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With the rapid growth of user demand for large language models (LLMs) in their work, the application market is driving intense competition among large language model providers (LLMPs). Users have different preferences and psychological perceptions towards the charging models of different LLMPs. LLMPs with different intelligence levels must design pricing strategies based on diverse user characteristics. To investigate the impact of user heterogeneity on the strategic pricing of competing LLMPs, this paper establishes a competitive model with two providers, comprising a highly intelligent initial LLM provider and a follower provider. Both providers can independently decide to adopt either a subscription model or a pay-per-use model, resulting in four pricing mode combinations (dual subscription SS, subscription-pay-per-use SD, pay-per-use-subscription DS, dual pay-per-use DD). The study shows that when the pay-per-use model is adopted, the user’s psychological perception of the “tick-tock effect” reduces the provider’s service price and profit, as the perceived psychological cost lowers the user’s valuation of the product, thereby decreasing demand. Furthermore, we analyze the equilibrium strategies for pricing mode selection by the two providers. The results indicate that the subscription model is not always advantageous for providers. Both providers will only choose to adopt the subscription model when both user usage frequency and perceived psychological cost are high. Conversely, when both user usage frequency and perceived psychological cost are low, the two providers will not simultaneously adopt the subscription model. Interestingly, as the product intelligence levels of the two providers converge, their choices of pricing modes are also more inclined to diverge. These insights guide LLMPs to strategically adjust their pricing models based on user behavioral patterns to maximize profitability in the competitive AI market.

Background Sterol-regulatory element binding protein 1 (SREBP1), an intracellular cholesterol sensor located in the endoplasmic reticulum, regulates the intracellular cholesterol by the Insig-Srebp-Scap pathway. Over-expression of SREBP1 can cause dyslipidemia. SREBP1 can regulate the metabolic pathway, and then promote the proliferation of tumor cells. However, there is no relevant research of metastasis and invasion in the field of colorectal cancer (CRC). Methods Expression of SREBP1 was manipulated in CRC cell lines with low and high level SREBP1 expression by transfectiong with plasmids containing the SREBP1 gene, or by shRNA. The effect of SREBP1 on cell migration was assayed. The expression of SREBP1, p65 and MMP7 were detected by western blot. Human umbilical vein endothelial cell was used for detection of angiogenesis by adding the culture supernatant from HT29 and SW620. The level of reactive oxygen species (ROS) was detected by Dihydroethidium (DHE) staining. NF-κB inhibitor SN50 was used to test the relationship of SREBP1, NF-κB pathway and MMP7. Results We found that the expression of SREBP1 in colon adenocarcinoma was significantly higher than that in noncancerous tissues, especially in the invasive tumor front including tumor budding. In vitro, SREBP1 over-expressed in colon cancer cell lines HT29 promoted angiogenesis in endothelial cells, increased ROS levels, phosphorylation of NF-κB-p65 and increases MMP7 expression. The effect of SREBP1 on expression of MMP7 was lost following treatment with the NF-κB inhibitor SN50. Conclusion Our results suggest that SREBP1 can promote the invasion and metastasis of CRC cells by means of promoting the expression of MMP7 related to phosphorylation of p65.

This study systematically reviewed 5,465 research articles related to data business and data value from 2010 to 2024. The sample literature was analyzed using Bradford’s Law, Price’s Law, and CiteSpace to identify and extract the core elements influencing the realization of data business value. Based on the sample literature, the multiple value forms of data resources and their inherent logical relationships were deeply explored. It aims to clarify the creation mechanism, circulation mechanism and value-added mechanism in the process of data value transformation centered on data assetization, commercialization and capitalization, and provides an in-depth analysis of the commercial value transformation process from the perspective of technology, market and institutional dimension. The results of the study show that data, as a new resource, presents unique value forms at various stages of development, it corresponds to different value generation mechanisms at different stages of its conversion process. The contribution of the study is two-fold. First, it systematically reviews the research in the field of data commercial value, clarifying the three value forms of data and proposing the three transformation stages of data value. Second, it does not only reflect the multi-dimensional characteristics of value generation in the process of data commercialization but also points out the importance of data asset management. These research results have far-reaching theoretical significance and practical implications for the in-depth understanding of the commercial value of data as well as the promotion of the process of data assetization, data commercialization and data capitalization.

Conventional duodenoscopy is challenging to perform in patients with a surgically altered anatomy (SAA). Short single-balloon enteroscopy (SBE) is an innovative alternative. We investigated the performance of short SBE in patients with SAA and explored risk factors for unsuccessful intubation. Patients who underwent short SBE from October 2019 to October 2023 were retrospectively analyzed. Successful enteroscopic intubation was defined as the endoscope reaching the papilla of Vater, the pancreaticobiliary-enteric anastomosis, or the target site of the afferent limb. In total, 99 short SBE procedures were performed in 64 patients (40 men, 24 women) with a mean age of 61 years (range, 36–86 years). The patients had a history of choledochoduodenostomy ( n  = 1), Billroth II gastrojejunostomy ( n  = 11), pancreaticoduodenectomy ( n  = 17), Roux-en-Y reconstruction with hepaticojejunostomy ( n  = 31), and Roux-en-Y reconstruction with total gastrectomy ( n  = 4). Successful enteroscopic intubation occurred in 32 of 64 (50.0%) patients, and in 57 of 99 (57.6%) procedures. No perforation or severe pancreatitis occurred. Multivariable analysis showed that Roux-en-Y reconstruction was a risk factor for intubation failure (hazard ratio, 4.2; 95% confidence interval, 1.1–15.8; p  = 0.033). Short SBE is efficacious and safe in patients with postsurgical anatomy. Roux-en-Y reconstruction adversely affects the success of short SBE intubation.

Objective Common bile duct (CBD) stones can spontaneously pass through the papilla. This study explored factors associated with stone passage by comparing differences in the clinical features of stones retained in the CBD and excreted stones. Methods Data were retrospectively collected for all patients who were hospitalized in our center between March 2016 and May 2021 with clinical, laboratory, or imaging evidence of CBD stones. All patients underwent endoscopic retrograde cholangiopancreatography (ERCP) and were classified into two groups: group A (stones extracted by ERCP, n = 86) and group B (stones discharged before ERCP, n = 15). Demographic data, biochemical and radiological findings were compared between the groups. Results Stone size (0.82 vs. 0.33 cm), and levels of total bilirubin (58.2 vs. 28.8 μmol/L), gamma-glutamyl transpeptidase (416.7 vs. 193.9 U/L), alkaline phosphatase (191.9 vs. 123.1 U/L), carbohydrate antigen 19-9 (603.7 vs. 37.2 U/mL), and α-L-fucosidase (37.4 vs. 22.6 U/L) were significantly higher in group A than in group B. Logistic regression analyses showed that stone size was the only factor significantly associated with spontaneous passage of CBD stones. Conclusions CBD stones less than 0.33 cm in size may be self-expelled through the papilla.

The salience network plays an important role in detecting stimuli related to behavior and integrating neural processes. The aim of this study was to investigate changes in functional connectivity of the salience network in insomnia patients. Independent component analysis combined with a dual regression approach was used to examine functional connectivity differences in the salience network between patients with insomnia (n = 33) and healthy controls (n = 33). Pearson correlation analysis was used to analyze the relationship between differences in functional connectivity and the clinical characteristics of insomnia patients. Compared to healthy controls, insomnia patients showed increased functional connectivity in the dorsal anterior cingulate cortex within the salience network, as well as greater connectivity between the salience network and other brain regions including the dorsolateral prefrontal cortex, superior frontal gyrus, sensorimotor area and brain stem. The correlation analysis showed that increased functional connectivity between the salience network and left dorsolateral prefrontal cortex was positively correlated with Pittsburgh Sleep Quality Index score. Increased functional connectivity between salience network and several brain regions may be related to hyperarousal in insomnia patients. The connectivity between salience network and dorsolateral prefrontal cortex may potentially be used as a neuroimaging biomarker of sleep quality.

BackgroundAmyotrophic lateral sclerosis (ALS) is a late-onset neurodegenerative disorder. Mitochondrial dysfunction is involved in the complex pathophysiology of ALS; however, the role of mitochondrial DNA (mtDNA) variants in ALS is poorly understood. We aimed to elucidate the role of mtDNA variants in the pathogenesis of ALS.MethodsThe mitochondrial haplogroups of 585 ALS patients and 371 healthy controls were determined; 38 ALS patients and 42 controls underwent long-range polymerase chain reaction combined with next-generation sequencing technology to analyze whole mitochondrial genome variants.ResultsA higher percentage of variants accumulated in ALS patients than in controls. Analysis of coding region variations that were further stratified by mtDNA genes revealed that nonsynonymous variants were more vulnerable in ALS patients than in controls, particularly in the ND4L, ND5, and ATP8 genes. Moreover, pathogenic nonsynonymous variants tended to over-represent in ALS patients. Unsurprisingly, nonsynonymous variants were not related to the phenotype. Haplogroup analysis did not found evidence of association between haplogroups with the risk of ALS, however, patients belonging to haplogroup Y and M7c were prone to develop later onset of ALS.ConclusionsThis is the first study to profile mtDNA variants in ALS patients from mainland China. Our results suggest that an increase in the number of nonsynonymous variants is linked to the pathogenesis of ALS. Moreover, haplogroup Y and M7c may modulate the clinical expression of ALS. Our findings provide independent, albeit limited, evidence for the role of mtDNA in the pathogenesis of ALS.

Identifying the progress of kidney injury may aid the effective treatment and intervention. Herein, we developed a fluorescent biosensor array for instantaneous and accurate identification of the kidney injury progression via “doubled” signals. The multichannel biosensor array consisted of polydopamine-polyethyleneimine (PDA-PEI) and multicolor-labelled different length of DNAs including AAAAA-Cyanine7 (5A-Cy7), AAAAAAAAAA-Texas Red (10A-Texas Red), and AAAAAAAAAAAAAAAAAAAA-VIC (20A-VIC). Facing to the variety of protein in urine with alterable charge accompanied with different progress of kidney injury, the composition of urine replaces the DNA signal molecules, forming their special fluorescence patterns. Taking the size of protein into consideration, the original three variables induced by the protein charge were extended to six variables induced by the two factors of protein particle size and charge difference, which could provide a more accurate strategy to identify the progress of kidney injury. Notably, this strategy not only opened up new perspective for identification the progress of kidney injury via the size and charge of urine protein, but also improved the resolving power of sensor array by increasing the number of sensor elements for extending their potential application to various diseases. Graphical abstract

 To evaluate the efficacy of endoscopic retrograde cholangiography (ERC)-guided biliary drainage as a preliminary method for reducing jaundice in patients with unresectable malignant hilar biliary obstruction (UMHBO), and to identify risk factors associated with sub-optimal jaundice reduction. A cohort of 33 patients with UMHBO, spanning from March 2016 to July 2024, was included in the study. A 30% reduction in total bilirubin (TB) was considered indicative of a favorable jaundice-reducing effect (TB before discharge/TB before ERC).  The rate of good jaundice-reducing effect was 78.8% (26/33) with the use of biliary plastic stents during the initial ERC. Notably, pre-ERC levels of gamma glutamyltranspeptidase (GGT) and alanine aminotransferase (ALT) were lower in the poor effect group compared to the good effect group (260.0 vs. 479.5 U/L, 55.0 vs. 84.5 U/L, respectively, P < 0.05). Carbohydrate antigen 19-9 (CA19-9) was higher in the poor effect group than in the good effect group (7948.6 vs. 542.1 U/ml, P < 0.05). However, binary logistic regression analysis did not reveal that pre-ERC levels of GGT, ALT, and CA19-9 were independent risk factors for poor jaundice reduction.  ERC with the placement of biliary plastic stents as the initial jaundice reducing method was available in UMHBO patients. Independent risk factors that lead to poor jaundice reduction were still elusive.

This study aimed to assess how a high-fat diet impacts the pharmacokinetics and safety characteristics of 8 mg Ondansetron hydrochloride tablets among healthy Chinese individuals. The findings presented here were obtained from a bioequivalence study, in which individuals were randomly assigned to consume Ondansetron hydrochloride tablets either following a meal or subsequent to a high-fat diet containing 978.6 kcal, with 54.6% of the calories derived from fat. The plasma concentrations of Ondansetron were measured through the utilization of high-performance liquid chromatography-mass spectrometry (LC-MS/MS) after collecting blood samples. For the computation of pharmacokinetic parameters, the non-compartmental module from Phoenix WinNonlin Version 8.2 was utilized Additionally, the BE module within WinNonLin was utilized to statistically analyze key pharmacokinetic metrics, including the maximum level of concentration (Cmax), the area beneath the concentration-time curve spanning from zero to the final quantifiable time point (AUC ), and the area beneath the concentration-time curve extending from zero to a theoretical limitless point (AUC ) in plasma. A total of 53 healthy subjects participated in the study and were divided into a fasted cohort and a postprandial cohort. Ondansetron had lower Cmax, AUC , and AUC in plasma when taken with food compared to when taken on an empty stomach, with the 90% confidence interval falling outside the acceptable range of 80.00%-125.00%.The occurrence of treatment-related side effects was comparable in both the fasted and postprandial groups, as was the incidence of adverse drug reactions. The study concluded that the high-fat meal had a notable impact on how Ondansetron is processed in the body. Healthy subjects tolerated all treatments well and safely under both postprandial and fasted conditions. http://www.chinadrugtrials.org.cn/index.html, identifier CTR20213116.