The tricalbin family of membrane contact site tethers is involved in the transcriptional responses of S. cerevisiae to glucose.

Cellular organelles maintain areas of close apposition with other organelles at which the cytosolic gap in between them is reduced to a minimum. These membrane contact sites (MCS) are vital for organelle communication and are formed by molecular tethers that physically connect opposing membranes. Although many regulatory pathways are known to converge at MCS, a link between MCS and transcriptional regulation-the primary mechanism through which cells adapt their metabolism to environmental cues-remains largely elusive. In this study, we performed RNA-sequencing on Saccharomyces cerevisiae cells lacking tricalbin proteins (Tcb1, Tcb2, Tcb3), a family of tethering proteins that connect the endoplasmic reticulum with the plasma membrane and Golgi, to investigate if gene expression is altered when MCS are disrupted. Our results indicate that in the tcb1Δ2Δ3Δ strain, pathways responsive to a high-glucose environment, including glycolysis, fermentation, amino acid synthesis, and low-affinity glucose uptake, are upregulated. Conversely, pathways crucial during glucose depletion, such as the tricarboxylic acid (TCA) cycle, respiration, high-affinity glucose uptake, and amino acid uptake are downregulated. In addition, we demonstrate that the altered gene expression of tcb1Δ2Δ3Δ in glucose metabolism correlates with increased growth, glucose consumption, CO2 production, and ethanol generation. In conclusion, our findings reveal that tricalbin protein deletion induces a shift in gene expression patterns mimicking cellular responses to a high-glucose environment. This suggests that MCS play a role in sensing and signaling pathways that modulate gene transcription in response to glucose availability.

Shear wave elastography-derived scoring system: application in the detection, subdivision and evaluation of systemic sclerosis.

OBJECTIVES: To locate the most valuable sites for shear wave elastography (SWE) evaluation and to develop a clinically applicable scoring system based on SWE for systemic sclerosis (SSc) and to verify the accuracy for detection and subdivision and the correlation by modified Rodnan total skin score (mRTSS). METHODS: SSc patients with limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) and symptomatic other rheumatic diseases (ORD) patients were included in this cross-sectional study. We assessed the skin stiffness at forehead, chest, abdomen, and bilateral fingers, hands, forearm, arms, thighs, legs, and feet, by palpation and SWE. Logistic regression was used to screen the most valuable sites for detection of SSc and subdivision of lcSSc and dcSSc, on which a scoring system was developed and verified. RESULTS: A total of 49 lcSSc, 51 dcSSc, and 36 ORD patients were included. The SWE-derived scoring system, including finger, hand, foot, arm, chest, and abdomen, reached a sensitivity and specificity of 80.0% and 94.4%, respectively, for diagnosing SSc at the cut-off value >24. The scoring system, including arm, chest, and abdomen, reached a sensitivity of 72.5% and specificity of 98.0% for subdividing dcSSc at the cut-off value >11. The kappa coefficient between the SWE-derived diagnosis and clinical diagnosis was 0.636 (P<0.001). The SWE-derived total scores of six sites had a strong correlation with mRTSS (r=0.757, p<0.001). CONCLUSIONS: The SWE-derived scoring system can be valuable in detection and evaluation of SSc in clinical application.

Recurrent stroke in a reproductive age women with patent foramen ovale.

BACKGROUND: Patent foramen ovale (PFO) is a known cause of ischemic stroke in young adults and combined oral contraceptives (COCs) are widely used by women of reproductive age. If young women with PFO are taking COCs, they may be subjected to a synergistic increase in the occurrence of stroke, though reports of ischemic stroke in this population are rare. We report a woman of reproductive age who was taking COC suffered repetitive ischemic strokes before a patent foramen ovale (PFO) was detected and closed, which may raise concerns in this field. CASE PRESENTATION: A 31-year-old woman presented to the emergency department with sudden-onset right upper- and lower-limb weakness and dysarthria for 1 hour, whose only risk factor of stroke was oral contraceptive use. On admission, she was alert with left gaze deviation, dysarthria, and right-sided hemiplegia. Her symptoms improved after receiving the revascularization therapy. About 24 hours later, her left eye experienced sudden painless vision loss. Then the PFO with a substantial right-to-left shunt was detected and then she received a trans-catheter closure of the defect. Over 3 months of follow-up, there were no signs of stroke, but visual loss persisted. CONCLUSION: This case of disabling stroke raises concerns regarding optimal management in primary and secondary prevention of stroke in young women on COCs with additional risk factors of stroke.

The dynamic features and microbial mechanism of nitrogen transformation for hydrothermal aqueous phase as fertilizer in dryland soil.

Hydrothermal aqueous phase (HAP) contains abundant organics and nutrients, which have potential to partially replace chemical fertilizers for enhancing plant growth and soil quality. However, the underlying reasons for low available nitrogen (N) and high N loss in dryland soil remain unclear. A cultivation experiment was conducted using HAP or urea to supply 160 mg N kg-1 in dryland soil. The dynamic changes of soil organic matters (SOMs), pH, N forms, and N cycling genes were investigated. Results showed that SOMs from HAP stimulated urease activity and ureC, which enhanced ammonification in turn. The high-molecular-weight SOMs relatively increased during 5-30 d and then biodegraded during 30-90 d, which SUV254 changed from 0.51 to 1.47 to 0.29 L-1 m-1. This affected ureC that changed from 5.58 to 5.34 to 5.75 lg copies g-1. Relative to urea, addition HAP enhanced ON mineralization by 8.40 times during 30-90 d due to higher ureC. It decreased NO3-N by 65.35%-77.32% but increased AOB and AOA by 0.25 and 0.90 lg copies g-1 at 5 d and 90 d, respectively. It little affected nirK and increased nosZ by 0.41 lg copies g-1 at 90 d. It increased N loss by 4.59 times. The soil pH for HAP was higher than that for urea after 11 d. The comprehensive effects of high SOMs and pH, including ammonification enhancement and nitrification activity inhibition, were the primary causes of high N loss. The core idea for developing high-efficiency HAP fertilizer is to moderately inhibit ammonification and promote nitrification.

Ability of the European League Against Rheumatism-Outcomes Measures in Rheumatology combined scoring system for grading dorsal joint space synovitis to accurately evaluate ultrasound-detected hand synovitis.

Background: The European League Against Rheumatism-Outcomes Measures in Rheumatology (EULAR-OMERACT) recommend only scanning dorsal spaces for scoring ultrasound-detected hand synovitis. This study evaluated the efficiency of the combined scoring system only depending on dorsal joint spaces synovitis in diagnosing and evaluating ultrasound-detected hand synovitis. Methods: The data of 56 patients who underwent hand joint ultrasonography exams in the Ultrasound Department of West China Hospital, Sichuan University were prospectively collected. The participants formed a random series. The images of each patient included gray-scale (GS) and power Doppler (PD) images of bilateral first to fifth metacarpophalangeal joints (MCP) and the thumb and second to fifth proximal interphalangeal joints (IP). The synovial thickness was measured quantitatively in GS images, and the synovial GS scores in the dorsal joint spaces and PD scores in the dorsal and volar joint spaces were calculated according to the combined EULAR-OMERACT scoring system. Results: The detection rate of synovitis in the first to fifth MCP, thumb and second to fifth proximal IP synovitis were 41.4% (232/560) and 33.9% (190/560), respectively. The sensitivity of only inspecting the dorsal joint spaces with GS ultrasound was 79.3% for MCP and 52.6% for the thumb and second to fifth proximal IPs. The PD scores were higher in the dorsal joint spaces than in the volar joint spaces (P value <0.001). The combined scores were higher than either the GS or PD scores alone in the dorsal joint spaces (P value of the combined scores vs. GS scores =0.001; P value of the combined scores vs. PD scores <0.001). Conclusions: Adopting the EULAR-OMERACT combined scoring standard is recommended to evaluate ultrasound-detected hand synovitis, as determined by the highest value of the GS scores or the PD scores. More specifically, PD scores can mainly be used to appraise the dorsal joint spaces. However, GS scores should be used to evaluate both the dorsal joint spaces and the volar joint spaces.

Renal functional outcomes after nephrectomy in patients with localized renal cell carcinoma and diabetes mellitus: a systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVE: Diabetes mellitus (DM), one of the most common comorbidities in patients with renal cell carcinoma (RCC), was proven to be an important prognostic factor of overall survival for these patients. Regarding the influence on renal function after nephrectomy, evidence is still scant. This systematic review and meta-analysis was conducted to provide a more reliable analysis of the association between DM and long-term renal functional outcomes after nephrectomy. METHODS: The PubMed, Web of Science, Embase and Cochrane Library (CENTRAL) databases were searched for eligible studies from inception to January 2023. Hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted to evaluate the association between DM and renal functional outcomes using a random effects model. Stata 17.0 software was used for statistical analysis. RESULTS: The meta-analysis included thirteen studies consisting of 8562 RCC patients who underwent nephrectomy. Preoperative comorbidity of DM was significantly associated with poor renal functional outcomes (HR = 1.91, 95% CI 1.48-2.48, p < 0.0001), regardless of ethnicity, follow-up time, body mass index (BMI) and age. However, in the radical nephrectomy subgroup, DM was not significantly associated with renal function decline (HR = 1.91, 95% CI 0.93-3.90, p = 0.0781). CONCLUSIONS: The aggregate evidence indicated that preexisting DM may be associated with poor renal functional outcomes in patients with RCC after nephrectomy, especially in patients receiving partial nephrectomy. Urologists should focus more on the glycemic management of these patients after nephrectomy. More high-quality studies are needed to explore the influence of DM on renal function outcomes in postoperative patients.

Advances and Applications of Cancer Organoids in Drug Screening and Personalized Medicine.

In recent years, the rapid emergence of 3D organoid technology has garnered significant attention from researchers. These miniature models accurately replicate the structure and function of human tissues and organs, offering more physiologically relevant platforms for cancer research. These intricate 3D structures not only serve as promising models for studying human cancer, but also significantly contribute to the advancement of various potential applications in the field of cancer research. To date, organoids have been efficiently constructed from both normal and malignant tissues originating from patients. Using such bioengineering platforms, simulations of infections and cancer processes, mutations and carcinogenesis can be achieved, and organoid technology is also expected to facilitate drug testing and personalized therapies. In conclusion, regenerative medicine has the potential to enhance organoid technology and current transplantation treatments by utilizing genetically identical healthy organoids as substitutes for irreversibly deteriorating diseased organs. This review explored the evolution of cancer organoids and emphasized the significant role these models play in fundamental research and the advancement of personalized medicine in oncology.

Inductive Paper-Based Flexible Contact Force Sensor Utilizing Natural Micro-Nanostructures of Paper: Simplicity, Economy, and Eco-Friendliness.

Inductive contact force sensors, known for their high precision and anti-interference capabilities, hold significant potential applications in fields such as wearable and medical monitoring devices. Most of the current research on inductive contact force sensors employed novel nanomaterials as sensitive elements to enhance their sensitivity and other performance characteristics. However, sensors developed through such methods typically involve complex preparation processes, high costs, and difficulty in biodegradation, which limit their further development. This article introduces a new flexible inductive contact force sensor using paper as a sensitive element. Paper inherently possesses micro- and nanostructures on its surface and interior, enabling it to sensitively convert changes in contact force into changes in displacement, making it suitable for use as the sensor's sensitive element. Additionally, the advantages of paper also include its great flexibility, low cost, wide availability, and biodegradability. Performance testing on this flexible sensor showed good repeatability, hysteresis, sensitivity, and consistency. When used in experiments for monitoring human motion and respiration, this sensor also exhibited great detection performance. The proposed inductive paper-based flexible contact force sensor, with its simple structure, easy manufacturing process, cost-effectiveness, eco-friendliness, and good sensing performance, provides new insights into research for contact force sensors.

Organoids: new frontiers in tumor immune microenvironment research.

The tumor microenvironment (TME) contains cells that regulate medication response and cancer growth in a major way. Tumor immunology research has been rejuvenated and cancer treatment has been changed by immunotherapy, a rapidly developing therapeutic approach. The growth patterns of tumor cells in vivo and the heterogeneity, complexity, and individuality of tumors produced from patients are not reflected in traditional two-dimensional tumor cell profiles. On the other hand, an in vitro three-dimensional (3D) model called the organoid model is gaining popularity. It can replicate the physiological and pathological properties of the original tissues in vivo. Tumor cells are the source of immune organoids. The TME characteristics can be preserved while preserving the variety of tumors by cultivating epithelial tumor cells with various stromal and immunological components. In addition to having genetic and physical similarities to human diseases and the ability to partially reconstruct the complex structure of tumors, these models are now widely used in research fields including cancer, developmental biology, regenerative mechanisms, drug development, disease modeling, and organ transplantation. This study reviews the function of organoids in immunotherapy and the tumor immune milieu. We also discuss current developments and suggest translational uses of tumor organoids in immuno-oncology research, immunotherapy modeling, and precision medicine.

The Role of Hydrogel Biomaterials in the Intervention of Wound Healing and Skin Regeneration via Exosomes: A Systematic Review and Meta-Analysis of Preclinical Animal Studies.

Significance: The combination of hydrogel biomaterials with exosomes to facilitate wound healing and skin regeneration is a promising approach. Recent Advances: Recent preclinical animal studies have focused on investigating the efficacy of hydrogel-based delivery systems for exosomes in promoting wound healing and skin regeneration. Critical Issues: Despite encouraging results, critical issues remain unresolved, such as optimizing hydrogel properties to enhance the efficacy of combined therapy with exosomes for wound and bridging the translational gap between preclinical and clinical applications. Future Directions: Future research endeavors should concentrate on refining hydrogel design to enhance exosome delivery efficacy, conducting rigorous clinical trials to assess the safety and efficacy of exosome-loaded hydrogels in human wound healing and skin regeneration, and exploring innovative strategies to maximize therapeutic outcomes.

Accurate assembly of thiophene-bridged titanium-oxo clusters with photocatalytic amine oxidation activity.

Designing and synthesizing well-defined crystalline catalysts for the photocatalytic oxidative coupling of amines to imines remains a great challenge. In this work, a crystalline dumbbell-shaped titanium oxo cluster, [Ti10O6(Thdc)(Dmg)2(iPrO)22] (Ti10, Thdc = 2,5-thiophenedicarboxylic acid, Dmg = dimethylglyoxime, iPrOH = isopropanol), was constructed through a facile one-pot solvothermal strategy and treated as a catalyst for the photocatalytic oxidative coupling of amines. In this structure, Thdc serves as the horizontal bar, while the {Ti5Dmg} layers on each side act as the weight plates. The molecular structure, light absorption, and photoelectrochemical properties of Ti10 were systematically investigated. Remarkably, the inclusion of the Thdc ligand, with the assistance of the Dmg ligand, broadens the light absorption spectrum of Ti10, extending it into the visible range. Furthermore, the effective enhancement of charge transfer within the Ti10 was achieved with the successful incorporation of the Thdc ligand, as opposed to PTC-211, where terephthalic acid replaces the Thdc ligand, while maintaining consistency in other aspects of Ti10. Building on this foundation, Ti10 was employed as a heterogeneous molecular photocatalyst for the catalytic oxidative coupling reaction of benzylamine (BA), demonstrating very high conversion activity and selectivity. Our study illustrates that the inclusion of ligands derived from Thdc enhances the efficiency of charge transfer in functionalized photocatalysts, significantly influencing the performance of photocatalytic organic conversion.

High stretchable and tough xylan-g-gelatin hydrogel via the synergy of chemical cross-linking and salting out for strain sensors.

Stretchable and tough hydrogels have been extensively used in tissue engineering scaffolds and flexible electronics. However, it is still a significant challenge to prepare hydrogels with both tensile strength and toughness by utilizing xylan, which is abundant in nature. Herein, we present a novel hydrogel of carboxymethyl xylan(CMX) graft gelatin (G) and doped with conductive hydroxyl carbon nanotubes (OCNT). CMX and G are combined through amide bonding as well as intermolecular hydrogen bonding to form a semi-interpenetrating hydrogel network. The hydrogel was further subjected to salting-out treatment, which induced the aggregation of the CMX-g-G molecular chain and the formation of chain bundles to toughen the hydrogel, the tensile strain, tensile stress, and toughness of CMX-g-G hydrogels were 1.547 MPa, 324 %, and 2.31 MJ m-3, respectively. In addition, OCNT was used as a conductive filler to impart electrical conductivity and further improve the mechanical properties of CMX-g-G/OCNT hydrogel, and a tensile strength of 1.62 MPa was obtained. Thus, the synthesized CMX-g-G/OCNT hydrogel can be used as a reliable and sensitive strain sensor for monitoring human activity. This study opens up new horizons for the preparation of xylan-based high-performance hydrogels.

Facile design of structurally robust, highly conductive and well-flexible hybrid film based on MXene, cellulose nanofiber and poly (3,4-ethylenedioxythiphoenes):polystyrene sulfonate for supercapacitors.

Robust, conductive and flexible electrode materials have been the focus of attention in portable, wearable electronics. However, it is still a significant challenge to achieve synergistic development of multiple properties simultaneously. Herein, we propose a combination of microscale design and nanostructures strategy to prepare MXene/cellulose nanofiber-poly (3,4-ethylenedioxythiphoenes):polystyrene sulfonate (Ti3C2Tx/CNF-PEDOT:PSS, TC-P) hybrid film by a simple in-situ polymerization and vacuum filtration process. CNF serves as the supporting skeleton of PEDOT:PSS, effectively mitigating its self-aggregation and structural deformation due to the expansion/contraction of the polymer network. And the CNF-PEDOT:PSS composite is capable to open up the interlayer space of Ti3C2Tx, which reduces the self-stacking of Ti3C2Tx nanosheets. The strong interactions among the three components enable the hybrid film electrode to possess both flexibility and high electrochemical properties. As a result, the film electrode exhibits a remarkable tensile strength of 77.4 MPa and an excellent conductivity of 162.5 S cm-1, as well as an outstanding areal specific capacitance of 896 mF cm-2 at 4 mA cm-2. Moreover, the assembled symmetric supercapacitor (SSC) device displays a large areal energy density of 62 µWh cm-2 at a power density of 800 µW cm-2 and demonstrates a long cycle life with 85.1 % capacitance retention after 10,000 GCD cycles. This study provides an effective strategy to balance mechanical flexibility and electrochemical properties, providing an inspiration to prepare flexible electrodes that are widely applied in a new generation of portable, wearable electronics.

Efficient Removal and Recovery of Ag from Wastewater Using Charged Polystyrene-Polydopamine Nanocoatings and Their Sustainable Catalytic Application in 4-Nitrophenol Reduction.

This study addresses the long-standing challenges of removing and recovering trace silver (Ag) ions from wastewater while promoting their sustainable catalysis utilization. We innovatively developed a composite material by combining charged sulfonated polystyrene (PS) with a PDA coating. This composite serves a dual purpose: effectively removing and recovering trace Ag+ from wastewater and enabling reused Ag for sustainable applications, particularly in the catalytic reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP). The PS-PDA demonstrated exceptional selectivity to trace Ag+ recycling, which is equal to 14 times greater than the commercial ion exchanger. We emphasize the distinct roles of different charged functional groups in Ag+ removal and catalytic reduction performance. The negatively charged SO3H groups exhibited the remarkable ability to rapidly enrich trace Ag ions from wastewater, with a capacity 2-3 times higher than that of positively-N+(CH3)3Cl and netural-CH2Cl-modified composites; this resulted in an impressive 96% conversion of 4-NP to 4-AP within just 25 min. The fixed-bed application further confirmed the effective treatment capacity of approximately 4400 L of water per kilogram of adsorbent, while maintaining an extremely low effluent Ag+ concentration of less than 0.1 mg/L. XPS investigations provided valuable insights into the conversion of Ag+ ions into metallic Ag through the enticement of negatively charged SO3H groups and the in situ reduction facilitated by PDA. This breakthrough not only facilitates the efficient extraction of Ag from wastewater but also paves the way for its environmentally responsible utilization in catalytic reactions.

Persistence of Contact Lens-Induced Corneal Parainflammation Following Lens Removal.

Purpose: Contact lens wear induces corneal parainflammation involving increased immune cell numbers after 24 hours' (CD11c+, Lyz2+, γδ-T cells) and six days' (Ly6G+ cells) wear. We investigated the time course of onset and resolution of these responses. Methods: LysMcre or C57BL/6J mice were fitted with a contact lens (four to 48 hours). Contralateral eyes did not wear lenses. After lens removal, Lyz2+, MHC-II+ or Ly6G+ cells were examined by quantitative imaging. RT-qPCR determined cytokine gene expression. Results: Lens wear for 24 hours increased corneal Lyz2+ cells versus contralateral eyes approximately two-fold. Corneas remained free of visible pathology. The Lyz2+ response was not observed after four or 12 hours' wear, nor after 12 hours' wear plus 12 hours' no wear. Lens removal after 24 hours' wear further increased Lyz2+ cells (∼48% after one day), which persisted for four days, returning to baseline by seven days. Lyz2+ cells in contralateral eyes remained at baseline. MHC-II+ cells showed a similar response but without increasing after lens removal. Lens wear for 48 hours showed reduced Lyz2+ cells versus 24 hours' wear with one day discontinuation, correlating with reduced IL-1ß and IL-18 gene expression. Lens wear for 24 hours did not induce Ly6G+ responses six days after removal. Conclusions: Lens-induced corneal parainflammation involving Lyz2+ cells requires 24 hours' wear but persists after lens discontinuation, requiring seven days for reversal. Lens wear for 48 hours may suppress initial Lyz2+ cell and cytokine responses. The significance of parainflammation during and after lens wear remains to be determined.

Effect of scutellarin on BV-2 microglial-mediated apoptosis in PC12 cells via JAK2/STAT3 signalling pathway.

Previous studies have shown that scutellarin inhibits the excessive activation of microglia, reduces neuronal apoptosis, and exerts neuroprotective effects. However, whether scutellarin regulates activated microglia-mediated neuronal apoptosis and its mechanisms remains unclear. This study aimed to investigate whether scutellarin can attenuate PC12 cell apoptosis induced by activated microglia via the JAK2/STAT3 signalling pathway. Microglia were cultured in oxygen-glucose deprivation (OGD) medium, which acted as a conditioning medium (CM) to activate PC12 cells, to investigate the expression of apoptosis and JAK2/STAT3 signalling-related proteins. We observed that PC12 cells apoptosis in CM was significantly increased, the expression and fluorescence intensity of the pro-apoptotic protein Bax and apoptosis-related protein cleaved caspase-3 were increased, and expression of the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) was decreased. Phosphorylation levels and fluorescence intensity of the JAK2/STAT3 signalling pathway-related proteins JAK2 and STAT3 decreased. After treatment with scutellarin, PC12 cells apoptosis as well as cleaved caspase-3 and Bax protein expression and fluorescence intensity decreased. The expression and fluorescence intensity of Bcl-2, phosphorylated JAK2, and STAT3 increased. AG490, a specific inhibitor of the JAK2/STAT3 signalling pathway, was used. Our findings suggest that AG490 attenuates the effects of scutellarin. Our study revealed that scutellarin inhibited OGD-activated microglia-mediated PC12 cells apoptosis which was regulated via the JAK2/STAT3 signalling pathway.

A real-world disproportionality analysis of the FDA adverse event reporting system events for ibuprofen.

INTRODUCTION: Ibuprofen is commonly used as an over-the-counter (OTC) antipyretic and analgesic. As the frequency of its use has increased, there has been a corresponding increase in reports of associated adverse events (AEs). However, these events have not been systematically reported in the literature. Meanwhile, the importance of effective pharmacovigilance in evaluating the benefits and risks of drugs is being recognized. METHODS: The data was obtained indirectly from FAERS using the OpenVigil 2 database, lexically mapped using software such as MySQL, Microsoft Excel, and the R language, and then subjected to four more rigorous algorithms to detect risk signals associated with ibuprofen AEs. RESULTS: By analyzing data from the past 18 years, 878 ibuprofen-related AEs were identified as primary AEs. Notably, unexpected reproductive system and breast diseases, etc., which were unexpected, were observed as important system organ classes (SOCs) associated with ibuprofen. Among the 651 preferred terms (PTs) that simultaneously satisfy the four arithmetic methods, renal tubular acidosis and lip oedema are proposed as new signals for ibuprofen AEs. CONCLUSION: This study explores the important and valuable potential AEs and ADRs of ibuprofen at the SOC and PT levels, respectively. To provide a reference on decision-making for ibuprofen to promote rational clinical dosing.

Pharmacovigilance analysis of orlistat adverse events based on the FDA adverse event reporting system (FAERS) database.

Objective: Based on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database, we analyzed the signals of potential adverse events (AEs) of orlistat in the real world to provide a reference for its safe clinical use. Methods: The FAERS database and OpenVigil 2.1 were used to obtain data on adverse events of orlistat from the first quarter of 2004 to the first quarter of 2023, and to analyze the population in which the adverse events occurred. And the signals of their potential adverse events were mined using reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN) and empirical Bayesian geometric mean (EBGM). Result: A total of 21,079 reports of adverse events with orlistat as the primary suspected drug were collected in this study. Using four disproportionate analyses, we screened 117 preferred terms (PTs) involving 18 system organ classes (SOCs). We found that the most common adverse events at SOC level for orlistat remained "gastrointestinal disorders", while "metabolism and nutrition disorders", "renal and urinary disorders", "musculoskeletal and connective tissue disorders" and "hepatobiliary disorders" also ranked high in the number of case reports. In addition, at the PT level, we identified several new signals of adverse events not mentioned in the specification, including "lipiduria", "anal haemorrhage", "rectal haemorrhage", "haematochezia", "sigmoiditis", "diverticulitis" and "muscle spasms". Conclusion: Most of the adverse events found in this study are consistent with the results described in the drug label. At the same time, we also found some new adverse events, which require more prospective studies to verify and elucidate their relationship with orlistat.

Free-electron interaction with nonlinear optical states in microresonators.

The short de Broglie wavelength and strong interaction empower free electrons to probe structures and excitations in materials and biomolecules. Recently, electron-photon interactions have enabled new optical manipulation schemes for electron beams. In this work, we demonstrate the interaction of electrons with nonlinear optical states inside a photonic chip-based microresonator. Optical parametric processes give rise to spatiotemporal pattern formation corresponding to coherent or incoherent optical frequency combs. We couple such "microcombs" to electron beams, demonstrate their fingerprints in the electron spectra, and achieve ultrafast temporal gating of the electron beam. Our work demonstrates the ability to access solitons inside an electron microscope and extends the use of microcombs to spatiotemporal control of electrons for imaging and spectroscopy.