Lung and Cutaneous Abscesses in a Patient with Ulcerative Colitis: A Case Report and Literature Review.

Aseptic abscess (AA) syndrome is a rare inflammatory disorder often associated with inflammatory bowel disease (IBD). Cases of IBD-associated AA have been reported in Japan, India, and Canada, but rarely in China. Herein, we present the case of a Chinese patient with IBD-associated AAs and review the literature on AA with underlying IBD. We report the case of a 48-year-old male patient with multiple AAs on his left hand and lungs who was successfully treated with prednisone. He had undergone cutaneous abscess incision and drainage twice in the previous 2 years. The patient presented to our hospital with ulcerative colitis and pain in the dorsum of the left hand. Pus from his hand and blood cultures revealed sterile cutaneous abscesses. Chest computed tomography examination during hospitalization revealed a lung abscess. The AA was unresponsive to cefotiam or cefoperazone-sulbactam. The patient's left hand and lung conditions did not improve until prednisone was administered. The patient was followed up as an outpatient for 3 months and recovered without any clinical symptoms. We retrieved 17 cases of IBD-associated AA from the literature. None of the patients showed evidence of infection and failed antibiotic treatment, and all improved with corticosteroid use. AA may be an extra-intestinal manifestation of IBD. Effective medications include corticosteroids and immunosuppressive agents. This case may increase the awareness of AA and aid in early identification.

A new strategy for Astragaloside IV in the treatment of diabetic kidney disease: Analyzing the regulation of ferroptosis and mitochondrial function of renal tubular epithelial cells.

In China, the Astragalus membranaceus root is used to treat chronic kidney disease. Astragaloside IV (AS-IV), the primary bioactive compound, exhibits anti-inflammatory and antioxidative properties; however, its renoprotective mechanism in diabetic kidney disease (DKD) remains unclear. The study aimed to investigate the protective effects of AS-IV on DKD revealing the underlying mechanisms. We established an early diabetic rat model by feeding a high-fat diet and administering low-dose streptozotocin. Twelve weeks post-treatment, renal function was evaluated using functional assays, histological analyses, immunohistochemistry, western blotting, and transmission electron microscopy. HK-2 cells exposed to high glucose conditions were used to examine the effect of AS-IV on oxidative stress, iron levels, reactive oxygen species (ROS), and lipid peroxidation. Network pharmacology, proteomics, molecular docking, and molecular dynamics simulation techniques were employed to elucidate the role of AS-IV in DKD. The results revealed that AS-IV effectively enhanced renal function and mitigated disease pathology, oxidative stress, and ferroptosis markers in DKD rats. In HK-2 cells, AS-IV lowered the levels of lipid peroxides, Fe2+, and glutathione, indicating the repair of ferroptosis-related mitochondrial damage. AS-IV reduced mitochondrial ROS while enhancing mitochondrial membrane potential and ATP production, indicating its role in combating mitochondrial dysfunction. Overall, in silico analyses revealed that AS-IV interacts with HMOX1, FTH1, and TFR1 proteins, supporting its efficacy in alleviating renal injury by targeting mitochondrial dysfunction and ferroptosis. AS-IV may play a renoprotective role by regulating mitochondrial dysfunction and inhibiting. HMOX1/FTH1/TFR1-induced ferroptosis. Accordingly, AS-IV could be developed for the clinical treatment of DKD-related renal injury.

Ferroptosis promotes valproate-induced liver steatosis in vitro and in vivo.

Valproic acid (VPA), a common antiepileptic drug, can cause liver steatosis after long-term therapy. However, an impact of ferroptosis on VPA-induced liver steatosis has not been investigated. In the study, treatment with VPA promoted ferroptosis in the livers of mice by elevating ferrous iron (Fe2+) levels derived from the increased absorption by transferrin receptor 1 (TFR1) and the decreased storage by ferritin (FTH1 and FTL), disrupting the redox balance via reduced levels of solute carrier family 7 member 11 (SLC7A11), glutathione (GSH), and glutathione peroxidase 4 (GPX4), and augmenting acyl-CoA synthetase long-chain family member 4 (ACSL4) -mediated lipid peroxide generation, accompanied by enhanced liver steatosis. All the changes were significantly reversed by co-treatment with an iron-chelating agent, deferoxamine mesylate (DFO) and a ferroptosis inhibitor, ferrostatin-1 (Fer-1). Similarly, the increases in Fe2+, TFR1, and ACSL4 levels, as well as the decreases in GSH, GPX4, and ferroportin (FPN) levels, were detected in VPA-treated HepG2 cells. These changes were also attenuated after co-treatment with Fer-1. It demonstrates that ferroptosis promotes VPA-induced liver steatosis through iron overload, inhibition of the GSH-GPX4 axis, and upregulation of ACSL4. It offers a potential therapy targeting ferroptosis for patients with liver steatosis following VPA treatment.

Peritumoral edema enhances MRI-based deep learning radiomic model for axillary lymph node metastasis burden prediction in breast cancer.

To investigate whether peritumoral edema (PE) could enhance deep learning radiomic (DLR) model in predicting axillary lymph node metastasis (ALNM) burden in breast cancer. Invasive breast cancer patients with preoperative MRI were retrospectively enrolled and categorized into low (< 2 lymph nodes involved (LNs+)) and high (≥ 2 LNs+) burden groups based on surgical pathology. PE was evaluated on T2WI, and intra- and peri-tumoral radiomic features were extracted from MRI-visible tumors in DCE-MRI. Deep learning models were developed for LN burden prediction in the training cohort and validated in an independent cohort. The incremental value of PE was evaluated through receiver operating characteristic (ROC) analysis, confirming the improvement in the area under the curve (AUC) using the Delong test. This was complemented by net reclassification improvement (NRI) and integrated discrimination improvement (IDI) metrics. The deep learning combined model, incorporating PE with selected radiomic features, demonstrated significantly higher AUC values compared to the MRI model and the DLR model in the training cohort (n = 177) (AUC: 0.953 vs. 0.849 and 0.867, p < 0.05) and the validation cohort (n = 111) (AUC: 0.963 vs. 0.883 and 0.882, p < 0.05). The complementary analysis demonstrated that PE significantly enhances the prediction performance of the DLR model (Categorical NRI: 0.551, p < 0.001; IDI = 0.343, p < 0.001). These findings were confirmed in the validation cohort (Categorical NRI: 0.539, p < 0.001; IDI = 0.387, p < 0.001). PE improved preoperative ALNM burden prediction of DLR model, facilitating personalized axillary management in breast cancer patients.

Theory-driven design of cadmium mineralizing layered double hydroxides for environmental remediation.

The environmental concern posed by toxic heavy metal pollution in soil and water has grown. Ca-based layered double hydroxides (LDHs) have shown exceptional efficacy in eliminating heavy metal cations through the formation of super-stable mineralization structures (SSMS). Nevertheless, it is still unclear how the intricate coordination environment of Ca2+ in Ca-based LDH materials affects the mineralization performance, which hinders the development and application of Ca-based LDH materials as efficient mineralizers. Herein, we discover that, in comparison to a standard LDH, the mineralization efficiency for Cd2+ ions may be significantly enhanced in the pentacoordinated structure of defect-containing Ca-5-LDH utilizing both density functional theory (DFT) and ab initio molecular dynamics (AIMD) simulations. Furthermore, the calcination-reconstruction technique can be utilized to successfully produce pentacoordinated Ca-5-LDH. Subsequent investigations verified that Ca-5-LDH exhibited double the mineralization performance (421.5 mg g-1) in comparison to the corresponding pristine seven coordinated Ca-7OH/H2O-LDH (191.2 mg g-1). The coordination-relative mineralization mechanism of Ca-based LDH was confirmed by both theoretical calculations and experimental results. The understanding of LDH materials and their possible use in environmental remediation are advanced by this research.

Prognostic value of sarcopenia and myosteatosis alterations on survival outcomes for esophageal squamous cell carcinoma before and after radiotherapy.

OBJECTIVE: We assessed the impact and prognostic significance of alterations in muscle quality and quantity (myosteatosis and sarcopenia, respectively) in patients with esophageal cancer treated with radiotherapy (RT). METHODS: We retrospectively pooled 258 patients with esophageal squamous cell cancer who underwent RT. Myosteatosis and sarcopenia were determined based on the skeletal muscle index derived from the muscle area and attenuation at the L3 level from computed tomography images. Subgroups were formed as 2 subgroups of non-sarcopenia/myosteatosis and sarcopenia/myosteatosis (with or without other muscle status) at either timepoint of RT, 3 subgroups of only-sarcopenia, only myosteatosis (without other muscle status), and the co-presence of sarcopenia and myosteatosis at either timepoint of RT, as well as 4 subgroups of continuous sarcopenia/myosteatosis, developed sarcopenia/myosteatosis, reduced sarcopenia/myosteatosis and non-sarcopenia/myosteatosis according to alterations of muscle status at both timepoints of RT. Overall survival (OS) was compared. Univariate and multivariate analyses based on Cox regression identified independent risk factors for prognosis. RESULTS: Either pre- or post-RT, patients with sarcopenia and myosteatosis (with or without other muscle status) had poor OS. Patients with only myosteatosis (without other muscle status) showed the best OS (1352 days pre-RT vs. 1648 days post-RT), while patients with concurrent myosteatosis and sarcopenia had the worst OS (907 days pre-RT vs. 706 days post-RT). The ascending order of OS for sarcopenia alterations was as follows: continuous sarcopenia (1093 days), non-sarcopenia (1740 days), developed sarcopenia (2187 days), and reduced sarcopenia (2208 days) (P = 0.002). The ascending order of OS for myosteatosis alterations was ranked as follows: continuous myosteatosis (1165 days), reduced myosteatosis (1275 days), developed myosteatosis (1783 days), and non-myosteatosis (1942 days) (P = 0.061). Univariate and multivariate Cox regression analyses revealed that increased age, longer tumor length, developed myosteatosis, and continuous myosteatosis were independent prognostic factors for OS. CONCLUSIONS: Muscle mass status at presentation and alterations in patients with esophageal cancer before and after RT should be considered prognostic indicators.

The Impact of Early Antibiotic Use on Clinical Outcomes of Patients Hospitalized with COVID-19: A Propensity Score-Matched Analysis.

Purpose: Early empiric antibiotics were prescribed to numerous patients during the Coronavirus disease 2019 (COVID-19) pandemic. However, the potential impact of empiric antibiotic therapy on the clinical outcomes of patients hospitalized with COVID-19 is yet unknown. Methods: In this retrospective cohort study, early antibiotics use cohort was defined as control group, which was compared with no antibiotic use and delayed antibiotic use cohorts for all-cause mortality during hospitalization. The 1:2 propensity score matched patient populations were further developed to adjust confounding factors. Survival curves were compared between different cohorts using a Log rank test to assess the early antibiotic effectiveness. Results: We included a total of 1472 COVID-19 hospitalized patients, of whom 87.4% (1287 patients) received early antibiotic prescriptions. In propensity-score-matched datasets, our analysis comprised 139 patients with non-antibiotic use (with 278 matched controls) and 27 patients with deferred-antibiotic use (with 54 matched controls). Patients with older ages, multiple comorbidities, severe and critical COVID-19 subtypes, higher serum infection indicators, and inflammatory indicators at admission were more likely to receive early antibiotic prescriptions. After adjusting confounding factors likely to influence the prognosis, there is no significant difference in all-cause mortality (HR=1.000(0.246-4.060), p = 1.000) and ICU admission (HR=0.436(0.093-2.04), p = 0.293), need for mechanical ventilation (HR=0.723(0.296-1.763), p = 0.476) and tracheal intubation (HR=1.338(0.221-8.103), p = 0.751) were observed between early antibiotics use cohort and non-antibiotic use cohort. Conclusion: Early antibiotics were frequently prescribed to patients in more severe disease condition at admission. However, early antibiotic treatment failed to demonstrate better clinical outcomes in hospitalized patients with COVID-19 in the propensity-score-matched cohorts.

Vascular plants and biocrusts ameliorate soil properties serving to increase the stability of the Great Wall of China.

The Great Wall, as a World Heritage Site, is constructed with rammed earth and is currently facing the threat of erosion from wind and rain. Vascular plants and biocrusts are the main coverings of the Great Wall, and their role in mitigating soil erosion has attracted increased amounts of attention; however, the understanding of their underlying mechanisms is limited. Here, we conducted an extensive survey of vascular plants, biocrusts, soil properties (soil organic and inorganic binding materials, aggregates, and texture), soil aggregate stability, and soil erodibility at the top of the Great Wall in four different defensive zones in Northwest China. Vascular plants covered 13.6 % to 63.9 % of the tops of the Great Wall, and their rich diversity was mainly derived from perennial herbs. Moss, lichen, and cyanobacterial crusts collectively covered 36.3 % to 67.8 % of the top of the Great Wall. Redundancy analysis and structural equation modeling revealed that the synergistic effects of vascular plants and biocrusts enhanced soil aggregation stability (including geometric mean diameter, GMD; water-stable macroaggregate content, R) by increasing the accumulation of soil organic carbon (SOC), amorphous iron oxide (Feo), and amorphous alumina (Alo) and promoting the formation of macroaggregates (ASD>0.25 mm) and microaggregates (ASD0.053-0.25 mm). Furthermore, soil erodibility was primarily influenced negatively by the synergistic promotion of SOC accumulation by vascular plants and biocrusts and positively by the reduction in soil sand (PSD>0.05 mm) content by biocrusts. Our work highlights the mechanisms and importance of vascular plants and biocrusts as natural covers for altering the intrinsic properties of soil for the protection of the Great Wall. These findings provide reliable theoretical support for the protection of the Great Wall from erosion by vascular plants and biocrusts and offer new insights for the conservation of global earthen sites and similar wall habitats.

Envafolimab Inhibits the Growth of Gastric Cancer Cells with Low PD-L1 Expression through the DDX20/NF-κB/TNF-α Signaling Pathway.

BACKGROUND: The mechanism of action of envafolimab (also known as KN035), a programmed death ligand 1 (PD-L1) inhibitor, in gastric adenocarcinoma patients with low PD-L1 expression is not well understood. AIMS: This study aimed to observe the efficacy of envafolimab in gastric adenocarcinoma with low PD-L1 expression and explore the underlying mechanisms. OBJECTIVE: The objective of this study was to explore the underlying mechanism of envafolimab in gastric cancer with low PD-L1 expression. METHOD: Cytotoxicity and proliferation were evaluated by a CCK8 assay. Transwell assays were used to detect the migration and invasion ability of gastric cancer cells. The effect of envafolimab on the apoptosis of gastric cancer cells was detected by flow cytometry. The effect of envafolimab on gastric cancer cells with low PD-L1 expression was investigated via proteomics and bioinformatics analysis. RESULT: A total of 19 patients with advanced gastric adenocarcinoma who received envafolimab monotherapy or combination therapy were reviewed. Among them, 4 patients had low PD-L1 expression, the objective response rate (ORR) was 75% (3/4), and the disease control rate (DCR) was 100% (4/4). In vitro experiments showed that envafolimab inhibited the proliferation, invasion, and migration of gastric cancer cells with low expression of PD-L1 and induced cell apoptosis. DDX20 may be the target of envafolimab in gastric cancer cells, and it is related to the NF-κB signaling pathway. Western blot results showed that the protein expressions of DDX20, NF-κB p65, and TNF-α in gastric cancer cells were decreased after adding envafolimab. Furthermore, the DDX20 gene was silenced by small interfering RNA to further study the effect of DDX20 on PDL1 low expression in gastric cancer cells. CONCLUSION: This study confirmed that envafolimab could inhibit the growth of gastric cancer cells with low PD-L1 expression by down-regulating DDX20 expression and regulating the NFκB/TNF-α signaling pathway.

A new magnetic resonance imaging-based PUMCH classification system for congenital cervical malformations: devising a standardised diagnosis pathway.

OBJECTIVES: To develop an innovative magnetic resonance imaging (MRI)-based PUMCH (Peking Union Medical College Hospital) classification system aimed at standardising the diagnosis of congenital cervical malformations (CCMs) by identifying their distinctive MRI features. METHODS: Seventy-nine consecutive patients with CCM underwent pre-treatment pelvic MRI; three experienced gynaecological radiologists retrospectively analysed these images. Qualitative assessments included Rock et al's classification; PUMCH classification; haematometra; cervical signal features; ovarian endometriosis; haematosalpinx; and uterine, vaginal, urinary, and musculoskeletal malformations. Quantitative assessments involved the uterine volume, sagittal cervical length, and maximum ovarian cross-sectional area. The surgical treatment types were also recorded. Statistical methods were used to incorporate differences in clinical features and surgical methods into our classification. RESULTS: Morphologically, CCMs were categorised into three types: type I (53%) was characterised by the presence of a cervix with visible cervical canals; type II (23%) featured an existing cervix with concealed cervical canals; and type III (24%) indicated cervical aplasia, which involves a blind end in the lower part of the uterine corpus. Haematometra was significantly more prevalent in patients with type I CCM than in those with type II (p < 0.001). There were three cervical signal patterns: no signal (27%), no evident layer differentiation (21%), and multi-layer differentiation with haematocele (52%). Most patients (94%) had complete vaginal atresia. Type I CCM patients had a higher likelihood of regaining normal uterovaginal anatomy compared to types II and III. CONCLUSIONS: Our proposed PUMCH classification system has a high potential for enhancing the efficiency of clinical diagnosis among patients with CCM. CRITICAL RELEVANCE STATEMENT: The proposed new PUMCH classification promised to elevate the conventional diagnostic trajectory for congenital cervical malformations, offering a valuable framework to refine the selection and planning of surgical interventions, thereby enhancing overall clinical efficacy. KEY POINTS: Effective classification of congenital cervical malformations is desirable to optimise the diagnostic process. We presented a PUMCH classification of congenital cervical malformations using pelvic MRI. The new classification significantly aids clinical triage for congenital cervical malformations.

Proteomic and lipidomic analysis of the mechanism underlying astragaloside IV in mitigating ferroptosis through hypoxia-inducible factor 1α/heme oxygenase 1 pathway in renal tubular epithelial cells in diabetic kidney disease.

ETHNOPHARMACOLOGICAL RELEVANCE: The limitations of modern medicine in mitigating the pathological process of diabetic kidney disease (DKD) necessitate novel, precise, and effective prevention and treatment methods. Huangqi, the root of Astragalus membranaceus Fisch. ex Bunge has been used in traditional Chinese medicine for various kidney ailments. Astragaloside IV (AS-IV), the primary pharmacologically active compound in A. membranaceus, is involved in lipid metabolism regulation; however, its potential in ameliorating renal damage in DKD remains unexplored. AIM OF THE STUDY: To elucidate the specific mechanism by which AS-IV moderates DKD progression. MATERIALS AND METHODS: A murine model of DKD and high glucose-induced HK-2 cells were treated with AS-IV. Furthermore, multiomics analysis, molecular docking, and molecular dynamics simulations were performed to elucidate the mechanism of action of AS-IV in DKD, which was validated using molecular biological methods. RESULTS: AS-IV regulated glucose and lipid metabolism in DKD, thereby mitigating lipid deposition in the kidneys. Proteomic analysis identified 12 proteins associated with lipid metabolism regulated by AS-IV in the DKD renal tissue. Additionally, lipid metabolomic analysis revealed that AS-IV upregulated and downregulated 4 beneficial and 79 harmful lipid metabolites, respectively. Multiomics analysis further indicated a positive correlation between the top-ranked differential protein heme oxygenase (HMOX)1 and the levels of various harmful lipid metabolites and a negative correlation with the levels of beneficial lipid metabolites. Furthermore, enrichment of both ferroptosis and hypoxia-inducible factor (HIF)-1 signaling pathways during the AS-IV treatment of DKD was observed using proteomic analysis. Validation results showed that AS-IV effectively reduced ferroptosis in DKD-affected renal tubular epithelial cells by inhibiting HIF-1α/HMOX1 pathway activity, upregulating glutathione peroxidase-4 and ferritin heavy chain-1 expression, and downregulating acyl-CoA synthetase long-chain family member-4 and transferrin receptor-1 expression. Our findings demonstrate the potential of AS-IV in mitigating DKD pathology by downregulating the HIF-1α/HMOX1 signaling pathway, thereby averting ferroptosis in renal tubular epithelial cells. CONCLUSIONS: AS-IV is a promising treatment strategy for DKD via the inhibition of ferroptosis in renal tubular epithelial cells. The findings of this study may help facilitate the development of novel therapeutic strategies.

Correlation between matrix metalloproteinase-2, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinases-1 and white matter hyperintensities in patients with cerebral small vessel disease based on cranial magnetic resonance 3D imaging.

OBJECTIVE: The objective of this study was to investigate the correlation between serum levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels and their ratios with the severity of white matter hyperintensities (WMHs) in patients with cerebral small vessel disease (CSVD). METHODS: This cross-sectional study was done on a prospective cohort of patients with CSVD. Qualitative and quantitative analyses of WMHs were performed using Fazekas grading and lesion prediction algorithm (LPA) methods. Biomarkers MMP-2, MMP-9, and TIMP-1 were measured to explore their correlation with the severity of WMHs. RESULTS: The sample consisted of 144 patients with CSVD. There were 63 male and 81 female patients, with an average age of 67.604 ± 8.727 years. Among these, 58.33% presented with white matter hyperintensities at Fazekas grading level 1, with an average total template volume of WMHs of 4.305 mL. MMP-2 (P = 0.025), MMP-9 (P = 0.008), TIMP-1 (P = 0.026), and age (P = 0.007) were identified as independent correlates of WMHs based on Fazekas grading. Independent correlates of the total template volume of WMHs included MMP-2 (P = 0.023), TIMP-1 (P = 0.046), age (P = 0.047), systolic blood pressure (P = 0.047), and homocysteine (Hcy) (P = 0.014). In addition, age (P = 0.003; P < 0.001), interleukin-6 (IL-6) (P < 0.001; P = 0.044), Hcy (P < 0.001; P < 0.001), glycated hemoglobin (HbA1c) (P = 0.016; P = 0.043), and chronic kidney disease (P < 0.001; P < 0.001) were associated with both WMHs Fazekas grading and the total template volume of WMHs. CONCLUSION: Serum levels of MMP-9, MMP-2, and TIMP-1 were independently associated with the Fazekas grading, while serum TIMP-1 and MMP-2 levels were independently related to the total template volume of WMHs. The association of TIMP-1 and MMP-2 with the severity of CSVD-related WMHs suggests their potential role as disease-related biomarkers. However, further research is required to uncover the specific mechanisms underlying these interactions.

Intensive Versus Moderate Statin-Based Therapies in Patients With Mild Ischemic Stroke: A Prospective Multicenter Cohort Study.

BACKGROUND: Statins are widely used for treating patients with ischemic stroke at risk of secondary cerebrovascular events. It is unknown whether Asian populations benefit from more intensive statin-based therapy for stroke recurrence. Therefore, in the present study we evaluated the effectiveness and safety of high-dose and moderate-dose statins for patients who had experienced mild ischemic stroke during the acute period. METHODS AND RESULTS: This multicenter prospective study included patients with mild ischemic stroke who presented within 72 hours of symptom onset. The outcomes of patients in the high-intensity and moderate-intensity statin treatment groups were compared, with the main efficacy outcome being stroke recurrence and the primary safety end point being intracranial hemorrhage. The propensity score matching method was employed to control for imbalances in baseline variables. Subgroup analyses were conducted to evaluate group differences. In total, the data of 2950 patients were analyzed at 3 months, and the data of 2764 patients were analyzed at 12 months due to loss to follow-up. According to the multivariable Cox analyses adjusted for potential confounders, stroke recurrence occurred similarly in the high-intensity statin and moderate-intensity statin groups (3 months: adjusted hazard ratio [HR], 1.12 [95% CI, 0.85-1.49]; P=0.424; 12 months: adjusted HR, 1.08 [95% CI, 0.86-1.34]; P=0.519). High-intensity statin therapy was associated with an increased risk of intracranial hemorrhage (3 months: adjusted HR, 1.81 [95% CI, 1.00-3.25]; P=0.048; 12 months: adjusted HR, 1.86 [95% CI, 1.10-3.16]; P=0.021). The results from the propensity score-matched analyses were consistent with those from the Cox proportional hazards analysis. CONCLUSIONS: Compared with moderate-intensity statin therapy, high-dose statin therapy may not decrease the risk of mild, noncardiogenic ischemic stroke recurrence but may increase the risk of intracranial hemorrhage. REGISTRATION: URL: www.chictr.org.cn/. Unique Identifier: ChiCTR1900025214.

Enhanced drug resistance suppression by serum-stable micelles from multi-arm amphiphilic block copolymers and tocopheryl polyethylene glycol 1000 succinate.

Aim: To develop a robust drug-delivery system using multi-arm amphiphilic block copolymers for enhanced efficacy in cancer therapy. Materials & methods: Two series of amphiphilic polymer micelles, PEG-b-PCLm and PEG-b-PCLm/TPGS, were synthesized. Doxorubicin (DOX) loading into the micelles was achieved via solvent dialysis. Results: The micelles displayed excellent biocompatibility, narrow size distribution, and uniform morphology. DOX-loaded micelles exhibited enhanced antitumor efficacy and increased drug accumulation at tumor sites compared with free DOX. Additionally, 4A-PEG47-b-PCL21/TPGS micelles effectively suppressed drug-resistant MCF-7/ADR cells. Conclusion: This study introduces a novel micelle formulation with exceptional serum stability and efficacy against drug resistance, promising for cancer therapy. It highlights innovative strategies for refining clinical translation and ensuring sustained efficacy and safety in vivo.

[Box: see text].

Synthesis of highly sensitive and multi-response Eu-MOF, fluorescence sensing properties and anti-counterfeiting applications.

A new Europium metal-organic framework (Eu-MOF), namely [Eu(dpa) (H2O)]·0.5(bpy)·4H2O}n (H4dpa = 5-(3,4-dicarboxyphenoxy) isophenic acid, bpy = protonated 4,4'-bipyridine) was synthesized and structurally characterized by elemental analyses, infrared spectroscopy, and X-ray single-crystal diffraction analyses. Eu-MOF shows a three-dimensional network structure based on EuIII ions and (dpa)4- ligands via µ4: η1, η2, η2, η2 coordination mode. Fluorescence analysis shows that Eu-MOF has excellent fluorescence sensing characteristics, which can efficiently and sensitively detect various pollutants in water: the limit of detection (LOD) of ratiometric fluorescence detection of ANI in water was 42.9 nM, which was better than the single-peak detection limit. In addition, the peak detection limits of Eu-MOF for Flu, ORN and NB were 120 nM, 27 nM and 94 nM, respectively. In addition, XPS, LUMO orbital energy level, fluorescence lifetime, ultraviolet absorption and other principles are used to explore the mechanism of fluorescence quenching. Surprisingly, Eu-MOF not only has excellent anti- counterfeiting ability and stability, can be used as anti-counterfeiting material in life, but also has good selectivity to Flu. Eu-MOF has obvious fluorescence quenching effect on Flu on paper under ultraviolet light, which can be used for rapid in situ imaging test paper of pesticide residues.

Anisotropic van der Waals Tellurene-Based Multifunctional, Polarization-Sensitive, In-Line Optical Device.

Polarization plays a paramount role in scaling the optical network capacity. Anisotropic two-dimensional (2D) materials offer opportunities to exploit optical polarization-sensitive responses in various photonic and optoelectronic applications. However, the exploration of optical anisotropy in fiber in-line devices, critical for ultrafast pulse generation and modulation, remains limited. In this study, we present a fiber-integrated device based on a single-crystalline tellurene nanosheet. Benefiting from the chiral-chain crystal lattice and distinct optical dichroism of tellurene, multifunctional optical devices possessing diverse excellent properties can be achieved. By inserting the in-line device into a 1.5 µm fiber laser cavity, we generated both linearly polarized and dual-wavelength mode-locking pulses with a degree of polarization of 98% and exceptional long-term stability. Through a twisted configuration of two tellurene nanosheets, we realized an all-optical switching operation with a fast response. The multifunctional device also serves as a broadband photodetector. Notably, bipolar polarization encoding communication at 1550 nm can be achieved without any external voltage. The device's multifunctionality and stability in ambient environments established a promising prototype for integrating polarization as an additional physical dimension in fiber optical networks, encompassing diverse applications in light generation, modulation, and detection.

MiPRIME: an integrated and intelligent platform for mining primer and probe sequences of microbial species.

MOTIVATION: Accurately detecting pathogenic microorganisms requires effective primers and probe designs. Literature-derived primers are a valuable resource as they have been tested and proven effective in previous research. However, manually mining primers from published texts is time-consuming and limited in species scop. RESULTS: To address these challenges, we have developed MiPRIME, a real-time Microbial Primer Mining platform for primer/probe sequences extraction of pathogenic microorganisms with three highlights: (i) comprehensive integration. Covering >40 million articles and 548 942 organisms, the platform enables high-frequency microbial gene discovery from a global perspective, facilitating user-defined primer design and advancing microbial research. (ii) Using a BioBERT-based text mining model with 98.02% accuracy, greatly reducing information processing time. (iii) Using a primer ranking score, PRscore, for intelligent recommendation of species-specific primers. Overall, MiPRIME is a practical tool for primer mining in the pan-microbial field, saving time and cost of trial-and-error experiments. AVAILABILITY AND IMPLEMENTATION: The web is available at {{https://www.ai-bt.com}}.

Maternal high fat diet induces circadian clock-independent endocrine alterations impacting the metabolism of the offspring.

Maternal obesity has long-term effects on offspring metabolic health. Among the potential mechanisms, prior research has indicated potential disruptions in circadian rhythms and gut microbiota in the offspring. To challenge this hypothesis, we implemented a maternal high fat diet regimen before and during pregnancy, followed by a standard diet after birth. Our findings confirm that maternal obesity impacts offspring birth weight and glucose and lipid metabolisms. However, we found minimal impact on circadian rhythms and microbiota that are predominantly driven by the feeding/fasting cycle. Notably, maternal obesity altered rhythmic liver gene expression, affecting mitochondrial function and inflammatory response without disrupting the hepatic circadian clock. These changes could be explained by a masculinization of liver gene expression similar to the changes observed in polycystic ovarian syndrome. Intriguingly, such alterations seem to provide the first-generation offspring with a degree of protection against obesity when exposed to a high fat diet.

Circulating exosomal circRNA-miRNA-mRNA network in a familial partial lipodystrophy type 3 family with a novel PPARG frameshift mutation c.418dup.

Familial Partial Lipodystrophy 3 (FPLD3) is a rare genetic disorder caused by loss-of-function mutations in the PPARG gene, characterized by a selective absence of subcutaneous fat and associated metabolic complications. However, the molecular mechanisms of FPLD3 remain unclear. In this study, we recruited a 17-year-old Chinese female with FPLD3 and her family, identifying a novel PPARG frameshift mutation (exon 4: c.418dup: p.R140Kfs*7) that truncates the PPARγ protein at the 7th amino acid, significantly expanding the genetic landscape of FPLD3. By performing next generation sequencing of circular RNAs (circRNAs), microRNAs (miRNAs), and mRNAs in plasma exosomes, we discovered 59 circRNAs, 57 miRNAs, and 299 mRNAs were significantly altered in the mutation carriers in the comparison of healthy controls. Integration analysis highlighted that the circ_0001597-miR-671-5p pair and 18 mRNAs might be incorporated into the metabolic regulatory networks of the FPLD3 induced by the novel PPARG mutation. Functional annotation suggested that these genes were significantly enriched in glucose and lipid metabolism related pathways. Among the circRNA-miRNA-mRNA network, we identified two critical regulators, EGR1, a key transcription factor known for its role in insulin signaling pathways and lipid metabolism, and AGPAT3, which gets involved in the biosynthesis of triglycerides and lipolysis. Circ_0001597 regulates the expression of these genes through miR-671-5p, potentially contributing to the pathophysiology of FPLD3. Overall, this study clarified a circulating exosomal circRNA-miRNA-mRNA network in a FPLD3 family with a novel PPARG mutation, providing evidence for exploring promising biomarkers and developing novel therapeutic strategies for this rare genetic disorder.