Light-Induced Quantum Reconfiguration of Oxyhydroxides for Photoanodes with 4.24% Efficiency and Stability Beyond 250 Hours.

Photoelectrochemical (PEC) water splitting is attracting significant research interest in addressing sustainable development goals in renewable energy. Current state-of-the-art, however, cannot provide photoanodes with simultaneously high efficiency and long-lasting lifetime. Here, large-scale NiFe oxyhydroxides-alloy hybridized co-catalyst layer that exhibits an applied bias photon-to-current efficiency (ABPE) of 4.24% in buried homojunction-free photoanodes and stability over 250 h is reported. These performances represent an increase over the present highest-performing technology by 408% in stability and the most stable competitor by over 330% in efficiency. These results originate from a previously unexplored mechanism of light-induced atomic reconfiguration, which rapidly self-generates a catalytic-protective amorphous/crystalline heterostructure at low biases. This mechanism provides active sites for reaction and insulates the photoanode from performance degradation. Photon-generated NiFe oxyhydroxides are more than 200% higher than the quantity that pure electrocatalysis would otherwise induce, overcoming the threshold for an efficient water oxidation reaction in the device. While of immediate interest in the industry of water splitting, the light-induced NiFe oxyhydroxides-alloy co-catalyst developed in this work provides a general strategy to enhance further the performances and stability of PEC devices for a vast panorama of chemical reactions, ranging from biomass valorization to organic waste degradation, and CO2-to-fuel conversion.

Formation mechanism and regulation analysis of trumpet leaf in Ginkgo biloba L.

Introduction: The research on plant leaf morphology is of great significance for understanding the development and evolution of plant organ morphology. As a relict plant, the G. biloba leaf morphology typically exhibits bifoliate and peltate forms. However, throughout its long evolutionary history, Ginkgo leaves have undergone diverse changes. Methods: This study focuses on the distinct "trumpet" leaves and normal fan-shaped leaves of G. biloba for analysis of their phenotypes, photosynthetic activity, anatomical observations, as well as transcriptomic and metabolomic analyses. Results: The results showed that trumpet-shaped G. biloba leaves have fewer cells, significant morphological differences between dorsal and abaxial epidermal cells, leading to a significantly lower net photosynthetic rate. Additionally, this study found that endogenous plant hormones such as GA, auxin, and JA as well as metabolites such as flavonoids and phenolic acids play roles in the formation of trumpet-shaped G. biloba leaves. Moreover, the experiments revealed the regulatory mechanisms of various key biological processes and gene expressions in the trumpet-shaped leaves of G. biloba. Discussion: Differences in the dorsal and abdominal cells of G. biloba leaves can cause the leaf to curl, thus reducing the overall photosynthetic efficiency of the leaves. However, the morphology of plant leaves is determined during the primordia leaf stage. In the early stages of leaf development, the shoot apical meristem (SAM) determines the developmental morphology of dicotyledonous plant leaves. This process involves the activity of multiple gene families and small RNAs. The establishment of leaf morphology is complexly regulated by various endogenous hormones, including the effect of auxin on cell walls. Additionally, changes in intracellular ion concentrations, such as fluctuations in Ca2+ concentration, also affect cell wall rigidity, thereby influencing leaf growth morphology.

Przewaquinone A inhibits Angiotensin II-induced endothelial diastolic dysfunction activation of AMPK.

BACKGROUND: Endothelial dysfunction (ED), characterized by markedly reduced nitric oxide (NO) bioavailability, vasoconstriction, and a shift toward a proinflammatory and prothrombotic state, is an important contributor to hypertension, atherosclerosis, and other cardiovascular diseases. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) is widely involved in cardiovascular development. Przewaquinone A (PA), a lipophilic diterpene quinone extracted from Salvia przewalskii Maxim, inhibits vascular contraction. PURPOSE: Herein, the goal was to explore the protective effect of PA on ED in vivo and in vitro, as well as the underlying mechanisms. METHODS: A human umbilical vein endothelial cell (HUVEC) model of ED induced by angiotensin II (AngII) was used for in vitro observations. Levels of AMPK, endothelial nitric oxide synthase (eNOS), vascular cell adhesion molecule-1 (VCAM-1), nitric oxide (NO), and endothelin-1 (ET-1) were detected by western blotting and ELISA. A mouse model of hypertension was established by continuous infusion of AngII (1000 ng/kg/min) for 4 weeks using osmotic pumps. Following PA and/or valsartan administration, NO and ET-1 levels were measured. The levels of AMPK signaling-related proteins in the thoracic aorta were evaluated by immunohistochemistry. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured using the tail cuff method. Isolated aortic vascular tone measurements were used to evaluate the vasodilatory function in mice. Molecular docking, molecular dynamics, and surface plasmon resonance imaging (SPRi) were used to confirm AMPK and PA interactions. RESULTS: PA inhibited AngII-induced vasoconstriction and vascular adhesion as well as activated AMPK signaling in a dose-dependent manner. Moreover, PA markedly suppressed blood pressure, activated vasodilation in mice following AngII stimulation, and promoted the activation of AMPK signaling. Furthermore, molecular simulations and SPRi revealed that PA directly targeted AMPK. AMPK inhibition partly abolished the protective effects of PA against endothelial dysfunction. CONCLUSION: PA activates AMPK and ameliorates endothelial dysfunction during hypertension.

Systemic therapy in the management of metastatic or locally recurrent adenoid cystic carcinoma of the salivary glands: a systematic review of the last decade.

IMPORTANCE: Recurrent/metastatic adenoid cystic carcinoma (R/M AdCC) presents a clinical challenge with limited treatment options, particularly in the face of unsatisfactory efficacy from current therapeutic approaches. This review underscores the unmet clinical needs in managing R/M AdCC, emphasising the imperative for novel therapeutic strategies to address this critical gap. OBJECTIVE: The primary objective of this review is to comprehensively analyse and assess trials investigating therapeutic approaches for R/M AdCC. Emphasis is placed on endpoints such as tumour response rates and progression-free survival. The specific interventions, populations, and outcomes examined in these trials will be detailed to provide a focused and informative systematic review. EVIDENCE REVIEW: The systematic search spanned databases, including PubMed, EMBASE, and the Cochrane database of systematic reviews. Employing terms like "Carcinoma, Adenoid Cystic" and "trial," the search focused on English full-text articles from April 1, 2010, to August 9, 2023. Inclusion criteria encompassed studies with patients having R/M AdCC, involving drug interventions. Study quality was assessed using the Newcastle-Ottawa Scale for retrospective studies, Cochrane ROBINS-I tool for non-randomised trials, and the ROB-2 tool for randomised controlled trials. FINDINGS: A total of 46 trials involving 1244 patients are included in this review, encompassing a variety of therapeutic approaches for R/M AdCC. Targeted therapies, particularly Apatinib at 500 mg, exhibit efficacy with a 47.1% objective response rate (ORR). Conversely, immunotherapeutic agents demonstrate suboptimal performance, with an overall ORR ranging from 0 to 18%. While Apatinib shows promise, the review underscores the imperative for a thorough exploration of drugs targeting unique mechanisms in the immunologically cold nature of R/M AdCC. CONCLUSIONS AND RELEVANCE: Substantial progress in systemic therapy for R/M AdCC is evident, driven by early-phase clinical trials, particularly with promising outcomes in VEGF-2 inhibitors. However, challenges persist, notably in immunotherapy due to the cancer's immunologically cold nature. Ongoing research, prioritising early-stage trials, is crucial, emphasising exploration of emerging therapies like cell therapy and antibody-drug conjugates. Transitioning to Phase III trials is essential for more precise therapeutic insights. Collaborative efforts and a focus on personalised precision medicine are vital for overcoming challenges and advancing our understanding of treatment efficacy in this rare cancer.

Predictive value of metabolism and its heterogeneity parameters measured by preoperative 18 F-FDG PET/CT for mediastinal occult lymph node metastasis in cN0 lung invasive adenocarcinoma.

OBJECTIVE: To explore the potential of intratumoral metabolism and its heterogeneous parameters, as measured by preoperative fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) imaging, to predict mediastinal occult lymph node metastasis in cN0 lung invasive adenocarcinoma. SUBJECTS AND METHODS: Seventy five patients were consecutively enrolled from January 2018 to December 2022. All patients underwent 18F-FDG PET/CT scans within two weeks before surgery, and had mediastinal lymph node metastasis confirmed by pathologic diagnosis after surgery. Metabolic parameters including the maximum standardized uptake value (SUVmax), mean SUV (SUVmean), maximum average SUV (SUVpeak), tumor metabolic volume (MTV), and metabolic heterogeneity (HF) were measured. The relationship between primary focal metabolism, its heterogeneity parameters, and occult mediastinal lymph node metastasis was analyzed using an independent-sample t-test, analysis of covariance, and Mann-Whitney U test. A multivariate logistic regression model was used to analyze independent risk factors for mediastinal lymph node metastasis, while the receiver operating characteristic (ROC) curve assessed the predictive value of metabolic heterogeneity parameters for mediastinal occult lymph node metastasis. RESULTS: A total of 20 out of 75 patients (26.7%) were pathologically confirmed to have mediastinal lymph node metastasis. Analysis of covariance showed that the SUVmax, SUVmean, SUVpeak and MTV were significantly higher in patients with metastasis than in those without (all P<0.05). The metabolic heterogeneity parameters HF2 and HF3 were significantly higher in patients with mediastinal lymph node metastasis than in those without (P=0.013, 0.001), but not HF1. Multivariate Logistic regression analysis identified that tumor size, SUVmax, SUVpeak, lymph node SUVmax, and HF2 of the primary tumor as independent risk factors for mediastinal lymph node metastasis. Metabolic heterogeneity 3 demonstrated high predictive value for mediastinal occult lymph node metastasis (AUC=0.720, P=0.004). CONCLUSION: Metabolism and heterogeneity, as measured by preoperative 18F-FDG PET/CT in lung invasive adenocarcinoma, potentially have clinical value for predicting mediastinal occult lymph node metastasis.

Stimulation by exosomes from hypoxia-preconditioned hair follicle mesenchymal stem cells facilitates mitophagy by inhibiting the PI3K/AKT/mTOR signaling pathway to alleviate ulcerative colitis.

Background: Ulcerative colitis (UC) is an intestinal inflammatory disease that is strongly associated with mitochondrial damage and dysfunction as well as mitophagy and lacks of satisfactory treatments. Hair follicle mesenchymal stem cell (HF-MSC)-derived exosomes owe benefit effectiveness on inflammatory therapies. Hypoxia-preconditioned HF-MSCs exhibit enhanced proliferation and migration abilities, and their exosomes exert stronger effects than normal exosomes. However, the therapeutic function of Hy-Exos in UC is unknown. Methods: The inflammation model was established with LPS-treated MODE-K cells, and the mouse UC model was established by dextran sulfate sodium (DSS) administration. The therapeutic effects of HF-MSC-derived exosomes (Exos) and hypoxia-preconditioned HF-MSC-derived exosomes (Hy-Exos) were compared in vitro and in vivo. Immunofluorescence staining and western blotting were used to explore the effects of Hy-Exos on mitochondrial function, mitochondrial fission and fusion and mitophagy. MiRNA sequencing analysis was applied to investigate the differences in components between Exos and Hy-Exos. Results: Hy-Exos had a better therapeutic effect on LPS-treated MODE-K cells and DSS-induced UC mice. Hy-Exos promoted colonic tight junction proteins expression, suppressed the oxidative stress response, and reduced UC-related inflammatory injury. Hy-Exos may exert these effects via miR-214-3p-mediated inhibition of the PI3K/AKT/mTOR signaling pathway, maintenance of mitochondrial dynamic stability, alleviation of mitochondrial dysfunction and enhancement of mitophagy. Conclusion: This study revealed a vital role for Hy-Exos in suppressing inflammatory progression in UC and suggested that miR-214-3p is a potential critical target for Hy-Exos in alleviating UC.

Oxaliplatin-induced upregulation of exosomal miR-424-3p derived from human bone marrow mesenchymal stem cells attenuates progression of gastric cancer cells.

Chemotherapy, particularly with oxaliplatin, is a key treatment for advanced gastric cancer (GC), and exosomes derived from human bone marrow mesenchymal stem cells (hBM-MSCs) play a vital role in the tumor microenvironment. The study aims to elucidate the previously unexplored role of exosomes derived from hBM-MSCs in GC tumorigenesis, especially under the influence of chemotherapy. We conducted an experimental study, utilizing miRNA sequencing and biological experiments, to analyze the tumorigenicity of exosomal miR-424-3p secreted by hBM-MSCs and its target gene RHOXF2 in GC cell lines. The results were confirmed through experimentation using a xenograft mouse model. This study demonstrated the role of hBM-MSCs in the GC microenvironment, focusing on their epithelial-mesenchymal transition (EMT) facilitation through exosomes, which led to enhanced tumorigenicity in GC cells. Intriguingly, this pro-tumor effect was abrogated when hBM-MSCs were treated with oxaliplatin. Exosomal miRNA sequencing revealed that oxaliplatin can upregulate the levels of miR-424-3p in exosomes secreted by hBM-MSCs, thereby inhibiting the EMT process in GC cells. Furthermore, miR-424-3p was identified to target and downregulate RHOXF2 expression, impeding the malignant behavior of GC cells both in vitro and in the mouse model. These findings uncover a potential hidden mechanism of oxaliplatin's anti-tumor action and propose the delivery of miR-424-3p via exosomes as a promising avenue for anti-tumor therapy.

Resection of extensive segments of inferior vena cava without reconstruction in the treatment of renal carcinoma with inferior vena cava tumor thrombus: A case report.

We present a 55-year-old male patient with right renal carcinoma with long inferior vena cava (IVC) tumor thrombus who underwent robot-assisted laparoscopic radical nephrectomy with extensive IVC resection and left renal vein ligation. The patient had a history of hematuria only prior to admission. Our case involved resection of the entire abdominal segment of the IVC and left renal vein without reconstruction. Unfortunately, the patient passed away over a year after the surgery due to brain metastasis.

N-glycosylation of SnRK2s affects NADPH maintenance in peroxisomes during prolonged ABA signalling.

Unfavourable conditions, such as prolonged drought and high salinity, pose a threat to the survival and agricultural yield of plants. The phytohormone ABA plays a key role in the regulation of plant stress adaptation and is often maintained at high levels for extended periods. While much is known about ABA signal perception and activation in the early signalling stage, the molecular mechanism underlying desensitization of ABA signalling remains largely unknown. Here we demonstrate that in the endoplasmic reticulum (ER)-Golgi network, the key regulators of ABA signalling, SnRK2.2/2.3, undergo N-glycosylation, which promotes their redistribution from the nucleus to the peroxisomes in Arabidopsis roots and influences the transcriptional response in the nucleus during prolonged ABA signalling. On the peroxisomal membrane, SnRK2s can interact with glucose-6-phosphate (G6P)/phosphate translocator 1 (GPT1) to maintain NADPH homeostasis through increased activity of the peroxisomal oxidative pentose phosphate pathway (OPPP). The resulting maintenance of NADPH is essential for the modulation of hydrogen peroxide (H2O2) accumulation, thereby relieving ABA-induced root growth inhibition. The subcellular dynamics of SnRK2s, mediated by N-glycosylation suggest that ABA responses transition from transcriptional regulation in the nucleus to metabolic processes in the peroxisomes, aiding plants in adapting to long-term environmental stress.

Metastatic patterns of subcarinal, right and left recurrent laryngeal nerve lymph nodes in thoracic esophageal squamous cell carcinoma without neoadjuvant therapy.

PURPOSE: This research aimed to clarify the metastatic patterns of subcarinal, right and left recurrent laryngeal nerve lymph nodes in thoracic esophageal squamous cell carcinoma and to investigate appropriate strategies for lymph node dissection. METHODS: Patients with thoracic esophageal squamous cell carcinoma receiving esophagectomy from December 2020 to April 2024 were retrospectively analyzed. Risk factors for subcarinal, right and left recurrent laryngeal nerve lymph nodes metastasis were determined by chi-square test and multivariate logistic regression analysis. We visualized the metastasis rates of these specific lymph nodes based on the different clinicopathological characteristics. Correlation between subcarinal, right and left recurrent laryngeal lymph nodes metastasis and postoperative complications were also analyzed. RESULTS: A total of 503 thoracic esophageal squamous carcinoma patients who underwent esophagectomy were enrolled. The metastasis rates of subcarinal, right and left recurrent laryngeal nerve lymph nodes were 10.3%, 10.3%, and 10.9%, respectively. The lymphovascular invasion status and tumor location were the significant predictors for subcarinal and right recurrent laryngeal nerve lymph nodes metastasis, respectively (P < 0.001 and P = 0.013). For left recurrent laryngeal nerve lymph node metastasis, younger age (P = 0.020) and presence of lymphovascular invasion (P = 0.009) were significant risk factors. Additionally, pulmonary infection is the most frequent postoperative complication in patients with dissection of subcarinal, right and left recurrent laryngeal lymph nodes. There was no significant difference in the incidence of anastomotic leakage (P = 0.872), pulmonary infection (P = 0.139), chylothorax (P = 0.702), and hoarseness (P = 0.179) between the subcarinal lymph node dissection cohort and the reservation cohort. The incidence of hoarseness significantly increased in both right (P = 0.042) and left (P = 0.010) recurrent laryngeal nerve lymph nodes dissection cohorts compared by the reservation cohorts, with incidence rates of 5.9% and 6.7%, respectively. CONCLUSIONS: The metastasis rates of subcarinal, right and left recurrent laryngeal nerve lymph nodes in thoracic esophageal squamous cell carcinoma were all over 10%. The dissection of subcarinal lymph nodes does not increase postoperative complications risk, while recurrent laryngeal nerve lymph nodes dissection significantly increases the incidence of hoarseness. Thus, lymph node dissection of subcarinal lymph nodes should be conducted routinely, while recurrent laryngeal nerve lymph nodes dissection may be selectively performed in specific patients.

Development and Validation of a Stromal-Immune Signature to Predict Prognosis in Intrahepatic Cholangiocarcinoma.

Background: Intrahepatic cholangiocarcinoma (ICC) is a highly desmoplastic tumor with poor prognosis even after curative resection. We investigated the associations between the composition of the ICC stroma and immune cell infiltration and aimed to develop a stromal-immune signature to predict prognosis in surgically treated ICC. Patients and methods: We recruited 359 ICC patients and performed immunohistochemistry to detect α-smooth muscle actin (α-SMA), CD3, CD4, CD8, Foxp3, CD68, and CD66b. Aniline was used to stain collagen deposition. Survival analyses were performed to detect prognostic values of these markers. Recursive partitioning for a discrete-time survival tree was applied to define a stromal-immune signature with distinct prognostic value. We delineated an integrated stromal-immune signature based on immune cell subpopulations and stromal composition to distinguish subgroups with different recurrence-free survival (RFS) and overall survival (OS) time. Results: We defined four major patterns of ICC stroma composition according to the distributions of α-SMA and collagen: dormant (α-SMAlow/collagenhigh), fibrogenic (α-SMAhigh/collagenhigh), inert (α-SMAlow/collagenlow), and fibrolytic (α-SMAhigh/collagenlow). The stroma types were characterized by distinct patterns of infiltration by immune cells. We divided patients into six classes. Class I, characterized by high CD8 expression and dormant stroma, displayed the longest RFS and OS, whereas Class VI, characterized by low CD8 expression and high CD66b expression, displayed the shortest RFS and OS. The integrated stromal-immune signature was consolidated in a validation cohort. Conclusion: We developed and validated a stromal-immune signature to predict prognosis in surgically treated ICC. These findings provide new insights into the stromal-immune response to ICC.

Machine learning prediction of pulmonary oxygen uptake from muscle oxygen in cycling.

The purpose of this study was to test whether a machine learning model can accurately predict VO2 across different exercise intensities by combining muscle oxygen (MO2) with heart rate (HR). Twenty young highly trained athletes performed the following tests: a ramp incremental exercise, three submaximal constant intensity exercises, and three severe intensity exhaustive exercises. A Machine Learning model was trained to predict VO2, with model inputs including heart rate, MO2 in the left (LM) and right legs (RM). All models demonstrated equivalent results, with the accuracy of predicting VO2 at different exercise intensities varying among different models. The LM+RM+HR model performed the best across all intensities, with low bias in predicted VO2 for all intensity exercises (0.08 ml/kg/min, 95% limits of agreement: -5.64 to 5.81), and a very strong correlation (r = 0.94, p < 0.001) with measured VO2. Furthermore, the accuracy of predicting VO2 using LM+HR or RM+HR was higher than using LM+RM, and higher than the accuracy of predicting VO2 using LM, RM, or HR alone. This study demonstrates the potential of a machine learning model combining MO2 and HR to predict VO2 with minimal bias, achieving accurate predictions of VO2 for different intensity levels of exercise.

Anti-Inflammatory Effect of Xanthones from Hypericum beanii on Macrophage RAW 264.7 Cells through Reduced NO Production and TNF-α, IL-1ß, IL-6, and COX-2 Expression.

Hypericum beanii N. Robson, a perennial upright herb, predominantly inhabits temperate regions. This species has been utilized for the treatment of various inflammation-related diseases. One new xanthone 3,7-dihydroxy-1,6-dimethoxyxanthone (1) and twenty-three known xanthones (2-24) were isolated from the aerial parts of H. beanii. The structure of the new compound was determined based on high-resolution electrospray ionization mass spectroscopy (HR-ESIMS), nuclear magnetic resonance (NMR), Infrared Spectroscopy (IR), ultraviolet spectrophotometry (UV) spectroscopic data. The anti-inflammatory effects of all the isolates were assessed by measuring the inhibitory effect on nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages. Compounds 3,4-dihydroxy-2-methoxyxanthone (15), 1,3,5,6-tetrahydroxyxanthone (19), and 1,3,6,7-tetrahydroxyxanthone (22) exhibited significant anti-inflammatory effects at a concentration of 10 µM with higher potency compared to the positive control quercetin. Furthermore, compounds 15, 19, and 22 reduced inducible NO synthase (iNOS), tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), IL-6, and cyclooxygenase 2 (COX-2) mRNA expression in the LPS-stimulated RAW 264.7 macrophages, suggesting that these compounds may mitigate the synthesis of the aforementioned molecules at the transcriptional level, provisionally confirming their anti-inflammatory efficacy.

Tumor-associated macrophage clusters linked to immunotherapy in a pan-cancer census.

Transcriptional heterogeneity of tumor-associated macrophages (TAMs) has been investigated in individual cancers, but the extent to which these states transcend tumor types and represent a general feature of cancer remains unclear. We performed pan-cancer single-cell RNA sequencing analysis across nine cancer types and identified distinct monocyte/TAM composition patterns. Using spatial analysis from clinical study tissues, we assessed TAM functions in shaping the tumor microenvironment (TME) and influencing immunotherapy. Two specific TAM clusters (pro-inflammatory and pro-tumor) and four TME subtypes showed distinct immunological features, genomic profiles, immunotherapy responses, and cancer prognosis. Pro-inflammatory TAMs resided in immune-enriched niches with exhausted CD8+ T cells, while pro-tumor TAMs were restricted to niches associated with a T-cell-excluded phenotype and hypoxia. We developed a machine learning model to predict immune checkpoint blockade response by integrating TAMs and clinical data. Our study comprehensively characterizes the common features of TAMs and highlights their interaction with the TME.

Generic Enrichment Method for Liquid Chromatography-Multiple Reaction Monitoring-Mass Spectrometry Assay for Quantitative Measurement of Biological Therapeutics in Serum.

PURPOSE: The study aims to leverage the capabilities of Liquid Chromatography-Multiple Reaction Monitoring Mass Spectrometry (LC-MRM), a key technique in quantifying therapeutic proteins in pharmacokinetic studies. The focus is on demonstrating an enrichment method using ProteoMiner beads, which can be integrated with LC-MRM to detect low-abundance biotherapeutics in serum, such as monoclonal antibodies and gene therapy products. METHODS: The ProteoMiner enrichment method was employed and integrated with LC-MRM. The lower limit of quantification of serum drug substance concentrations was compared with that achievable with immuno-enrichment. The method used commercially available reagents, eliminating the need for assay-specific antibodies and reducing potential bias and development time. RESULTS: The ProteoMiner enrichment method showed comparable performance to immuno-enrichment, meeting traditional assay requirements in terms of precision, accuracy, and specificity. CONCLUSIONS: The ProteoMiner enrichment method, when combined with LC-MRM, offers a reliable and efficient alternative to immuno-enrichment for detecting and quantifying low-abundance biotherapeutics in serum. This approach, which uses commercially available reagents, can eliminate the bias and time associated with the development of assay-specific antibodies. It holds significant potential for accelerating pharmacokinetic analysis in both early and late stages of pharmaceutical development.

Esophageal ulcer and multisystem inflammatory syndrome after COVID-19: A case report.

BACKGROUND: Multisystem inflammatory syndrome in adults (MIS-A) is a rare but severe disease occurring several weeks after severe acute respiratory syndrome coronavirus 2 infection. It develops in adults with inflammation of different organs including the gastrointestinal tract, heart, kidneys, skin and hematopoietic system. CASE SUMMARY: We present a 58-year-old Chinese man diagnosed with MIS-A. His chief complaints were fever, generalized fatigue and anorexia, accompanied with rashes on his back. Further examination showed cardiac, renal and liver injury. He had melena and gastroscopy indicated esophageal ulcer and severe esophagitis. Repeated blood and sputum culture did not show growth of bacteria or fungi. Antibiotic treatment was stopped due to unsatisfactory performance. His condition improved after prednisone and other supportive treatment. CONCLUSION: Gastrointestinal involvement in MIS-A is not uncommon. Intestinal involvement predominates, and esophageal involvement is rarely reported. Esophageal ulcer with bleeding could also be a manifestation of MIS-A.

Preovulation body mass index and pregnancy after first frozen embryo transfer in patients with polycystic ovary syndrome and insulin resistance.

OBJECTIVE: To examine the association between preovulation body mass index and pregnancy outcomes after frozen embryo transfer in patients with polycystic ovary syndrome with insulin resistance. DESIGN: This was a single-center, retrospective cohort study. SUBJECTS: Women with infertility, diagnosed with polycystic ovary syndrome and insulin resistance, and treated at the Reproductive Medicine Center, Second People's Hospital of Nanning, China, between January 2020 and August 2023, were included. EXPOSURE: Patients were divided into four groups according to their body mass index (BMI): slim (<18.5 kg/m2), normal (18.5≤ BMI <24 kg/m2), overweight (24≤ BMI <28 kg/m2), or obese (≥28 kg/m2). MAIN OUTCOME MEASURES: The main pregnancy outcomes included rates of embryo implantation, biochemical pregnancy, clinical pregnancy, and ongoing pregnancy. RESULTS: In total, 282 eligible patients were included. A linear association was observed between the BMI and clinical pregnancy outcomes of the first frozen embryo transfer (P for nonlinearity>0.05). After accounting for all potential variables, each 1 kg/m2 increase in BMI was linked to a 2% decrease in the embryo implantation rate (P<0.05), 11% decrease in the frequency of biochemical pregnancy (P<0.05), and 9% decrease in the both clinical (P<0.05) and ongoing pregnancy rates. CONCLUSION: In patients with polycystic ovary syndrome and insulin resistance, a higher BMI was associated with lower rates of embryo implantation, biochemical pregnancy, clinical pregnancy, and ongoing pregnancy.

The implication of anti-Ro60 with or without anti-Ro52 antibody in patients with systemic lupus erythematosus.

OBJECTIVES: Anti-Ro60 and anti-Ro52 autoantibodies are frequently used as diagnostic biomarkers for Sjogren's disease, but their clinical significance in systemic lupus erythematosus (SLE) is not well characterised. METHODS: Patients fulfilling SLE classification criteria were studied according to their anti-Ro status. We defined Ro positivity (Ro+) as those who have either anti-Ro60 or anti-Ro52 positivity. Patient characteristics and disease outcomes, including High Disease Activity Status (HDAS) defined as an ever attainment of SLEDAI2K ≥10, adjusted mean SLEDAI (AMS), and time-adjusted mean clinical SLEDAI (excluding serologic activities) were compared using linear or logistic regressions. Furthermore, isolated or dual positivity of anti-Ro60 and anti-Ro52 were studied. RESULTS: Out of 409 patients, 47.2% were Ro+. Ro+ patients were predominantly Asian, had positive dsDNA and hypocomplementemia. They showed a higher likelihood of HDAS (OR 1.65, 95% CI 1.10-2.48, p= 0.015), AMS > 4 (OR 1.84, 1.18-2.88, p= 0.007), and more frequent use of glucocorticoids (OR 1.87, 1.16-3.03, p= 0.011) and immunosuppressants (OR 2.0, 1.26-3.17, p= 0.003). Additionally, 24.4% of Ro+ patients experienced sicca symptoms, and hypergammaglobulinemia was significantly more common. Multivariate analysis confirmed that Asian ethnicity, severe flares, AMS, hypocomplementemia, rheumatoid factor, proteinuria, leucopenia, and sicca symptoms were significantly linked to Ro positivity. CONCLUSION: Anti-Ro positivity is associated with higher disease activity and increased treatment needs. Ro positivity correlates with laboratory abnormalities such as hypocomplementemia and leucopenia. These findings highlight the importance of anti-Ro60/Ro52 testing in the clinical evaluation of SLE.

Light-activated hypoxia-sensitive biomimetic decoy efficiently cascading photodynamic-chemo therapy for breast cancer.

The hypoxic microenvironment within the tumor microenvironment of breast cancer imposes a challenge in overcoming chemotherapy resistance. In this investigation, we designed a novel strategy utilizing a light-controlled cascade targeting nanomedicine specifically tailored for enhanced immune therapy of breast cancer. Albumin nanoparticle was achieved by crosslinking, followed by loading TPZ and Ce6, and subsequent modification to enable selective binding with CD44 hyaluronic acid to form nanomedicine. Encouragingly, it was demonstrated the remarkable ability of the nanomedicine to effectively internalize into cellular entities, thereby inducing apoptosis in 4T1 cells efficiently in vitro when exposed to light irradiation. In vivo assessments showcased the exceptional aptitude of the nanomedicine not only for preferential accumulation within tumor tissues, but also for substantial suppression of tumor growth. Immune mechanisms have shown that nanomedicine treatment promoted the maturation of DCs in vivo, enhanced the proportion of CD8+ T cells in the spleen and tumor, and simultaneously upregulated the ratio of M1 macrophages favorable for anti-tumor effects. These outcomes collectively advance a fresh perspective for the clinical breast cancer therapy.