Analysis of changes in social isolation, loneliness, or both, and subsequent cognitive function among older adults: Findings from a nationwide cohort study.

INTRODUCTION: The study aimed to investigate the associations of changes in social isolation, loneliness, or both, with cognitive function. METHODS: Data were from 7299 older adults in the Chinese Longitudinal Healthy Longevity Survey. We defined four change patterns (no, incident, transient, and persistent) for social isolation and loneliness, and created nine-category variable to represent the joint changes. Tobit regression models and Cox models were performed. RESULTS: Incident, transient, and persistent social isolation or loneliness may accelerate cognitive decline (p < 0.05). Incident, transient, and persistent social isolation were associated with higher cognitive impairment risk, while only persistent loneliness was associated with higher cognitive impairment risk (p < 0.001). Notably, short-term or persistent social isolation was associated with accelerated cognitive decline and incident cognitive impairment, regardless of different loneliness change status (p < 0.05). DISCUSSION: Short-term or persistent social isolation and persistent loneliness may be a salient risk factor for cognitive decline and cognitive impairment. HIGHLIGHTS: Incident, transient, and persistent social isolation were associated with accelerated cognitive decline and higher cognitive impairment risk. Persistent loneliness was associated with accelerated cognitive decline and higher cognitive impairment risk. Short-term or persistent social isolation with concurrent different loneliness change status accelerated cognitive decline and higher cognitive impairment risk.

Development of a 166.6 MHz ß = 1 higher-order-mode-damped superconducting cavity.

The storage ring of the high energy photon source will be driven by five 166.6 MHz ß = 1 quarter-wave superconducting cavities operating at 4 K. A higher-order-mode-damped superconducting cavity was designed with excellent rf and mechanical properties based on the successful development of the proof-of-principle cavity. The mechanical design of the dressed cavity was focused on addressing stress safety throughout the processes, tunability, frequency detuning due to pressure fluctuation, and Lorentz force, among other factors. A new liquid helium vessel was designed along with a comprehensive stiffening scheme to mitigate the surging peak stress on the cavity resulting from the significantly unequal beam pipe size. In the first batch, three cavities were manufactured, and surface preparations were carefully conducted to eliminate defects and etching traces while ensuring cleanliness. The cavity's Q0 at the design voltage of 1.5 MV reached 3.8 × 109 at 4 K, comfortably surpassing the design goal. Field emission onset was not observed during the entire test up to a peak electric field of 60 MV/m, thanks to the optimized processing procedures. Subsequently, one cavity was welded with the newly designed helium vessel and vertically tested at 2 K, achieving an rf performance comparable to the bare cavities, demonstrating the success of the jacketed cavity. This paper presents the design, fabrication, surface preparation, and cryogenic tests of the first higher-order-mode-damped 166.6 MHz ß = 1 superconducting cavity.

Hsp47 promotes biogenesis of multi-subunit neuroreceptors in the endoplasmic reticulum.

Protein homeostasis (proteostasis) deficiency is an important contributing factor to neurological and metabolic diseases. However, how the proteostasis network orchestrates the folding and assembly of multi-subunit membrane proteins is poorly understood. Previous proteomics studies identified Hsp47 (Gene: SERPINH1), a heat shock protein in the endoplasmic reticulum lumen, as the most enriched interacting chaperone for gamma-aminobutyric type A (GABAA) receptors. Here, we show that Hsp47 enhances the functional surface expression of GABAA receptors in rat neurons and human HEK293T cells. Furthermore, molecular mechanism study demonstrates that Hsp47 acts after BiP (Gene: HSPA5) and preferentially binds the folded conformation of GABAA receptors without inducing the unfolded protein response in HEK293T cells. Therefore, Hsp47 promotes the subunit-subunit interaction, the receptor assembly process, and the anterograde trafficking of GABAA receptors. Overexpressing Hsp47 is sufficient to correct the surface expression and function of epilepsy-associated GABAA receptor variants in HEK293T cells. Hsp47 also promotes the surface trafficking of other Cys-loop receptors, including nicotinic acetylcholine receptors and serotonin type 3 receptors in HEK293T cells. Therefore, in addition to its known function as a collagen chaperone, this work establishes that Hsp47 plays a critical and general role in the maturation of multi-subunit Cys-loop neuroreceptors.

ESF1 positively regulates MDM2 and promotes tumorigenesis.

Eighteen S rRNA factor 1 (ESF1) is a predominantly nucleolar protein essential for embryogenesis. Our previous studies have suggested that Esf1 is a negative regulator of the tumor suppressor protein p53. However, it remains unclear whether ESF1 contributes to tumorigenesis. In this current research, we find that increased ESF1 expression correlates with poor survival in multiple tumors including pancreatic cancer. ESF1 is able to regulate cell proliferation, migration, DNA damage-induced apoptosis, and tumorigenesis. Mechanistically, ESF1 physically interacts with MDM2 and is essential for maintaining the stability of MDM2 protein by inhibiting its ubiquitination. Additionally, ESF1 also prevented stress-induced stabilization of p53 in multiple cancer cells. Hence, our findings suggest that ESF1 is a potent regulator of the MDM2-p53 pathway and promotes tumor progression.

An optimal combination of four active components in Huangqin decoction for the synergistic sensitization of irinotecan against colorectal cancer.

BACKGROUND: Irinotecan (CPT-11) is a first-line treatment for advanced colorectal cancer (CRC). Four components (baicalin, baicalein, wogonin, and glycyrrhizic acid) derived from Huangqin Decoction (HQD) have been proven to enhance the anticancer activity of CPT-11 in our previous study. OBJECTIVE: This study aimed to determine the optimal combination of the four components for sensitizing CPT-11 as well as to explore the underlying mechanism. METHODS: The orthogonal design method was applied to obtain candidate combinations (Cmb1-9) of the four components. The influence of different combinations on the anticancer effect of CPT-11 was first evaluated in vitro by cell viability, wound healing ability, cloning formation, apoptosis, and cell cycle arrest. Then, a CRC xenograft mice model was constructed to evaluate the anticancer effect of the optimal combination in vivo. Potential mechanisms of the optimal combination exerting a sensitization effect combined with CPT-11 against CRC were analyzed by targeted metabolomics. RESULTS: In vitro experiments determined that Cmb8 comprised of baicalin, baicalein, wogonin, and glycyrrhizic acid at the concentrations of 17 µM, 47 µM, 46.5 µM and 9.8 µM respectively was the most effective combination. Importantly, the cell viability assay showed that Cmb8 exhibited synergistic anticancer activity in combination with CPT-11. In in vivo experiments, this combination (15 mg/kg of baicalin, 24 mg/kg of baicalein, 24 mg/kg of wogonin, and 15 mg/kg of glycyrrhizic acid) also showed a synergistic anticancer effect. Meanwhile, inflammatory factors and pathological examination of the colon showed that Cmb8 could alleviate the gastrointestinal damage induced by CPT-11. Metabolic profiling of the tumors suggested that the synergistic anticancer effect of Cmb8 might be related to the regulation of fatty acid metabolism. CONCLUSION: The optimal combination of four components derived from HQD for the synergistic sensitization of CPT-11 against CRC was identified.

Two new cucurbitane-type triterpenoid saponins from the fruit of Citrullus colocynthis.

Two new cucurbitane-type triterpenoid saponins, 2,20ß,22ß-trihydroxy-16α,23(R)-epoxycucurbita-1,5,24-triene-3,11-dione 2-O-ß-D-glucopyranoside (1), 2,20ß,22α-trihydroxy-16α,23(S)-epoxycucurbita-1,5,11,24-tetraene-3-one 2-O-ß-D-glucopyranoside (2) were isolated from the fruit of Citrullus colocynthis (L.) Schrad. Their structures were elucidated by mass spectrometry, IR, 1D, and 2D NMR spectroscopy, etc. Besides, both of the compounds showed significant hepatoprotective activities at 10 µM against paracetamol-induced HepG2 cell damage.

Temporal discounting predicts procrastination in the real world.

People procrastinate, but why? One long-standing hypothesis is that temporal discounting drives procrastination: in a task with a distant future reward, the discounted future reward fails to provide sufficient motivation to initiate work early. However, empirical evidence for this hypothesis has been lacking. Here, we used a long-term real-world task and a novel measure of procrastination to examine the association between temporal discounting and real-world procrastination. To measure procrastination, we critically measured the entire time course of the work progress instead of a single endpoint, such as task completion day. This approach allowed us to compute a fine-grained metric of procrastination. We found a positive correlation between individuals' degree of future reward discounting and their level of procrastination, suggesting that temporal discounting is a cognitive mechanism underlying procrastination. We found no evidence of a correlation when we, instead, measured procrastination by task completion day or by survey. This association between temporal discounting and procrastination offers empirical support for targeted interventions that could mitigate procrastination, such as modifying incentive systems to reduce the delay to a reward and lowering discount rates.

Synergistically active Fe3O4 magnetic and EDTA modified cellulose cotton fabric using chemical method and their effective pollutants removal ability from wastewater.

A unique combination of cotton fabric (CF) with a mixture of EDTA and APTES Fe3O4 magnetic particles was developed and utilized for the first time as an adsorbent for removing pollutants from wastewater. Initially, Fe3O4 was synthesized using the co-precipitation method. Further, the surface of Fe3O4 was modified by introducing amino functional groups through a reaction with APTES, resulting in Fe3O4-NH2. Following this, the surface of carbon fiber (CF) was altered using ethylenediaminetetraacetic acid (EDTA) to create CF@EDTA. Through the use of EDC-HCl and NHS, Fe3O4-NH2 was attached to the surface of CF@EDTA, resulting in the final product CF@EDTA/Fe3O4. Subsequently, the prepared CF@EDTA/Fe3O4 was utilized to adsorb metal pollutants from wastewater, with a thorough analysis conducted using various characterization techniques including FTIR, SEM, EDX, XRD, VSM, and XPS to study the materials. The study specifically aimed to assess the adsorption performance of our cotton-based material towards As(III) and Cr3+ metal ions. The pH study was also performed. Results indicated that the material exhibited an adsorption capacity of approximately 714 mg/g for As(III) ions and 708 mg/g for Cr3+ ions. The Langmuir and Freundlich models, as well as pseudo-first and second-order models were also analyzed. The Langmuir and pseudo-second-order models were found to best fit the data. In terms of regeneration and reusability, the materials showed straightforward regeneration and recyclability for up to 15 cycles. The remarkable adsorption capacity, combined with the unique blend of cotton and Fe3O4 magnet, along with its recyclability, positions our material CF@EDTA/Fe3O4 as a promising contender for wastewater treatment and other significant areas in water research.

Biosafety assessments of hexafluoropropylene trimer derivative as a fluorinated cooling fluid for electronics.

The Internet Data Center (IDC) is one of the most important infrastructures in the field of information technology. The cooling system for heat dissipation of IDC is indispensable due to it generates a large amount of heat during its calculation process, which may potentially harm its normal operation. Electronic fluorinated fluids have been widely used in cooling systems of IDC with stable physical and chemical properties. However, the biological toxicity of electronic fluorinated fluids has not been fully evaluated and there is a lack of unified safety standards, which may pose potential risks to the environment and human health. Here, hexafluoropropylene terpolymer (HFPT) as an example has been systematically studied, fully considering the application scenarios of data centers. Also, the emergency effects of fluorinated coolants in mammalian models from the perspectives of inhalation, skin contact, accidental entry into eyes, accidental ingestion, and chronic toxicity, are evaluated. Multiple in vivo experiments have proven that HFPT not only has stable physical and chemical properties, that can maintain the safe operation of IDC, but also has low physiological toxicity to mammals and can provide health benefits to data center staff and the assurance of surrounding environment. This study proves the good biological safety of electronic fluorinated fluids and provides a reference for environmental assessment and risk management of liquid cooling technology in IDC. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-024-00234-3.

Risk Factors and Clinical Outcomes of Renal Thrombotic Microangiopathy in Children with Lupus Nephritis in Terms of Pathological and Clinical Features.

BACKGROUND: Thrombotic microangiopathy (TMA) is an important risk factor for the prognosis of lupus nephritis (LN). Patients with LN complicated with TMA tend to be critically ill with high mortality and poor prognosis. In the present study, we retrospectively analyzed the clinical manifestations, laboratory results, renal pathological manifestations, and prognosis of children with LN-TMA and analyzed the risk factors for end-stage renal disease (ESRD) in children with LN-TMA. METHODS: Seventy-four patients with LN and renal TMA (rTMA) were selected and compared to 128 LN controls without TMA (1:2 ratio) matched according to demographics, pathological type and treatments. RESULTS: The mean values of systolic blood pressure, diastolic blood pressure (DBP), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), urinary protein quantitation (PRO), urine red blood cells, N-acetyl-ß-D-glucosidase (NAG), retinol-binding protein, systemic lupus erythematosus disease activity score (SLEDAI), and activity index (AI) scores in the TMA group were all higher than those in the non-TMA group (p < 0.05 and p < 0.01). The mean values of complement C3, hemoglobin, platelets, estimated glomerular filtration rate, and chronic index (CI) score in the TMA group were all lower than those in the non-TMA group (p < 0.05 and p < 0.01). The number of cases of glomerular crescent, fibrous crescent, endocapillary proliferation, tubular atrophy, interstitial fibrosis, C3 and C1q deposition in the TMA group was higher than that in the non-TMA group (p < 0.05 and p < 0.01). The 3-year and 5-year renal survival rates in the TMA group (88.93% vs. 97.00%, p < 0.05) and TMA group (61.41% vs. 82.31%, p < 0.05) were significantly lower than those in the non-TMA group. Multivariate Cox regression analysis showed that serum creatinine before treatment (≥110 µmol/L), TMA and interstitial fibrosis were independent risk factors for the development of ESRD in LN children. CONCLUSION: The general condition of children with TMA is critical, and the prognosis is poor. Early detection, early treatment and the development of new treatments are key to improving LN-TMA outcomes in children.

The Enhanced Photoluminescence Properties of Carbon Dots Derived from Glucose: The Effect of Natural Oxidation.

The investigation of the fluorescence mechanism of carbon dots (CDs) has attracted significant attention, particularly the role of the oxygen-containing groups. Dual-CDs exhibiting blue and green emissions are synthesized from glucose via a simple ultrasonic treatment, and the oxidation degree of the CDs is softly modified through a slow natural oxidation approach, which is in stark contrast to that aggressively altering CDs' surface configurations through chemical oxidation methods. It is interesting to find that the intensity of the blue fluorescence gradually increases, eventually becoming the dominant emission after prolonging the oxidation periods, with the quantum yield (QY) of the CDs being enhanced from ~0.61% to ~4.26%. Combining the microstructure characterizations, optical measurements, and ultrafiltration experiments, we hypothesize that the blue emission could be ascribed to the surface states induced by the C-O and C=O groups, while the green luminescence may originate from the deep energy levels associated with the O-C=O groups. The distinct emission states and energy distributions could result in the blue and the green luminescence exhibiting distinct excitation and emission behaviors. Our findings could provide new insights into the fluorescence mechanism of CDs.

Biomechanical and histological changes associated with riboflavin ultraviolet-A-induced CXL with different irradiances in young human corneal stroma.

Keratoconus (KC) is a degenerative condition affecting the cornea, characterized by progressive thinning and bulging, which can ultimately result in serious visual impairment. The onset and progression of KC are closely tied to the gradual weakening of the cornea's biomechanical properties. KC progression can be prevented with corneal cross-linking (CXL), but this treatment has shortcomings, and evaluating its tissue stiffening effect is important for determining its efficacy. In this field, the shortage of human corneas has made it necessary for most previous studies to rely on animal corneas, which have different microstructure and may be affected differently from human corneas. In this research, we have used the lenticules obtained through small incision lenticule extraction (SMILE) surgeries as a source of human tissue to assess CXL. And to further improve the results' reliability, we used inflation testing, personalized finite element modeling, numerical optimization and histology microstructure analysis. These methods enabled determining the biomechanical and histological effects of CXL protocols involving different irradiation intensities of 3, 9, 18, and 30 mW/cm2, all delivering the same total energy dose of 5.4 J/cm2. The results showed that the CXL effect did not vary significantly with protocols using 3-18 mW/cm2 irradiance, but there was a significant efficacy drop with 30 mW/cm2 irradiance. This study validated the updated algorithm and provided guidance for corneal lenticule reuse and the effects of different CXL protocols on the biomechanical properties of the human corneal stroma.

Research on Improved Crystallization Properties and Underlying Mechanism of the Sb2Te3 Phase-Change Thin Film by Inserting Sn15Sb85 Layers.

As a non-volatile semiconductor memory technology, phase-change memory has a wide range of application prospects as a result of the excellent comprehensive performance. In this paper, multilayer thin films based on Sb2Te3 material were designed and prepared by inserting the Sn15Sb85 layer. The thermal and electrical properties of superlattice-like Sb2Te3/Sn15Sb85 phase-change films can be adjusted by controlling the thickness ratio of Sb2Te3/Sn15Sb85. In comparison to the monolayer Sb2Te3 film, the multilayer layer Sb2Te3/Sn15Sb85 materials have a higher crystallization temperature, larger crystallization activation energy, and longer data lifetime, indicating the great improvement of thermal stability. The changes in the phase structure and vibrational modes of multilayer Sb2Te3/Sn15Sb85 films were characterized by X-ray diffraction and Raman spectroscopy, respectively. The presence of Sn15Sb85 layers restrains grain growth and refines the grain size. The multilayer Sb2Te3/Sn15Sb85 films exhibit better surface flatness, smaller surface potential undulation, and lower thickness variations than single-layer Sb2Te3. Phase-change memory cells based on the [Sb2Te3 (1 nm)/Sn15Sb85 (9 nm)]5 thin film has a lower threshold voltage (1.9 V) and threshold current (3.1 µA) compared to the Ge2Sb2Te5 film. Meanwhile, the electrical heating model of a phase-change memory cell based on a [Sb2Te3 (1 nm)/Sn15Sb85 (9 nm)]5 multilayer structure was established by multiphysics coupling analysis, proving the great improvement in heat transfer performance and efficiency. The experimental and theoretical studies confirm that the insertion of the Sn15Sb85 layer can significantly improve the crystallization properties of Sb2Te3 films, paving the way for optimizing the phase-change materials by regulating the microstructural parameters.

Observation of Diverse Asymmetric Structures in High-Dimensional Einstein-Podolsky-Rosen Steering.

Einstein-Podolsky-Rosen (EPR) steering, a distinctive quantum correlation, reveals a unique and inherent asymmetry. This research delves into the multifaceted asymmetry of EPR steering within high-dimensional quantum systems, exploring both theoretical frameworks and experimental validations. We introduce the concept of genuine high-dimensional one-way steering, wherein a high Schmidt number of bipartite quantum states is demonstrable in one steering direction but not reciprocally. Additionally, we explore two criteria to certify the lower and upper bounds of the Schmidt number within a one-sided device-independent context. These criteria serve as tools for identifying potential asymmetric dimensionality of EPR steering in both directions. By preparing two-qutrit mixed states with high fidelity, we experimentally observe asymmetric structures of EPR steering in the C^{3}⊗C^{3} Hilbert space. Our Letter offers new perspectives to understand the asymmetric EPR steering beyond qubits and has potential applications in asymmetric high-dimensional quantum information tasks.

The sublethal concentration of acetamiprid suppresses the population growth of 2 species of wheat aphids, Sitobion miscanthi and Schizaphis graminum (Hemiptera: Aphididae).

Sitobion miscanthi and Schizaphis graminum (Rondani) are the 2 main aphid species that occur simultaneously, causing significant loss to wheat production. Acetamiprid has been used to control a variety of pests, including aphids. In this study, the sublethal effect of acetamiprid on S. miscanthi and S. graminum was evaluated using life-table analyses. The results showed that acetamiprid has a high toxicity to S. miscanthi and S. graminum with a LC50 of 1.90 and 3.58 mg/L at 24 h, respectively. The adult longevity and fecundity of S. miscanthi and S. graminum F0 generation were significantly reduced after being exposed to a sublethal concentration of acetamiprid. Additionally, the sublethal concentration of acetamiprid had negative transgenerational effects on S. miscanthi and S. graminum, which showed a significant decrease in fecundity and population life-table parameters involving age-stage-specific survival rate (sxj), age-specific survival rate (lx), and intrinsic rate of increase (r). Furthermore, the population projections showed that the total population size of S. miscanthi and S. graminum was significantly lower in the aphid group exposed to sublethal concentration of acetamiprid compared to the control group. These results suggest that sublethal concentration of acetamiprid suppresses the population growth of S. miscanthi and S. graminum. This finding is beneficial to the control of wheat aphids, and is important to fully understand the role of acetamiprid in integrated pest management.

Predictive models for functional cure in patients with CHB receiving PEG-IFN therapy based on HBsAg quantification through meta-analysis.

BACKGROUND AND AIMS: The efficacy of achieving HBsAg clearance through pegylated interferon (PEG-IFNα) therapy in patients with chronic hepatitis B (CHB) remains uncertain, especially regarding the probability of achieving functional cure among patients with varying baseline HBsAg levels. We aimed to investigate the predictive value of HBsAg quantification for HBsAg seroclearance in CHB patients undergoing PEG-IFNα treatment. METHODS: A systematic search was conducted in PubMed, Embase, and the Cochrane Library up to January 11, 2022. Subgroup analyses were performed for HBeAg-positive and HBeAg-negative patients, PEG-IFNα monotherapy and PEG-IFNα combination therapy, treatment-naive and treatment-experienced patients, and patients with or without liver cirrhosis. RESULTS: This predictive model incorporated 102 studies. The overall HBsAg clearance rates at the end of treatment (EOT) and the end of follow-up (EOF) were 10.6% (95% CI 7.8-13.7%) and 11.1% (95% CI 8.4-14.1%), respectively. Baseline HBsAg quantification was the most significant factor. According to the model, it is projected that when baseline HBsAg levels are 100, 500, 1500, and 10,000 IU/ml, the HBsAg clearance rates at EOF could reach 53.9% (95% CI 40.4-66.8%), 32.1% (95% CI 24.8-38.7%), 14.2% (95% CI 9.8-18.8%), and 7.9% (95% CI 4.2-11.8%), respectively. Additionally, treatment-experienced patients with HBeAg-negative status, and without liver cirrhosis exhibited higher HBsAg clearance rates after PEG-IFNα treatment. CONCLUSION: A successful predictive model has been established to predict the achievement of functional cure in CHB patients receiving PEG-IFNα therapy.

Diffuse hyperpigmentation with guttate hypopigmentation: a new pigmentary disorder.

Diffuse hyperpigmentation with guttate hypopigmentation (DHGH) is a new acquired pigmentary disorder. Only a few cases have previously been reported in the Chinese population, in Chinese. To summarise the clinical, dermoscopic, and histopathological findings of DHGH in the English literature, to improve the recognition and management of this condition. This was a retrospective study to summarise the clinical, dermoscopic, and pathological findings of nine cases of DHGH. All nine patients with DHGH were female. The age at onset varied from 6 to 24 years (median 17 years). Patients were generally in good health without systemic disease. The lesions were often generalised to the trunk and extremities without any discomfort. Typical lesions were characterised by multiple uniform hypopigmented spots, 2-5 mm in diameter, irregularly distributed over diffuse hyperpigmentation. Dermoscopy revealed multiple blurred patchy areas of brownish pigmentation, sparse linear and dotted vessels, and perifollicular pigmentation on a white to bright white background, surrounded by brown hyperpigmentation. Histopathological findings included mild abnormal pigment of the epidermis, focal vacuolar degeneration of the basal cells, mild pigment incontinence and perivascular lymphocytic infiltration in the dermis. DHGH is a new entity with distinctive clinical manifestations that differ from those of other known pigmentary disorders. So far, DHGH has only been reported in the Chinese population. It may not be uncommon and has not received much attention due to the few reports. The aetiology and pathogenesis of DHGH are still unknown and require further investigation.

A new chemical derivatization reagent sulfonyl piperazinyl for the quantification of fatty acids using LC-MS/MS.

In our previous study, a chemical derivatization reagent named 5-(dimethylamino) naphthalene-1-sulfonyl piperazine (Dns-PP) was developed to enhance the chromatographic retention and the mass spectrometric response of free fatty acids (FFAs) in reversed-phase liquid chromatography coupled with electrospray ionization-mass spectrometry (RPLC-ESI-MS). However, Dns-PP exhibited strong preferences for long-chain FFAs, with limited improvement for short- or medium-chain FFAs. In this study, a new series of labeling reagents targeting FFAs were designed, synthesized, and evaluated. Among these reagents, Tmt-PP (N2, N2, N4, N4-tetramethyl-6-(4-(piperazin-1-ylsulfonyl) phenyl)-1,3,5-triazine-2,4-diamine) exhibited the best MS response and was selected for further evaluations. We compared Tmt-PP with Dns-PP and four commonly used carboxyl labeling reagents from existing studies, demonstrating the advantages of Tmt-PP. Further comparisons between Tmt-PP and Dns-PP in measuring FFAs from biological samples revealed that Tmt-PP labeling enhanced the MS response for about 80 % (30/38) of the measured FFAs, particularly for short- and medium-chain FFAs. Moreover, Tmt-PP labeling significantly improved the chromatographic retention of short-chain FFAs. To ensure accurate quantification, we developed a stable isotope-labeled Tmt-PP (i.e., d12-Tmt-PP) to react with chemical standards and serve as one-to-one internal standards (IS). The method was validated for accuracy, precision, sensitivity, linearity, stability, extraction efficiency, as well as matrix effect. Overall, this study introduced a new chemical derivatization reagent Tmt-PP (d12-Tmt-PP), providing a sensitive and accurate option for quantifying FFAs in biological samples.

Zerumbone alleviated bleomycin-induced pulmonary fibrosis in mice via SIRT1/Nrf2 pathway.

Pulmonary fibrosis (PF) is a persistent interstitial lung condition for which effective treatment options are currently lacking. Zerumbone (zerum), a humulane sesquiterpenoid extracted from Zingiber zerumbet Smith, has been documented in previous studies to possess various pharmacological benefits. The aim of this study was to observe and investigate the therapeutic effects and mechanisms of zerum on pulmonary fibrosis. We utilized a transforming growth factor (TGF)-ß1-induced human lung fibroblast (MRC-5) activation model and a bleomycin-induced pulmonary fibrosis mouse model. Cell counting kit 8 (CCK8) and cell migration assays were performed to assess the effects of zerum on MRC-5 cells. Masson's trichrome, Hematoxylin and Eosin (HE), and Sirius Red staining were conducted for pathological evaluation of lung tissue. Western blot experiments were conducted to measure the protein expression levels of Collagen I, α-SMA, Nrf2, and SIRT1. Immunofluorescence and immunohistochemistry assays were used to detect the expression of reactive oxygen species (ROS), Nrf2, and α-SMA. ELISA was employed to measure the levels of MDA, SOD, and GSH-Px. Our findings from in vitro and in vivo studies demonstrated that zerum significantly inhibited the migration ability of TGF-ß1-induced MRC-5 cells, reduced ROS production in TGF-ß1-induced MRC-5 cells and pulmonary fibrosis mice, and decreased the expression of Collagen I and α-SMA proteins. Additionally, zerum activated the SIRT1/Nrf2 signaling pathway in TGF-ß1-induced MRC-5 cells and pulmonary fibrosis mice. Knockdown of SIRT1 abolished the anti-fibrotic effects of zerum. These results suggest that zerum inhibits TGF-ß1 and BLM-induced cell and mouse pulmonary fibrosis by activating the SIRT1/Nrf2 pathway.

Oxidative Tandem Cyclization of Aromatic Acids with (Benzo)thiophenes: One-Pot Access to Planar Sulfur-Containing Polycyclic Heteroarenes for Lipid-Droplet-Targeted Probes.

The efficient construction of π-conjugated polycyclic heteroarenes represents a significant task in the field of functional materials. A one-step oxidative tandem cyclization of aromatic acids with (benzo)thiophenes was developed to access planar sulfur-containing polycyclic heteroarenes. This protocol undergoes intermolecular cross-dehydrogenative coupling followed by intramolecular Friedel-Crafts acylation and provides a facile pathway to planar polycyclic compounds from inexpensive reactants. The synthesized heteroarenes serving as lipid-droplet-targeted probes exhibit outstanding performance with favorable biocompatibility and photostability.