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Rui Feng Li,1,* Liang Fen Wang,1,2,* Hai Ying Zhang,3 Meng Jie He1 1Department of Clinical Pharmacy, Sichuan Provincial Women’s and Children’s Hospital/The Affiliated Women’s and Children’s Hospital of Chengdu Medical College, Chengdu, People’s Republic of China; 2Department of Pharmacy, 363 hospital, Chengdu, People’s Republic of China; 3Medical Intensive Care Unit, Sichuan Provincial Women’s and Children’s Hospital/The Affiliated Women’s and Children’s Hospital of Chengdu Medical College, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Meng Jie He, Department of Clinical Pharmacy, Sichuan Provincial Women’s and Children’s Hospital/The Affiliated Women’s and Children’s Hospital of Chengdu Medical College, No. 290, Shayan West 2nd Street, Chengdu, 610014, People’s Republic of China, Email mengjie161003@163.comAbstract: Niclofolan is a commonly used veterinary drug worldwide. We reported a case of acute niclofolan intoxication in a pregnant woman. We recorded in detail her toxic symptoms, including nausea, vomiting, asthenia, blurred vision, and aberrant blood values. Notably stillbirth was recorded for the first time as indicating its human reproductive toxicity. We also found that an oral therapeutic dosage as described in the literature was likely to lead to stillbirth. Furthermore, we described the treatments received by the patient, including critical care, drug therapy, and plasma exchange, the outcomes of which were excellent. By studying this case, we aimed to enhance recognition and treatment of niclofolan intoxication and to raise concern regarding veterinary drug abuse and exposure risk.Keywords: niclofolan intoxication, reproductive toxicity, intensive healthcare, case report

Objective: To explore the efficacy and factors affecting the treatment of gastric cancer liver metastasis (GCLM) with immune checkpoint inhibitors (ICI). Methods: This is a retrospective cohort study. Clinical and pathological data of 588 patients with GCLM treated at the Department of General Surgery, First Medical Center, People's Liberation Army General Hospital, from January 2018 to December 2022 were retrospectively collected. There were 491 males and 97 females, aged ( M (IQR)) 60(14) years (range: 18 to 86 years). Patients were divided into an ICI treatment group ( n =142) and a non-ICI treatment group ( n =446) based on whether they received ICI therapy. Clinical and pathological data between the two groups were compared using the χ 2 test or Mann-Whitney U test. Propensity score matching (PSM) was performed with cT stage, cN stage, surgical treatment, targeted therapy, and biomarkers as covariates, using a 1∶1 nearest neighbor matching method with a caliper value of 0.2. Univariate and multivariate analyses were conducted using Cox proportional hazards regression models, with relevant variables selected through forward stepwise regression. Survival curves were plotted using the Kaplan-Meier method, and group differences were compared using the Log-rank test. Subgroup analysis was conducted to identify potential beneficiary populations for ICI through forest plots. Results: After PSM, 114 patients were included in each group, and there were no statistically significant differences in the baseline data between the two groups (all P >0.05). The results of Cox multivariate analysis after PSM showed that cN2-3 stage ( HR =1.348, 95% CI : 1.091 to 1.665, P =0.006) and peritoneal metastasis ( HR =1.877, 95% CI :1.360 to 2.590, P <0.01) were independent risk factors for survival in GCLM patients; radical surgery ( HR =0.391, 95% CI : 0.305 to 0.501, P <0.01), immunotherapy ( HR =0.630, 95% CI : 0.503 to 0.788, P <0.01), and deficient DNA mismatch repair (dMMR) or combined positive score (CPS)≥5 ( HR =0.454, 95% CI : 0.320 to 0.644, P <0.01) were independent protective factors for survival in GCLM patients. After PSM, the overall survival was 12.4 (13.0) months in the non-immunotherapy group and 17.6 (17.8) months in the immunotherapy group (Log-rank test: P =0.029). Subgroup analysis showed that female patients, those with primary tumors located in the upper stomach, cN2-3 stage, one liver metastasis, synchronous liver metastasis, receiving targeted therapy, and those with dMMR or CPS≥5 were more likely to benefit from ICI therapy (all P <0.05). Conclusions: ICI prolongs overall survival in GCLM patients. Female patients, those with primary tumors located in the upper stomach, cN2-3 stage, one liver metastasis, synchronous liver metastasis, receiving targeted therapy, and those with dMMR or CPS≥5 are more likely to benefit from ICI therapy.

Rationale: When gland-preserving treatments are unsuccessful, sialoadenectomy is typically conducted for patients afflicted with submandibular gland diseases. The definitive treatment modality for these individuals is the removal of both the gland and the associated ducts. During surgery, the gland and the majority of the ducts can be excised utilizing the lateral transcervical approach, with residual ducts unlikely to develop pathology. After sialoadenectomy, the recurrence of salivary gland stones is extremely rare. Although there are some relevant speculations, to the best of our knowledge, there are no comprehensive reports of larger recurrent stone-related cases available., Patient Concerns: We present 2 instances of recurrent sialoliths in the residual Wharton duct following sialoadenectomy. In our cases, it was not until several years later that both patients presented with symptoms. The patients, a 51-year-old male and a 28-year-old female, presented with swelling and purulent discharge in the right floor of the mouth., Diagnoses: Computed tomography scans revealed irregular high-density masses in the floor of the mouth, indicative of sialolithiasis., Interventions: The intraoral incision exposed the recurrent sialoliths, which were successfully removed along with the residual duct., Outcomes: There were no complications in both cases., Lessons: This report aims to clarify potential mechanisms behind recurrent sialoliths in residual Wharton ducts after submandibular gland excision, warranting further investigation to improve patient management. New stones may form again in the residual duct even if the glands were removed. With the risk of recurrent sialoliths after resection of the gland, multiway preventive management can optimize outcomes., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc.)

Pyrene, a representative polycyclic aromatic hydrocarbon, frequently occurs in aquatic environments and is associated with lethal impacts on humans and wildlife. This study examined the impact of pyrene on Alexandrium pacificum , a dinoflagellate responsible for harmful algal blooms, and their capability to bioremove pyrene. In a 96 h exposure experiment, A. pacificum effectively reduced the pyrene concentration in seawater to 50, 100, and 200 μg/L, with a combined removal efficiency of 96% in seawater. Furthermore, the study noted a significant reduction in the synthesis of GTX4, GTX1, NEO, and GTX3 toxins in A. pacificum cells exposed to 50 and 200 μg/L of pyrene. Concurrently, exposure to pyrene resulted in marked declines in the growth and photosynthetic efficiency of A. pacificum . Proteomics analysis results showed an upregulation of proteins related to endocytosis, such as HSPA and Arf, while proteins associated with paralytic shellfish toxin (PST) synthesis, specifically SxtU and SxtH, showed a downregulation trend. In summary, the findings of this study preliminarily elucidate the molecular mechanisms underlying A. pacificum 's response to pyrene, reveal the impact of pyrene on PST synthesis, and suggest that A. pacificum holds significant potential for pyrene biodegradation.

The identification of distribution characteristics, pollution sources, and potential human health risks of heavy metals in groundwater is crucial for the scientific planning and rational development of groundwater resources in arid-semiarid regions. In this study, 46 groundwater samples were collected and analyzed using hydrogeochemical modeling and multivariate statistical analysis methods to reveal the pollution characteristics and speciation distribution of 11 heavy metals （As, B, Pb, Sb, Tl, Mn, Ba, Cd, Co, Cr, and Al） in the Datong Basin. The absolute principal component-linear regression （APCS-MLR） model and health risk assessment model （HRA） were employed to determine the sources and health risk levels of heavy metals in groundwater. The results showed that： ① As, B, Pb, Sb, and Tl in groundwater exceeded the Class Ⅲ groundwater quality standards, indicating severe pollution, while Mn showed mild pollution, with heavy metal concentrations generally higher in the central region compared to those in the southern, eastern, and western regions. ② The predominant speciation forms of As, B, Pb, Sb, and Tl were HAsO 4 2- （91.71%）, H 3 BO 3 （97.61%）, PbCO 3 （88.08%）, Sb（OH） 6 - （99.81%）, and Tl + （94.84%）, respectively, with pH being one of the key factors affecting the distribution of heavy metal species. ③ The main sources of heavy metal pollution were soil migration sources （Co, Cd, and Cr）, industrial sources （Al, Pb, Sb, and B）, mining sources （Tl and Mn）, and natural sources （Ba and As）, with industrial sources accounting for the largest proportion （34%）, followed by natural sources （29%）, mining sources （20%）, and soil migration sources （18%）. The health risk assessment results for specific sources of heavy metals indicated that industrial activities and natural sources were the main contributors to the carcinogenic risk for adults （54.68%） and children （67.51%）, with As posing the highest carcinogenic risk. Mining activities were the major contributor to non-carcinogenic risk （56.69% for adults, 56.97% for children）, with higher risks associated with Tl and As.

The wide dissemination of multidrug-resistant (MDR) Gram-negative bacteria poses a significant global health and security concern. As developing new antibiotics is generally costly, fastidious, and time-consuming, there is an urgent need for alternative therapeutic strategies to address the gap in antibiotic discovery void. This study aimed to investigate the activity of colistin (CS) in combination with a natural product, rutin (RT), to combat against Salmonella Typhimurium ( S. Tm) in vitro and in vivo. The results showed that a combination with RT enabled the potentiation of CS efficacy. Further mechanistic analysis indicated that RT disrupted iron homeostasis to inactivate the PmrA/PmrB system, thereafter reducing the bacterial membrane modifications for enhancing CS binding. Besides enhancing bactericidal activity of CS, RT was also observed to mitigate the CS-induced nephrotoxicity, by which the dosing limitation of CS was overcome for better pathogen clearance. The animal trial eventually confirmed the in vivo synergistic interaction of RT with CS to treat the bacterial infection. To sum up, the present study uncovered the potential of RT as a viable adjuvant of CS to eradicate the infection and protect the hosts, which might serve as a promising alternative to combat infections caused by MDR Gram-negative bacteria.

Transition metal oxide interfaces have garnered great attention due to their fascinating properties that are absent in their bulk counterparts. The high mobility and coexistence of superconductivity and magnetism at these interfaces remain compelling research topics. Here, we first report superconductivity in the 2DEG formed at the LaFeO 3 /SrTiO 3 interfaces, characterized by a superconducting transition temperature ( T c ) of 333 mK and a superconducting layer thickness of 13.7 nm. The observation of a Berezinskii-Kosterlitz-Thouless transition at low temperatures indicates the two-dimensional nature of the superconductivity. Such two-dimensional superconductivity can be tuned by applying a gate voltage ( V g ) across the SrTiO 3 substrate, showing a dome-shaped T c - V g dependence. Moreover, we observe a hysteretic behavior in the magnetoresistance in the superconducting regime, and the underlying mechanism requires further investigation. Our results unveil the superconducting characteristics of 2DEG at LaFeO 3 /SrTiO 3 interfaces and offer a new compelling platform to investigate emergent quantum phenomena at oxide interfaces.

Two dimensional β-ketoamine covalent organic frameworks (2D TP-COFs) are one category of promising metal-free catalysts for photocatalytic overall water splitting (OWS) because of their unusual stability and versatile electronic/optical properties. However, none of the currently reported TP-COFs can accomplish the hydrogen evolution (HER) and oxygen evolution reactions (OER) simultaneously without adding any sacrificial agents and cocatalysts. To address this challenging issue, we rationally designed 23 2D TP-COFs by regulating the linkage groups and comprehensively evaluated their OWS activity by using the first-principles method. First, the electronic band structure calculations at the HSE06 level reveal that the band gap can be reasonably adjusted with values ranging from 1.67-3.16 eV. Among these 23 systems, 10 TP-COFs are realized to match well with both the chemical potentials of H 2 /H + and O 2 /H 2 O, which are capable of visible-light-driven OWS from an electronic perspective. Further thermal activity results on OWS demonstrate that only Hep-BDA (heptazine-aniline) and Bpy-4 (bipyrimidinamine) based COFs can satisfy the completely spontaneous of HER and OER under light irradiation and neutral conditions. Importantly, the calculated small exciton binding energies and high carrier mobility for Hep-BDA and Bpy-4 TP-COFs propose they are potentially applied in photocatalytic OWS. We also achieved the theoretical energy conversion efficiency of Hep-BDA can reach as high as 13.01%. Because there are very few successful applications of TP-COFs on OWS, this theoretical work not only offers valuable insights and innovative ideas for the exploration of novel metal-free photocatalysts for OWS but also supplies a direction for the development of new TP-COF derivatives.

Two-dimensional electronic spectroscopy (2DES) has high spectral resolution and is a useful tool for studying atomic dynamics. In this paper, we show a smallest unit of electromagnetically induced transparency (EIT) for 2DES, i.e., a three-level system. It is found that the original main peak is split into four small ones due to the introduction of EIT. It suggests that the homogeneous broadening of 2DES can be effectively reduced by EIT. Moreover, in sharp contrast to a constant height, the height of the peaks will manifest a damped oscillation with respect to the population time. It seems that the quantum-beat phenomenon appears. These findings may help us obtain more information about the dynamics of excited states., (© 2025 Author(s). Published under an exclusive license by AIP Publishing.)

Introduction: Hyperglycemia and hyperlipidemia are the hallmarks of type 2 diabetes mellitus (T2DM). T2DM is a systemic metabolic disease caused by insulin resistance and malfunctioning pancreatic β-cells. Although ginseng (the roots of Panax ginseng C.A. Meyer) can be used to treat T2DM, the underlying mechanism is unclear., Objectives: To assess the role and mechanism of, γ-aminobutyric acid-fructosyl-glucose (GABAFG), a maillard reaction product of ginseng, in T2DM treatment., Methods: The metabolism of GABAFG in serum and tissues was analyzed via ultra-high performance liquid chromatography-Q exactive-mass spectrometry (UHPLC-QE-MS). The molecular mechanisms of GABAFG in pancreatic β-cells (in vivo and in vitro) were investigated via Western blotting, qPCR and immunofluorescence. In addition, the results were validated via high-throughput sequencing and serum metabolomics., Results: GABAFG alleviated the elevation of blood glucose and blood lipids in HFD/STZ-induced T2DM mice. Also, GABAFG reduced the insulin resistance-associated IRS-1 signaling axis in pancreatic β-cells in vitro. Mechanistically, GABAFG targeted the nuclear translocation of TFEB inhibited apoptosis of pancreatic β-cells by enhancing autophagolysosome function. In addition, GABAFG remodeled the gut microbiota. Specifically, GABAFG increased Akkermansia, decreased Romboutsia abundance, and decreased serum glycerophospholipid metabolism, thus alleviating T2DM-induced dyslipidemia., Conclusion: This is the first study to assess the pharmacological effects of ginseng-derived GABAFG in T2DM. Therefore, this study provides a new theoretical basis for understanding ginseng effect in metabolic diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier B.V.)

Purpose: To develop a simple and convenient inflammation-nutrition-adiposity biomarker to complement the TNM staging system, further assess the prognosis of patients with colorectal cancer cachexia., Methods: This study was a multi-centre cohort study. The triceps skinfold thickness-albumin index (TA) was calculated by combining the triceps skinfold thickness (TSF) and serum albumin levels. Kaplan-Meier analysis and Cox proportional risk regression models were used to assess the relationship between the TA and all-cause mortality. Internal validation was carried out., Results: We included 1025 patients with colorectal cancer cachexia, 61.2% of whom were male, with a mean age of 58.91 (12.45) years. As the TA increased, overall mortality decreased in female patients (hazard ratio [HR], 0.95) but not in male patients (HR, 0.99). Multivariate Cox analysis showed that patients in the normal TA group had a significantly lower risk of death than those in the low TA group (HR, 0.53, 95% CI, 0.40-0.72). Patients with a normal TA had a lower risk of malnutrition, poor quality of life, and poor short-term prognosis than those with a low TA., Conclusions: TA index enables clinicians to assess the prognosis of patients as early as possible to improve the survival of patients with colorectal cancer cachexia.