RsaL is a self-regulatory switch that controls alternative biosynthesis of two AHL-type quorum sensing signals in Pseudomonas aeruginosa PA1201.

Pseudomonas aeruginosa is a ubiquitous and metabolically versatile microorganism naturally found in soil and water. It is also an opportunistic pathogen in plants, insects, animals, and humans. In response to increasing cell density, P. aeruginosa uses two acyl-homoserine lactone (AHL) quorum-sensing (QS) signals (i.e., N-3-oxo-dodecanoyl homoserine lactone [3-oxo-C12-HSL] and N-butanoyl-homoserine lactone [C4-HSL]), which regulate the expression of hundreds of genes. However, how the biosynthesis of these two QS signals is coordinated remains unknown. We studied the regulation of these two QS signals in the rhizosphere strain PA1201. PA1201 sequentially produced 3-oxo-C12-HSL and C4-HSL at the early and late growth stages, respectively. The highest 3-oxo-C12-HSL-dependent elastase activity was observed at the early stage, while the highest C4-HSL-dependent rhamnolipid production was observed at the late stage. The atypical regulator RsaL played a pivotal role in coordinating 3-oxo-C12-HSL and C4-HSL biosynthesis and QS-associated virulence. RsaL repressed lasI transcription by binding the -10 and -35 boxes of the lasI promoter. In contrast, RsaL activated rhlI transcription by binding the region encoding the 5'-untranslated region of the rhlI mRNA. Further, RsaL repressed its own expression by binding a nucleotide motif located in the -35 box of the rsaL promoter. Thus, RsaL acts as a molecular switch that coordinates the sequential biosynthesis of AHL QS signals and differential virulence in PA1201. Finally, C4-HSL activation by RsaL was independent of the Las and Pseudomonas quinolone signal (PQS) QS signaling systems. Therefore, we propose a new model of the QS regulatory network in PA1201, in which RsaL represents a superior player acting at the top of the hierarchy.

Effects of Dietary Supplementation of Bile Acids on Growth, Glucose Metabolism, and Intestinal Health of Spotted Seabass (Lateolabrax maculatus).

An 8-week feeding trial was performed to investigate the effects of dietary bile acids on growth, glucose metabolism, and intestinal health in spotted seabass (Lateolabrax maculatus) reared at high temperatures (33 °C). The fish (20.09 ± 1.12 g) were fed diets supplemented with bile acids: 0 (Con), 400 (BA400), 800 (BA800), and 1200 (BA1200) mg/kg, respectively. The results showed that the growth was promoted in fish at the BA800 treatment compared with the control (p < 0.05). Increased enzyme activities and transcripts of gluconeogenesis in the liver were observed, whereas decreased enzyme activities and transcripts of glycolysis, as well as glycogen content, were shown in the BA800 treatment (p < 0.05). The transcripts of bile acid receptors fxr in the liver were up-regulated in the BA800 treatment (p < 0.05). A bile acid supplementation of 800 mg/kg improved the morphological structure in the intestine. Meanwhile, intestinal antioxidant physiology and activities of lipase and trypsin were enhanced in the BA800 treatment. The transcripts of genes and immunofluorescence intensity related to pro-inflammation cytokines (il-1ß, il-8, and tnf-α) were inhibited, while those of genes related to anti-inflammation (il-10 and tgf-ß) were induced in the BA800 treatment. Furthermore, transcripts of genes related to the NF-κB pathway in the intestine (nfκb, ikkα, ikkß, and ikbα1) were down-regulated in the BA800 treatment. This study demonstrates that a dietary bile acid supplementation of 800 mg/kg could promote growth, improve glucose metabolism in the liver, and enhance intestinal health by increasing digestive enzyme activity and antioxidant capacity and inhibiting inflammatory response in L. maculatus.

Nomogram prediction of vessels encapsulating tumor clusters in small hepatocellular carcinoma ≤ 3 cm based on enhanced magnetic resonance imaging.

BACKGROUND: Vessels encapsulating tumor clusters (VETC) represent a recently discovered vascular pattern associated with novel metastasis mechanisms in hepatocellular carcinoma (HCC). However, it seems that no one have focused on predicting VETC status in small HCC (sHCC). This study aimed to develop a new nomogram for predicting VETC positivity using preoperative clinical data and image features in sHCC (≤ 3 cm) patients. AIM: To construct a nomogram that combines preoperative clinical parameters and image features to predict patterns of VETC and evaluate the prognosis of sHCC patients. METHODS: A total of 309 patients with sHCC, who underwent segmental resection and had their VETC status confirmed, were included in the study. These patients were recruited from three different hospitals: Hospital 1 contributed 177 patients for the training set, Hospital 2 provided 78 patients for the test set, and Hospital 3 provided 54 patients for the validation set. Independent predictors of VETC were identified through univariate and multivariate logistic analyses. These independent predictors were then used to construct a VETC prediction model for sHCC. The model's performance was evaluated using the area under the curve (AUC), calibration curve, and clinical decision curve. Additionally, Kaplan-Meier survival analysis was performed to confirm whether the predicted VETC status by the model is associated with early recurrence, just as it is with the actual VETC status and early recurrence. RESULTS: Alpha-fetoprotein_lg10, carbohydrate antigen 199, irregular shape, non-smooth margin, and arterial peritumoral enhancement were identified as independent predictors of VETC. The model incorporating these predictors demonstrated strong predictive performance. The AUC was 0.811 for the training set, 0.800 for the test set, and 0.791 for the validation set. The calibration curve indicated that the predicted probability was consistent with the actual VETC status in all three sets. Furthermore, the decision curve analysis demonstrated the clinical benefits of our model for patients with sHCC. Finally, early recurrence was more likely to occur in the VETC-positive group compared to the VETC-negative group, regardless of whether considering the actual or predicted VETC status. CONCLUSION: Our novel prediction model demonstrates strong performance in predicting VETC positivity in sHCC (≤ 3 cm) patients, and it holds potential for predicting early recurrence. This model equips clinicians with valuable information to make informed clinical treatment decisions.

Caffeic acid phenethyl ester restores mitochondrial homeostasis against peritoneal fibrosis induced by peritoneal dialysis through the AMPK/SIRT1 pathway.

Increasing evidence suggests that peritoneal fibrosis induced by peritoneal dialysis (PD) is linked to oxidative stress. However, there are currently no effective interventions for peritoneal fibrosis. In the present study, we explored whether adding caffeic acid phenethyl ester (CAPE) to peritoneal dialysis fluid (PDF) improved peritoneal fibrosis caused by PD and explored the molecular mechanism. We established a peritoneal fibrosis model in Sprague-Dawley rats through intraperitoneal injection of PDF and lipopolysaccharide (LPS). Rats in the PD group showed increased peritoneal thickness, submesothelial collagen deposition, and the expression of TGFß1 and α-SMA. Adding CAPE to PDF significantly inhibited PD-induced submesothelial thickening, reduced TGFß1 and α-SMA expression, alleviated peritoneal fibrosis, and improved the peritoneal ultrafiltration function. In vitro, peritoneal mesothelial cells (PMCs) treated with PDF showed inhibition of the AMPK/SIRT1 pathway, mitochondrial membrane potential depolarization, overproduction of mitochondrial reactive oxygen species (ROS), decreased ATP synthesis, and induction of mesothelial-mesenchymal transition (MMT). CAPE activated the AMPK/SIRT1 pathway, thereby inhibiting mitochondrial membrane potential depolarization, reducing mitochondrial ROS generation, and maintaining ATP synthesis. However, the beneficial effects of CAPE were counteracted by an AMPK inhibitor and siSIRT1. Our results suggest that CAPE maintains mitochondrial homeostasis by upregulating the AMPK/SIRT1 pathway, which alleviates oxidative stress and MMT, thereby mitigating the damage to the peritoneal structure and function caused by PD. These findings suggest that adding CAPE to PDF may prevent and treat peritoneal fibrosis.

Development and evaluation of a multi-target droplet digital PCR assay for highly sensitive and specific detection of Yersinia pestis.

BACKGROUND: Plague, caused by the bacterium Yersinia pestis, is a zoonotic disease that poses considerable threats to human health. Nucleic acid tests are crucial for plague surveillance and the rapid detection of Y. pestis. However, inhibitors in complex samples such as soil and animal tissues often hamper nucleic acid detection, leading to a reduced rate of identifying low concentrations of Y. pestis. To address this challenge, we developed a sensitive and specific droplet digital polymerase chain reaction (ddPCR) assay for detecting Y. pestis DNA from soil and animal tissue samples. METHODS: Three genes (ypo2088, caf1, and pla) from Y. pestis were used to develop a multi-target ddPCR assay. The limits of detection (LoD), reproducibility, and specificity were assessed for bacterial genomic DNA samples. The ability of the assay to detect low concentrations of Y. pestis DNA from simulated soil and mouse liver tissue samples was respectively evaluated and compared with that of quantitative real-time PCR (qPCR). RESULTS: The results showed that the ddPCR LoDs ranged from 6.2 to 15.4 copies/reaction for the target genes, with good reproducibility and high specificity for Y. pestis. By testing 130 soil and mouse liver tissue samples spiked with Y. pestis, the ddPCR assay exhibited a better sensitivity than that of the qPCR assay used in the study, with LoDs of 102 colony forming units (CFU)/100 mg soil and 103 CFU/20 mg liver. Moreover, the assay presented good quantitative linearity (R2 = 0.99) for Y. pestis at 103-106 CFU/sample for soil and liver samples. CONCLUSION: The ddPCR assay presented good performance for detecting Y. pestis DNA from soil and mouse tissue samples, showing great potential for improving the detection rate of low concentrations of Y. pestis in plague surveillance and facilitating the early diagnosis of plague cases.

Exploring the Biological Pathways of Siderophores and Their Multidisciplinary Applications: A Comprehensive Review.

Siderophores are a class of small molecules renowned for their high iron binding capacity, essential for all life forms requiring iron. This article provides a detailed review of the diverse classifications, and biosynthetic pathways of siderophores, with a particular emphasis on siderophores synthesized via nonribosomal peptide synthetase (NRPS) and non-NRPS pathways. We further explore the secretion mechanisms of siderophores in microbes and plants, and their role in regulating bioavailable iron levels. Beyond biological functions, the applications of siderophores in medicine, agriculture, and environmental sciences are extensively discussed. These applications include biological pest control, disease treatment, ecological pollution remediation, and heavy metal ion removal. Through a comprehensive analysis of the chemical properties and biological activities of siderophores, this paper demonstrates their wide prospects in scientific research and practical applications, while also highlighting current research gaps and potential future directions.

CoPS/Co 4 S 3 Heterojunction with Highly Exposed Active Sites and Dual-site Synergy for Effective Hydrogen Evolution Reactions.

Cobalt phosphosulphide (CoPS) has recently been recognized as a potentially effective electrocatalyst for the hydrogen evolution reaction (HER). However, there have been no research on the design of CoPS-based heterojunctions to boost their HER performance. Herein, CoPS/Co4S3 heterojunction was prepared by phosphating treatment based on defect-rich flower-like Co1-xS precursors. The high specific surface area of nanopetals, together with the heterojunction structure with inhomogeneous strain, exposes more active sites in the catalyst. The electronic structure of the catalyst is reconfigured as a result of the interfacial interactions, which promote the catalyst's ability to adsorb hydrogen and conduct electricity. The synergistic effect of the Co and S dual-site further enhance the catalytic activity. The catalyst has overpotentials of 61 and 70 mV to attain a current density of 10 mA cm-2 in acidic and alkaline media, respectively, which renders it competitive with previously reported analogous catalysts. This work proposes an effective technique for constructing transition metal phosphosulfide heterojunctions, as well as the development of an efficient HER electrocatalyst.

Meta-analysis: Over-the-scope clips in patients at high risk of re-bleeding following upper gastrointestinal tract bleeding.

BACKGROUND: Acute non-variceal upper gastrointestinal bleeding (UGIB) is challenging in patients at high risk of re-bleeding in whom standard endoscopic treatment (ST) has limited effectiveness. Over-the-scope clips (OTSC) have shown promise in these patients although their precise role remains uncertain. AIMS: To confirm the role of OTSC in patients with UGIB at high risk of re-bleeding. METHODS: We systematically searched CENTRAL, MEDLINE and Embase from January 1st, 1970 to April 24, 2024 for randomised controlled trials (RCTs) comparing OTSC and ST in acute non-variceal UGIB with high re-bleeding risk. The GRADE framework assessed evidence certainty, while trial sequential analysis (TSA) controlled random errors and evaluated conclusion validity. RESULTS: We analysed four RCTs (319 patients); pooled risk ratio (RR) for clinical success at initial endoscopy favoured OTSC (RR = 1.30, 95% CI = 1.08-1.56, p = 0.006, I2 = 58%, moderate certainty of evidence). TSA showed the desired sample size was 410 and the cumulative Z curve crossing the trial sequential monitoring boundary. The pooled RR for re-bleeding within 30 days favoured OTSC (RR = 0.53, 95% CI = 0.30-0.94, p = 0.03, I2 = 0%, moderate certainty of evidence). There was no significant difference in 30-day mortality, or length of hospital or ICU stay. CONCLUSIONS: Moderate certainty evidence supports OTSC as a superior initial treatment for acute non-variceal UGIB with high re-bleeding risk. Further large-scale studies are needed to confirm OTSCs' role by exploring other prognostic outcomes and assessing cost-effectiveness and potential complications.

Benefits and Risks of Antihyperlipidemic Medication in Adults with Different Low-Density Lipoprotein Cholesterol Based on the Number Needed to Treat.

PURPOSE: The objective of this investigation is to examine the benefits and potential risks of these drugs in individuals by varying baseline low-density lipoprotein cholesterol (LDL-C) values, utilizing the concept of the number needed to treat (NNT). METHODS: We extensively searched electronic databases, such as PubMed, EMBASE, Cochrane, and Web of Science, up to 6 August 2023. Baseline LDL-C values were stratified into four categories: < 100, 100-129, 130-159, and ≥ 160 mg/dL. Risk ratios (RRs) and NNT values were computed. RESULTS: This analysis incorporated data from 46 randomized controlled trials (RCTs), encompassing a total of 237,870 participants. The meta-regression analysis demonstrated an incremental diminishing risk of major adverse cardiovascular events (MACE) with increasing baseline LDL-C values. Statins exhibited a significant reduction in MACE [number needed to treat to benefit (NNTB) 31, 95% confidence interval (CI) 25-37], but this effect was observed only in individuals with baseline LDL-C values of 100 mg/dL or higher. Ezetimibe and PCSK9 inhibitors also were effective in reducing MACE (NNTB 18, 95% CI 11-41, and NNTB 18, 95% CI 16-24). Notably, the safety outcomes of statins and ezetimibe did not reach statistical significance, while the incidence of injection-site reactions with PCSK9 inhibitors was statistically significant [number needed to treat to harm (NNTH) 41, 95% CI 80-26]. CONCLUSION: Statins, ezetimibe, and PCSK9 inhibitors demonstrated a substantial capacity to reduce MACE, particularly among individuals whose baseline LDL-C values were relatively higher. The NNT visually demonstrates the gradient between baseline LDL-C and cardiovascular disease (CVD) risk. SYSTEMATIC REVIEW REGISTRATION: Registration: PROSPERO identifier number: CRD42023458630.

Efficacy and safety of thalidomide in gastrointestinal angiodysplasias: systematic review and meta-analysis with trial sequential analysis of randomized controlled trials.

Background: Gastrointestinal (GI) angiodysplasias is a potential cause of life-threatening bleeding. Thalidomide may have a certain effect on the treatment. Objectives: We aim to evaluate the efficacy and safety of thalidomide and used trial sequential analysis (TSA) to assess the need for further randomized controlled trials (RCTs). Design: Meta-analysis of RCTs. Data sources and methods: We systematically searched Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE), Embase, WanFang, and China National Knowledge Infrastructure databases for RCTs evaluating thalidomide in GI angiodysplasias without language restrictions. We used a random-effects model to obtain pool data and followed Grading of Recommendations Assessment, Development and Evaluation framework. TSA was employed to control the risk of random errors and to evaluate the validity of our conclusions. Results: Three RCTs were included involving 279 patients with the proportion of small intestinal angiodysplasias of 87.1%. Thalidomide led to improved mean change of hemoglobin level [mean difference (MD): 3.06, 95% confidence interval: 2.66-3.46] without severe adverse effects occurring. Other secondary endpoints, including effective response rate, cessation of bleeding after treatment, hospitalization rate because of bleeding, change in duration of hospital stays for bleeding, transfused red cell requirements, and overall adverse effects, also showed significantly better outcomes in the thalidomide group compared to the control group. TSA for all outcomes exceeded required information sizes, and cumulative Z curve all traverse trial sequential monitoring boundary. Conclusion: Almost all of the evidence was of moderate quality, suggesting that thalidomide holds promise for treating GI angiodysplasias, with favorable safety profiles. TSA suggests that conducting large-scale real-world research is recommended over relying solely on RCTs conducted within the same population and trial design. Trial registration: This meta-analysis protocol was registered on PROSPERO (CRD42023480621).

Comparison of Global Alignment and Proportion (GAP) Score and SRS-Schwab ASD Classification in the Analysis of Surgical Outcomes for Adult Spinal Deformity.

Study design: The GAP score predicted post-operative mechanical complications more effectively whereas SRS-Schwab classification improved evaluation of postoperative PROMs. Objective: The study compared the GAP Score and SRS-Schwab Classification in predicting surgical outcomes for adult spinal deformity (ASD) and elucidated whether both systems should be included in the preoperative planning. Materials and methods: Radiographic measurements and health-related quality of life scores at baseline, 6 weeks after surgery, and the last follow-up were collected from a cohort of 69 ASD patients subjected to long segment spinal fusion surgery after they were grouped by GAP score and SRS-Schwab classification respectively. Fisher's exact test and receiver operator characteristic (ROC) curve analysis was used to compare the incidence of mechanical complications and the discriminant capacity during revision surgery between the two groups. Postoperative patient-reported outcomes measures (PROMs) were compared by one-way ANOVA, and the proportions of MCID achieved for PROMs compared by chi-square test between the two groups. Results: The overall incidence of mechanical complications and revision surgery were 42% and 8.7%. Both GAP score and its categories predicted mechanical complications and revision surgery, but the GAP score system could not predict the improvements of PROMs. The SRS-Schwab classification could predict the occurrence of postoperative mechanical complications and improvements of postoperative PROMs between the aligned, moderately misaligned and severely misaligned groups (P < 0.05). Conclusion: Hence, a comprehensive surgical strategy for postoperative planning may improve patients' quality of life and minimize mechanical complications.

Epigenetic Insights Into Necrotizing Enterocolitis: Unraveling Methylation-Regulated Biomarkers.

Necrotizing enterocolitis (NEC) is a multifactorial gastrointestinal disease with high morbidity and mortality among premature infants. This study aimed to identify novel methylation-regulated biomarkers in NEC intestinal tissue through multiomics analysis. We analyzed DNA methylation and transcriptome datasets from ileum and colon tissues of patients with NEC. We identify methylation-related differential genes (MrDEGs) based on the rule that the degree of methylation in the promoter region is inversely proportional to RNA transcription. These MrDEGs included ADAP1, GUCA2A, BCL2L14, FUT3, MISP, USH1C, ITGA3, UNC93A and IL22RA1. Single-cell data revealed that MrDEGs were mainly located in the intestinal epithelial part of intestinal tissue. These MrDEGs were verified through Target gene bisulfite sequencing and RT-qPCR. We successfully identified and verified the ADAP1, GUCA2A, IL22RA1 and MISP, primarily expressed in intestinal epithelial villus cells through single-cell data. Through single-gene gene set enrichment analysis, we found that these genes participate mainly in the pathological process of T-cell differentiation and the suppression of intestinal inflammation in NEC. This study enhances our understanding of the pathogenesis of NEC and may promote the development of new precision medicine methods for NEC prediction and diagnosis.

MXene-Based Soft Humidity-Driven Actuator with High Sensitivity and Fast Response.

Soft actuators possessing notable mechanical deformations, high sensitivity, and fast response speed play a crucial role in various applications, such as artificial muscles, soft robots, and intelligent devices. In this study, a smart humidity-driven actuator was successfully fabricated by utilizing MXene/cellulose nanofiber (CNF)/LiCl (MCL) through vacuum-assisted filtration with fast response speed and high sensitivity. Utilizing the excellent humidity responsiveness of MXene/CNF and the robust hygroscopicity of LiCl, the synergistic effect of these materials enhances the hygroscopic properties and response speed of the actuator. The MCL actuator demonstrates excellent actuation performance, fast deformation, and reliable cyclic stability. To illustrate the extensive potential of the soft actuator, a range of applications, from bionic devices to soft grippers and crawling actuators, are showcased. Remarkably, the crawling actuator demonstrates sustained crawling motion without necessitating a humidity switch, relying on the humidity gradient from water droplets, and exhibits spontaneous directional motions within a certain range, which makes it a promising prospect in the field of soft robotics.

LM-Gel Plasticine Based on Binary Cooperative with Kneadable Shaping and Conductivity.

Liquid metal (LM)-based polymers have received growing interest for wearable health monitoring, electronic skins, and soft robotics. However, fabricating multifunctional LM-based polymers, in particular, featuring a convenient shaping ability while offering excellent deformability and conductivity remains a challenge. To overcome this obstacle, here, we propose a strategy to prepare LM-Gel "plasticine" (LGP) with great deformability, which is composed of a PVA (poly(vinyl alcohol)) soft network and an LM conductive phase. LGP can be easily constructed into different shapes such as plasticine and can be applied to different conditions (such as building a 3D circuit, circuit repair, and switch). Meanwhile, LGP has great conductivity (2.3 × 104 S/m) after surface annealing. Besides, LGP has a good electric heating performance, which shows the potential for application in wearable heating devices. Thus, this approach not only provides a way to prepare LM-polymer plasticine but also provides a novel perspective toward extending the applied range of LM-polymer composites.

The Impact of Nanomaterials on Photosynthesis and Antioxidant Mechanisms in Gramineae Plants: Research Progress and Future Prospects.

As global food security faces challenges, enhancing crop yield and stress resistance becomes imperative. This study comprehensively explores the impact of nanomaterials (NMs) on Gramineae plants, with a focus on the effects of various types of nanoparticles, such as iron-based, titanium-containing, zinc, and copper nanoparticles, on plant photosynthesis, chlorophyll content, and antioxidant enzyme activity. We found that the effects of nanoparticles largely depend on their chemical properties, particle size, concentration, and the species and developmental stage of the plant. Under appropriate conditions, specific NMs can promote the root development of Gramineae plants, enhance photosynthesis, and increase chlorophyll content. Notably, iron-based and titanium-containing nanoparticles show significant effects in promoting chlorophyll synthesis and plant growth. However, the impact of nanoparticles on oxidative stress is complex. Under certain conditions, nanoparticles can enhance plants' antioxidant enzyme activity, improving their ability to withstand environmental stresses; excessive or inappropriate NMs may cause oxidative stress, affecting plant growth and development. Copper nanoparticles, in particular, exhibit this dual nature, being beneficial at low concentrations but potentially harmful at high concentrations. This study provides a theoretical basis for the future development of nanofertilizers aimed at precisely targeting Gramineae plants to enhance their antioxidant stress capacity and improve photosynthesis efficiency. We emphasize the importance of balancing the agricultural advantages of nanotechnology with environmental safety in practical applications. Future research should focus on a deeper understanding of the interaction mechanisms between more NMs and plants and explore strategies to reduce potential environmental impacts to ensure the health and sustainability of the ecosystem while enhancing the yield and quality of Gramineae crops.

The LANCET robotic system can improve surgical efficiency in total hip arthroplasty: A prospective randomized, multicenter, parallel-controlled clinical trial.

Objective: To evaluate the accuracy and safety of the LANCET robotic system, a robot arm assisted operation system for total hip arthroplasty via a multicenter clinical randomized controlled trial. Methods: A total of 116 patients were randomized into two groups: LANCET robotic arm assisted THA group (N = 58) and the conventional THA group (N = 58). General information about the patients was collected preoperatively. Operational time and bleeding were recorded during the surgery. The position of the acetabular prosthesis was evaluated by radiographs one week after surgery and compared with preoperative planning. Harris score, hip mobility, prosthesis position and angle and complications were compared between the two groups at three months postoperatively. Results: None of the 111 patients who ultimately completed the 3-month follow-up experienced adverse events such as hip dislocation and infection during follow-up. In the RAA group, 52 (92.9 %) patients were located in the Lewinnek safe zone and 49 (87.5 %) patients were located in the Callanan safe zone. In the control group were 47 (85.5 %) and 44 (80.0 %) patients, respectively. In the RAA group, 53 (94.6 %) patients had a postoperative acetabular inclination angle and 51 (91.1 %) patients had an acetabular version angle within a deviation of 5° from the preoperative plan. These numbers were significantly higher than those of the control group, which consisted of 42 (76.4 %) and 34 (61.8 %) patients respectively. There were no significant differences between the two groups of subjects in terms of general condition, intraoperative bleeding, hip mobility, and adverse complications. Conclusion: The results of this prospective randomized, multicenter, parallel-controlled clinical study demonstrated that the LANCET robotic system leads conventional THA surgery in accuracy of acetabular cup placement and does not differ from conventional THA surgery in terms of postoperative hip functional recovery and complications. The translational potential of this article: In the past, the success rate of total hip arthroplasty (THA) relied heavily on the surgeon's experience. As a result, junior doctors needed extensive training to become proficient in this technique. However, the introduction of surgical robots has significantly improved this situation. By utilizing robotic assistance, both junior and senior doctors can perform THA quickly and efficiently. This advancement is crucial for the widespread adoption of THA, as patients can now receive surgical treatment in local facilities instead of overwhelming larger hospitals and straining medical resources. Moreover, the development of surgical robots with fully independent intellectual property rights holds immense value in overcoming the limitations of high-end medical equipment. This aligns with the objectives outlined in the 14th Five Year Plan for National Science and Technology Strategy.

Layered Double Hydroxide-Based PdCux@LDH Alloy Nanozyme for a Singlet Oxygen-Boosted Sonodynamic Therapy.

Redox nanozymes have demonstrated tremendous promise in disrupting cellular homeostasis toward cancer therapy, but a dysfunctional competition of diverse activities makes it normally restricted by the complex tumor microenvironment (TME). As palladium nanocrystals can achieve the precise regulation of the enzyme-like activity by regulating exposed crystal planes, noble metal nanoalloys can enhance the enzyme-like activity by promoting electron transfer and enhanced active sites. Herein, bimetallic nanoalloys with optimized enzymatic activity were intelligently designed via the interaction between the Pd and layered double hydroxide, denoted as PdCux@LDH. This PdCux@LDH is able to produce long-lived singlet oxygen (1O2) with high efficiency and selectivity for ultrasound-improved cancer therapy. In addition, this PdCux@LDH nanozyme demonstrated unique surface-dependent multienzyme-mimicking activities for catalyzing cascade reactions: oxidase (OXD)- and catalase (CAT)-mimicking activities. Interestingly, ultrasound (US) stimulation can further improve the dual-enzyme-mimicking activities and impart superior reactive oxygen species (ROS) generation activity, thereby further consuming nicotinamide adenine dinucleotide (NADH) to cause mitochondrial dysfunction, resulting in a highly efficient alloy nanozyme-mediated cancer therapy. This work opens a new research avenue to apply nanozymes for effective sonodynamic therapies (SDT).

Structural and mechanistic investigations on CC bond forming α-oxoamine synthase allowing L-glutamate as substrate.

Carbon­carbon (C-C) bonds serve as the fundamental structural backbone of organic molecules. As a critical CC bond forming enzyme, α-oxoamine synthase is responsible for the synthesis of α-amino ketones by performing the condensation reaction between amino acids and acyl-CoAs. We previously identified an α-oxoamine synthase (AOS), named as Alb29, involved in albogrisin biosynthesis in Streptomyces albogriseolus MGR072. This enzyme belongs to the α-oxoamine synthase family, a subfamily under the pyridoxal 5'-phosphate (PLP) dependent enzyme superfamily. In this study, we report the crystal structures of Alb29 bound to PLP and L-Glu, which provide the atomic-level structural insights into the substrate recognition by Alb29. We discover that Alb29 can catalyze the amino transformation from L-Gln to L-Glu, besides the condensation of L-Glu with ß-methylcrotonyl coenzyme A. Subsequent structural analysis has revealed that one flexible loop in Alb29 plays an important role in both amino transformation and condensation. Based on the crystal structure of the S87G mutant in the loop region, we capture two distinct conformations of the flexible loop in the active site, compared with the wild-type Alb29. Our study offers valuable insights into the catalytic mechanism underlying substrate recognition of Alb29.

Elucidating the unexpected importance of intermediate-volatility organic compounds (IVOCs) from refueling procedure.

Evaporative emissions release organic compounds comparable to gasoline exhaust in China. However, the measurement of intermediate volatility organic compounds (IVOCs) is lacking in studies focusing on gasoline evaporation. This study sampled organics from a real-world refueling procedure and analyzed the organic compounds using comprehensive two-dimensional gas chromatography coupled with a mass spectrometer (GC×GC-MS). The non-target analysis detected and quantified 279 organics containing 93 volatile organic compounds (VOCs, 64.9 ± 7.4 % in mass concentration), 182 IVOCs (34.9 ± 7.4 %), and 4 semivolatile organic compounds (SVOCs, 0.2 %). The refueling emission profile was distinct from that of gasoline exhaust. The b-alkanes in the B12 volatility bin are the most abundant IVOC species (1.9 ± 1.4 µg m-3) in refueling. A non-negligible contribution of 17.5 % to the ozone formation potential (OFP) from IVOCs was found. Although IVOCs are less in concentration, secondary organic aerosol potential (SOAP) from IVOCs (58.1 %) even exceeds SOAP from VOCs (41.6 %), mainly from b-alkane in the IVOC range. At the molecular level, the proportion of cyclic compounds in SOAP (12.1 %) indeed goes above its mass concentration (3.1 %), mainly contributed by cyclohexanes and cycloheptanes. As a result, the concentrations and SOAP of cyclic compounds (>50 %) could be overestimated in previous studies. Our study found an unexpected contribution of IVOCs from refueling procedures to both ozone and SOA formation, providing new insights into secondary pollution control policy.

PGC-1α drives small cell neuroendocrine cancer progression towards an ASCL1-expressing subtype with increased mitochondrial capacity.

Adenocarcinomas from multiple tissues can converge to treatment-resistant small cell neuroendocrine (SCN) cancers comprised of ASCL1, POU2F3, NEUROD1, and YAP1 subtypes. We investigated how mitochondrial metabolism influences SCN cancer (SCNC) progression. Extensive bioinformatics analyses encompassing thousands of patient tumors and human cancer cell lines uncovered enhanced expression of PGC-1α, a potent regulator of mitochondrial oxidative phosphorylation (OXPHOS), across several SCNC types. PGC-1α correlated tightly with increased expression of the lineage marker ASCL1 through a positive feedback mechanism. Analyses using a human prostate tissue-based SCN transformation system showed that the ASCL1 subtype has heightened PGC-1α expression and OXPHOS activity. PGC-1α inhibition diminished OXPHOS, reduced SCNC cell proliferation, and blocked SCN prostate tumor formation. PGC-1α overexpression enhanced OXPHOS, tripled the SCN prostate tumor formation rate, and promoted commitment to the ASCL1 lineage. These findings reveal the metabolic heterogeneity among SCNC subtypes and identify PGC-1α-induced OXPHOS as a regulator of SCNC lineage plasticity.