Recent research progress on tumour-specific responsive hydrogels.

Most existing hydrogels, even recently developed injectable hydrogels that undergo a reversible sol-gel phase transition in response to external stimuli, are designed to gel immediately before or after implantation/injection to prevent the free diffusion of materials and drugs; however, the property of immediate gelation leads to a very weak tumour-targeting ability, limiting their application in anticancer therapy. Therefore, the development of tumour-specific responsive hydrogels for anticancer therapy is imperative because tumour-specific responses improve their tumour-targeting efficacy, increase therapeutic effects, and decrease toxicity and side effects. In this review, we introduce the following three types of tumour-responsive hydrogels: (1) hydrogels that gel specifically at the tumour site; (2) hydrogels that decompose specifically at the tumour site; and (3) hydrogels that react specifically with tumours. For each type, their compositions, the mechanisms of tumour-specific responsiveness and their applications in anticancer treatment are comprehensively discussed.

High bioavailable testosterone levels increase the incidence of isolated REM sleep behavior disorder: Results from multivariable and network Mendelian randomization analysis.

OBJECTIVES: To explore the causal relationships between sex hormone levels and incidence of isolated REM sleep behavior disorder (iRBD). METHODS: In our study, we utilized Genome-Wide Association Studies (GWAS) data for iRBD, including 9447 samples with 1061 cases of iRBD provided by the International RBD Study Group. Initially, we conducted a two-sample univariate MR analysis to explore the impact of sex hormone-related indicators on iRBD. This was followed by the application of multivariable MR methods to adjust for other hormone levels and potential confounders. Finally, we undertook a network MR analysis, employing brain structure Magnetic Resonance Imaging (MRI) characteristics as potential mediators, to examine whether sex hormones could indirectly influence the incidence of iRBD by affecting brain structure. RESULTS: Bioavailable testosterone (BioT) is an independent risk factor for iRBD (Odds Ratio [95 % Confidence Interval] = 2.437 [1.308, 4.539], P = 0.005, corrected-P = 0.020), a finding that remained consistent even after adjusting for other sex hormone levels and potential confounders. Additionally, BioT appears to indirectly increase the risk of iRBD by reducing axial diffusivity and increasing the orientation dispersion index in the left cingulum and cingulate gyrus. CONCLUSIONS: Our research reveals that elevated levels of BioT contribute to the development of iRBD. However, the specific impact of BioT on different sexes remains unclear. Furthermore, high BioT may indirectly lead to iRBD by impairing normal pathways in the left cingulum and cingulate gyrus and fostering abnormal pathway formation.

Machine learning based on metabolomics unveils neutrophil extracellular trap-related metabolic signatures in non-small cell lung cancer patients undergoing chemoimmunotherapy.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the primary form of lung cancer, and the combination of chemotherapy with immunotherapy offers promising treatment options for patients suffering from this disease. However, the emergence of drug resistance significantly limits the effectiveness of these therapeutic strategies. Consequently, it is imperative to devise methods for accurately detecting and evaluating the efficacy of these treatments. AIM: To identify the metabolic signatures associated with neutrophil extracellular traps (NETs) and chemoimmunotherapy efficacy in NSCLC patients. METHODS: In total, 159 NSCLC patients undergoing first-line chemoimmunotherapy were enrolled. We first investigated the characteristics influencing clinical efficacy. Circulating levels of NETs and cytokines were measured by commercial kits. Liquid chromatography tandem mass spectrometry quantified plasma metabolites, and differential metabolites were identified. Least absolute shrinkage and selection operator, support vector machine-recursive feature elimination, and random forest algorithms were employed. By using plasma metabolic profiles and machine learning algorithms, predictive metabolic signatures were established. RESULTS: First, the levels of circulating interleukin-8, neutrophil-to-lymphocyte ratio, and NETs were closely related to poor efficacy of first-line chemoimmunotherapy. Patients were classed into a low NET group or a high NET group. A total of 54 differential plasma metabolites were identified. These metabolites were primarily involved in arachidonic acid and purine metabolism. Three key metabolites were identified as crucial variables, including 8,9-epoxyeicosatrienoic acid, L-malate, and bis(monoacylglycerol)phosphate (18:1/16:0). Using metabolomic sequencing data and machine learning methods, key metabolic signatures were screened to predict NET level as well as chemoimmunotherapy efficacy. CONCLUSION: The identified metabolic signatures may effectively distinguish NET levels and predict clinical benefit from chemoimmunotherapy in NSCLC patients.

Application of Multi-Rod Constructs for the Revision of Thoracolumbar Fractures.

OBJECTIVE: The revision procedure for failure of internal fixation after thoracolumbar fracture is controversial. Combined anterior and posterior surgery is associated with higher risk more intraoperative bleeding and tissue damage. The success rate of simple anterior surgery needs further confirmation, and posterior surgery lacks stability of internal fixation. This study evaluates the feasibility and surgical effect of multi-rod constructs in the revision of thoracolumbar fractures. METHODS: Eleven patients with thoracolumbar fractures who underwent previous construct failure and were treated with revision and internal fixation with the multi-rod technique from March 2017 to September 2018 were analyzed. The original internal fixation was removed and replaced in the medial insertion of satellite rods and bone graft. The average follow-up time was 15.97 months. The intraoperation blood loss, the time of the operation, activation and discharge and the rate of rod fracture were calculated. The sagittal Cobb angle before revision, after revision and at the last follow-up were compared. The clinical effect was evaluated by visual analogue scale (VAS) and Oswestry Disability Index questionnaire (ODI). RESULTS: The average operation time was 107 min, the intraoperative blood loss was 131.81 mL, the active time was 1.59 days, and the discharge time was 10.89 days. No rod fractured again during the follow-up period. The paired t-test was used to compare the Cobb angle, VAS score, and ODI before and after surgery. There was significant difference in the sagittal Cobb angle between the pre-revision and the posterior sagittal position (p = 0.000), and no significant difference was found between post-revision and last follow-up (p = 0.551). VAS and ODI were greatly improved at the last follow-up. CONCLUSION: The literature on revision of thoracolumbar fractures is insufficient and comprises varying opinions. This paper proposes a new treatment option. The application of the multi-rod constructs in the revision of thoracolumbar fractures is safe, simple, and effective and might provide guidance for future clinical work.

Integrating Vision-Language Models for Accelerated High-Throughput Nutrition Screening.

Addressing the critical need for swift and precise nutritional profiling in healthcare and in food industry, this study pioneers the integration of vision-language models (VLMs) with chemical analysis techniques. A cutting-edge VLM is unveiled, utilizing the expansive UMDFood-90k database, to significantly improve the speed and accuracy of nutrient estimation processes. Demonstrating a macro-AUCROC of 0.921 for lipid quantification, the model exhibits less than 10% variance compared to traditional chemical analyses for over 82% of the analyzed food items. This innovative approach not only accelerates nutritional screening by 36.9% when tested amongst students but also sets a new benchmark in the precision of nutritional data compilation. This research marks a substantial leap forward in food science, employing a blend of advanced computational models and chemical validation to offer a rapid, high-throughput solution for nutritional analysis.

A Case of Klebsiella pneumoniae infection.

INTRODUCTION: In recent years, hypervirulent Klebsiella pneumoniae (hvKp) has attracted increasing attention. It usually causes liver abscesses, which spread through the bloodstream to other parts such as the eyes, brain, lungs. 5.5% of all paroxysmal sympathetic hyperactivity syndrome are associated with infection, hydrocephalus, brain tumors, and some unknown causes. Younger patients with focal lesions of the brain parenchyma are at higher risk of paroxysmal sympathetic hyperactivity (PSH). CASE PRESENTATION: This case report details the clinical features of Klebsiella pneumoniae diagnosed in a healthy individual. In addition to liver abscesses, bacteremia, and hyperglycemia, there are also brain abscesses, hernias, and postoperative paroxysmal sympathetic hyperactivity, an unexpected association between diseases or symptoms. The patient stabilized after comprehensive treatment, including early drainage of abscesses, rapid pathogen diagnosis, and timely and appropriate antibiotics. At a two-month follow-up, no signs of infection recurrence were noted, and the patient regained neurological function and could participate in regular physical activity. DISCUSSION: Symptoms of Klebsiella pneumoniae infection usually appear gradually, and misdiagnosis is common. When young patients suddenly develop high fever and abscess at a particular site, Klebsiella pneumoniae infection should be considered routine. Paroxysmal sympathetic hyperactivity syndrome caused by infection is rare, but a clinical score (PSH assessment measure, PSH-AM score) should be performed when clinical features appear. Early diagnosis and treatment can improve the prognosis.

[The expression and prognosis prediction of CFL-1 in head and neck squamous cell carcinoma].

PURPOSE: The purpose of this study was to explore the expression, prognostic value and immune correlation of Cofilin 1 protein(CFL-1) in head and neck squamous cell carcinoma(HNSCC). METHODS: The expression and prognostic value of CFL-1 in head and neck squamous cell carcinoma(HNSCC) was explored in the cancer genome map database (TCGA) and gene expression total databases (GEO), and the potential immune pathway of CFL-1 in HNSCC was revealed by GESA and cibersoft analysis. The data were statistically analyzed using SPSS 26.0 software package. RESULTS: CFL-1 was significantly up-regulated in HNSCC tissue. The expression level of CFL-1 was significantly correlated with the overall survival status of HNSCC. High expression of CFL-1 was significantly associated with a lower overall survival rate. In addition, multivariate Cox survival analysis showed that CFL-1 expression was independent predictors of poor prognosis of HNSCC. GESA and cibersoft analysis showed that the imbalance of CFL-1 expression affected multiple signal pathways and infiltration of immune cells. CONCLUSIONS: CFL-1 is highly expressed in HNSCC and is significantly associated with poor prognosis of NHSCC. It is a potential prognostic marker of HNSCC.

Laser Acupuncture versus Liraglutide in Treatment of Obesity: A Multi-Institutional Retrospective Cohort Study.

BACKGROUND: Obesity is a global concern, driving the search for alternative treatments beyond lifestyle changes and medications. Laser acupuncture (LA) shows promise in obesity management, yet few studies compare it with FDA-approved medications. This study aimed to assess and compare LA's impact with liraglutide on weight reduction in obese individuals. METHODS: Data from the Chang Gung Research Database (CGRD) (2013-2018) were analyzed. Primary outcomes included changes in body weight and BMI within 180 days, with secondary outcomes measuring the proportion achieving 5%, 10%, and 15% weight loss. Adverse events were also assessed. RESULTS: Of 745 subjects (173 LA users, 572 liraglutide users), LA users lost more weight by day 180 (5.82 ± 4.39 vs. 2.38 ± 5.75 kg; p < 0.001) and had a greater BMI reduction (-2.27 ± 1.73 vs. -0.93 ± 2.25 kg/m2; p < 0.001). More LA users achieved 5% and 10% weight loss compared to liraglutide users (64.2% vs. 22.7%, 26.6% vs. 4.2%; all p < 0.001). After balancing baseline differences, LA's benefits remained significant. No adverse events were reported with LA. CONCLUSIONS: LA may offer superior weight reduction compared to liraglutide. Future studies should explore LA alone or in combination with liraglutide for obesity management.

Surface-Imprinted Polysiloxane with Recognition Ability Based on an ITO Layer for Rapid Detection of Fusarium oxysporum f. sp. cubense by the Naked Eye.

Direct observation by the naked eye of fluorescence-stained microbes adsorbed on surface imprinted polymers (SIPs) is highly challenging and limited by speed, accuracy and the semiquantitative nature of the method. In this study, we tested for the presence of spores of Fusarium oxysporum f. sp. cubense race 4 (Foc4), which cause severe banana Fusarium wilt disease and reduces the area of banana plants. This kind of spore can become dormant in soil, which means that the detection of secreted molecules (molecular imprinting) in soil may be inaccurate; detection methods such as polymerase chain reaction (PCR) and Raman spectroscopy are more accurate but time-consuming and inconvenient. Therefore, a semiquantitative and rapid SIP detection method for Foc4 was proposed. Based on the ITO conductive layer, a reusable and naked-eye-detectable Foc4-PDMS SIP film was prepared with a site density of approximately 9000 mm-2. Adsorption experiments showed that when the Foc4 spore concentration was between 104 to 107 CFU/mL, the number of Foc4 spores adsorbed and the fluorescence intensity were strongly correlated with the concentration and could be fully distinguished by the naked eye after fluorescence staining. Adsorption tests on other microbes showed that the SIP film completely recognized only the Foc series. All the results were highly consistent with the naked-eye observations after fluorescence staining, and the results of the Foc4-infected soil experiment were also close to the ideal situation. Taken together, these results showed that Foc4-PDMS SIPs have the ability to rapidly and semiquantitatively detect the concentration of Foc in soil, which can provide good support for banana cultivation. This method also has potential applications in the detection of other fungal diseases.

Bloodmeals fuel dengue virus replication in the female mosquito Aedes aegypti.

Vector competence defines the ability of a vector to acquire, host, and transmit a pathogen. Understanding the molecular determinants of the mosquitos' competence to host dengue virus (DENV) holds promise to prevent its transmission. To this end, we employed RNA-seq to profile mRNA transcripts of the female Aedes aegypti mosquitos feeding on naïve vs viremic mouse. While most transcripts (12,634) did not change their abundances, 360 transcripts showed decreases. Biological pathway analysis revealed representatives of the decreased transcripts involved in the wnt signaling pathway and hippo signaling pathway. One thousand three hundred fourteen transcripts showed increases in abundance and participate in 21 biological pathways including amino acid metabolism, carbon metabolism, fatty acid metabolism, and oxidative phosphorylation. Inhibition of oxidative phosphorylation with antimycin A reduced oxidative phosphorylation activity and ATP concentration associated with reduced DENV replication in the Aedes aegypti cells. Antimycin A did not affect the amounts of the non-structural proteins 3 and 5, two major components of the replication complex. Ribavirin, an agent that reduces GTP concentration, recapitulated the effects of reduced ATP concentration on DENV replication. Knocking down one of the oxidative phosphorylation components, ATP synthase subunit ß, reduced DENV replication in the mosquitos. In summary, our results suggest that DENV enhances metabolic pathways in the female Aedes aegypti mosquitos to supply nutrients and energy for virus replication. ATP synthase subunit ß knockdown might be exploited to reduce the mosquitos' competence to host and transmit DENV. IMPORTANCE: Through evolution, the mosquito-borne viruses have adapted to the blood-feeding behaviors of their opportunist hosts to fulfill a complete lifecycle in humans and mosquitos. Disruption in the mosquitos' ability to host these viruses offers strategies to prevent diseases caused by them. With the advent of genomic tools, we discovered that dengue virus (DENV) benefited from the female mosquitos' bloodmeals for metabolic and energetic supplies for replication. Chemical or genetic disruption in these supplies reduced DENV replication in the female mosquitos. Our discovery can be exploited to produce genetically modified mosquitos, in which DENV infection leads to disruption in the supplies and thereby reduces replication and transmission. Our discovery might be extrapolated to prevent mosquito-borne virus transmission and the diseases they cause.

Prostate Cancer Recurrence: Examining the Role of Salvage Radiotherapy Field and Risk Factors for Regional Disease Recurrence Captured on 18F-DCFPyL PET/CT.

PURPOSE: The role of elective pelvic nodal irradiation in salvage radiotherapy (sRT) remains controversial. Utilizing 18F-DCFPyL PET/CT, this study aimed to investigate differences in disease distribution after whole pelvic (WPRT) or prostate bed (PBRT) radiotherapy and to identify risk factors for pelvic lymph node (LN) relapse. METHODS: This retrospective study included patients with PSA > 0.1 ng/mL post-radical prostatectomy (RP) or post-RP and sRT who underwent 18F-DCFPyL PET/CT. Disease distribution on 18F-DCFPyL PET/CT after sRT was compared using Chi-square tests. Risk factors were tested for association with pelvic LN relapse after RP and salvage PBRT using logistic regression. RESULTS: 979 18F-DCFPyL PET/CTs performed at our institution between 1/1/2022 - 3/24/2023 were analyzed. There were 246 patients meeting criteria, of which 84 received salvage RT after RP (post-salvage RT group) and 162 received only RP (post-RP group). Salvage PBRT patients (n = 58) had frequent pelvic nodal (53.6%) and nodal-only (42.6%) relapse. Salvage WPRT patients (n = 26) had comparatively lower rates of pelvic nodal (16.7%, p = 0.002) and nodal-only (19.2%, p = 0.04) relapse. The proportion of distant metastases did not differ between the two groups. Multiple patient characteristics, including ISUP grade and seminal vesicle invasion, were associated with pelvic LN disease in the post-RP group. CONCLUSION: At PSA persistence or progression, salvage WPRT resulted in lower rates of nodal involvement than salvage PBRT, but did not reduce distant metastases. Certain risk factors increase the likelihood of pelvic LN relapse after RP and can help inform salvage RT field selection.

Oncological outcomes in minimally invasive vs. open distal pancreatectomy: a systematic review and network meta-analysis.

Background: Advancements in surgical techniques have improved outcomes in patients undergoing pancreatic surgery. To date there have been no meta-analyses comparing robotic and laparoscopic approaches for distal pancreatectomies (DP) in patients with pancreatic adenocarcinoma (PDAC). This systematic review and network meta-analysis aims to explore the oncological outcomes of laparoscopic distal pancreatectomy (LDP), robotic distal pancreatectomy (RDP) and open distal pancreatectomy (ODP). Methods: A systematic search was conducted for studies reporting laparoscopic, robotic or open surgery for DP. Frequentist network meta-analysis of oncological outcomes (overall survival, resection margins, tumor recurrence, examined lymph nodes, administration of adjuvant therapy) were performed. Results: Fifteen studies totalling 9,301 patients were included in the network meta-analysis. 1,946, 605 and 6,750 patients underwent LDP, RDP and ODP respectively. LDP (HR: 0.761, 95% CI: 0.642-0.901, p = 0.002) and RDP (HR: 0.757, 95% CI: 0.617-0.928, p = 0.008) were associated with overall survival (OS) benefit when compared to ODP. LDP (HR: 1.00, 95% CI: 0.793-1.27, p = 0.968) was not associated with OS benefit when compared to RDP. There were no significant differences between LDP, RDP and ODP for resection margins, tumor recurrence, examined lymph nodes and administration of adjuvant therapy. Conclusion: This study highlights the longer OS in both LDP and RDP when compared to ODP for patients with PDAC. Systematic Review Registration: https://www.crd.york.ac.uk/, PROSPERO (CRD42022336417).

Radiomics models of contrast-enhanced computed tomography for predicting the activity and prognosis of acute pancreatitis.

BACKGROUND: The modified pancreatitis activity scoring system (mPASS) was proposed to assess the activity of acute pancreatitis (AP) while it doesn't include indicators that directly reflect pathophysiology processes and imaging characteristics. OBJECTIVES: To determine the threshold of admission mPASS and investigate radiomics and laboratory parameters to construct a model to predict the activity of AP. METHODS: AP inpatients at institution 1 were randomly divided into training and validation groups based on a 5:5 ratio. AP inpatients at Institution 2 were served as test group. The cutoff value of admission mPASS scores in predicting severe AP was selected to divide patients into high and low level of disease activity group. LASSO was used in screening features. Multivariable logistic regression was used to develop radiomics model. Meaningful laboratory parameters were used to construct combined model. RESULTS: There were 234 (48 years ± 10, 155 men) and 101 (48 years ± 11, 69 men) patients in two institutions. The threshold of admission mPASS score was 112.5 in severe AP prediction. The AUC of the radiomics model was 0.79, 0.72, and 0.76 and that of the combined model incorporating rad-score and white blood cell were 0.84, 0.77, and 0.80 in three groups for activity prediction. The AUC of the combined model in predicting disease without remission was 0.74. CONCLUSIONS: The threshold of admission mPASS was 112.5 in predicting severe AP. The model based on CECT radiomics has the ability to predict AP activity. Its ability to predict disease without remission is comparable to mPASS. CRITICAL RELEVANCE STATEMENT: This work is the first attempt to assess the activity of acute pancreatitis using contrast-enhanced CT radiomics and laboratory parameters. The model provides a new method to predict the activity and prognosis of AP, which could contribute to further management. KEY POINTS: Radiomics features and laboratory parameters are associated with the activity of acute pancreatitis. The combined model provides a new method to predict the activity and prognosis of AP. The ability of the combined model is comparable to the modified Pancreatitis Activity Scoring System.

The Potential Neurological Impact of Intraoperative Hyponatremia Using Histidine-Tryptophan-Ketoglutarate Cardioplegia Infusion in Adult Cardiac Surgery.

Background and Objectives: The relationship between histidine-tryptophan-ketoglutarate (HTK)-induced hyponatremia and brain injury in adult cardiac surgery patients is unclear. This study analyzed postoperative neurological outcomes after intraoperative HTK cardioplegia infusion. Materials and Methods: A prospective cohort study was conducted on 60 adult patients who underwent cardiac surgery with cardiopulmonary bypass. Of these patients, 13 and 47 received HTK infusion and conventional hyperkalemic cardioplegia, respectively. The patients' baseline characteristics, intraoperative data, brain injury markers, Mini-Mental State Examination (MMSE) scores, and quantitative electroencephalography (qEEG) data were collected. Electrolyte changes during cardiopulmonary bypass, the degree of hyponatremia, and any associated brain insults were evaluated. Results: The HTK group presented with acute hyponatremia during cardiopulmonary bypass, which was intraoperatively corrected through ultrafiltration and normal saline administration. Postoperative sodium levels were higher in the HTK group than in the conventional cardioplegia group. The change in neuron-specific enolase levels after cardiopulmonary bypass was significantly higher in the HTK group (p = 0.043). The changes showed no significant differences using case-control matching. qEEG analysis revealed a significant increase in relative delta power in the HTK group on postoperative day (POD) 7 (p = 0.018); however, no significant changes were noted on POD 60. The MMSE scores were not significantly different between the two groups on POD 7 and POD 60. Conclusions: HTK-induced acute hyponatremia and rapid correction with normal saline during adult cardiac surgeries were associated with a potential short-term but not long-term neurological impact. Further studies are required to determine the necessity of correction for HTK-induced hyponatremia.

Ba2Ga2F6(IO3)(PO4): the first fluoride-containing iodate-phosphate with a 1D [Ga2F6(IO3)(PO4)]4- helix chain.

Herein, the first F-containing iodate-phosphate, namely Ba2Ga2F6(IO3)(PO4), was prepared via a hydrothermal reaction, in which HPF6 (70 wt% solution in water) was used as the source of both fluoride and phosphate anions for the first time. Ba2Ga2F6(IO3)(PO4) features an unprecedented 1D [Ga2F6(IO3)(PO4)]4- helix chain, composed of a 1D Ga(1)(IO3)O4F chain via the bridging of 0D Ga(2)(PO4)F5. The UV-Vis spectrum shows that Ba2Ga2F6(IO3)(PO4) has a wide bandgap with a short-UV absorption edge (4.35 eV; 253 nm). Birefringence measurement under a polarizing microscope shows that Ba2Ga2F6(IO3)(PO4) displays a moderate birefringence of 0.072@550 nm, which is consistent with the value (0.070@550 nm) obtained by DFT calculations, indicating that Ba2Ga2F6(IO3)(PO4) has potential applications as a short-UV birefringent material. This study highlights the crucial role played by the incorporation of specific functional groups into compounds, shedding light on their contribution to promising inorganic functional materials.

Relay Annulation of Ammonium Ylides with Oxindole-Derived α,ß-Unsaturated Ketimines: Catalytic Construction of Spiro-polycyclic Oxindoles.

An ammonium ylide-based relay annulation was disclosed, which uses DABCO as the catalyst and oxindole-derived α,ß-unsaturated ketimines and γ-bromo-crotonates as the starting materials. This method enables the rapid assembly of a series of structurally novel spiro-polycyclic oxindoles containing a bicyclo[4.1.0]heptane moiety through simultaneous generation of three new bonds and two rings in one step under mild reaction conditions.

Integrated Network Pharmacology Analysis and Experimental Validation to Elucidate the Mechanism of Acteoside in Treating Diabetic Kidney Disease.

Background: Acteoside, an active ingredient found in various medicinal herbs, is effective in the treatment of diabetic kidney disease (DKD); however, the intrinsic pharmacological mechanism of action of acteoside in the treatment of DKD remains unclear. This study utilizes a combined approach of network pharmacology and experimental validation to investigate the potential molecular mechanism systematically. Methods: First, acteoside potential targets and DKD-associated targets were aggregated from public databases. Subsequently, utilizing protein-protein interaction (PPI) networks, alongside GO and KEGG pathway enrichment analyses, we established target-pathway networks to identify core potential therapeutic targets and pathways. Further, molecular docking facilitated the confirmation of interactions between acteoside and central targets. Finally, the conjectured molecular mechanisms of acteoside against DKD were verified through experimentation on unilateral nephrectomy combined with streptozotocin (STZ) rat model. The underlying downstream mechanisms were further investigated. Results: Network pharmacology identified 129 potential intersected targets of acteoside for DKD treatment, including targets such as AKT1, TNF, Casp3, MMP9, SRC, IGF1, EGFR, HRAS, CASP8, and MAPK8. Enrichment analyses indicated the PI3K-Akt, MAPK, Metabolic, and Relaxin signaling pathways could be involved in this therapeutic context. Molecular docking revealed high-affinity binding of acteoside to PIK3R1, AKT1, and NF-κB1. In vivo studies validated the therapeutic efficacy of acteoside, demonstrating reduced blood glucose levels, improved serum Scr and BUN levels, decreased 24-hour urinary total protein (P<0.05), alongside mitigated podocyte injury (P<0.05) and ameliorated renal pathological lesions. Furthermore, this finding indicates that acteoside inhibits the expression of pyroptosis markers NLRP3, Caspase-1, IL-1ß, and IL-18 through the modulation of the PI3K/AKT/NF-κB pathway. Conclusion: Acteoside demonstrates renoprotective effects in DKD by regulating the PI3K/AKT/NF-κB signaling pathway and alleviating pyroptosis. This study explores the pharmacological mechanism underlying acteoside's efficacy in DKD treatment, providing a foundation for further basic and clinical research.

Contemporary Management of Pediatric Brainstem Tumors.

Brain tumors are the second most common malignancy in childhood. Around 15-20% of pediatric brain tumors occur in the brainstem. The most common type of brainstem tumor are diffuse tumors in the ventral pons, whereas focal tumors tend to arise from the midbrain, medulla, and dorsal pons. Glioma is the most common pathological entity. Contemporary management consists of surgery, radiotherapy, chemotherapy, and other adjuvant treatment. Surgical options range from biopsy to radical excision. Biopsy can be performed for diagnostic and prognostic purposes, or in the setting of clinical trials, mainly for diffuse intrinsic pontine gliomas. For focal tumors, surgeons need to carefully balance clinical outcomes against possible neurological sequelae in order to achieve maximal safe resection. Radiotherapy is essential for control of high-grade tumors and may be applied to residual or recurrent low-grade tumors. Proton therapy may provide similar efficacy and less neurotoxicity in comparison to conventional photon therapy. Oncological treatment continues to evolve from conventional chemotherapy to targeted therapy, immunotherapy, and other novel treatment methods and holds great potential as adjuvant therapy for pediatric brainstem tumors.

1,5-Hydrogen atom transfer of α-iminyl radical cations: a new platform for relay annulation for pyridine derivatives and axially chiral heterobiaryls.

The exploitation of new reactive species and novel transformation modes for their synthetic applications have significantly promoted the development of synthetic organic methodology, drug discovery, and advanced functional materials. α-Iminyl radical cations, a class of distonic ions, exhibit great synthetic potential for the synthesis of valuable molecules. For their generation, radical conjugate addition to α,ß-unsaturated iminium ions represents a concise yet highly challenging route, because the in situ generated species are short-lived and highly reactive and they have a high tendency to cause radical elimination (ß-scission) to regenerate the more stable iminium ions. Herein, we report a new transformation mode of the α-iminyl radical cation, that is to say, 1,5-hydrogen atom transfer (1,5-HAT). Such a strategy can generate a species bearing multiple reactive sites, which serves as a platform to realize (asymmetric) relay annulations. The present iron/secondary amine synergistic catalysis causes a modular assembly of a broad spectrum of new structurally fused pyridines including axially chiral heterobiaryls, and exhibits good functional group tolerance. A series of mechanistic experiments support the α-iminyl radical cation-induced 1,5-HAT, and the formation of several radical species in the relay annulations. Various synthetic transformations of the reaction products demonstrate the usefulness of this relay annulation protocol for the synthesis of significant molecules.

[Application of metagenomic next-generation sequencing technology in preterm infants with sepsis following antibiotic use]. / å®åŸºå› ç»„äºŒä»£æµ‹åºæŠ€æœ¯åœ¨æŠ—ç”Ÿç´ ä½¿ç”¨åŽçš„æ—©äº§å„¿è´¥è¡€ç—‡ä¸­çš„åº”ç”¨.

OBJECTIVES: To explore the value of metagenomic next-generation sequencing (mNGS) technology in the etiological diagnosis of sepsis in preterm infants following antibiotic use. METHODS: A retrospective analysis of medical records for 45 preterm infants with sepsis who were treated at Henan Provincial People's Hospital. All patients received antibiotic treatment for ≥3 days and underwent both blood culture and mNGS testing. The detection rates of pathogens by blood culture and mNGS testing were compared. RESULTS: The positive detection rate of pathogens by blood mNGS was higher than that by blood culture (44% vs 4%; P<0.001). Blood mNGS detected 28 strains of pathogens, including 23 bacteria, 4 fungi, and 1 Ureaplasma parvum. Blood culture identified one case each of Rhodotorula mucilaginosa and Klebsiella pneumoniae. In the group treated with antibiotics for >10 days, the positive rate of blood mNGS testing was higher than that of blood culture (40% vs 3%; P<0.001); similarly, in the group treated with antibiotics for ≤10 days, the positive rate of blood mNGS testing was also higher than that of blood culture (53% vs 7%; P=0.020). Treatment plans were adjusted based on blood mNGS results for 13 patients, with an effectiveness rate of 85% (11/13). CONCLUSIONS: In preterm infants with sepsis following antibiotic use, the positive rate of pathogen detection by blood mNGS is higher than that by blood culture and is unaffected by the duration of antibiotic use. Therefore, mNGS testing can be considered for confirming pathogens when clinical suspicion of infection is high but blood culture fails to detect the pathogen.