Shuangdan Jiedu Decoction improved LPS-induced acute lung injury by regulating both cGAS-STING pathway and inflammasome.

ETHNOPHARMACOLOGICAL RELEVANCE: Shuangdan Jiedu Decoction (SJD) is a formula composed of six Chinese herbs with heat-removing and detoxifying, antibacterial, and anti-inflammatory effects, which is clinically used in the therapy of various inflammatory diseases of the lungs including COVID-19, but the therapeutic material basis of its action as well as its molecular mechanism are still unclear. AIM OF THE STUDY: The study attempted to determine the therapeutic effect of SJD on LPS-induced acute lung injury (ALI), as well as to investigate its mechanism of action and assess its therapeutic potential for the cure of inflammation-related diseases in the clinical setting. MATERIALS AND METHODS: We established an ALI model by tracheal drip LPS, and after the administration of SJD, we collected the bronchoalveolar lavage fluid (BALF) and lung tissues of mice and examined the expression of inflammatory factors in them. In addition, we evaluated the effects of SJD on the cyclic guanosine monophosphate-adenosine monophosphate synthase -stimulator of interferon genes (cGAS-STING) and inflammasome by immunoblotting and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: We demonstrated that SJD was effective in alleviating LPS-induced ALI by suppressing the levels of pro-inflammatory cytokines in the BALF, improving the level of lung histopathology and the number of neutrophils, as well as decreasing the inflammatory factor-associated gene expression. Importantly, we found that SJD could inhibit multiple stimulus-driven activation of cGAS-STING and inflammasome. Further studies showed that the Chinese herbal medicines in SJD had no influence on the cGAS-STING pathway and inflammasome alone at the formulated dose. By increasing the concentration of these herbs, we observed inhibitory effects on the cGAS-STING pathway and inflammasome, and the effect exerted was maximal when the six herbs were combined, indicating that the synergistic effects among these herbs plays a crucial role in the anti-inflammatory effects of SJD. CONCLUSIONS: Our research demonstrated that SJD has a favorable protective effect against ALI, and its mechanism of effect may be associated with the synergistic effect exerted between six Chinese medicines to inhibit the cGAS-STING and inflammasome abnormal activation. These results are favorable for the wide application of SJD in the clinic as well as for the development of drugs for ALI from herbal formulas.

A Two-Step Dry Etching Model for Non-Uniform Etching Profile in Gate-All-Around Field-Effect Transistor Manufacturing.

The Gate-All-Around Field-Effect Transistor (GAAFET) is proposed as a successor to Fin Field-Effect Transistor (FinFET) technology to increase channel length and improve the device performance. The GAAFET features a complex multilayer structure, which complicates the manufacturing process. One of the most critical steps in GAAFET fabrication is the selective lateral etching of the SiGe layers, essential for forming the inner-spacer. Industry commonly encounters a non-uniform etching profile during this step. In this paper, a continuous two-step dry etching model is proposed to investigate the mechanism behind the formation of the non-uniform profiles. The model consists of four modules: anisotropic etching simulation, Ge atom diffusion simulation, Si/SiGe etch selectivity calculation and SiGe selective etching simulation. By calibrating and verifying this model with experimental data, the edge rounding and gradient etching rates along the sidewall surface are successfully simulated. Based on further examination of the influence of chamber pressure on the profile using this model, the inner-spacer shape is improved experimentally by appropriately reducing the chamber pressure. This work aims to provide valuable insights for etching process recipes in advanced GAAFETs manufacturing.

Pb6Ba3Si2S8I10: a new thiohalide with a quasi-two-dimensional structure and wide band gap.

Pb-based chalcogenides display abundant structural diversity and distinguished properties. Based on a mixed anion and dimensional reduction combined strategy, a wide band gap Pb-based thiohalide, Pb6Ba3Si2S8I10, has been rationally designed and synthesized experimentally by the flux method. The compound crystallizes in the R3̄c space group with cell parameters a = 9.7925(2) Å, b = 9.7925(2) Å, and c = 70.628(3) Å and is composed of [SiS4] tetrahedra and unprecedented [PbI5S2] polyhedral units, resulting in a unique quasi-two-dimensional structure, which enriches the chemical and structural diversity of Pb-based thiohalides. The experimental band gap of Pb6Ba3Si2S8I10 was determined to be 2.80 eV. Based on statistical analyses and to the best of our knowledge, it is the largest experimental optical band gap among the known Pb-based thiohalides. The results demonstrate the feasibility of using highly electropositive Ba atoms to regulate the dimensions of the structural framework of thiohalides and give new insights into the structure and property modifications of thiohalides by the mixed anion and dimensional reduction combined strategy.

Carbonic anhydrase-embedded ZIF-8 membrane reactor with improved the recycling and stability for efficient CO2 capture.

Carbonic anhydrase (CA) enzyme-based absorption technology for CO2 capture has been intensively investigated. However, low solubility of CO2 and poor stability of CA severely limits its industrial utilization. Here, hydrolyzed polyacrylonitrile (PAN) membrane (HPAN) was first modified by polyethyleneimine (PEI) with a large number of amino groups, which has a strong affinity for CO2. Then, ZIF-8 was grown in situ on the surface of HPAN/PEI membrane by using the metal chelation of PEI and Zn2+. In this process, CA was embedded inside ZIF-8 by co-precipitation (CA@HPAN/PEI/ZIF-8). The resultant CA@HPAN/PEI/ZIF-8 exhibited high catalytic activity for CO2 capture compared with free CA, which was due to the synergistic enhancement of CO2 capture by PEI and ZIF-8 with high affinity to CO2 and enzymatic catalysis. The yield of CaCO3 by CA@HPAN/PEI/ZIF-8 in the process of one-time conversion of CO2 was 13.6-fold higher than free CA. Furthermore, the CA@HPAN/PEI/ZIF-8 showed better thermal stability, storage and reusability than free CA. Free CA retained only 18.3 % of its original activity after 18 days of storage, whereas CA@HPAN/PEI/ZIF-8 remained 48.7 % of its original activity. The total CaCO3 yield by CA@HPAN/PEI/ZIF-8 was 74.9-fold that of free CA after 8 consecutive rounds of CO2 conversion.

Self-Illuminating Copper-Luminol Coordination Polymers for Bioluminescence Imaging of Oxidative Damage.

Timely detection of reactive oxygen species (ROS) accumulated during inflammation is essential for an early disease diagnosis. Compared to fluorescence probes with limited sensitivity and accuracy, chemiluminescence (CL) imaging offers the potential for highly sensitive molecular visualization of ROS by minimizing background interferences. However, the development of bright and easily manufacturable CL probes for ROS imaging remains challenging. In this study, a novel chemiluminescent nanoprobe named Cu-Lum@NPs for ROS imaging in inflammation was synthesized by using a one-step solvothermal method. The Cu-Lum@NPs, which are composed of coordination polymers containing copper ions and luminol (Lum), demonstrate intrinsic peroxidase-like activity that relies on Cu(I) as the catalytic active center to initiate the Fenton reaction. This catalytic process facilitates the decomposition of hydrogen peroxide (H2O2) into hydroxyl radicals (•OH) and superoxide anion radicals (O2•-), leading to the oxidation of Lum and inducing strong luminescence. Cu-Lum@NPs, displaying nanozyme characteristics, were observed to accelerate and enhance the ROS-responsive luminescence (10-1600-fold in solution and over 100-fold in neutrophils) and notably extend persistent luminescence. The Cu-Lum@NPs allowed for CL imaging of endogenous ROS in living cells and animals with an outstanding signal-to-noise ratio exceeding 96 and facilitated oxidative damage luminescence imaging for tissue-specific detection. The study presents Cu-Lum@NPs, a highly sensitive and easily manufacturable chemiluminescent nanoprobe for ROS imaging both in vitro and in vivo, exhibiting enhanced luminescence and prolonged persistence for ROS-related disease detection.

New magnetic proxies to reveal source and bioavailability of heavy metals in contaminated soils.

Environmental magnetism plays an important role in monitoring heavy metal pollution, but most studies are confined to indicating only the levels of heavy metals using magnetic parameters. This study established new magnetic proxies for accurately depicting the sources and bioavailability of heavy metals in contaminated soils. We observed different relationships between χ and SIRM in the soils contaminated by non-ferrous metal smelting compared to those polluted by coal combustion and steel smelting. Furthermore, we found that the soft magnetic components (IRMsoft) in the soils were mainly controlled by the non-ferrous metal smelting activities, while the hard magnetic components (HIRM) might be affected by the iron erosion. These new magnetic proxies enriched the source composition spectrum and improved the accuracy of the source apportionment analyses (principal component analysis and positive matrix factorization), yielding a result that was comparable to that by Pb isotope fingerprinting. We also found strong relationships between magnetic parameters (especially IRMsoft) and bioavailable fractions of heavy metals, indicating that magnetic measurement may be a powerful tool for monitoring the bioavailability of heavy metals. This study expands the application fields of magnetism in environmental science research.

Leveraging adrenergic receptor blockade for enhanced nonalcoholic fatty liver disease treatment via a biomimetic nanoplatform.

Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation, steatosis and fibrosis. Sympathetic nerves play a critical role in maintaining hepatic lipid homeostasis and regulating fibrotic progression through adrenergic receptors expressed by hepatocytes and hepatic stellate cells; however, the use of sympathetic nerve-focused strategies for the treatment of NAFLD is still in the infancy. Herein, a biomimetic nanoplatform with ROS-responsive and ROS-scavenging properties was developed for the codelivery of retinoic acid (RA) and the adrenoceptor antagonist labetalol (LA). The nanoplatform exhibited improved accumulation and sufficient drug release in the fibrotic liver, thereby achieving precise codelivery of drugs. Integration of adrenergic blockade effectively interrupted the vicious cycle of sympathetic nerves with hepatic stellate cells (HSCs) and hepatocytes, which not only combined with RA to restore HSCs to a quiescent state but also helped to reduce hepatic lipid accumulation. We demonstrated the excellent ability of the biomimetic nanoplatform to ameliorate liver inflammation, fibrosis and steatosis. Our work highlights the tremendous potential of a sympathetic nerve-focused strategy for the management of NAFLD and provides a promising nanoplatform for the treatment of NAFLD.

In Situ Built ZnS/MXene Heterostructure by a Mild Method for Inhibiting Polysulfide Shuttle in Li-S Batteries.

With high specific surface area, excellent polysulfide conversion activity, and fast electron/ion transfer at the interface, MXene-derived heterostructures can be employed as catalysts for lithium-sulfur (Li-S) batteries to accelerate sulfur redox kinetics and suppress shuttle effect. However, the preparation of MXene-derived heterostructures often requires high-temperature reactions, which can easily lead to the oxidation of MXene and sacrifice the electrical conductivity. Herein, a catalytic two-dimensional heterostructure (ZnS/MXene) was successfully synthesized via a mild method. The MXene skeleton retains the original nanosheet structure without oxidation. The in situ-grown ZnS nanospheres prevent the restacking of MXene nanosheets, which not only increases the active sites, but also guarantees channels for the fast passage of lithium ions. The interfacial built-in electric field further promotes electron/ion migration, thereby expediting the polysulfide conversion and suppressing the shuttle effect. Consequently, the batteries using ZnS/MXene modified separators exhibit a high initial discharge capacity of 1230 mAh g-1 at 0.1 C and a low decaying rate of 0.082% per cycle after 500 cycles at 0.5 C. This work offers a reference for the fabrication of MXene-based heterostructure in Li-S batteries.

The Potential Role of Artemisinins Against Neurodegenerative Diseases.

Artemisinin (ART) and its derivatives, collectively referred to as artemisinins (ARTs), have been approved for the treatment of malaria for decades. ARTs are converted into dihydroartemisinin (DHA), the only active form, which is reductive in vivo. In this review, we provide a brief overview of the neuroprotective potential of ARTs and the underlying mechanisms on several of the most common neurodegenerative diseases, particularly considering their potential application in those associated with cognitive and motor impairments including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). ARTs act as autophagy balancers to alleviate AD and PD. They inhibit neuroinflammatory responses by regulating phosphorylation of signal transduction proteins, such as AKT, PI3K, ERK, NF-[Formula: see text]B, p38 MAPK, I[Formula: see text]B[Formula: see text]. In addition, ARTs regulate GABAergic signaling in a dose-dependent manner. Although they competitively inhibit the binding of gephyrin to GABAergic receptors, low doses of ARTs enhance GABAergic signaling. ARTs can also inhibit ferroptosis, activate the Akt/Bcl-2, AMPK, or ERK/CREB pathways to reduce oxidative stress, and maintain mitochondrial homeostasis, protecting neurons from oxidative stress injury. More importantly, ARTs structurally combine with and suppress [Formula: see text]-Amyloid (A[Formula: see text]-induced neurotoxicity, reduce P-tau, and maintain O-GlcNAcylation/Phosphorylation balance, leading to relieved pathological changes in neurodegenerative diseases. Collectively, these natural properties endow ARTs with unique potential for application in neurodegenerative diseases.

One-Step Dry-Etching Fabrication of Tunable Two-Hierarchical Nanostructures.

Two-hierarchical nanostructures, characterized by two distinct configurations along the height direction, exhibit immense potential for applications in various fields due to their significantly enhanced controllable degree compared to single-order structures. However, due to the limitations imposed by planar technology, the realization of two-hierarchical nanostructures encounters huge challenges. In this work, we developed a one-step etching method based on inductively coupled plasma reactive ion etching for two-hierarchical nanostructures. Thanks to the shrinking effect of the Cr mask and the generation of a passivation layer during etching, the target materials experienced two different states from vertical etching to shrink etching. Consequently, the achieved two-hierarchical nanostructure configuration features a cross-section of an upper triangle and a lower rectangle, showing higher controllable degrees compared to the one-order ones. Both the mask pattern and etching parameters play crucial roles, by which two-hierarchical structures with diversiform shapes can be constructed controllably. This method for two-hierarchical nanostructures offers advantages including excellent control over structural properties, high processing efficiency, uniformity across large areas, and universality in materials. This developed strategy not only presents a simple and rapid nanofabrication platform for realizing optoelectronic devices, but also provides innovative ideas for designing the next generation of high-performance devices.

Comparative life cycle assessment of PBAT from fossil-based and second-generation generation bio-based feedstocks.

With the increasing demand for plastics, plastic pollution is growing rapidly. A significant amount of plastic has leaked into the environment, leading to severe environmental issues. Biodegradable plastics are considered promising alternatives to conventional durable plastics, and the environmental impacts of biodegradable plastics have received increasing attention. Poly (butylene adipate-co-terephthalate) (PBAT) is a commercial and cost-competitive biodegradable polymer and has been applied in the packaging and agriculture sectors. The environmental performances of PBAT with second-generation feedstocks from forestry waste have been rarely investigated. Since China is the leading global producer and exporter of PBAT polymer, Chinese cradle-to-gate life cycle inventories of PBAT were compiled in this study. A comparative life cycle assessment (LCA) was conducted to explore the potential for environmental performance of PBAT with second-generation bio-based feedstock compared to fossil-based PBAT and conventional plastics. The results showed that feedstocks contributed to more than 70 % of 18 environmental impact categories of fossil-based PBAT. In comparison, PBAT with second-generation bio-based feedstock reduces the environmental loads in 16 impact categories by 15-85 %, and renewable energy substitution has the potential to reduce environmental impacts by 10 %. Bio-based PBAT performs better than PVC, PP, HDPE, LDPE, and PET in 16 impact categories by 15-80 %. Bio-based PBAT has GWP of 3.72 kg CO2 eq, which is 37 % lower than fossil-based PBAT (5.89 kg CO2 eq) and 18-32 % lower than conventional plastics. Since feedstock dominates the environmental performance of PBAT, the development of biomanufacturing technologies for bio-based polymers and chemicals could significantly improve environmental performance of biodegradable plastics and promote the sustainable development of the plastic industry. Results could serve as the basis for environmental impact and mitigation strategies for biodegradable plastics with bio-based feedstocks, as well as the sustainable development of the PBAT industry.

Aligned fibrous scaffolds promote directional migration of breast cancer cells via caveolin-1/YAP-mediated mechanosensing.

Tumorigenesis and metastasis are highly dependent on the interactions between the tumor and the surrounding microenvironment. In 3D matrix, the fibrous structure of the extracellular matrix (ECM) undergoes dynamic remodeling during tumor progression. In particular, during the late stage of tumor development, the fibers become more aggregated and oriented. However, it remains unclear how cancer cells respond to the organizational change of ECM fibers and exhibit distinct morphology and behavior. Here, we used electrospinning technology to fabricate biomimetic ECM with distinct fiber arrangements, which mimic the structural characteristics of normal or tumor tissues and found that aligned and oriented nanofibers induce cytoskeletal rearrangement to promote directed migration of cancer cells. Mechanistically, caveolin-1(Cav-1)-expressing cancer cells grown on aligned fibers exhibit increased integrin ß1 internalization and actin polymerization, which promoted stress fiber formation, focal adhesion dynamics and YAP activity, thereby accelerating the directional cell migration. In general, the linear fibrous structure of the ECM provides convenient tracks on which tumor cells can invade and migrate. Moreover, histological data from both mice and patients with tumors indicates that tumor tissue exhibits a greater abundance of isotropic ECM fibers compared to normal tissue. And Cav-1 downregulation can suppress cancer cells muscle invasion through the inhibition of YAP-dependent mechanotransduction. Taken together, our findings revealed the Cav-1 is indispensable for the cellular response to topological change of ECM, and that the Cav-1/YAP axis is an attractive target for inhibiting cancer cell directional migration which induced by linearization of ECM fibers.

Neuroimaging analysis reveals distinct cerebral perfusion responses to fasting-postprandial metabolic switching in Alzheimer's disease patients.

AIMS: Extended fasting-postprandial switch intermitting time has been shown to affect Alzheimer's disease (AD). Few studies have investigated the cerebral perfusion response to fasting-postprandial metabolic switching (FMS) in AD patients. We aimed to evaluate the cerebral perfusion response to FMS in AD patients. METHODS: In total, 30 AD patients, 32 mild cognitive impairment (MCI) patients, and 30 healthy control individuals (HCs) were included in the quantification of cerebral perfusion via cerebral blood flow (CBF). The cerebral perfusion response to FMS was defined as the difference (ΔCBF) between fasting and postprandial CBF. RESULTS: Patients with AD had a regional negative ΔCBF in the anterior temporal lobe, part of the occipital lobe and the parietal lobe under FMS stimulation, whereas HCs had no significant ΔCBF. The AD patients had lower ΔCBF values in the right anterior temporal lobe than the MCI patients and HCs. ΔCBF in the anterior temporal lobe was negatively correlated with cognitive severity and cognitive reserve factors in AD patients. CONCLUSIONS: AD patients exhibited a poor ability to maintain cerebral perfusion homeostasis under FMS stimulation. The anterior temporal lobe is a distinct area that responds to FMS in AD patients and negatively correlates with cognitive function.

Rutin enhances mitochondrial function and improves the developmental potential of vitrified ovine GV-stage oocyte.

Vitrification of oocyte has become an important component of assisted reproductive technology and has important implications for animal reproduction and the preservation of biodiversity. However, vitrification adversely affects mitochondrial function and oocyte developmental potential, mainly because of oxidative damage. Rutin is a highly effective antioxidant, but no information is available to the effect of rutin on the mitochondrial function and development in vitrified oocytes. Therefore, we studied the effects of rutin supplementation of vitrification solution on mitochondrial function and developmental competence of ovine germinal vesicle (GV) stage oocytes post vitrification. The results showed that supplementation of vitrification solution with 0.6 mM rutin significantly increased the cleavage rate (71.6 % vs. 59.3 %) and blastocyst rate (18.9 % vs. 6.8 %) compared to GV-stage oocytes in the vitrified group. Then, we analyzed the reactive oxygen species (ROS), glutathione (GSH), mitochondrial activity and membrane potential (ΔΨm), endoplasmic reticulum (ER) Ca2+, and annexin V (AV) of vitrified sheep GV-stage oocytes. Vitrified sheep oocytes exhibited increased levels of ROS and Ca2+, higher rate of AV-positive oocytes, and decreased mitochondrial activity, GSH and ΔΨm levels. However, rutin supplementation in vitrification solution decreased the levels of ROS, Ca2+ and AV-positive oocytes rate, and increased the GSH and ΔΨm levels in vitrified oocytes. Results revealed that rutin restored mitochondrial function, regulated Ca2+ homeostasis and decreased apoptosis potentially caused by mitophagy in oocytes. To understand the mechanism of rutin functions in vitrified GV-stage oocytes in sheep, we analyzed the transcriptome and found that rutin mediated oocytes development and mitochondrial function, mainly by affecting oxidative phosphorylation and the mitophagy pathways. In conclusion, supplementing with 0.6 mM rutin in vitrification solution significantly enhanced developmental potential through improving mitochondrial function and decreased apoptosis potentially caused by mitophagy after vitrification of ovine GV-stage oocytes.

Bacteriophage λ exonuclease and a 5'-phosphorylated DNA guide allow PAM-independent targeting of double-stranded nucleic acids.

Sequence-specific recognition of double-stranded nucleic acids is essential for molecular diagnostics and in situ imaging. Clustered regularly interspaced short palindromic repeats and Cas systems rely on protospacer-adjacent motif (PAM)-dependent double-stranded DNA (dsDNA) recognition, limiting the range of targetable sequences and leading to undesired off-target effects. Using single-molecule fluorescence resonance energy transfer analysis, we discover the enzymatic activity of bacteriophage λ exonuclease (λExo). We show binding of 5'-phosphorylated single-stranded DNA (pDNA) to complementary regions on dsDNA and DNA-RNA duplexes, without the need for a PAM-like motif. Upon binding, the λExo-pDNA system catalytically digests the pDNA into nucleotides in the presence of Mg2+. This process is sensitive to mismatches within a wide range of the pDNA-binding region, resulting in exceptional sequence specificity and reduced off-target effects in various applications. The absence of a requirement for a specific motif such as a PAM sequence greatly broadens the range of targets. We demonstrate that the λExo-pDNA system is a versatile tool for molecular diagnostics, DNA computing and gene imaging applications.

Predictive machine learning models based on VASARI features for WHO grading, isocitrate dehydrogenase mutation, and 1p19q co-deletion status: a multicenter study.

The objective of our study was to develop predictive models using Visually Accessible Rembrandt Images (VASARI) magnetic resonance imaging (MRI) features combined with machine learning techniques to predict the World Health Organization (WHO) grade, isocitrate dehydrogenase (IDH) mutation status, and 1p19q co-deletion status of high-grade gliomas. To achieve this, we retrospectively included 485 patients with high-grade glioma from the First Affiliated Hospital of Xinjiang Medical University, of which 312 patients were randomly divided into a training set (n=218) and a test set (n=94) in a 7:3 ratio. Twenty-five VASARI MRI features were selected from an initial set of 30, and three machine learning models - Multilayer Perceptron (MP), Bernoulli Naive Bayes (BNB), and Logistic Regression (LR) - were trained using the training set. The most informative features were identified using recursive feature elimination. Model performance was assessed using the test set and an independent validation set of 173 patients from Beijing Tiantan Hospital. The results indicated that the MP model exhibited the highest predictive accuracy on the training set, achieving an area under the curve (AUC) close to 1, indicating perfect discrimination. However, its performance decreased in the test and validation sets; particularly for predicting the 1p19q co-deletion status, the AUC was only 0.703, suggesting potential overfitting. On the other hand, the BNB model demonstrated robust generalization on the test and validation sets, with AUC values of 0.8292 and 0.8106, respectively, for predicting IDH mutation status and 1p19q co-deletion status, indicating high accuracy, sensitivity, and specificity. The LR model also showed good performance with AUCs of 0.7845 and 0.8674 on the test and validation sets, respectively, for predicting IDH mutation status, although it was slightly inferior to the BNB model for the 1p19q co-deletion status. In conclusion, integrating VASARI MRI features with machine learning techniques shows promise for the non-invasive prediction of glioma molecular markers, which could guide treatment strategies and improve prognosis in glioma patients. Nonetheless, further model optimization and validation are necessary to enhance its clinical utility.

Comparative analysis of the femoral neck system (FNS) vs. cannulated cancellous screws (CCS) in the treatment of Middle-aged and elderly patients with femoral neck fractures: clinical outcomes and biomechanical insights.

PURPOSE: This study aimed to compare the clinical outcomes and differences in biomechanical characteristics between the femoral neck system (FNS) and cannulated cancellous screws (CCSs) in the treatment of femoral neck fractures. METHODS: This study retrospectively analysed a cohort of 38 registered cases of femoral neck fractures treated surgically with either the FNS (n = 17) or CCSs (n = 21) between January 2020 and December 2023. Indicators such as fluoroscopy frequency, length of hospital stay, and fracture healing time were compared between the two groups. Functional status was evaluated via the Harris hip score (HHS) and visual analogue scale (VAS), whereas prognosis was assessed based on changes in the neck shaft angle and femoral neck shortening. Additionally, six sets of femoral neck fracture models were developed based on Pauwels angles of 30°, 40°, 50°, 60°, 70°, and 80°. Two experimental groups, FNS and CCS, were established, and a joint reaction force of 1800 N was applied to the proximal femur. The displacement, stress, and stiffness of the components of interest in the different models were tested and compared. RESULTS: The distributions of all the baseline characteristics were similar between the two groups (p > 0.05). The FNS group presented significantly shorter fluoroscopy frequency, length of hospital stay, and fracture healing time (p < 0.05). Harris and VAS scores were higher in the FNS group than in the CCS group (p < 0.05). Postoperative changes in the neck shaft angle and femoral neck shortening were significantly lower in the FNS group than in the CCS group (p < 0.05). The results of the finite element analysis indicated that the maximum stress on the femoral head and varus angle were generally lower in the FNS group than in the CCS group and that the maximum displacement of the femoral head and FNS was generally lower in the FNS group than in the CCS group. However, the superiority of FNS over CCS decreased with increasing Pauwels angle. Additionally, the effectiveness of FNS in limiting displacement of the femoral neck upper wall was not as favourable as that of CCS. CONCLUSIONS: The treatment of femoral neck fractures with FNS is superior and contributes to improved hip joint function. Biomechanical research has confirmed its structural stability and advantages in resisting femoral head varus. However, challenges to its fixation efficacy persist, particularly at higher Pauwels angles.

Micro-polluted water source purification of root channel wetland in Jiaxing, China.

Root channel wetlands, as a new type of nature-imitating wetland system, provide a paradigm for micro-polluted water source purification; however, there is a knowledge gap on root channel wetlands' pollution removal effects and their main influencing factors after longtime operation. This study collected the turbidity, ammonia nitrogen (NH3-N), total nitrogen (TN), total phosphorus (TP), permanganate index (CODMn), dissolved oxygen (DO), and chemical oxygen demand (COD) at the inlet and outlet of Shijiuyang (SJY) wetland and Guanjinggang (GJG) wetland in Jiaxing City, China, from 2019 to 2021. The results showed that root channel wetlands had better water quality improvement effects. The SJY wetland had larger removal rates for DO, CODMn, and turbidity compared with the GJG wetland. In contrast, other water quality indexes have similar removal rates at both wetlands. The influencing factor analysis showed that water purification agent, flow, pH, and water temperature have large influences on the removal rates of pollutants for both wetlands. To address high turbidity and excessive DO, which are the primary pollutants affecting the two wetlands, implementing the diversion river before the pretreatment area and incorporating ecological floating beds in the deep purification area are recommended solutions to mitigate these issues. Compared with conventional general constructed wetlands, root channel wetlands are a more cost-effective and sustainable technology. The research is conducive to improving understanding of root channel wetland purification for micro-polluted water sources and enhancing water supply security capability in the plains water network area of the Yangtze River Delta region. PRACTITIONER POINTS: Compared with conventional general constructed wetlands, root channel wetlands are more cost-effective and sustainable technology. The SJY wetland demonstrated better removal rates for DO, CODMn, and turbidity, indicating a higher purification capacity compared to GJG wetland. Flow rate and pH are the primary factors influencing the GJG wetland, while the waterpurification agent and water temperature are the main factors affecting water quality in the SJY wetland.

Phillyrin and its metabolites exert antipyretic effects by targeting the NAD+ binding domain of GAPDH, MDH2 and IDH2.

BACKGROUND: Fever is one of the main pathophysiological reactions that occurs during the acute phase of various diseases. Excessive body temperature can lead to various adverse consequences such as brain tissue damage and abnormal immune responses. Phillyrin (Phr) is the main active ingredient in Forsythia suspensa (Thunb.) Vahl (Lian Qiao) and has antipyretic effects; however, its antipyretic mechanism of action remains unclear. PURPOSE: This study aimed to explore the antipyretic mechanisms of Phr and provide a new treatment plan for fever. METHODS: The antipyretic effects of Phr were evaluated using a mouse model of pneumonia fever. The main metabolites of Phr involved in its antipyretic function were identified using a mitochondrial temperature-sensitive probe. Further synthesis of the main metabolite, phillygenin (Phg), an alkynylated probe, was performed, and chemical proteomics was used to capture and analyze its direct target for antipyretic effects. The mechanism of action of Phg and its antipyretic targets was explored using metabolomics and various molecular biology methods. RESULTS: Phr showed significant antipyretic and anti-inflammatory effects in a mouse model of lipopolysaccharide-induced fever. Phg reversibly targeted the nicotinamide adenine dinucleotide (NAD+) binding domain of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), malate dehydrogenase 2 (MDH2), and isocitrate dehydrogenase 2 (IDH2) to inhibit their enzymatic activity. In-depth analysis of cellular metabolomics and mitochondrial stress testing indicated that inhibition of GAPDH, MDH2, and IDH2 enzyme activity by Phg led to a decrease in cellular energy supply and heat production regulated by glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation signaling pathways. Phg specifically targeted macrophages and inhibited LPS-induced macrophage activation by downregulating GAPDH enzyme activity, thereby exerting anti-inflammatory effects. In vivo experiments also confirmed that the antipyretic effect of Phr in LPS-induced fever model mice was related to its main metabolites, Phg and Phg-sulfonate (Phg-S), which directly targeted the NAD+ binding domain of GAPDH, IDH2, and MDH2, inhibiting the activity of these enzymes, thereby reducing energy supply and regulating febrile-related inflammatory factors. CONCLUSION: This study reported for the first time that the antipyretic effect of Phr is produced by targeting GAPDH, IDH2, and MDH2 to regulate energy supply and febrile-related inflammatory factors through its main metabolites Phg and Phg-S. This study not only provides potential drugs for fever treatment but also provides new ideas for improving clinical fever treatment plans.

Aggregation-Induced Emission-Active Photosensitizer-Mediated Photodynamic Therapy for Anti-Psoriasis.

Hyperproliferative keratinocytes and subcutaneous inflammation contribute to the characteristic symptoms of psoriasis, including erythema, scales, or scaly plaques on the skin. These symptoms significantly affect patients' quality of life and cause severe physical and psychological distress. However, current treatment strategies have limited therapeutic effect and may lead to adverse side effects. In this study, we present the novel organic photosensitizer TBTDC [5-(((5-(7-(4-(diphenylamino)phenyl)benzo[c][1,2,5]thiadiazol-4-yl)thiophen-2-yl)methylene)amino)-3-methylthiophene-2,4-dicarbonitrile] nanoparticles (NPs) with aggregation-induced emission (AIE) characteristics to mediate photodynamic therapy (TBTDC NP-PDT) for psoriasis treatment. We demonstrate that TBTDC NPs effectively generate reactive oxygen species upon light irradiation and lead to significant apoptosis of psoriatic keratinocytes. Furthermore, TBTDC NPs exhibit high cellular uptake in diseased keratinocytes and induce endoplasmic reticulum stress (ERS)-mediated autophagy, which can also enhance apoptosis. Importantly, TBTDC NPs show no cytotoxicity toward keratinocytes. These unique properties of TBTDC NPs enable remarkable therapeutic effects against psoriasis-like skin lesions and related inflammation in vivo. Overall, our AIE-active TBTDC NP-PDT represents a promising strategy for treating psoriasis in clinical settings.