = 0.000), and lower rate of TTR ≥ 65% (23.5% vs. 70.1%, P = 0.001), but with no significant increase in bleeding risk. A total of 89 patients underwent long-term INR follow-up, of which 58 (65.2%) patients achieved TTR ≥ 65%. Patients with poor TTR had significantly lower body weight (56.3 vs. 63.7 kg, P = 0.020) and lower rate of stable INR achievement (64.5% vs. 89.7%, P = 0.002). All 94 patients had SAMeTT2R2 score ≥ 2. There was no linear association between SAMeTT2R2 score and the rate of TTR ≥ 65% (P trend = 0.095). Chinese ischemic stroke patients with NVAF on warfarin can safely and quickly achieve therapeutic INR using Roberts’ age-adjusted protocol and can obtain a good TTR. Lower body weight may be a predictor of poor TTR and INR > 4. Patients who have not attained stable INR after adjusting the dose five times are at high risk for poor TTR. SAMeTT2R2 score may not predict TTR in Chinese ischemic stroke patients with NVAF.

Surface enhanced fluorescence (SEF) based on noble metal nanoparticles is an effective means to achieve high sensitivity in fluorescence detection. Currently, the physical mechanism behind enhanced fluorescence is not fully understood. This paper measures the fluorescence signals of Dihydroporphyrin f methyl ether (CPD4) under both single-photon and two-photon excitation based on submicrometer silver particles with rough morphologies, achieving enhancement factors of 34 and 45 times, respectively. On this basis, by combining the radiative field characteristics produced by the silver particles, a stimulated radiation model of molecules is established to elucidate the changes in the molecular photophysical process when influenced by silver particles. Moreover, the fluorescence lifetime of the molecules was measured, showing that the presence of silver particles induces an increase in the molecular radiative decay rate, causing the fluorescence lifetime to decay from 3.8 ns to 3 ns. The results indicate that the fluorescence enhancement primarily originates from the submicrometer silver particles’ enhancement effect on the excitation light. Additionally, the fluorescence signal emitted by the molecules couples with the silver particles, causing the local surface plasmon resonances generated by the silver particles to also emit light signals of the same frequency. Under the combined effect, the fluorescence of the molecules is significantly enhanced. The findings provide a theoretical foundation for understanding the fluorescence enhancement mechanism of silver particles, adjusting the enhancement effect, and developing enhanced fluorescence detection devices based on submicrometer silver particles, holding significant practical importance.

Due to its excellent electrical performance, mechanical reliability, and thermal stability, electroplated gold is still the most commonly used material for movable beams in RF MEMS switches. This paper investigates the influence of process conditions on the quality and growth rate of gold electroplating, and the optimized process parameters for the gold electroplating process are obtained. The characterization of the optimized electroplated gold layer shows that it has small surface roughness and excellent thermal stability. With this optimized gold electroplating process, the RF MEMS switches are fabricated and hermetic packaged. In order to obtain the temperature environment adaptability of the packaged switch, the influence of working temperature is studied. The temperature effects on mechanical performance (includes pull-in voltage and lifetime) and RF performance (includes insertion loss and isolation) are revealed.

Abstract A full integration of miniaturized transparent energy device (lithium-ion battery), electronic device (thin-film transistor) and sensing device (photodetector) to form a monolithic integrated microsystem greatly enhances the functions of transparent electronics. Here, InGaZnO is explored to prepare the above devices and microsystem due to its multifunctional properties. A transparent lithium-ion battery with InGaZnO as anode (capacity~9.8 μAh cm−2) is proposed as the on-chip power source. Then, thin-film transistor with InGaZnO as channel (mobility~23.3 cm2 V−1 s−1) and photodetector with InGaZnO as photosensitive layer (responsivity~0.35 A W−1) are also prepared on the substrate for constructing an fully integrated transparent microsystem. Each device displays acceptable performance. Moreover, alternating-current signals can be successfully charged into the lithium-ion battery by using the thin-film transistor as the on-chip rectifier and also the photodetector works well by using the charged battery as the on-chip power, demonstrating collaborative capabilities of each device to achieve systematic functions.

Abstract Background Globally, gastric cancer (GC) is one of the world’s most widespread malignancies, with persistent high mortality and morbidity rates. Increasing evidence now suggests that microRNAs (miRNAs) participate in many biological processes, with miR-455-3p having key roles in the progression of diverse cancers. Nevertheless, miR-455-3p function and expression in GC remain unclear. Methods We explored miR-455-3p expression in GC using quantitative polymerase chain reaction (qPCR). To further examine the effect of miR-455-3p in GC, after transfecting miR-455-3p mimics or inhibitors into GC cells, 5-ethynyl-2’-deoxyuridine (EdU) incorporation and colony formation assays were performed to examine cell proliferation. Flow cytometry was used to detect apoptosis, and expression levels of Bax, Bcl-2, Snail, N-cadherin, E-cadherin, and Caspase-3 were assessed by western blotting (WB). Using online databases and luciferase assays, we identified armadillo repeat-containing protein 8 (ARMC8) as a promising target of miR-455-3p. A mouse tumor model was established to investigate actions of miR-455-3p in vivo. Expression levels of C-myc, cyclinD1, and β-catenin were examined using WB and immunofluorescence. Results MiR-455-3p expression was attenuated in GC tissue and cell lines. MiR-455-3p overexpression inhibited GC cell proliferation, epithelial-mesenchymal transition (EMT), as well as facilitated apoptosis, while suppression of miR-455-3p had the opposite effects. From luciferase assays, we confirmed that ARMC8 was a novel and direct downstream target gene of miR-455-3p, and that the tumor suppressive role of miR-455-3p was in part reversed due to ARMC8 overexpression. Moreover, miR-455-3p inhibited GC growth in vivo via ARMC8. We also observed that miR-455-3p repressed canonical Wnt pathway activation by binding to ARMC8. Conclusions MiR-455-3p exerted tumor inhibitory effects in GC by targeting ARMC8. Therefore, intervening in the miR-455-3p/ARMC8/Wnt/βcatenin axis could be a promising novel treatment strategy for GC.