Arachidonic acid metabolism as a novel pathogenic factor in gastrointestinal cancers.

Gastrointestinal (GI) cancers are a major global health burden, representing 20% of all cancer diagnoses and 22.5% of global cancer-related deaths. Their aggressive nature and resistance to treatment pose a significant challenge, with late-stage survival rates below 15% at five years. Therefore, there is an urgent need to delve deeper into the mechanisms of gastrointestinal cancer progression and optimize treatment strategies. Increasing evidence highlights the active involvement of abnormal arachidonic acid (AA) metabolism in various cancers. AA is a fatty acid mainly metabolized into diverse bioactive compounds by three enzymes: cyclooxygenase, lipoxygenase, and cytochrome P450 enzymes. Abnormal AA metabolism and altered levels of its metabolites may play a pivotal role in the development of GI cancers. However, the underlying mechanisms remain unclear. This review highlights a unique perspective by focusing on the abnormal metabolism of AA and its involvement in GI cancers. We summarize the latest advancements in understanding AA metabolism in GI cancers, outlining changes in AA levels and their potential role in liver, colorectal, pancreatic, esophageal, gastric, and gallbladder cancers. Moreover, we also explore the potential of targeting abnormal AA metabolism for future therapies, considering the current need to explore AA metabolism in GI cancers and outlining promising avenues for further research. Ultimately, such investigations aim to improve treatment options for patients with GI cancers and pave the way for better cancer management in this area.

Delivery of miR-15b-5p via magnetic nanoparticle-enhanced bone marrow mesenchymal stem cell-derived extracellular vesicles mitigates diabetic osteoporosis by targeting GFAP.

Diabetic osteoporosis (DO) presents significant clinical challenges. This study aimed to investigate the potential of magnetic nanoparticle-enhanced extracellular vesicles (GMNPE-EVs) derived from bone marrow mesenchymal stem cells (BMSCs) to deliver miR-15b-5p, thereby targeting and downregulating glial fibrillary acidic protein (GFAP) expression in rat DO models. Data was sourced from DO-related RNA-seq datasets combined with GEO and GeneCards databases. Rat primary BMSCs, bone marrow-derived macrophages (BMMs), and osteoclasts were isolated and cultured. EVs were separated, and GMNPE targeting EVs were synthesized. Bioinformatic analysis revealed a high GFAP expression in DO-related RNA-seq and GSE26168 datasets for disease models. Experimental results confirmed elevated GFAP in rat DO bone tissues, promoting osteoclast differentiation. miR-15b-5p was identified as a GFAP inhibitor, but was significantly downregulated in DO and enriched in BMSC-derived EVs. In vitro experiments showed that GMNPE-EVs could transfer miR-15b-5p to osteoclasts, downregulating GFAP and inhibiting osteoclast differentiation. In vivo tests confirmed the therapeutic potential of this approach in alleviating rat DO. Collectively, GMNPE-EVs can effectively deliver miR-15b-5p to osteoclasts, downregulating GFAP expression, and hence, offering a therapeutic strategy for rat DO.

A serine carboxypeptidase-like acyltransferase catalyzes consecutive four-step reactions of hydrolyzable tannin biosynthesis in Camellia oleifera.

Hydrolyzable tannins (HTs), a class of polyphenolic compounds found in dicotyledonous plants, are widely used in food and pharmaceutical industries because of their beneficial effects on human health. Although the biosynthesis of simple HTs has been verified at the enzymatic level, relevant genes have not yet been identified. Here, based on the parent ion-fragment ion pairs in the feature fragment data obtained using UPLC-Q-TOF-/MS/MS, galloyl phenolic compounds in the leaves of Camellia sinensis and C. oleifera were analyzed qualitatively and quantitatively. Correlation analysis between the transcript abundance of serine carboxypeptidase-like acyltransferases (SCPL-ATs) and the peak area of galloyl products in Camellia species showed that SCPL3 expression was highly correlated with HT biosynthesis. Enzymatic verification of the recombinant protein showed that CoSCPL3 from C. oleifera catalyzed the four consecutive steps involved in the conversion of digalloylglucose to pentagalloylglucose. We also identified the residues affecting the enzymatic activity of CoSCPL3 and determined that SCPL-AT catalyzes the synthesis of galloyl glycosides. The findings of this study provide a target gene for germplasm innovation of important cash crops that are rich in HTs, such as C. oleifera, strawberry, and walnut.

Unravelling the role of intratumoral bacteria in digestive system cancers: current insights and future perspectives.

Recently, research on the human microbiome, especially concerning the bacteria within the digestive system, has substantially advanced. This exploration has unveiled a complex interplay between microbiota and health, particularly in the context of disease. Evidence suggests that the gut microbiome plays vital roles in digestion, immunity and the synthesis of vitamins and neurotransmitters, highlighting its significance in maintaining overall health. Conversely, disruptions in these microbial communities, termed dysbiosis, have been linked to the pathogenesis of various diseases, including digestive system cancers. These bacteria can influence cancer progression through mechanisms such as DNA damage, modulation of the tumour microenvironment, and effects on the host's immune response. Changes in the composition and function within the tumours can also impact inflammation, immune response and cancer therapy effectiveness. These findings offer promising avenues for the clinical application of intratumoral bacteria for digestive system cancer treatment, including the potential use of microbial markers for early cancer detection, prognostication and the development of microbiome-targeted therapies to enhance treatment outcomes. This review aims to provide a comprehensive overview of the pivotal roles played by gut microbiome bacteria in the development of digestive system cancers. Additionally, we delve into the specific contributions of intratumoral bacteria to digestive system cancer development, elucidating potential mechanisms and clinical implications. Ultimately, this review underscores the intricate interplay between intratumoral bacteria and digestive system cancers, underscoring the pivotal role of microbiome research in transforming diagnostic, prognostic and therapeutic paradigms for digestive system cancers.

Age and BMI have different effects on subcutaneous, visceral, liver, bone marrow, and muscle adiposity, as measured by CT and MRI.

OBJECTIVE: We analyzed quantitative computed tomography (CT) and chemical shift-encoded magnetic resonance imaging (MRI) data from a Chinese cohort to investigate the effects of BMI and aging on different adipose tissue (AT) depots. METHODS: In 400 healthy, community-dwelling individuals aged 22 to 83 years, we used MRI to quantify proton density fat fraction (PDFF) of the lumbar spine (L2-L4) bone marrow AT (BMAT), the psoas major and erector spinae (ES) muscles, and the liver. Abdominal total AT, visceral AT (VAT), and subcutaneous AT (SAT) areas were measured at the L2-L3 level using quantitative CT. Partial correlation analysis was used to evaluate the relationship of each AT variable with age and BMI. Multiple linear regression analysis was performed in which each AT variable was evaluated in turn as a function of age and the other five independent AT measurements. RESULTS: Of the 168 men, 29% had normal BMI (<24.0 kg/m2), 47% had overweight (24.0-27.9 kg/m2), and 24% had obesity (≥ 28.0 kg/m2). In the 232 women, the percentages were 46%, 32%, and 22%, respectively. Strong or very strong correlations with BMI were found for total AT, VAT, and SAT in both sexes. BMAT and ES PDFF was strongly correlated with age in women and moderately correlated in men. In both sexes, BMAT PDFF correlated only with age and not with any of the other AT depots. Psoas PDFF correlated only with ES PDFF and not with age or the other AT depots. Liver PDFF correlated with BMI and VAT and weakly with SAT in men. VAT and SAT correlated with age and each other in both sexes. CONCLUSIONS: Age and BMI are both associated with adiposity, but their effects differ depending on the type of AT.

PolyQ-expanded ataxin-2 aggregation impairs cellular processing-body homeostasis via sequestering the RNA helicase DDX6.

Ataxin-2 (Atx2) is a polyglutamine (polyQ) tract-containing RNA-binding protein, while its polyQ expansion may cause protein aggregation that is implicated in the pathogenesis of neurodegenerative diseases such as spinocerebellar ataxia type 2 (SCA2). However, the molecular mechanism underlying how Atx2 aggregation contributes to the proteinopathies remains elusive. Here, we investigated the influence of Atx2 aggregation on the assembly and functionality of cellular processing bodies (P-bodies) by using biochemical and fluorescence imaging approaches. We have revealed that polyQ-expanded (PQE) Atx2 sequesters the DEAD-box RNA helicase (DDX6), an essential component of P-bodies, into aggregates or puncta via some RNA sequences. The N-terminal like-Sm (LSm) domain of Atx2 (residues 82-184) and the C-terminal helicase domain of DDX6 are responsible for the interaction and specific sequestration. Moreover, sequestration of DDX6 may aggravate pre-mRNA mis-splicing, and interfere with the assembly of cellular P-bodies, releasing the endoribonuclease MARF1 that promotes mRNA decay and translational repression. Rescuing the DDX6 protein level can recover the assembly and functionality of P-bodies, preventing targeted mRNA from degradation. This study provides a line of evidence for sequestration of the P-body components and impairment of the P-body homeostasis in dysregulating RNA metabolism, which is implicated in the disease pathologies and a potential therapeutic target.

Synergy of metallic Co and oxygen vacancy sites in Co/Ce-MOF catalysts for efficiently promoting lignin derived phenols and macromolecular lignin hydrodeoxygenation.

The enhanced utilization of biomass-derived chemicals for the generation of high value aromatics through an advanced catalytic strategy has captured considerable attention within the realm of eco-friendly manufacturing. This work presented four innovative three-dimensional rod-shaped mesoporous Ce-based MOF materials, which were coupled with a H-donor solvent to facilitate vanillin hydrodeoxygenation and macromolecular lignin. Under the optimized conditions (30 mg CoCe@C catalyst, 2 MPa N2 pressure, 15 mL isopropanol, 190 °C, and 5 h), the CoCe@C catalyst achieved nearly complete conversion of vanillin and demonstrated 87.8 % selectivity in the hydrogen-donor solvent. The characterization findings suggested that the synergy between metallic Co and oxygen vacancy sites enabled the effective activation of CHO group in vanillin, leading to formation of reactive product MMP. In addition, the optimal CoCe@C catalyst could also achieve macromolecular lignin hydrodeoxygenation to obtain high yield of lignin oil products with narrower molecular weight distribution. This study presented a viable approach for the concurrent utilization of lignin derivatives in the generation of high value fuels and chemicals.

Enhanced pyroptosis induction with pore-forming gene delivery for osteosarcoma microenvironment reshaping.

Osteosarcoma is the most common malignant bone tumor without efficient management for improving 5-year event-free survival. Immunotherapy is also limited due to its highly immunosuppressive tumor microenvironment (TME). Pore-forming gasdermins (GSDMs)-mediated pyroptosis has gained increasing concern in reshaping TME, however, the expressions and relationships of GSDMs with osteosarcoma remain unclear. Herein, gasdermin E (GSDME) expression is found to be positively correlated with the prognosis and immune infiltration of osteosarcoma patients, and low GSDME expression was observed. A vector termed as LPAD contains abundant hydroxyl groups for hydrating layer formation was then prepared to deliver the GSDME gene to upregulate protein expression in osteosarcoma for efficient TME reshaping via enhanced pyroptosis induction. Atomistic molecular dynamics simulations analysis proved that the hydroxyl groups increased LPAD hydration abilities by enhancing coulombic interaction. The upregulated GSDME expression together with cleaved caspase-3 provided impressive pyroptosis induction. The pyroptosis further initiated proinflammatory cytokines release, increased immune cell infiltration, activated adaptive immune responses and create a favorable immunogenic hot TME. The study not only confirms the role of GSDME in the immune infiltration and prognosis of osteosarcoma, but also provides a promising strategy for the inhibition of osteosarcoma by pore-forming GSDME gene delivery induced enhanced pyroptosis to reshape the TME of osteosarcoma.

Genotype Distribution and Prevalence of High-Risk Human Papillomavirus among Pregnant Women and Maternal-Fetal Pregnancy Outcomes in a Tertiary Hospital in Beijing, China.

BACKGROUND: High-risk human papillomavirus (HR-HPV) infection is the primary reason for cervical cancer and precancerous lesions in females. Specific immune alterations in pregnancy led to greater HR-HPV replication and reduced clearance of HR-HPV infection. This study retrospectively obtained and analyzed data from a tertiary hospital in Beijing, China. We aimed to ascertain both the genotype distribution and prevalence of HR-HPV in pregnant females. Moreover, we sought to analyze the association of HR-HPV with maternal-fetal pregnancy outcomes. METHODS: The retrospective observational cohort study was divided into two parts. Part I evaluated the genotype distribution and prevalence of HR-HPV. It encompassed 6285 pregnant women who underwent a routine pregnancy check-up, Thin Prep cytology test (TCT), and HR-HPV diagnosis during weeks 12-14 of gestation between January 1, 2013, and December 31, 2021. Part II analyzed the association between HR-HPV infection and maternal-fetal pregnancy outcome. Through a nearest-neighbor 1:1 propensity score matching (PSM), we matched HR-HPV-positive and HR-HPV-negative pregnant women using caliper width equal to 0.02. After PSM, 171 HR-HPV-positive and 171 HR-HPV-negative pregnant women were included to analyze the association between HR-HPV infection and maternal-fetal pregnancy outcome. RESULTS: In total 737 (11.73%) pregnant women were HR-HPV positive. The five most common genotypes of HR-HPV were HPV-52 (2.90%), HPV-58 (2%), HPV-16 (1.94%), HPV-51 (1.38%), and HPV-39 (1.29%). As for age-specific HPV prevalence, a "U-shaped" pattern was observed. The first and second peaks were detected in pregnant females aged <25 years and those aged ≥35 years, respectively. Our study found no significant difference between the HR-HPV-positive and the HR-HPV-negative pregnant females in the following maternal-fetal pregnancy outcomes: spontaneous abortion (1.2% for HR-HPV positive, 0% for HR-HPV negative, p = 0.478), preterm delivery (4.7% for HR-HPV positive, 5.3% for HR-HPV negative, p = 0.804), premature rupture of membrane (28.8% for HR-HPV positive, 22.8% for HR-HPV negative, p = 0.216), preeclampsia (7.6% for HR-HPV positive, 7.6% for HR-HPV negative, p = 1), oligohydramnios (8.2% for HR-HPV positive, 7% for HR-HPV negative, p = 0.683), fetal growth restriction (1.8% for HR-HPV positive, 0.6% for HPV negative, p = 0.615), placenta previa (1.2% for HR-HPV positive, 0.6% for HR-HPV negative, p = 1), postpartum hemorrhage (8.9% for HR-HPV positive, 11.2% for HR-HPV negative, p = 0.47). There was also no significant difference in delivery mode or birth weight between the two groups. CONCLUSIONS: HPV-16, 52, and 58 were the most prevalent infection genotypes in pregnant females. The study showed no significant differences between HR-HPV-positive and HR-HPV-negative groups in the maternal-fetal pregnancy outcomes.

Combination therapy involving HSP90 inhibitors for combating cancer: an overview of clinical and preclinical progress.

The molecular chaperone heat shock protein 90 (HSP90) regulates multiple crucial signalling pathways in cancer by driving the maturation of key signalling components, thereby playing a crucial role in tumorigenesis and drug resistance in cancer. Inhibition of HSP90 results in metastable conformational collapse of its client proteins and their proteasomal degradation. Considerable efforts have been devoted to the development of small-molecule inhibitors targeting HSP90, and more than 20 inhibitors have been evaluated in clinical trials for cancer therapy. However, owing to disadvantages such as organ toxicity and drug resistance, only one HSP90 inhibitor has been approved for use in clinical settings. In recent years, HSP90 inhibitors used in combination with other anti-cancer therapies have shown remarkable potential in the treatment of cancer. HSP90 inhibitors work synergistically with various anti-cancer therapies, including chemotherapy, targeted therapy, radiation therapy and immunotherapy. HSP90 inhibitors can improve the pharmacological effects of the above-mentioned therapies and reduce treatment resistance. This review provides an overview of the use of combination therapy with HSP90 inhibitors and other anti-cancer therapies in clinical and preclinical studies reported in the past decade and summarises design strategies and prospects for these combination therapies. Altogether, this review provides a theoretical basis for further research and application of these combination therapies in the treatment of cancer.

Three Liquid-Liquid Phase Separation-Related Genes Associated with Prognosis in Glioma.

Purpose: Dysregulated liquid-liquid phase separation (LLPS) instigates tumorigenesis through biomolecular condensate dysfunction. However, the association between LLPS-associated genes and glioma remains underexplored. Patients and Methods: Differentially expressed genes (DEGs) of glioma were obtained from the GSE50161 dataset, including 34 glioma and 13 normal samples. We analyzed differentially expressed LLPS-related genes in glioma from public databases. These genes informed refined molecular subtyping on the TCGA-glioma dataset. CIBERSORT assessed immune cell infiltration across three subclusters. A prognostic model was devised using univariate and lasso Cox regressions on intersecting genes. Prognostic gene expression was validated in glioma cells via RT-qPCR. Results: A total of 673 differentially expressed LLPS-associated genes were identified in glioma. Three distinct molecular subtypes (C1, C2, and C3) of glioma were obtained with a marked variance in the expression of immune checkpoint genes PD1 and PDL1. Differences in immune cell infiltration were observed across subtypes. In addition, a tri-gene prognostic signature (TAGLN2, NTNG2, and IGF2BP2) was derived with significant survival differences between high and low-risk groups. The prognostic model displayed impressive AUC values for 1, 3, and 5-year survival in both training and validation sets. Further analysis highlighted a notable correlation between the three prognostic genes and immune cells in glioma samples. Furthermore, we found the upregulation of TAGLN2 and IGF2BP2 and the downregulation of NTNG2 in glioma tumors and cells. Conclusion: This study innovatively uncovers the significant role of LLPS-related genes in glioma tumor grading and prognosis. The constructed tri-gene prognostic model holds promise for enhancing personalized prognosis assessments and optimizing immunotherapy strategies for glioma patients.

Cysteine- and glycine-rich protein 1 predicts prognosis and therapy response in patients with acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous disease with a poor prognosis. The current risk stratification system is essential but remains insufficient to select the best schedules. Cysteine-rich protein 1 (CSRP1) is a member of the CSRP family and associated with poor clinicopathological features in many tumors. This study aimed to explore the clinical significance and molecular mechanisms of cysteine- and glycine-rich protein 1 (CSRP1) in AML. RT-qPCR was used to detect the relative expression of CSRP1 in our clinical cohort. Functional enrichment analysis of CSRP1-related differentially expressed genes was carried out by GO/KEGG enrichment analysis, immune cell infiltration analysis, and protein-protein interaction (PPI) network. The OncoPredict algorithm was implemented to explore correlations between CSRP1 and drug resistance. CSRP1 was highly expressed in AML compared with normal samples. High CSRP1 expression was an independent poor prognostic factor. Functional enrichment analysis showed neutrophil activation and apoptosis were associated with CSRP1. In the PPI network, 19 genes were present in the most significant module, and 9 of them were correlated with AML prognosis. The high CSRP1 patients showed higher sensitivity to 5-fluorouracil, gemcitabine, rapamycin, cisplatin and lower sensitivity to fludarabine. CSRP1 may serve as a potential prognostic marker and a therapeutic target for AML in the future.

Reference Values for Paravertebral Muscle Size and Myosteatosis in Chinese Adults, a Nationwide Multicenter Study.

RATIONALE AND OBJECTIVES: The paravertebral muscles, characterized by their susceptibility to severe size loss and fat infiltration in old age, lack established reference values for age-related variations in muscle parameters. This study aims to fill this gap by establishing reference values for paravertebral muscles in a Chinese adult population. MATERIALS AND METHODS: This cross-sectional study utilized the baseline data from the prospective cohort China Action on Spine and Hip (CASH). A total of 4305 community-dwelling participants aged 21-80 years in China were recruited between 2013 and 2017. Pregnant women, individuals with metal implants, limited mobility or diseases/conditions (spinal tumor, infection, etc.) affecting lumbar vertebra were excluded from the study. Psoas and paraspinal muscles were measured in quantitative computed tomography (QCT) images at the L3 and L5 levels using Osirix software. Age-related reference values for muscle area, density, and fat fraction were constructed as percentile charts using the lambda-mu-sigma (LMS) method. RESULTS: The paravertebral muscles exhibited an age-related decline in muscle area and density, coupled with an increase in muscle fat fraction. Between the ages of 25 and 75, the reductions in psoas and paraspinal muscle cross-sectional area at the L3 level were - 0.47%/yr and - 0.53%/yr in men, and - 0.19%/yr and - 0.23%/yr in women, respectively. Notably, accelerated muscle loss was observed during menopause and postmenopause in women (45-75 years) and intermittently during middle and old age in men (35-55 and 60-75 years). Besides, the age-related decreases in PSMA, PMA, and PSMD and the increases in PSMFF were more pronounced in L5 than in L3 CONCLUSION: This study shows distinct patterns of accelerated muscle loss were identified in menopausal and postmenopausal women and in middle-aged and old men. The findings contribute valuable information for future investigations on paravertebral muscle loss and myosteatosis.

Evaluation of the Nutritional Quality of Chinese Processed Meat Products: Comparison of Two Nutrient Profile Models.

Processed meat products are one of the most consumed pre-packaged foods in China. They are also group-1 carcinogens, whose consumption has proved to be positively associated with the risk of noncommunicable diseases (NCDs). The purpose of this study is to analyze the nutrient content on the food label of processed meat products based on the China Standardized Database for the Composition of Pre-packaged Food and the National Open Database of the UK and France. The Chilean front-of-pack warning label (FOPWL) and the Chinese Healthier Choice Logo were used to compare the nutrient content of processed meat products from the three countries. It was found that cured meat products have the highest median energy (483 kcal/100 g), total fat content (38.7 g/100 g), and sodium content (2076 mg/100 g) and dried meat products have the highest median protein content (30.2 g/100 g) and carbohydrate content (38.2 g/100 g). In addition, there were significant differences in energy content and contents of total fat, protein, and carbohydrate across different products of the three countries (p < 0.001). A large number of processed meat products currently collected did not meet the criteria of the Chilean FOPWL and the Chinese Healthier Choice Logo. This study provided information on the healthiness of Chinese processed meat products and provided data for improving food formulations for different categories of processed meat products.

[Spatial and Temporal Distribution and Risk Assessment of Heavy Metals in Surface Water of Changshou Lake Reservoir, Chongqing].

To understand the water pollution status and environmental risks of Changshou Lake, the concentrations of heavy metals (Cr, Cu, Zn, As, Cd, and Pb) in the water were collected and analyzed during different seasons. The study investigated temporal and spatial variations, distribution characteristics, pollution levels, and health risks associated with heavy metals in Changshou Lake. The results showed that all six heavy metals were below than the Class Ⅰ standard of the Surface Water Environmental Quality Standard (GB 3838-2002), but recent years have witnessed an increasing trend, with Cu, As, and Pb showing a significant increase (P<0.05). The temporal and spatial distributions of these heavy metals were different. Temporally, Cr and Cd concentrations in surface water were higher in summer, As and Zn were higher in spring, and Pb and Cu were higher in autumn and winter. Spatially, the concentrations of Cr, As, Cu, Zn, and Pb showed higher concentrations in the southern outlet of the reservoir, the northwestern Longxi River inlet, and the central part of the reservoir, whereas Cd was higher in the northern stagnant area. The overall levels of heavy metals in the water body of Changshou Lake were low, with Cr and Cu slightly polluted, while other heavy metals were identified as having an insignificant pollution level. Drinking water was the primary exposure pathway to carcinogenic and non-carcinogenic heavy metals in surface water bodies. The health risk values of Cr and As in water bodies were high, ranging from 6.2×10-10 to 3.0×10-4 and 5.1×10-8 to 3.9×10-5, respectively. The corresponding contribution rates for children and adults to the total health risk were high, with Cr accounting for 87.18% and 87.20%, respectively, while As accounted for 12.73% and 12.71%, respectively. Therefore, it is crucial to prioritize environmental risks associated with Cr and Cu, as well as the health risks associated with Cr and As in Changshou Lake These findings provide a scientific foundation for water pollution control and environmental quality improvement in Changshou Lake, and rational development and utilization of water resources.

Two-Dimensional Biodegradable Black Phosphorus Nanosheets Promote Large Full-Thickness Wound Healing through In Situ Regeneration Therapy.

Large full-thickness skin lesions have been one of the most challenging clinical problems in plastic surgery repair and reconstruction. To achieve in situ skin regeneration and perfect clinical outcomes, we must address two significant obstacles: angiogenesis deficiency and inflammatory dysfunction. Recently, black phosphorus has shown great promise in wound healing. However, few studies have explored the bio-effects of BP to promote in situ skin regeneration based on its nanoproperties. Here, to investigate whether black phosphorus nanosheets have positive bio-effects on in situ skin repair, we verified black phosphorus nanosheets' positive effects on angiogenic and anti-inflammatory abilities in vitro. Next, the in vivo evaluation performed on the rat large full-thickness excisional wound splinting model more comprehensively showed that the positive bio-effects of black phosphorus nanosheets are multilevel in wound healing, which can effectively enhance anti-inflammatory ability, angiogenesis, collagen deposition, and skin re-epithelialization. Then, multiomics analysis was performed to explore further the mechanism of black phosphorus nanosheets' regulation of endothelial cells in depth. Molecular mechanistically, black phosphorus nanosheets activated the JAK-STAT-OAS signaling pathway to promote cellular function and mitochondrial energy metabolism in endothelial cells. This study can provide a theoretical basis for applying two-dimensional black phosphorus nanosheets as nanomedicine to achieve in situ tissue regeneration in complex human pathological microenvironments, guiding the subsequent optimization of black phosphorus.

Ultra-high-performance liquid chromatography with tandem mass spectrometry method for cellular toxicity and pharmacokinetic study of PEG1K polymers.

Polyethylene glycol (PEG) is one of the most commonly used polymers in drug delivery systems. The investigation of the pharmacokinetic behavior of PEG is important for revealing the toxicity and efficiency of PEG-related Nano-drug delivery systems. A high through-put and selective ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) method coupled with collision-induced dissociation (CID) in source technique was developed and validated to determine PEG1K polymers in cellular samples in this study. The countless precursor ions of PEG1K are dissociated in the source to generate numerous product ions which have different numbers of subunits. The transition of [M+H]+ precursor ions → product ions at m/z 177.1 (four subunits)→89.1 (two subunits) was selected to determine PEG1K due to its high sensitivity. The UHPLC-MS/MS method coupled with CID in the source showed good linearity over the range of 0.1-10 µg/mL. Intra-day and inter-day accuracies and precisions of the assay were all within ± 12.39%. The assay was successfully applied to a cellular pharmacokinetic study of PEG1K in human breast cancer cells. The cytotoxicity of PEG1K polymers was also studied and the results indicated that the cytotoxicity of PEG1K was not significant in the range of 5-1200 µg/mL.

Six-point scleral fixation of a three-looped haptics one-piece posterior chamber intraocular lens by a single suture.

To evaluate a novel technique for six-point scleral fixation of a three-looped haptics posterior chamber intraocular lens (PCIOL) by a single suture. Nine eyes of nine patients were studied from September 2021 to March 2023. All patients had undergone vitrectomy. Only a single 9-0 polypropylene suture was used for scleral fixation. The three looped haptics were fixed at 12, 4, and 8 o'clock with six-point scleral fixation. The entire procedure took about 30 min. Among the nine patients, eight (88.8%) eyes had a significant improvement in best-corrected visual acuity, whereas one (11.2%) eye showed no change. No intraoperative or postoperative complications were observed. By ultrasonic biomicroscopy examination, intraocular lenses were well positioned and stable with no tilt in the horizontal and vertical axis. The method of six-point scleral fixation of a three-looped haptics PCIOL by a single suture is safe and effective.

The Impact of Esketamine Combined with Dexmedetomidine on Laparoscopic Gallbladder Surgery: A Randomized Controlled Trial.

Objective: To assess the efficacy of combining esketamine with dexmedetomidine in laparoscopic gallbladder surgery. Methods: We investigated 110 laparoscopic cholecystectomy patients at Jinan Central Hospital, affiliated with Shandong First Medical University, from April 2019 to March 2020. Patients were randomly assigned to the control group (n = 55) or observation group (n = 55). The control group received dexmedetomidine intravenously at 1 µg/kg and a continuous infusion at 0.5 µg•kg-1•h-1. The observation group received esketamine and dexmedetomidine, with intravenous esketamine at 0.4 mg/kg and a continuous infusion at 0.1 mg/(kg•h). We measured heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) at four-time points: before anesthesia (T0), 30 minutes after anesthesia (T1), extubation (T2), and awakening (T3). We also assessed wake time, post-anesthesia care unit (PACU) stay, and Ramasy and visual analogue scale (VAS) scores at 2, 6, 12, and 24 hours post-surgery. Results: At T0, no significant changes occurred in HR, SBP, and DBP in both groups (P > .05). However, at T1 and T2, HR, SBP, and DBP gradually decreased, with the control group exhibiting lower levels than the observation group (P < .05). These levels returned to baseline at T3. PACU residence and wake times showed no significant differences (P > .05). At 2 hours post-operation, Ramasy scores significantly dropped in the observation group versus the control group (P < .05). At 6, 12, and 24 hours post-operation, Ramasy scores exhibited no significant differences (P > .05). Moreover, at 2, 6, and 12 hours post-operation, VAS scores in the observation group were notably lower than in the control group (P < .05). At 24 hours post-operation, VAS scores revealed no significant differences (P > .05). Adverse reactions within 3 days post-operation did not differ significantly between the groups (P > .05). Conclusions: Combining esketamine with dexmedetomidine enhances the quality of laparoscopic cholecystectomy, alleviates postoperative agitation, accelerates cognitive function recovery, reduces cognitive function impairment, and merits clinical consideration.