Uncovering the pharmacological mechanisms of Patchouli essential oil for treating ulcerative colitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Pogostemonis Herba has long been used in traditional Chinese medicine to treat inflammatory disorders. Patchouli essential oil (PEO) is the primary component of Pogostemonis Herba, and it has been suggested to offer curative potential when applied to treat ulcerative colitis (UC). However, the pharmacological mechanisms of PEO for treating UC remain to be clarified. AIM OF THE STUDY: To elucidate the pharmacological mechanisms of PEO for treating UC. METHODS AND RESULTS: In the present study, transcriptomic and network pharmacology approaches were combined to clarify the mechanisms of PEO for treating UC. Our results reveal that rectal PEO administration in UC model mice significantly alleviated symptoms of UC. In addition, PEO effectively suppressed colonic inflammation and oxidative stress. Mechanistically, PEO can ameliorate UC mice by modulating gut microbiota, inhibiting inflammatory targets (OPTC, PTN, IFIT3, EGFR, and TLR4), and inhibiting the PI3K-AKT pathway. Next, the 11 potential bioactive components that play a role in PEO's anti-UC mechanism were identified, and the therapeutic efficacy of the pogostone (a bioactive component) in UC mice was partially validated. CONCLUSION: This study highlights the mechanisms through which PEO can treat UC, providing a rigorous scientific foundation for future efforts to develop and apply PEO for treating UC.

Bioactive nanocomposite hydrogel enhances postoperative immunotherapy and bone reconstruction for osteosarcoma treatment.

Osteosarcoma, a malignant bone tumor often characterized by high hedgehog signaling activity, residual tumor cells, and substantial bone defects, poses significant challenges to both treatment response and postsurgical recovery. Here, we developed a nanocomposite hydrogel for the sustained co-delivery of bioactive magnesium ions, anti-PD-L1 antibody (αPD-L1), and hedgehog pathway antagonist vismodegib, to eradicate residual tumor cells while promoting bone regeneration post-surgery. In a mouse model of tibia osteosarcoma, this hydrogel-mediated combination therapy led to remarkable tumor growth inhibition and hence increased animal survival by enhancing the activity of tumor-suppressed CD8+ T cells. Meanwhile, the implanted hydrogel improved the microenvironment of osteogenesis through long-term sustained release of Mg2+, facilitating bone defect repair by upregulating the expression of osteogenic genes. After 21 days, the expression levels of ALP, COL1, RUNX2, and BGLAP in the Vis-αPD-L1-Gel group were approximately 4.1, 5.1, 5.5, and 3.4 times higher than those of the control, respectively. We believe that this hydrogel-based combination therapy offers a potentially valuable strategy for treating osteosarcoma and addressing the tumor-related complex bone diseases.

Unlocking the structure and cation synergistic modulation of Prussian blue analogues with double redox mechanism for improved aqueous nonmetallic ion storage.

Prussian blue analogs (PBAs) exhibit high energy density and a good electrochemical stability window in aqueous non-metallic ion batteries, which is conducive to achieving high energy output and stable operation. Additionally, their synthesis process is simple and environmentally friendly, meeting the demands of sustainable development. However, the poor conductivity, structural stability issues, and inadequate ion diffusion pathways limit their application in batteries. To overcome these challenges, researchers have adopted various optimization strategies: enhancing the conductivity of PBAs by compositing with high-conductivity carbon materials such as graphite, carbon nanotubes, or graphene; optimizing synthesis conditions such as temperature and reaction time to improve the defect and structural water content of PBAs, thereby enhancing their stability and electrochemical performance; employing surface modification techniques, such as conductive polymer encapsulation and acid etching, to improve their electrochemical stability and ion transport performance; and optimizing ion diffusion efficiency and battery kinetics by selecting suitable electrolytes and additives. These comprehensive measures contribute to improving the electrochemical performance of PBAs and promoting the development of their commercial applications. Based on prior research advancements, we introduce a novel synergistic regulation strategy: the creation of multi-redox-active centers to augment the transport capability of non-metallic ions and the optimization of defect structures through the establishment of a metal ion concentration gradient, thereby enhancing both electrochemical stability and performance.

Validation of the Global Leadership Initiative on Malnutrition Criteria for Predicting Adverse Outcomes in Acute Pancreatitis.

Background and Aim: The Global Leadership Initiative on Malnutrition (GLIM) has proposed criteria for the diagnosis of malnutrition. No studies validated the GLIM criteria in acute pancreatitis (AP). The present study aimed to validate the predictive capacity of GLIM criteria for adverse outcomes in AP patients. Patients and Methods: Clinical data of 269 patients with AP were analyzed retrospectively. The Nutritional Risk Screening 2002 (NRS2002) was chosen as the screening tool. Multivariate logistic regression analyses evaluated the adverse clinical outcomes in malnourished patients. Results: Overall, 160 patients (59.5%) were at nutritional risk and 38 (14.1%) were malnourished. Reduced muscle mass/ low body mass index + inflammation combinations contributed most to malnutrition overall and in each subgroup. The malnourished group had lower hemoglobin, neutrophils, albumin, total cholesterol, and triglycerides than the well-nourished group. The malnourished group had higher hospitalization costs (CNY, 11319.34 vs 9258.22, p <0.001) and more local complications (34.2% vs 14.7%, p =0.009) than the well-nourished group. There was an interaction between malnutrition and overweight/obesity on local complications (p for interaction = 0.023). Multivariate logistic regression showed malnutrition was significantly associated with local complications (OR 12.2, 95% CI: 2.51-59.37), infectious complications (OR 9.95, 95% CI: 1.25-79.44) and composite adverse outcome (OR 4.78, 95% CI: 1.05-21.73) in the overweight/obesity subgroup. There was no association between malnutrition and the rate of various adverse outcomes in the non-overweight/obesity subgroup. Additionally, we observed an association between malnutrition and composite adverse outcome (OR 6.75, 95% CI: 1.49-30.68) in patients <70 years only in females. Conclusion: Malnourished AP patients were more likely to have adverse outcomes than well-nourished patients. Malnutrition was associated with various adverse outcomes only in the overweight/obesity subgroups.

Diversity analysis of panicle traits in Chinese prickly ash germplasm resources and their influence on its systematic classification.

This study aimed to reveal the diversity and variation in panicle traits of the Chinese prickly ash and clarify their influence on the its systematic classification to provide a theoretical basis and technical support for the efficient utilization of Chinese prickly ash germplasm resources and breeding. Sixteen panicle traits were identified from 35 Chinese prickly ash germplasm resources from 2021 to 2022. The diversity of these panicle traits and their role in the plant's systematic classification were studied using variance, correlation, cluster, and principal component analyses. Cluster analysis showed that the 35 Chinese prickly ash germplasm resources could be divided into two groups with Euclidean distances of 25. Further analysis showed that yield traits such as panicle length, panicle width, primary branching, grain number per panicle, and grain weight per panicle were significantly positively correlated with grain chlorophyll content, while grain anthocyanin content was negatively correlated with both panicle (panicle length, panicle width, panicle length to width ratio, primary branching, grain number per panicle, and grain weight per panicle) and grain characteristics (single grain weight, thousand-grain weight, grain length, grain width and fruit shape index). In conclusion, Chinese prickly ash germplasms have diverse panicle traits. Z. armatum has dark green grains, long and wide panicles, a long conical shape, many primary branches, high grain weight, and high grain number per panicle. In contrast, Z. bungeanum has bright red seeds, a panicle width larger than its length, short and conical panicles, a small number of primary branches, and low grain weight per panicle and number of grains per panicle. Overall, Z. armatum had a significant yield advantage over Z. bungeanum.

Effect of low-intensity pulsed ultrasound on postoperative rehabilitation of rotator cuff tears: Protocol for a systematic review and meta-analysis.

BACKGROUND: Rotator cuff tears are a common shoulder injury that significantly impacts patients' daily lives and work abilities. Although surgical treatment methods for rotator cuff tears have been continuously improved with advances in medical technology, postoperative rehabilitation remains challenging. Therefore, finding effective rehabilitation treatments is crucial for improving patient prognosis and enhancing quality of life. This study will aim to systematically evaluate the impact of low-intensity pulsed ultrasound (LIPUS) on postoperative rehabilitation of rotator cuff tears, comprehensively assessing the efficacy and safety of LIPUS in postoperative recovery. METHODS: This protocol will search multiple databases including PubMed/MEDLINE, Embase, Cochrane Library, CNKI, Scopus, and Web of Science to identify randomized controlled trials related to LIPUS for postoperative rehabilitation of rotator cuff tears. The search will encompass literature published from the inception of the databases up to April 2024. Methodological quality assessment and data extraction will be conducted using the Cochrane Handbook for Systematic Reviews of Interventions and PRISMA guidelines. Meta-analysis will be performed on appropriate studies using either random-effects or fixed-effects models, and subgroup analyses will be conducted to explore potential heterogeneity. Studies meeting the inclusion criteria will be included in the analysis. All analyses will be performed using Stata version 16.0. RESULTS: The incidence of rotator cuff tear rates will be assessed by imaging techniques such as MRI or ultrasound. Pain intensity will be scored using standardized pain assessment scales, such as the Visual Analog Scale (VAS). Improved range of motion (ROM) in shoulder flexion, abduction, and rotation. Functional outcomes will be evaluated using effective measures such as Constant-Murley scores (CMS) and shoulder joint scores by American Shoulder and Elbow Surgeons (ASES). Adverse events associated with LIPUS therapy, including skin irritation, increased pain, or any other complications. Subgroup analysis will also be carried out if possible. DISCUSSION AND CONCLUSION: Following the meta-analysis, we will assess the overall effect of LIPUS on postoperative rehabilitation of rotator cuff tears, and further explore its impact on aspects such as pain relief, functional improvement, and postoperative complications. It is anticipated that this study will provide comprehensive evidence regarding the role of LIPUS in postoperative rehabilitation of rotator cuff tears, guiding clinical practice and future research. The resultant manuscript will be submitted for publication in a peer-reviewed journal. PROTOCOL REGISTRATION NUMBER: CRD42024530798.

Isolated short stature as the only presenting symptom of glycogen storage disease type 0a in a Chinese child: A case report.

RATIONALE: Glycogen storage disease type 0a (GSD0a) is a rare autosomal recessive disorder caused by glycogen synthase deficiency. Short stature is a characteristic feature in 29% of GSD0a patients, but isolated short stature as the only presenting symptom is exceedingly rare, with only 2 cases reported worldwide. PATIENT CONCERNS: A 4-year-old girl presented with persistent growth retardation despite previous treatment for renal tubular acidosis. DIAGNOSES: Based on clinical presentation and whole exome sequencing results, the patient was diagnosed with GSD0a. INTERVENTIONS: Uncooked cornstarch therapy was initiated at 2 g/kg every 6 hours. OUTCOMES: After 3 years of treatment, the patient's height SDS improved from -2.24 to -1.06, with enhanced glycemic control and no complications. LESSONS: This case emphasizes considering GSD0a in unexplained short stature and the value of continuous glucose monitoring. Early diagnosis and treatment can optimize growth in GSD0a patients.

Characteristics of stachyose-induced effects on gut microbiota and microbial metabolites in vitro associated with obesity in children.

Childhood obesity presents a serious health concern associated with gut microbiota alterations. Dietary interventions targeting the gut microbiota have emerged as promising strategies for managing obesity in children. This study aimed to elucidate the impact of stachyose (STS) supplementation on the gut microbiota composition and metabolic processes in obese children. Fecal samples were collected from 40 obese children (20 boys and 20 girls) aged between 6 and 15 and in vitro fermentation was conducted with or without the addition of STS, respectively, followed by 16S rRNA amplicon sequencing and analysis of short-chain fatty acids (SCFAs) and gases. Notably, our results revealed that STS supplementation led to significant alterations in gut microbiota composition, including an increase in the abundance of beneficial bacteria such as Bifidobacterium and Faecalibacterium, and a decrease in harmful bacteria including Escherichia-Shigella, Parabacteroides, Eggerthella, and Flavonifractor. Moreover, STS supplementation resulted in changes in SCFAs production, with significant increases in acetate levels and reductions in propionate and propionate, while simultaneously reducing the generation of gases such as H2S, H2, and NH3. The Area Under the Curve (AUC)-Random Forest algorithm and PICRUSt 2 were employed to identify valuable biomarkers and predict associations between the gut microbiota, metabolites, and metabolic pathways. The results not only contribute to the elucidation of STS's modulatory effects on gut microbiota but also underscore its potential in shaping metabolic activities within the gastrointestinal environment. Furthermore, our study underscores the significance of personalized nutrition interventions, particularly utilizing STS supplementation, in the management of childhood obesity through targeted modulation of gut microbial ecology and metabolic function.

Stimulating Electron Delocalization of Lanthanide Elements through High-Entropy Confinement to Promote Electrocatalytic Water Splitting.

High-entropy alloys (HEAs) have aroused extensive attention in the field of catalysis. However, due to the integration of multiple active sites in HEA, it exhibits excessive adsorption behavior resulting in difficult desorption of active species from the catalyst surfaces, which hinders the catalytic efficiency. Therefore, adjusting the adsorption strength of the active site in HEA to enhance the catalytic activity is of great importance. By introducing rare-earth (RE) elements into the high-entropy alloy, the delocalization of 4f electrons can be achieved through the interaction between the multimetal active site and RE, which benefits to regulate the adsorption strength of the HEA surface. Herein, the RE Ce-modified hexagonal-close-packed PtRuFeCoNiZn-Ce/C HEAs are synthesized and showed an excellent electrocatalytic activity for hydrogen evolution reaction and oxygen evolution reaction with ultralow overpotentials of 4, 7 and 156, 132 mV, respectively, to reach 10 mA cm-2 in 0.5 M H2SO4 and 1.0 M KOH solutions, and the assembled water electrolysis cell only requires a voltage of 1.43 V to reach 10 mA cm-2, which is much better than the performance of PtRuFeCoNiZn/C. Combined with the results of in situ attenuated total reflection infrared spectroscopy and density functional theory (DFT), the fundamental reasons for the improvement of catalyst activity come from two aspects: (i) local lattice distortion of HEA caused by the introduction of RE with large atomic radius induces 4f orbital electron delocalization of RE elements and enhances electron exchange between RE and active sites. (ii) The electronegativity difference between the RE element and the active site forms a surface dipole in HEA, which optimizes the adsorption of the active intermediate by the HEA surface site. This study provides an insightful idea for the rational design of high-performance HEA- and RE-based electrocatalysts.

Co-existence of two plasmids harboring transferable resistance-nodulation-division pump gene cluster, tmexCD1-toprJ1, and colistin resistance gene mcr-8 in Klebsiella pneumoniae.

BACKGROUND: The emergence of plasmid-mediated mobile colistin resistance (mcr) gene poses a great challenge to the clinical application of polymyxins. To date, mcr-1 to mcr-10 have been found in animals, humans, and the environment. Among them, mcr-8 was first identified in Klebsiella pneumoniae (K. pneumoniae) of swine origin, and then mcr-8.1 to mcr-8.5 were successively identified. Notably, K. pneumoniae is the major host of the mcr-8 gene in both animals and humans. This study aims to explore the characteristics of K. pneumoniae strains carrying the mcr-8 gene and tmexCD1-toprJ1 gene cluster and investigate the correlation between these two antibiotic resistance genes. METHODS: The isolates from the poultry farms and the surrounding villages were identified by mass spectrometer, and the strains positive for mcr-1 to mcr-10 were screened by polymerase chain reaction (PCR). The size of the plasmid and the antimicrobial resistance genes carried were confirmed by S1-nuclease pulsed-field gel electrophoresis (S1-PFGE) and Southern hybridization, and the transferability of the plasmid was verified by conjugation experiments. Antimicrobial susceptibility testing (AST) and whole genome sequencing (WGS) were used to characterize the strains. RESULTS: Two K. pneumoniae isolates (KP26 and KP29) displaying polymyxin resistance were identified as mcr-8 gene carriers. Besides that, tigecycline-resistant gene cluster tmexCD1-toprJ1 was also found on the other plasmid which conferred strain resistance to tigecycline. Through epidemiological analysis, we found that the mcr-8 gene has dispersed globally, circulating in the human, animals, and the environment. Furthermore, our analysis suggests that the coexistence of mcr-8 and tmexCD1-toprJ1 on a single plasmid might evolved through plasmid recombination. CONCLUSIONS: Although the mcr-8 and tmexCD1-toprJ1 gene clusters in the two strains of K. pneumoniae in this study were on two different plasmids, they still pose a potential threat to public health, requiring close monitoring and further study.

Case report: A case of primary renal osteosarcoma.

RATIONALE: Primary renal osteosarcoma is an exceedingly rare malignant tumor. Fewer than 30 cases have been reported in the literature since 1936. Furthermore, it has a high risk of metastasis and a poor overall prognosis rate. PATIENTS CONCERNS: In this report, we present a case of osteosarcoma originating from the left kidney (21 cm × 18 cm × 11 cm) with adhesions of the descending colon mesentery and the abdominal wall. A 63-year-old male patient presented with flank pain and gross hematuria. DIAGNOSES: A computed tomography scan revealed that the lesion with irregular margins was observed at the lower pole of the left kidney. Enhanced CT scan showed significant inhomogeneous enhancement of the lesion, with non-enhancing necrotic areas. A radical nephrectomy was performed. The immunohistochemistry results support the diagnosis of osteosarcoma. INTERVENTIONS: Postoperatively, the patient participated in clinical trials and received treatment with a PD-1 antibody (2 weeks/once). OUTCOMES: At the one-year follow-up, the patient reported late-stage systemic cancer-related pain, necessitating daily pain relief medication. Unfortunately, the patient passed away 18 months after the surgery. LESSONS: The case reported here is an exceedingly rare malignant osteosarcoma that originated from the kidney with the invasion of the descending colon mesentery and the abdominal wall. The patient received treatment with a PD-1 antibody (2 weeks/once). However, the patient passed away 18 months after the surgery. With the application of genetic testing technology and advancements in molecular biology, it was expected that specific targeted therapies for this condition would emerge in the future.

Causal relationship between obesity and anorectal abscess: a Mendelian randomization study.

Background: Observational studies have indicated that obesity is a risk factor for anorectal abscess (ARB). However, it remains unclear whether a causal genetic relationship exists between obesity and ARB. Methods: Univariate and multivariate Mendelian randomization (MR) were conducted using data from a large, published genome-wide association study (GWAS) of European ancestry to infer a causal relationship between obesity and ARB. Inverse variance weighted (IVW) analysis served as the primary analysis method, with results reported as odds ratios (OR). Results: MR analysis revealed that body mass index (BMI) positively affects ARB (OR 1.974, 95% confidence interval (CI) 1.548-2.519, p = 4.34 × 10-8). The weighted median method (OR = 1.879, 95% CI 1.248-2.829, p = 0.002) and Bayesian model averaging (BMA) (OR = 1.88, 95% CI 1.477-2.392, p = 2.85 × 10-7) also demonstrated consistent results. Subsequently, the impact of several obesity-related characteristics on ARB was assessed. Body fat percentage (BF), whole body fat mass (FM), waist circumference (WC), and hip circumference (HC) were found to be causally associated with an increased risk of ARB. However, these associations vanished after adjusting for BMI effects. Conclusion: The study confirms a positive causal effect of obesity on ARB, highlighting that reasonable weight control is an important strategy to reduce the incidence of ARB.

Can proximal gastrectomy with double-tract reconstruction replace total gastrectomy? a meta-analysis of randomized controlled trials and propensity score-matched studies.

BACKGROUND: According to the 5th edition of the Japanese Guidelines for the Treatment of Gastric Cancer, proximal gastrectomy is recommended for patients with early upper gastric cancer who can retain the distal half of the residual stomach after R0 resection. However, a large number of recent clinical studies suggest that surgical indications for proximal gastrectomy in the guidelines may be too narrow. Therefore, this meta-analysis included patients with early and advanced gastric cancer and compared short- and long-term postoperative outcomes between the two groups. At the same time, we only had high-quality clinical studies such as propensity score-matched studies and randomized controlled trials, which made our research more authentic and credible. METHODS: Data were retrieved from PubMed, EMBASE, Medline, and Cochrane Library up to June 2023, and included treatment outcomes after proximal gastrectomy with double-tract reconstruction and total gastrectomy with Roux-en-Y reconstruction. The primary results were Early-phase complications(Anastomotic leakage, Anastomotic bleeding, Abdominal abscess, Abdominal infection, Pulmonary infection, Incision infection, Intestinal obstruction, Dumping syndrome, Pancreatic fistula), Late-phase complications(Intestinal obstruction, Anastomosis stricture, Dumping syndrome, Reoperation, Internal hernia, Incidence of endoscopic gastroesophageal reflux), Serious complications (≥ Grade III C-D score), Quality of life[Gastroesophageal reflux symptom evaluation (Visick score)(≥ III), Los Angeles classification(C or D)], Nutritional status(Hemoglobin, Receipt of vitamin B12 supplementation), Oncologic Outcomes(The 5-year overall survival rates). Secondary outcomes were surgical outcomes (Operative time, Estimated blood loss, Postoperative hospital stay, Number of harvested lymph nodes, Gas-passing, Postoperative mortality).The Cochrane risk-of-bias tool and Newcastle‒Ottawa scale were used to assess the quality of the included studies. RESULTS: After screening, 11 studies were finally included, including 1154 patients. Results from the combined literature showed that total gastrectomy had a significant advantage over proximal gastrectomy with double-tract reconstruction in mean operating time (MD = 4.92, 95% CI: 0.22∼9.61 P = 0.04). However, meta-analysis results showed that Hemoglobin (MD = 7.12, 95% CI:2.40∼11.84, P = 0.003) and Receipt of vitamin B12 supplementation (OR = 0.12, 95% CI:0.05∼0.26, P < 0.00001) in the proximal gastrectomy with double-tract reconstruction group were better than those in the total gastrectomy with Roux-en-Y reconstruction group. There is no significant difference between the proximal gastrectomy with double-tract reconstruction and the total gastrectomy with Roux-en-Y reconstruction group in Early-phase complications(OR = 1.14,95% CI:0.79∼1.64, P = 0.50), Late-phase complications(OR = 1.37,95% CI:0.78∼2.39, P = 0.27), Gastroesophageal reflux symptom evaluation (Visick score)(≥ III)(OR = 0.94,95% CI:0.14∼1.07 P = 0.07), Los Angeles classification(C or D)(OR = 0.33,95% CI:0.01∼8.21, P = 0.50), the 5-year overall survival rates (HR = 1.01, 95% CI: 0.83 ~ 1.23, P = 0.89). CONCLUSION: Proximal gastrectomy with double-tract anastomosis is a safe and feasible treatment for upper gastric carcinoma. However, the operating time was slightly longer in the proximal gastrectomy with double-tract group compared to the total gastrectomy with Roux-en-Y group. The two groups were comparable to the total gastrectomy with Roux-en-Y group in terms of serious complications (≥ Grade III C-D score), early-phase complications, late-phase complications, and quality of life. Although the scope of proximal gastrectomy is smaller than that of total gastrectomy, it does not affect the 5-year survival rate, indicating good tumor outcomes for patients. Compared to total gastrectomy with Roux-en-Y group, proximal gastrectomy with double-tract reconstruction had higher hemoglobin levels, lower probability of vitamin B12 supplementation, and better long-term efficacy. In conclusion, proximal gastrectomy with double-tract reconstruction is considered one of the more rational surgical approaches for upper gastric cancer.

The effect of large channel-based foraminoplasty on lumbar biomechanics in percutaneous endoscopic discectomy: a finite element analysis.

BACKGROUND: This study aimed to evaluate the effect of foraminoplasty using large-channel endoscopy during TESSYS on the biomechanics of the lumbar spine. METHODS: A complete lumbar spine model, M1, was built using 3D finite elements, and models M2 and M3 were constructed to simulate the intraoperative removal of the superior articular process of L5 using a trephine saw with diameters of 5 mm and 8.5 mm, respectively, and applying normal physiological loads on the different models to simulate six working conditions-anterior flexion, posterior extension, left-right lateral bending, and left-right rotation-to investigate the displacement and facet joint stress change of the surgical segment, and the disc stress change of the surgical and adjacent segments. RESULTS: Compared with the M1 model, the M2 and M3 models showed decreased stress at the L4-5 left FJ and a significant increase in stress at the right FJ in forward flexion. In the M2 and M3 models, the L4-5 FJ stresses were significantly greater in left lateral bending or left rotation than in right lateral bending or right rotation. The right FJ stress in M3 was greater during left rotation than that in M2, and that in M2 was greater than that in M1. The L4-5disc stress in the M3 model was greater during posterior extension than that in the M1 and M2 models. The L4-5disc stress in the M3 model was greater in the right rotation than in the M2 model, and that in the M2 model was greater than that in the M1 model. CONCLUSION: Foraminoplasty using large-channel endoscopy could increase the stress on the FJ and disc of the surgical segment, which suggested unnecessary and excessive resection should be avoided in PTED to minimize biomechanical disruption.

Triboelectric Nanogenerators: State of the Art.

The triboelectric nanogenerator (TENG), as a novel energy harvesting technology, has garnered widespread attention. As a relatively young field in nanogenerator research, investigations into various aspects of the TENG are still ongoing. This review summarizes the development and dissemination of the fundamental principles of triboelectricity generation. It outlines the evolution of triboelectricity principles, ranging from the fabrication of the first TENG to the selection of triboelectric materials and the confirmation of the electron cloud overlapping model. Furthermore, recent advancements in TENG application scenarios are discussed from four perspectives, along with the research progress in performance optimization through three primary approaches, highlighting their respective strengths and limitations. Finally, the paper addresses the major challenges hindering the practical application and widespread adoption of TENGs, while also providing insights into future developments. With continued research on the TENG, it is expected that these challenges can be overcome, paving the way for its extensive utilization in various real-world scenarios.

Self-assembled nanoparticles of costunolide and glycyrrhizic acid for enhanced ulcerative colitis treatment.

Ulcerative colitis (UC) is a persistent inflammatory condition that specifically targets the colon and rectum. Existing therapies fail to adequately address the clinical requirements of people suffering from this ailment. Despite the acknowledged potential of nanomedicines in the field of anti-inflammatory treatment, their widespread use in clinical settings is impeded by their expensive nature and the uncertainty surrounding their safety profiles. This study illustrates that two naturally occurring phytochemicals, Costunolide (COS) and Glycyrrhizic acid (GA), form carrier-free, multifunctional spherical nanoparticles (NPs) through noncovalent interactions, such as π-π stacking and hydrogen bonding. The COS-GA NPs displayed a synergistic anti-inflammatory effect, providing much more evidently improved therapeutic benefits for dextran sodium sulfate (DSS)-induced UC mice due to more effective reduction in inflammation and oxidative stress than did equal dosages of COS or GA used alone. In addition, COS-GA NPs have biocompatibility and biosafety properties unique to them. This study will serve as affirmation of the potential of COS-GA NPs as innovative natural anti-inflammatory and antioxidant activities and also such agents as drug discovery in UC, leading possibly to better outcomes in people living with this disabling condition.

Loureirin C improves mitochondrial function by promoting NRF2 nuclear translocation to attenuate oxidative damage caused by renal ischemia-reperfusion injury.

Acute kidney injury (AKI) is a common clinical syndrome worldwide, with no effective treatment strategy. Renal ischemia-reperfusion (IR) injury is one of the main AKI features, and the excessive reactive oxygen species (ROS) production during reperfusion causes severe oxidative damage to the kidney. Loureirin C (LC), an active ingredient in the traditional Chinese medicine Chinese dragon's blood, possesses excellent antioxidative properties, but its role in renal IR injury is not clear. In this study, we evaluated the protective effects of LC against renal IR injury in vivo and in vitro by establishing a mice renal IR injury model and a human proximal renal tubular epithelial cell (HK-2) hypoxia/reoxygenation (HR) model. We found that LC ameliorated renal function and tissue structure injury and inhibited renal oxidative stress and ferroptosis in vivo. In vitro, LC scavenged ROS and attenuated mitochondrial dysfunction in HK-2 cells, thereby inhibiting oxidative cellular injury. Furthermore, we found that LC effectively promoted nuclear factor erythroid 2-related factor 2 (NRF2) nuclear translocation and activated downstream target genes heme oxygenase 1 (HO-1) and NADPH quinone oxidoreductase-1 (NQO-1) to enhance cellular antioxidant function. Moreover, NRF2 knockdown and pharmacological inhibition of NRF2 partially eliminated the protective effect of LC. These results confirm that LC can effectively inhibit renal IR injury, and the mechanism may be associated with NRF2 activation by LC.

Reverse Hydrogen Spillover on Metal Oxides for Water-Promoted Catalytic Oxidation Reactions.

Understanding the water-involved mechanism on metal oxide surface and the dynamic interaction of water with active sites is crucial in solving water poisoning in catalytic reactions. Herein, this work solves this problem by designing the water-promoted function of metal oxides in the ethanol oxidation reaction. In situ multimodal spectroscopies unveil that the competitive adsorption of water-dissociated *OH species with O2 at Sn active sites results in water poisoning and the sluggish proton transfer in CoO-SnO2 imparts water-resistant effect. Carbon material as electron donor and proton transport channel optimizes the Co active sites and expedites the reverse hydrogen spillover from CoO to SnO2. The water-promoted function arises from spillover protons facilitating O2 activation on the SnO2 surface, leading to crucial *OOH intermediate formation for catalyzing C-H and C-C cleavage. Consequently, the tailored CoO-C-SnO2 showcases a remarkable 60-fold enhancement in ethanol oxidation reaction compared to bare SnO2 under high-humidity conditions.

Antitumor efficacy and potential mechanism of FAP-targeted radioligand therapy combined with immune checkpoint blockade.

Radiotherapy combined with immune checkpoint blockade holds great promise for synergistic antitumor efficacy. Targeted radionuclide therapy delivers radiation directly to tumor sites. LNC1004 is a fibroblast activation protein (FAP)-targeting radiopharmaceutical, conjugated with the albumin binder Evans Blue, which has demonstrated enhanced tumor uptake and retention in previous preclinical and clinical studies. Herein, we demonstrate that 68Ga/177Lu-labeled LNC1004 exhibits increased uptake and prolonged retention in MC38/NIH3T3-FAP and CT26/NIH3T3-FAP tumor xenografts. Radionuclide therapy with 177Lu-LNC1004 induced a transient upregulation of PD-L1 expression in tumor cells. The combination of 177Lu-LNC1004 and anti-PD-L1 immunotherapy led to complete eradication of all tumors in MC38/NIH3T3-FAP tumor-bearing mice, with mice showing 100% tumor rejection upon rechallenge. Immunohistochemistry, single-cell RNA sequencing (scRNA-seq), and TCR sequencing revealed that combination therapy reprogrammed the tumor microenvironment in mice to foster antitumor immunity by suppressing malignant progression and increasing cell-to-cell communication, CD8+ T-cell activation and expansion, M1 macrophage counts, antitumor activity of neutrophils, and T-cell receptor diversity. A preliminary clinical study demonstrated that 177Lu-LNC1004 was well-tolerated and effective in patients with refractory cancers. Further, scRNA-seq of peripheral blood mononuclear cells underscored the importance of addressing immune evasion through immune checkpoint blockade treatment. This was emphasized by the observed increase in antigen processing and presentation juxtaposed with T cell inactivation. In conclusion, our data supported the efficacy of immunotherapy combined with 177Lu-LNC1004 for cancer patients with FAP-positive tumors.