Allergies to Allergens from Cats and Dogs: A Review and Update on Sources, Pathogenesis, and Strategies.

Inhalation allergies caused by cats and dogs can lead to a range of discomforting symptoms, such as rhinitis and asthma, in humans. With the increasing popularity of and care provided to these companion animals, the allergens they produce pose a growing threat to susceptible patients' health. Allergens from cats and dogs have emerged as significant risk factors for triggering asthma and allergic rhinitis worldwide; however, there remains a lack of systematic measures aimed at assisting individuals in recognizing and preventing allergies caused by these animals. This review provides comprehensive insights into the classification of cat and dog allergens, along with their pathogenic mechanisms. This study also discusses implementation strategies for prevention and control measures, including physical methods, gene-editing technology, and immunological approaches, as well as potential strategies for enhancing allergen immunotherapy combined with immunoinformatics. Finally, it presents future prospects for the prevention and treatment of human allergies caused by cats and dogs. This review will improve knowledge regarding allergies to cats and dogs while providing insights into potential targets for the development of next-generation treatments.

Cyberbullying Victimization and Perpetration in Adolescents: A Longitudinal Moderated Mediation Model.

Although cyberbullying victimization significantly impacts cyberbullying behaviors, research on its longitudinal mechanisms and protective factors remains scarce. A total of 1465 Chinese adolescents (52.2% female) with an average age of 16.14 (SD = 0.40) participated in a three-wave longitudinal study with 3-month intervals. Cyberbullying victimization positively predicted cyberbullying perpetration 6 months later, and this effect was mediated by impairment in personality functioning. Mindfulness buffered the predictive effect of cyberbullying victimization on impairment in personality functioning and mitigated the negative impact of impairment in personality functioning on cyberbullying perpetration. Further findings revealed that the indirect effect of impairment in personality functioning was more pronounced when levels of mindfulness were low, and higher levels of mindfulness could disrupt the mediating pathway of impairment in personality functioning between cyberbullying victimization and perpetration. The findings highlighted the importance of promoting the positive development of adolescents' personality functioning and fostering mindfulness skills to reduce cyberbullying among adolescents.

Simultaneous Degradation of AFB1 and ZEN by CotA Laccase from Bacillus subtilis ZJ-2019-1 in the Mediator-Assisted or Immobilization System.

The global prevalence of aflatoxin B1 (AFB1) and zearalenone (ZEN) contamination in food and feed poses a serious health risk to humans and animals. Recently, enzymatic detoxification has received increasing attention, yet most enzymes are limited to degrading only one type of mycotoxin, and free enzymes often exhibit reduced stability and activity, limiting their practicality in real-world applications. In this study, the laccase CotA gene from ZEN/AFB1-degrading Bacillus subtilis ZJ-2019-1 was cloned and successfully expressed in Escherichia coli BL21, achieving a protein yield of 7.0 mg/g. The recombinant CotA (rCotA) completely degraded AFB1 and ZEN, with optimal activity at 70 °C and pH 7.0. After rCotA treatment, neither AFB1 nor ZEN showed significantly cytotoxicity to mouse macrophage cell lines. Additionally, the AFB1/ZEN degradation efficiency of rCotA was significantly enhanced by five natural redox mediators: acetosyringone, syringaldehyde, vanillin, matrine, and sophoridin. Among them, the acetosyringone-rCotA was the most effective mediator system, which could completely degrade 10 µg of AFB1 and ZEN within 1 h. Furthermore, the chitosan-immobilized rCotA system exhibited higher degradation activity than free rCotA. The immobilized rCotA degraded 27.95% of ZEN and 41.37% of AFB1 in contaminated maize meal within 12 h, and it still maintained more than 40% activity after 12 reuse cycles. These results suggest that media-assisted or immobilized enzyme systems not only boost degradation efficiency but also demonstrate remarkable reusability, offering promising strategies to enhance the degradation efficiency of rCotA for mycotoxin detoxification.

Simultaneous occurrence of thyroblastoma and papillary carcinoma.

Not required for Clinical Vignette.

Unsupervised Degradation Representation Learning for Unpaired Restoration of Images and Point Clouds.

Restoration tasks in low-level vision aim to restore high-quality (HQ) data from their low-quality (LQ) observations. To circumvents the difficulty of acquiring paired data in real scenarios, unpaired approaches that aim to restore HQ data solely on unpaired data are drawing increasing interest. Since restoration tasks are tightly coupled with the degradation model, unknown and highly diverse degradations in real scenarios make learning from unpaired data quite challenging. In this paper, we propose a degradation representation learning scheme to address this challenge. By learning to distinguish various degradations in the representation space, our degradation representations can extract implicit degradation information in an unsupervised manner. Moreover, to handle diverse degradations, we develop degradation-aware (DA) convolutions with flexible adaption to various degradations to fully exploit the degrdation information in the learned representations. Based on our degradation representations and DA convolutions, we introduce a generic framework for unpaired restoration tasks. Based on our framework, we propose UnIRnet and UnPRnet for unpaired image and point cloud restoration tasks, respectively. It is demonstrated that our degradation representation learning scheme can extract discriminative representations to obtain accurate degradation information. Experiments on unpaired image and point cloud restoration tasks show that our UnIRnet and UnPRnet achieve state-of-the-art performance.

Effect of potassium on the agronomic traits and fruit quality of Goji (Lycium barbarum L.).

To investgate the effects of potassium (K) application on the agronomic traits and fruit quality of Lycium barbarum L. (Goji), three levels of K fertilizer, namely LK (25 g/plant), CK (50 g/plant), and HK (75 g/plant), were applied to plants in phytotron for observing and measuring relevant indicators. The investigation involved seven agronomic traits: plant height, plant stem diameter, new branch increment, yield of fresh fruits per plant, dry fruit quantity within 50 g, ratio of different grade fruits, and ratio of longitudinal diameter to transverse diameter of Goji fruits. The results showed that K application level had significant effect on ratio of the longitudinal diameter to the transverse diameter of fresh Goji fruits, and that the influence on other agronomic traits was slight. In the meanwhile, the concentrations of amino acids, betaine, polysaccharides and flavonoids of Goji fruits in different levels of K fertilizer were tested. The K treatment increased the content of glutamic acid, and decreased that of flavonoids (P < 0.05), whereas the content of other amino acids, polysaccharides and betaine were unaffected. A total of 132 flavonoid metabolites was identified. Among them, K treatment up-regulated 36 metabolites and down-regulated 30 metabolites (P < 0.05). The results provided a basis for balanced K supply to regulate the agronomic traits and nutrients of Goji fruits.

Balancing the benefits and risks of China's national salt iodization policy over 30 years using disability-adjusted life years (DALYs): a systematic review and meta-analysis.

Both insufficient and excessive iodine intake can lead to thyroid-related disorders. Although China has made progress in eliminating iodine deficiency over the past few decades, the incidence of thyroid cancer is increasing. Currently, there is a lack of relevant research on the tradeoff between the benefits and risks of salt iodization in China. In this study, we developed a method that combines the total probability algorithm and disease burden to evaluate the appropriate amount of salt iodization. Following the principle of minimizing the comprehensive disease burden and using the metabolic model of human iodine nutrition. Based on the average national iodine level in water, the optimal iodine content in Chinese salt is determined to be 17 mg/kg. However, iodine content in water is not evenly distributed in China. Approximately 3.23% of administrative villages have water iodine concentrations exceeding 80 ug/L, eliminating the need for iodine fortification in salt. Approximately 83.51% of administrative villages need to continue implementing the salt iodization policy, with the optimal iodine content in salt ranging from 15 to 18 mg/kg. In 13.16% of administrative villages, the iodine content in salt is determined based on the local water iodine concentration, ranging from 0 to 15 mg/kg. Our study cracks open a window of insight suggesting that the optimal iodine content for salt is lower than the existing benchmark dictated by the prevailing policy in China. Hence, there is an urgent need to refine and advance the iodine supplementation strategy in salt to pave the way for precision medicine and health-centric iodine supplementation strategies.

Duct ligation/de-ligation model: exploring mechanisms for salivary gland injury and regeneration.

Sialadenitis and sialadenitis-induced sialopathy are typically caused by obstruction of the salivary gland ducts. Atrophy of the salivary glands in experimental animals caused by duct ligation exhibits a histopathology similar to that of salivary gland sialadenitis. Therefore, a variety of duct ligation/de-ligation models have been commonly employed to study salivary gland injury and regeneration. Duct ligation is mainly characterised by apoptosis and activation of different signaling pathways in parenchymal cells, which eventually leads to gland atrophy and progressive dysfunction. By contrast, duct de-ligation can initiate the recovery of gland structure and function by regenerating the secretory tissue. This review summarizes the animal duct ligation/de-ligation models that have been used for the examination of pathological fundamentals in salivary disorders, in order to unravel the pathological changes and underlying mechanisms involved in salivary gland injury and regeneration. These experimental models have contributed to developing effective and curative strategies for gland dysfunction and providing plausible solutions for overcoming salivary disorders.

A novel polymer platform for endoscopic tattooing with high efficacy and safety.

Endoscopic tattooing plays a pivotal role in modern endoscopic localization of gastrointestinal lesions, facilitating further surgical intervention and aiding in the postoperative identification and repositioning of lesions. However, traditional endoscopic tattoo dyes often suffer from drawbacks such as side effects, short tattoo duration, and high overall costs. In this study, we developed polyvinylpyrrolidone (PVP)-modified polypyrrole (PPy) nanoparticles by oxidizing pyrrole in a PVP aqueous solution to create a PPy/PVP nanoparticle solution. This innovation aims to enhance endoscopic tattooing efficiency and mitigate the limitations associated with current tattooing methods. Both in vitro and in vivo evaluations confirmed the biosafety of PPy/PVP nanoparticles. Endoscopic tattooing experiments conducted in a pig model demonstrated the dye's stability within the digestive tract. Similarly, subcutaneous tissue tattooing experiments performed in a mouse model revealed the sustained stability of the PPy/PVP tattoo dye for at least 180 days. With its robust stability, safety, and longevity, PPy/PVP nanoparticles hold promise as novel tattoo dyes for marking intestinal lesion sites. This advancement has the potential to enhance the accuracy of lesion localization and long-term tracking.

Cbl and Cbl-b ubiquitin ligases are essential for intestinal epithelial stem cell maintenance.

Receptor tyrosine kinases (RTKs) control stem cell maintenance vs. differentiation decisions. Casitas B-lineage lymphoma (CBL) family ubiquitin ligases are negative regulators of RTKs, but their stem cell regulatory roles remain unclear. Here, we show that Lgr5+ intestinal stem cell (ISC)-specific inducible Cbl-knockout (KO) on a Cblb null mouse background (iDKO) induced rapid loss of the Lgr5 Hi ISCs with transient expansion of the Lgr5 Lo transit-amplifying population. LacZ-based lineage tracing revealed increased ISC commitment toward enterocyte and goblet cell fate at the expense of Paneth cells. Functionally, Cbl/Cblb iDKO impaired the recovery from radiation-induced intestinal epithelial injury. In vitro, Cbl/Cblb iDKO led to inability to maintain intestinal organoids. Single-cell RNA sequencing in organoids identified Akt-mTOR (mammalian target of rapamycin) pathway hyperactivation upon iDKO, and pharmacological Akt-mTOR axis inhibition rescued the iDKO defects. Our results demonstrate a requirement for Cbl/Cblb in the maintenance of ISCs by fine-tuning the Akt-mTOR axis to balance stem cell maintenance vs. commitment to differentiation.

Modified Dautrey's Procedure for Recurrent Temporomandibular Joint Dislocation.

This study introduced and analyzed the clinical effects of a modified Dautrey's procedure, involving down-fracture of the zygomatic arch and articular tubercle augmentation, for the treatment of recurrent TMJ dislocation. Recurrent TMJ dislocation patients were treated using the modified Dautrey's procedure. The recurrence of joint dislocation, maximal mouth opening (MMO), and pain were evaluated postoperatively. A total of 7 patients were treated using the modified procedure, with no instances of facial nerve injury. No recurrences occurred during the follow-up period of 0.5 to 5 years. The average MMO was 35.4 mm and 35.7 mm before the operation and during follow-up, respectively. The modified Dautrey's procedure was effective and particularly suitable for elderly patients with abnormal muscle control, resulting in low recurrence.

Occurrence, distribution characteristics and exposure assessment of perchlorate in the environment in China.

Recognizing the extent of perchlorate pollution in the environment is critical to preventing and mitigating potential perchlorate harm to human health. The presence and distribution of perchlorate in Chinese environmental matrixes (water, atmosphere, and soil) were systematically investigated and comprehensively analyzed, and cumulative perchlorate exposure at the regional level was assessed using a combined aggregate exposure pathway method. The results showed that perchlorate is ubiquitous in the environment of China with significant regional differences. The total perchlorate exposure levels in each region of China ranked as South China > Southwest China > East China > North China > Northeast China > Northwest China. Although the average exposure dose of 0.588 (95 %CI: 0.142 -1.914) µg/kg bw/day being lower than the reference dose of 0.70 µg/kg bw/day, it was observed that the intake of perchlorate in some regions exceed this reference dose. Oral ingestion was the primary route of perchlorate exposure (89.97-96.57 % of the total intake), followed by dermal contact (3.21-9.16 %) and respiratory inhalation. Food and drinking water were the main sources of total perchlorate intake, contributing 52.54 % and 31.12 % respectively, with the latter contributing significantly more in southern China than in northern China. In addition, perchlorate exposure from dust sources was also noteworthy, as its contribution was as high as 23.18 % in some regions. These findings will improve understanding of the perchlorate risk and serve as a critical reference for policymakers in crafting improved environmental management and risk mitigation strategies in China and other nations.

Highly Efficient and Unsupervised Framework for Moving Object Detection in Satellite Videos.

Moving object detection in satellite videos (SVMOD) is a challenging task due to the extremely dim and small target characteristics. Current learning-based methods extract spatio-temporal information from multi-frame dense representation with labor-intensive manual labels to tackle SVMOD, which needs high annotation costs and contains tremendous computational redundancy due to the severe imbalance between foreground and background regions. In this paper, we propose a highly efficient unsupervised framework for SVMOD. Specifically, we propose a generic unsupervised framework for SVMOD, in which pseudo labels generated by a traditional method can evolve with the training process to promote detection performance. Furthermore, we propose a highly efficient and effective sparse convolutional anchor-free detection network by sampling the dense multi-frame image form into a sparse spatio-temporal point cloud representation and skipping the redundant computation on background regions. Coping these two designs, we can achieve both high efficiency (label and computation efficiency) and effectiveness. Extensive experiments demonstrate that our method can not only process 98.8 frames per second on 1024 ×1024 images but also achieve state-of-the-art performance.

A Metric of Societal Burden Based on Virus Succession to Determine Economic Losses and Health Benefits of China's Lockdown Policies: Model Development and Validation.

BACKGROUND: The COVID-19 pandemic had a profound impact on the global health system and economic structure. Although the implementation of lockdown measures achieved notable success in curbing the spread of the pandemic, it concurrently incurred substantial socioeconomic costs. OBJECTIVE: The objective of this study was to delineate an equilibrium between the economic losses and health benefits of lockdown measures, with the aim of identifying the optimal boundary conditions for implementing these measures at various pandemic phases. METHODS: This study used a model to estimate the half-lives of the observed case fatality rates of different strains. It was based on global infection and death data collected by the World Health Organization and strain sequence time series data provided by Nextstrain. The connection between the health benefits and economic losses brought by lockdown measures was established through the calculation of disability-adjusted life years. Taking China's city lockdowns as an example, this study determined the cost-benefit boundary of various lockdown measures during the evolution of COVID-19. RESULTS: The study reveals a direct proportionality between economic losses due to lockdowns and the observed case fatality rates of virus strains, a relationship that holds true irrespective of population size or per capita economic output. As SARS-CoV-2 strains evolve and population immunity shifts, there has been a notable decrease in the observed case fatality rate over time, exhibiting a half-life of roughly 8 months. This decline in fatality rates may offset the health benefits of maintaining unchanged lockdown measures, given that the resultant economic losses might exceed the health benefits. CONCLUSIONS: The initial enforcement of lockdown in Wuhan led to significant health benefits. However, with the decline in the observed case fatality rate of the virus strains, the economic losses increasingly outweighed the health benefits. Consequently, it is essential to consistently refine and enhance lockdown strategies in accordance with the evolving fatality and infection rates of different virus strains, thereby optimizing outcomes in anticipation of future pandemics.

Outcomes of endoscopic submucosal dissection versus esophagectomy for poorly differentiated superficial esophageal squamous cell carcinoma: A 10-year cohort study.

BACKGROUNDS: The efficacy of endoscopic submucosal dissection (ESD) to treat poorly differentiated superficial esophageal squamous cell carcinoma (SESCC) is unclear. AIMS: To exploring the efficacy and prognosis of ESD treatment poorly differentiated SESCC compared with esophagectomy. METHODS: A retrospective cohort study was conducted, the data of poorly differentiated SESCC patients who received ESD or esophagectomy from Jan 2011 to Jan 2021 were analyzed. Overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), and procedure-related variables were compared between ESD and esophagectomy group. RESULTS: 95 patients underwent ESD, while 86 underwent esophagectomy. No significant differences were found between the two groups in OS (P = 0.587), DSS (P = 0.172), and RFS (P = 0.111). Oncologic outcomes were also similar between the two groups in propensity score-matched analysis. For T1a ESCC, the rates of R0 resection, LVI or nodal metastasis and additional therapy were similar between ESD and esophagectomy groups. But for T1b ESCC, the rates of positive resection margin and additional therapy were significantly higher in ESD group than those in esophagectomy group. CONCLUSIONS: ESD is a minimally invasive procedure that has comparable oncologic outcomes with esophagectomy for treatment poorly differentiated T1a ESCC. However, ESD is not suitable for poorly differentiated T1b ESCC, additional surgery or radiochemotherapy should be required.

Unrevealing the therapeutic potential of artesunate against emerging zoonotic Babesia microti infection in the murine model.

Babesiosis, a zoonotic blood protozoal disease, threatens humans and animals and is difficult to treat due to growing antimicrobial resistance. The study aimed to investigate the therapeutic efficacy of artesunate (AS), a well-known derivative of artemisinin, against Babesia microti (B. microti) using a murine infection model. Male BALB/c mice (6 weeks old; 15 per group) were chosen and randomly divided into 1) the control group, 2) the B. microti group, and 3) the B. microti + artesunate treatment groups. AS treatment at 2 mg/kg, 4 mg/kg, and 8 mg/kg of body weight significantly (p < 0.05) reduced the B. microti load in blood smears in a dose-dependent manner. Additionally, AS treatment mitigated the decrease in body weight and restored the normal state of the liver and spleen viscera index compared to the B. microti-infected group after 28 days. Hematological analysis revealed significant increases in RBC, WBC, and PLT counts post-AS treatment compared to the B. microti-infected group. Furthermore, AS administration resulted in significant reductions in total protein, bilirubin, ALT, AST, and ALP levels, along with reduced liver and spleen inflammation and lesions as observed through histopathological analysis. AS also elicited dose-dependent changes in mRNA and protein expression levels of apoptotic, proinflammatory, and anti-inflammatory cytokines in the liver compared to the control and B. microti-infected groups. Immunolabeling revealed decreased expression of apoptotic and inflammation-related proteins in AS-treated hepatic cytoplasm compared to the B. microti-infected group. AS also in dose-dependent manner decreased apoptotic protein and increased Bcl-2. Overall, these findings underscore the potential of AS as an anti-parasitic candidate in combating B. microti pathogenesis in an in vivo infection model, suggesting its promise for clinical trials as a treatment for babesiosis.

Optical enhancement mode 2 improves the detection rate of gastric neoplastic lesion in high-risk populations: A multicenter randomized controlled clinical study.

OBJECTIVES: Detection of early neoplastic lesions is crucial for improving the survival rates of patients with gastric cancer. Optical enhancement mode 2 is a new image-enhanced endoscopic technique that offers bright images and can improve the visibility of neoplastic lesions. This study aimed to compare the detection of neoplastic lesions with optical enhancement mode 2 and white-light imaging (WLI) in a high-risk population. METHODS: In this prospective multicenter randomized controlled trial, patients were randomly assigned to optical enhancement mode 2 or WLI groups. Detection of suspicious neoplastic lesions during the examinations was recorded, and pathological diagnoses served as the gold standard. RESULTS: A total of 1211 and 1219 individuals were included in the optical enhancement mode 2 and WLI groups, respectively. The detection rate of neoplastic lesions was significantly higher in the optical enhancement mode 2 group (5.1% vs. 1.9%; risk ratio, 2.656 [95% confidence interval, 1.630-4.330]; p < 0.001). The detection rate of neoplastic lesions with an atrophic gastritis background was significantly higher in the optical enhancement mode 2 group (8.6% vs. 2.6%, p < 0.001). The optical enhancement mode 2 group also had a higher detection rate among endoscopists with different experiences. CONCLUSIONS: Optical enhancement mode 2 was more effective than WLI for detecting neoplastic lesions in the stomach, and can serve as a new method for screening early gastric cancer in clinical practice. CLINICAL REGISTRY: United States National Library of Medicine (https://www. CLINICALTRIALS: gov), ID: NCT040720521.

Heterozygous Spink1 c.194+2T>C mutation promotes chronic pancreatitis after acute attack in mice.

BACKGROUND & AIMS: Mutations in genes, including serine protease inhibitor Kazal-type 1 (SPINK1), influence disease progression following sentinel acute pancreatitis event (SAPE) attacks. SPINK1 c.194+2T > C intron mutation is one of the main mutants of SPINK1，which leads to the impairment of SPINK1 function by causing skipping of exon 3. Research on the pathogenesis of SAPE attacks would contribute to the understanding of the outcomes of acute pancreatitis. Therefore, the aim of the study was to clarify the role of SPINK1 c.194+2T > C mutation in the CP progression after an AP attack. METHODS: SAPE attacks were induced in wildtype and SPINK mutant (Spink1 c.194+2T > C) mice by cerulein injection. The mice were sacrificed at 24 h, 14 d, 28 d, and 42 d post-SAPE. Data-independent acquisition (DIA) proteomic analysis was performed for the identification of differentially expressed protein in the pancreatic tissues. Functional analyses were performed using THP-1 and HPSCs. RESULTS: Following SAPE attack, the Spink1 c.194+2T > C mutant mice exhibited a more severe acute pancreatitis phenotype within 24 h. In the chronic phase, the chronic pancreatitis phenotype was more severe in the Spink1 c.194+2T > C mutant mice after SAPE. Proteomic analysis revealed elevated IL-33 level in Spink1 c.194+2T > C mutant mice. Further in vitro analyses revealed that IL-33 induced M2 polarization of macrophages and activation of pancreatic stellate cells. CONCLUSION: Spink1 c.194+2T > C mutation plays an important role in the prognosis of patients following SAPE. Heterozygous Spink1 c.194+2T > C mutation promotes the development of chronic pancreatitis after an acute attack in mice through elevated IL-33 level and the induction of M2 polarization in coordination with pancreatic stellate cell activation.

Comparative metabolomics combined with genome sequencing provides insights into novel wolfberry-specific metabolites and their formation mechanisms.

Wolfberry (Lycium, of the family Solanaceae) has special nutritional benefits due to its valuable metabolites. Here, 16 wolfberry-specific metabolites were identified by comparing the metabolome of wolfberry with those of six species, including maize, rice, wheat, soybean, tomato and grape. The copy numbers of the riboflavin and phenyllactate degradation genes riboflavin kinase (RFK) and phenyllactate UDP-glycosyltransferase (UGT1) were lower in wolfberry than in other species, while the copy number of the phenyllactate synthesis gene hydroxyphenyl-pyruvate reductase (HPPR) was higher in wolfberry, suggesting that the copy number variation of these genes among species may be the main reason for the specific accumulation of riboflavin and phenyllactate in wolfberry. Moreover, the metabolome-based neighbor-joining tree revealed distinct clustering of monocots and dicots, suggesting that metabolites could reflect the evolutionary relationship among those species. Taken together, we identified 16 specific metabolites in wolfberry and provided new insight into the accumulation mechanism of species-specific metabolites at the genomic level.

Effects of different nitrogen application rates and picking batches on the nutritional components of Lycium barbarum L. fruits.

Lycium barbarum L., commonly known as wolfberry, is not only a traditional Chinese medicine but also a highly nutritious food. Its main nutrients include L. barbarum polysaccharide, flavonoid polyphenols, carotenoids, alkaloids, and other compounds, demonstrating its wide application value. This study investigated the effects of nitrogen application on the accumulation of the main nutrients and metabolites in wolfberry fruits under three different nitrogen application rates, namely, N1 (20% nitrogen (N) reduction, 540 kg·ha-2), N2 (medium N, 675 kg·ha-2), and N3 (20% nitrogen increase, 810 kg·ha-2,which is a local conventional nitrogen application amount.). Additionally, due to continuous branching, blossoming, and fruiting of wolfberry plants during the annual growth period, this research also explored the variation in nutritional composition among different harvesting batches. The contents of total sugar and polysaccharide in wolfberry fruit were determined by Fehling reagent method and phenol-sulfuric acid method, respectively;The content of betaine in fruit was determined by high-performance liquid chromatography,and the flavonoids and carotene in the wolfberry fruits were determined by spectrophotometry. Analysis of data over three consecutive years revealed that as nitrogen application increased, the total sugar content in wolfberry fruits initially decreased and then increased. The levels of L. barbarum polysaccharides, total flavonoids, and total carotenoids initially increased and then decreased, while the betaine content consistently increased. Different picking batches significantly impacted the nutrient content of wolfberry fruits. Generally, the first batch of summer wolfberry fruits had greater amounts of total sugar and flavonoids, whereas other nutrients peaked in the third batch. By employing a broadly targeted metabolomics approach, 926 different metabolites were identified. The top 20 differentially abundant metabolites were selected for heatmap generation, revealing that the contents of L-citrulline, 2-methylglutaric acid, and adipic acid increased proportionally to the nitrogen gradient. Conversely, the dibutyl phthalate and 2, 4-dihydroxyquinoline contents significantly decreased under high-nitrogen conditions. The remaining 15 differentially abundant metabolites, kaempferol-3-O-sophorosid-7-O-rhamnoside, trigonelline, and isorhamnosid-3-O-sophoroside, initially increased and then decreased with increasing nitrogen levels. Isofraxidin, a common differentially abundant metabolite across all treatments, is a coumarin that may serve as a potential biomarker for wolfberry fruit response to nitrogen. Differentially abundant metabolites were analyzed for GO pathway involvement, revealing significant enrichment in metabolic pathways and biosynthesis of secondary metabolites under different nitrogen treatments. In conclusion, a nitrogen application of 675 kg·ha-2, 20% less than the local farmers' actual application, was most beneficial for the quality of four-year-old Ningqi 7 wolfberry fruits. Consumers who purchase wolfberry-dried fruit for health benefits should not consider only the first batch of summer wolfberry fruits. These results offer a broader perspective for enhancing the quality and efficiency of the wolfberry industry.