A gut-derived hormone regulates cholesterol metabolism.

The reciprocal coordination between cholesterol absorption in the intestine and de novo cholesterol synthesis in the liver is essential for maintaining cholesterol homeostasis, yet the mechanisms governing the opposing regulation of these processes remain poorly understood. Here, we identify a hormone, Cholesin, which is capable of inhibiting cholesterol synthesis in the liver, leading to a reduction in circulating cholesterol levels. Cholesin is encoded by a gene with a previously unknown function (C7orf50 in humans; 3110082I17Rik in mice). It is secreted from the intestine in response to cholesterol absorption and binds to GPR146, an orphan G-protein-coupled receptor, exerting antagonistic downstream effects by inhibiting PKA signaling and thereby suppressing SREBP2-controlled cholesterol synthesis in the liver. Therefore, our results demonstrate that the Cholesin-GPR146 axis mediates the inhibitory effect of intestinal cholesterol absorption on hepatic cholesterol synthesis. This discovered hormone, Cholesin, holds promise as an effective agent in combating hypercholesterolemia and atherosclerosis.

Upregulation of CYR61 by TGF-ß and YAP signaling exerts a counter-suppression of hepatocellular carcinoma.

Transforming growth factor-ß (TGF-ß) and Hippo signaling are two critical pathways engaged in cancer progression by regulating both oncogenes and tumor suppressors, yet how the two pathways coordinately exert their functions in the development of hepatocellular carcinoma (HCC) remains elusive. In this study, we firstly conducted an integrated analysis of public liver cancer databases and our experimental TGF-ß target genes, identifying CYR61 as a pivotal candidate gene relating to HCC development. The expression of CYR61 is downregulated in clinical HCC tissues and cell lines than that in the normal counterparts. Evidence revealed that CYR61 is a direct target gene of TGF-ß in liver cancer cells. In addition, TGF-ß-stimulated Smad2/3 and the Hippo pathway downstream effectors YAP and TEAD4 can form a protein complex on the promoter of CYR61, thereby activating the promoter activity and stimulating CYR61 gene transcription in a collaborative manner. Functionally, depletion of CYR61 enhanced TGF-ß- or YAP-mediated growth and migration of liver cancer cells. Consistently, ectopic expression of CYR61 was capable of impeding TGF-ß- or YAP-induced malignant transformation of HCC cells in vitro and attenuating HCC xenograft growth in nude mice. Finally, transcriptomic analysis indicates that CYR61 can elicit an antitumor program in liver cancer cells. Together, these results add new evidence for the crosstalk between TGF-ß and Hippo signaling and unveil an important tumor suppressor function of CYR61 in liver cancer.

1T'-transition metal dichalcogenide monolayers stabilized on 4H-Au nanowires for ultrasensitive SERS detection.

Unconventional 1T'-phase transition metal dichalcogenides (TMDs) have aroused tremendous research interest due to their unique phase-dependent physicochemical properties and applications. However, due to the metastable nature of 1T'-TMDs, the controlled synthesis of 1T'-TMD monolayers (MLs) with high phase purity and stability still remains a challenge. Here we report that 4H-Au nanowires (NWs), when used as templates, can induce the quasi-epitaxial growth of high-phase-purity and stable 1T'-TMD MLs, including WS2, WSe2, MoS2 and MoSe2, via a facile and rapid wet-chemical method. The as-synthesized 4H-Au@1T'-TMD core-shell NWs can be used for ultrasensitive surface-enhanced Raman scattering (SERS) detection. For instance, the 4H-Au@1T'-WS2 NWs have achieved attomole-level SERS detections of Rhodamine 6G and a variety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike proteins. This work provides insights into the preparation of high-phase-purity and stable 1T'-TMD MLs on metal substrates or templates, showing great potential in various promising applications.

Decoding dynamic visual scenes across the brain hierarchy.

Understanding the computational mechanisms that underlie the encoding and decoding of environmental stimuli is a crucial investigation in neuroscience. Central to this pursuit is the exploration of how the brain represents visual information across its hierarchical architecture. A prominent challenge resides in discerning the neural underpinnings of the processing of dynamic natural visual scenes. Although considerable research efforts have been made to characterize individual components of the visual pathway, a systematic understanding of the distinctive neural coding associated with visual stimuli, as they traverse this hierarchical landscape, remains elusive. In this study, we leverage the comprehensive Allen Visual Coding-Neuropixels dataset and utilize the capabilities of deep learning neural network models to study neural coding in response to dynamic natural visual scenes across an expansive array of brain regions. Our study reveals that our decoding model adeptly deciphers visual scenes from neural spiking patterns exhibited within each distinct brain area. A compelling observation arises from the comparative analysis of decoding performances, which manifests as a notable encoding proficiency within the visual cortex and subcortical nuclei, in contrast to a relatively reduced encoding activity within hippocampal neurons. Strikingly, our results unveil a robust correlation between our decoding metrics and well-established anatomical and functional hierarchy indexes. These findings corroborate existing knowledge in visual coding related to artificial visual stimuli and illuminate the functional role of these deeper brain regions using dynamic stimuli. Consequently, our results suggest a novel perspective on the utility of decoding neural network models as a metric for quantifying the encoding quality of dynamic natural visual scenes represented by neural responses, thereby advancing our comprehension of visual coding within the complex hierarchy of the brain.

Integration of single-cell and RNA-seq data to explore the role of focal adhesion-related genes in osteoporosis.

Integrin-based focal adhesion is one of the major mechanosensory in osteocytes. The aim of this study was to mine the hub genes associated with focal adhesion and investigate their roles in osteoporosis based on the data of single-cell RNA sequencing and RNA-sequencing. Two hub genes (FAM129A and RNF24) with the same expression trend and AUC values greater than 0.7 in both GSE56815 and GSE56116 cohorts were uncovered. The nomogram was created to predict the risk of OP based on two hub genes. Subsequently, the competing endogenous RNA network was established based on two hub genes, 14 microRNAs and five long noncoding RNAs. Meanwhile, transcription factors-hub gene network was established based on two hub genes and 14 TFs. Finally, 73 drugs were predicted, of which there were 13 drugs targeting FAM129A and 66 drugs targeting RNF24. In both mouse and human blood samples, FAM129A expression was decreased in granulocytes and RNF24 expression was increased in monocytes. In the mouse experiment, FAM129A and anti-RNF24 were found to partially alleviate the progression of osteoporosis. In conclusion, two hub genes related to focal adhesion were identified by combined scRNA-seq and RNA-seq analyses, which might supply a new insight for the treatment and evaluation of OP.

Anti-PD-L1 antibody TQB2450 combined with tyrosine kinase receptor inhibitor AL2846 for immunotherapy-refractory advanced hepatocellular carcinoma and esophageal squamous cell carcinoma: A prospective phase 1b cohort study.

BACKGROUND: Effective systemic therapy remains limited for advanced esophageal squamous cell carcinoma (ESCC) and hepatocellular carcinoma (HCC), particularly after prior failed treatment with immune checkpoint inhibitors (ICIs). Theoretically, a combination of tyrosine kinase inhibitors (TKIs) with ICIs may restore immunotherapy sensitivity. METHODS: In this phase 1b study, patients received AL2846, an antiangiogenic TKI with multiple targets (c-MET, VEGFR1, c-KIT, Axl, RET, KDR, and VEGFR3), in combination with an anti-PD-L1 antibody (TQB2450) until disease progression, intolerable toxicity, death, or discontinuation for any cause. The primary end points included overall response rate (ORR) and safety, with secondary end points encompassing progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and duration of response. RESULTS: Between November 2021 and September 2022, 18 patients with ESCC and 15 patients with HCC, whose ORR was 11.1% (95% confidence interval [CI], 3.1%-32.8%) and 0%, respectively, were enrolled. Adverse events (AEs) of any grade and treatment-related AEs were documented in 32 patients (97.0%) and 31 patients (93.9%), respectively. Grade 3 or higher AEs were observed in 10 patients (30.3%), with vomiting (6.1%) and infectious pneumonia (9.1%) being the most prevalent. Median PFS and OS values were 3.22 months (95% CI, 1.35-5.68 months) and 5.98 months (95% CI, 3.71-8.87 months), respectively, in patients with ESCC, and 5.55 months (95% CI, 2.66 months to not evaluable [NE]) and 16.72 months (95% CI, 4.86 months to NE), respectively, in patients with HCC. The DCRs were 66.7% (95% CI, 43.75%-83.72%) in patients with ESCC and 73.3% (95% CI, 48.05%-89.10%) in patients with HCC. CONCLUSIONS: Combined TQB2450 and AL2846 therapy exhibited a favorable safety profile in immunotherapy-refractory patients with advanced ESCC and HCC.

Biomedical Utility of Non-Enzymatic DNA Amplification Reaction: From Material Design to Diagnosis and Treatment.

Nucleic acid nanotechnology has become a promising strategy for disease diagnosis and treatment, owing to remarkable programmability, precision, and biocompatibility. However, current biosensing and biotherapy approaches by nucleic acids exhibit limitations in sensitivity, specificity, versatility, and real-time monitoring. DNA amplification reactions present an advantageous strategy to enhance the performance of biosensing and biotherapy platforms. Non-enzymatic DNA amplification reaction (NEDAR), such as hybridization chain reaction and catalytic hairpin assembly, operate via strand displacement. NEDAR presents distinct advantages over traditional enzymatic DNA amplification reactions, including simplified procedures, milder reaction conditions, higher specificity, enhanced controllability, and excellent versatility. Consequently, research focusing on NEDAR-based biosensing and biotherapy has garnered significant attention. NEDAR demonstrates high efficacy in detecting multiple types of biomarkers, including nucleic acids, small molecules, and proteins, with high sensitivity and specificity, enabling the parallel detection of multiple targets. Besides, NEDAR can strengthen drug therapy, cellular behavior control, and cell encapsulation. Moreover, NEDAR holds promise for constructing assembled diagnosis-treatment nanoplatforms in the forms of pure DNA nanostructures and hybrid nanomaterials, which offer utility in disease monitoring and precise treatment. Thus, this paper aims to comprehensively elucidate the reaction mechanism of NEDAR and review the substantial advancements in NEDAR-based diagnosis and treatment over the past five years, encompassing NEDAR-based design strategies, applications, and prospects.

Optimizing Electron Spin-Polarized States of MoSe2/Cr2Se3 Heterojunction-Embedded Carbon Nanospheres for Superior Sodium/Potassium-Ion Battery Performances.

The principal challenges faced by sodium-ion batteries (SIBs) and potassium-ion batteries (KIBs) revolve around identifying suitable host materials capable of accommodating metal ions with larger dimensions and addressing the issue of sluggish chemical kinetics. Herein, a MoSe2/Cr2Se3 heterojunction uniformly embedded is fabricated in nitrogen-doped hollow carbon nanospheres (MoSe2/Cr2Se3@N-HCSs) as an electrode material for SIBs and KIBs. Cr2Se3 exhibits spontaneous antiparallel alignment of magnetic moments. Mo2+ doping is employed to regulate the electron spin states of Cr2Se3. Moreover, the MoSe2 and Cr2Se3 heterojunctions induce a lattice mismatch at the heterostructure interface, resulting in spin-polarized states or localized magnetic moments at the interface, potentially contributing to spin-polarized surface capacitance. MoSe2/Cr2Se3@N-HCSs demonstrate a high capacity of 498 mAh g-1 at 0.1 A g-1 with good cycling stability (capacity of 405 mAh g-1 and a coulombic efficiency of 99.8% after 1000 cycles). Additionally, density functional theory (DFT) calculations simulate the accumulation of spin-polarized charges at the MoSe2/Cr2Se3@N-HCSs heterojunction interface, dependent on the surface electron density of the antiferromagnetic Cr2Se3 and the surface spin polarization near the Fermi level. After regulating the electron spin states through Mo-doping, the band gap of the material decreases. These significant findings provide novel insights into the design and synthesis of electrode materials with exceptional performance characteristics for batteries.

Spontaneous Compositional-Interfacial Co-Modification Engineering via Ion Exchange Reaction Between Perovskite and Electron-Transporting Layer for Exceptionally Long-Term Stability of Photovoltaics.

The long-term stability of perovskite solar cells (PSCs) is still challenging for commercialization and mainly linked to the life span of perovskite films. Herein, a spontaneous compositional-interfacial co-modification strategy is developed based on the ion exchange reaction by introducing ammonium hexafluorophosphate (NH4PF6) into antisolvent to form gradient structures through a simple one-step solvent engineering. With the assistance of the ion exchange reaction, NH4PF6 forms a multifunctional structure to protect perovskite films from both internal and external factors for the exceptionally long-term stability of photovoltaics. The reason for this is linked to the high hydrophobicity of NH4PF6 for preventing H2O invasion, suppressing ion migration by forming hydrogen bonding, and reducing perovskite defects. The resulting unencapsulated devices show exceptionally long-term stability under standardized the International Summit on Organic Photovoltaic Stability (ISOS) protocols, with over 94%, 81%, and 83% retained power conversion efficiencies after aging tests under N2 (ISOS-D-1I), ambient air (ISOS-D-1), and 85 °C (ISOS-D-2I) for 14016, 2500, and 1248 h, respectively. These performances compare well with the state-of-the-art stability of inverted PSCs. Further investigations are conducted to study the evolution of macroscopic morphology and microscopic crystal structure in aged perovskite films, aiming to provide evidence supporting the aforementioned improvements in stability.

Element Diffusion Induced Carrier Transport Enhancement in High-Performance CZTSSe Self-Powered Photodetector.

Cu2ZnSn(S,Se)4 (CZTSSe) has attracted great interest in thin-film solar cells due to its excellent photoelectric performance in past decades, and recently is gradually expanding to the field of photodetectors. Here, the CZTSSe self-powered photodetector is prepared by using traditional photovoltaic device structure. Under zero bias, it exhibits the excellent performance with a maximum responsivity of 0.77 A W-1, a high detectivity of 8.78 × 1012 Jones, and a wide linear dynamic range of 103 dB. Very fast response speed with the rise/decay times of 0.576/1.792 µs, and ultra-high switching ratio of 3.54 × 105 are obtained. Comprehensive electrical and microstructure characterizations confirm that element diffusion among ITO, CdS, and CZTSSe layers not only optimizes band alignment of CdS/CZTSSe, but also suppresses the formation of interface defects. Such a suppression of interface defects and spike-like band alignment significantly inhibit carrier nonradiative recombination at interface and promote carrier transport capability. The low trap density in CZTSSe and low back contact barrier of CZTSSe/Mo could be responsible for the very fast response time of photodetector. This work definitely provides guidance for designing a high performance self-powered photodetector with high photoresponse, high switching ratio, fast response speed, and broad linear dynamic range.

A Novel Classification System of Renal Hilar Tumors for Surgical Guidance: Technique, Outcome, and Safety.

BACKGROUND: This study was designed to develop an innovative classification and guidance system for renal hilar tumors and to assess the safety and effectiveness of robot-assisted partial nephrectomy (RAPN) for managing such tumors. METHODS: A total of 179 patients undergoing RAPN for renal hilar tumors were retrospectively reviewed. A novel classification system with surgical techniques was introduced and the perioperative features, tumor characteristics, and the efficacy and safety of RAPN were compared within subgroups. RESULTS: We classified the tumors according to our novel system as follows: 131 Type I, 35 Type II, and 13 Type III. However, Type III had higher median R.E.N.A.L., PADUA, and ROADS scores compared with the others (all p < 0.001), indicating increased operative complexity and higher estimated blood loss [180.00 (115.00-215.00) ml]. Operative outcomes revealed significant disparities between Type III and the others, with longer operative times [165.00 (145.00-200.50) min], warm ischemia times [24.00 (21.50-30.50) min], tumor resection times [13.00 (12.00-15.50) min], and incision closure times [22.00 (20.00-23.50) min] (all p < 0.005). Postoperative outcomes also showed significant differences, with longer durations of drain removal (77.08 ± 18.16 h) and hospitalization for Type III [5.00 (5.00-6.00) d] (all p < 0.05). Additionally, Type I had a larger tumor diameter than the others (p = 0.009) and pT stage differed significantly between the subtypes (p = 0.020). CONCLUSIONS: The novel renal hilar tumor classification system is capable of differentiating the surgical difficulty of RAPN and further offers personalized surgical steps tailored to each specific classification. It provides a meaningful tool for clinical practice.

Low cycle number multiplex PCR: A novel strategy for the construction of amplicon libraries for next-generation sequencing.

Multiplex PCR is a critical step when preparing amplicon library for next-generation sequencing. However, there are several challenges related to multiplex PCR including poor uniformity, nonspecific amplification, and primer-dimers. To address these issues, we propose a novel solution strategy that involves using a low cycle number (<10 cycles) in multiplex PCR and then employing carrier DNAs and magnetic beads for the selection of targeted products. This technique improves the amplicon uniformity while also reducing primer-dimers and PCR artifacts. To evaluate our technique, we initially utilized 120 DNA fragments from mouse genome containing single nucleotide polymorphism (SNP) sites. Sequencing results demonstrated that with only 7 cycles of multiplex PCR, 95.8% of the targeted SNP sites were mapped, with a coverage of at least 1×. The average sequencing depth of all amplicons was 1705.79 ± 1205.30×; 87% of them reached a coverage depth that exceeded 0.2-fold of the average sequencing depth. Our method had a greater uniformity (87%) when compared to Hi-Plex PCR (53.3%). Furthermore, we validated our strategy by randomly selecting 90 primer pairs twice from the initial set of 120 primer-pairs. Next, we used the same protocol to prepare amplicon libraries. The two groups had an average sequencing depth of 1013.30 ± 585.57× and 219.10 ± 158.27×, respectively; over 84% of the amplicons had a sequencing depth that exceeded 0.2-fold of average depth. These results suggest that the use of a low cycle number in multiplex PCR is a cost-effective and efficient approach for the preparation of amplicon libraries.

A Novel Postconditioning Approach Attenuates Myocardial Ischaemia-Reperfusion Injury in Rats.

Background: Ischaemia-reperfusion injury (IRI) is the damage that occurs when blood flow is restored to a tissue or organ after a period of ischaemia. Postconditioning is a therapeutic strategy aimed at reducing the tissue damage caused by IRI. Postconditioning in rodents is a useful tool to investigate the potential mechanisms of postconditioning. Currently, there is no convenient approach for postconditioning rodents. Methods: Rats were subjected to a balloon postconditioning procedure. A balloon was used to control the flow in the vessel. This allowed for easy and precise manipulation of perfusion. Evans blue and triphenyltetrazolium chloride (TTC) double staining were used to determine the infarct size. Apoptosis in the myocardium was visualised and quantified by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Western blotting was performed to assess the expression of key apoptotic proteins, i.e., B-cell lymphoma 2 (Bcl-2), Bcl-2 Associated X (Bax), and cleaved caspase-3. Results: The balloon control approach to postconditioning provided accurate control of coronary blood flow and simplified the postconditioning manipulation. Infarct size reduction was observed in IRI rats after post-conditioning. There was a decrease in cardiac apoptosis in IRI rats after conditioning, as detected by TUNEL staining. IRI rats showed increased Bcl-2 levels and decreased Bax and cleaved caspase-3 levels in the myocardium. Conclusions: Postconditioning was successfully applied in rats using this novel approach. Postconditioning with this approach reduced infarct size and apoptosis in the area at risk.

Error-Tolerant Amplification and Simulation of the Ultrastrong-Coupling Quantum Rabi Model.

Cat-state qubits formed by photonic cat states have a biased noise channel, i.e., one type of error dominates over all the others. We demonstrate that such biased-noise qubits are also promising for error-tolerant simulations of the quantum Rabi model (and its varieties) by coupling a cat-state qubit to an optical cavity. Using the cat-state qubit can effectively enhance the counterrotating coupling, allowing us to explore several fascinating quantum phenomena relying on the counterrotating interaction. Moreover, another benefit from biased-noise cat qubits is that the two main error channels (frequency and amplitude mismatches) are both exponentially suppressed. Therefore, the simulation protocols are robust against parameter errors of the parametric drive that determines the projection subspace. We analyze three examples: (i) collapse and revivals of quantum states; (ii) hidden symmetry and tunneling dynamics; and (iii) pair-cat-code computation.

Impact of different progesterone timings on live birth rates for blastocyst frozen embryo transfer cycles.

RESEARCH QUESTION: Do different timings of progesterone administration for day 5 and day 6 blastocysts affect the live birth rate (LBR) of artificial frozen embryo transfer (FET) cycles? DESIGN: This retrospective cohort study included 1362 patients who underwent artificial FET cycles. The effects of 6 and 7 days of progesterone administration prior to blastocyst transfer on clinical outcomes were compared in day 5 and day 6 blastocysts. Univariable and multivariable regression analyses were undertaken. RESULTS: In all patients, LBR was comparable between the two groups (51.8% versus 47.9%, P = 0.165). For day 6 blastocysts, after adjusting for confounders, the 7-day progesterone regimen resulted in a significantly higher LBR (44.8% versus 36.4%, P = 0.039, adjusted OR = 1.494, 95% CI 1.060-2.106) and lower pregnancy loss rate (15.4% versus 25.2%, P = 0.031, adjusted OR = 0.472, 95% CI 0.260-0.856) compared with the 6-day progesterone regimen. For day 5 blastocysts, there were no significant differences in pregnancy outcomes between the two regimens, but the rate of low birthweight was higher with the 7-day progesterone regimen than with the 6-day progesterone regimen (13.9% versus 6.7%, P = 0.032). CONCLUSIONS: In all blastocyst analyses, no difference in LBR was found between the 6- and 7-day progesterone regimens in artificial FET cycles. For day 6 blastocysts, LBR was significantly higher with the 7-day progesterone regimen than with the 6-day progesterone regimen, whereas for day 5 blastocysts, pregnancy outcomes were comparable between the two regimens.

Lenvatinib, sintilimab plus transarterial chemoembolization for advanced stage hepatocellular carcinoma: A phase II study.

BACKGROUND & AIMS: Our retrospective study has suggested encouraging outcomes of lenvatinib combined with PD-1 inhibitor and transarterial chemoembolization (TACE) on advanced hepatocellular carcinoma (HCC). This phase II trial was conducted to prospectively investigate the efficacy and safety of lenvatinib, sintilimab (a PD-1 inhibitor) plus TACE (Len-Sin-TACE) in patients with advanced stage HCC. METHODS: This was a single-arm phase II trial. Patients with BCLC stage C HCC were recruited. They received lenvatinib (bodyweight ≥60 kg, 12 mg; bodyweight <60 kg, 8 mg) orally once daily, sintilimab (200 mg) intravenously once every 3 weeks, and on demand TACE. The primary endpoint was progression-free survival (PFS) per mRECIST. RESULTS: Thirty patients were enrolled. The primary endpoint was met with a median PFS of 8.0 (95% confidence interval [CI]: 6.1-9.8) months per mRECIST, which was the same as that per RECIST 1.1. The objective response rate was 60.0% per mRECIST and 30.0% per RECIST 1.1. The disease control rate was 86.7% per mRECIST/RECIST 1.1. The median duration of response was 7.4 (95% CI: 6.6-8.2) months per mRECIST (n = 18) and 4.3 (95% CI: 4.0-4.6) months per RECIST 1.1 (n = 9). The median overall survival was 18.4 (95% CI: 14.5-22.3) months. Treatment-related adverse events (TRAEs) occurred in 28 patients (93.3%) and grade 3 TRAEs were observed in 12 patients (40.0%). There were no grade 4/5 TRAEs. CONCLUSIONS: Len-Sin-TACE showed promising antitumour activities with a manageable safety profile in patients with advanced stage HCC. The preliminary results need to be further evaluated with phase III randomized trials.

Faecalibacterium prausnitzii-derived extracellular vesicles alleviate chronic colitis-related intestinal fibrosis by macrophage metabolic reprogramming.

Faecalibacterium prausnitzii (F. prausnitzii) has been recognized for its various intestinal and extraintestinal benefits to human. And reduction of F. prausnitzii has been linked to an increased risk of intestinal fibrosis in patients of Crohn's disease (CD). In this study, oral administration of either live F. prausnitzii or its extracellular vesicles (FEVs) can markedly mitigate the severity of fibrosis in mice induced by repetitive administration of DSS. In vitro experiment revealed that FEVs were capable of directing the polarization of peripheral blood mononuclear cells (PBMCs) towards an M2b macrophage phenotype, which has been associated with anti-fibrotic activities. This effect of FEV was found to be stable under various conditions that promote the development of pro-fibrotic M1/M2a/M2c macrophages. Proteomics and RNA sequencing were performed to uncover the molecular modulation of macrophages by FEVs. Notably, we found that FEVs reprogramed every metabolism of macrophages by damaging the mitochondria, and inhibited oxidative phosphorylation and glycolysis. Moreover, FEV-treated macrophages showed a decreased expression of PPARγ and an altered lipid processing phenotype characterized by decreased cholesterol efflux, which may promote energy reprogramming. Taken together, these findings identify FEV as a driver of macrophage reprogramming, suggesting that triggering M2b macrophage polarization by oral admiration of FEV may serve as strategy to alleviate hyperfibrotic intestine conditions in CD.

On-site analysis and rapid identification of citrus herbs by miniature mass spectrometry and machine learning.

BACKGROUND: Natural medicines present a considerable analytical challenge due to their diverse botanical origins and complex multi-species composition. This inherent complexity complicates their rapid identification and analysis. Tangerine peel, a product of the Citrus species from the Rutaceae family, is widely used both as a culinary ingredient and in traditional Chinese medicine. It is classified into two primary types in China: Citri Reticulatae Pericarpium (CP) and Citri Reticulatae Pericarpium Viride (QP), differentiated by harvest time. A notable price disparity exists between CP and another variety, Citri reticulatae "Chachi" (GCP), with differences being based on the original variety. METHODS: This study introduces an innovative method using portable miniature mass spectrometry for swift on-site analysis of QP, CP, and GCP, requiring less than a minute per sample. And combined with machine learning to differentiate the three types on site, the method was used to try to distinguish GCP from different storage years. RESULTS: This novel method using portable miniature mass spectrometry for swift on-site analysis of tangerine peels enabled the characterization of 22 compounds in less than one minute per sample. The method simplifies sample processing and integrates machine learning to distinguish between the CP, QP, and GCP varieties. Moreover, a multiple-perceptron neural network model is further employed to specifically differentiate between CP and GCP, addressing the significant price gap between them. CONCLUSIONS: The entire analytical time of the method is about 1 minute, and samples can be analyzed on site, greatly reducing the cost of testing. Besides, this approach is versatile, operates independently of location and environmental conditions, and offers a valuable tool for assessing the quality of natural medicines.

Comparison of 1-stage and 2-stage Managements for Common Bile Duct Stones and Gallstones (CBDS): A Retrospective Study.

OBJECTIVE: The aim of this study was to evaluate the efficacy, safety, and surgical outcomes of 2-stage management, namely preoperative endoscopic retrograde cholangiopancreatography (ERCP) + laparoscopic cholecystectomy (ERCP+LC) or LC + postoperative ERCP (LC+ERCP), as well as 1-stage management, LC + laparoscopic common bile duct exploration (LCBDE) for treating patients with gallstones and common bile duct stones (CBDS). METHODS: This retrospective study analyzed the data of 180 patients with common bile duct stones (CBDS) who were admitted to the Department of General Surgery at Tongji Hospital, Tongji University, between January 2019 and June 2021. The study included 3 groups: ERCP+LC (group 1), LC+ERCP (group 2), and LC+LCBDE (group 3), each consisting of 60 patients. Clinical metrics of the patients were collected and compared among the groups. RESULTS: Group 3 had the shortest operation duration and hospital stay compared with group 1 and group 2. In addition, group 3 had the lowest long-term postoperative complications, particularly the recurrence rate of CBDS. The total cost was also the lowest in group 3. Furthermore, patients in group 3 had the lowest postoperative amylase levels. All patients in the study achieved successful stone clearance. There were no significant differences in the conversion to other procedures rate, postoperative alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, and mortality among the three groups (P > 0.05). CONCLUSIONS: Both 1-stage management and 2-stage management are effective treatments for CBDS. The LC+LCBDE management is a safe treatment option, offering shorter hospital stays and operation duration, lower costs, and fewer complications.

Antibiotic allergy prevalence and documentation quality in Massachusetts long-term care facilities: A cross-sectional survey.

BACKGROUND: Antimicrobial resistance poses a significant global health challenge, particularly affecting older adults who are more susceptible to infections and their complications. Accurate diagnosis and documentation of antibiotic allergies are essential for effective antimicrobial stewardship. Despite the recognized overdiagnosis of antibiotic allergies, comprehensive studies on this subject in long-term care (LTC) settings are limited. OBJECTIVE: To determine the point prevalence of antibiotic allergies and documentation quality in Massachusetts LTC facilities. METHODS: We conducted a cross-sectional, 1-day point prevalence survey from July 1, 2023, to March 31, 2024, across 20 participating LTC facilities in Massachusetts in partnership with the Massachusetts Department of Public Health. The survey assessed the prevalence and documentation of antibiotic allergies among 2345 residents. Multivariable logistic regression was used to explore associations between documented penicillin allergy and demographic factors, including non-penicillin antibiotic allergies. RESULTS: The overall point prevalence of documented antibiotic allergies was 39.1%, with the most frequently reported classes being penicillins at 23.1%, sulfonamides at 15.4%, and cephalosporins at 5.2%. Significant documentation gaps were identified, with up to 92.8% of the allergy records found to be incomplete. Factors associated with documented penicillin allergies included female sex (adjusted odds ratio [aOR], 1.50; 95% CI, 1.16-1.94), White race (aOR, 1.92; 95% CI, 1.25-2.94), having allergies to non-penicillin antibiotics (aOR, 2.89; 95% CI, 2.33-3.59), and receipt of antibiotic (aOR, 2.13; 95% CI, 1.68-2.71). CONCLUSION: The high prevalence of documented antibiotic allergies and the notable deficiencies in their documentation underscore the urgent need for enhanced antibiotic evaluation, documentation practices, and penicillin delabeling in LTC facilities.